**Table 4.**

*Chemical characterization of terpenoids detected in vegetable oils.*

*trans*-pinocarveol, borneol, 4-terpineol, 3-pinanone, 2-pinen-10-ol, myrtenal, verbenone, α-cubebene, camphor, α-copaene, β-elemene, β-bourbonene, β-selinene, 2-norpinene, aristolen, γ-cadinene, calarene, α-amorphene, β-bisabolene, δ-cadinene. While the main terpenoids in the following oils were: flaxseed (α-pinene, camphene, verbenene, 2-β-pinene, 3-carene, α-terpinene, DL-limonene, 1,8-cineole, γ-terpinene, and α-terpinolene), rapeseed (*p*-cymene), and sesame seed (2-norpinene). Other vegetable oils have different terpene profiles [18, 19] (**Table 4**).

#### **6. Application of chromatographic techniques in Sacha inchi seed oil**

There are few reports about the chemical characterization of the terpenoids in the Sacha inchi oil (**Table 5**). The separation of the different analytes from the sterol fraction was conducted using the following columns: SAC™-5/Merck (Phase: 5% diphenyl/95% dimethyl polysiloxane), HP-5/Agilent J&W (Phase: 5% phenyl-methylpolysiloxane), and SPB-5/Merck (5% diphenyl/95% dimethyl polysiloxane). While the separation of volatile compounds was carried out using columns with high polar (DB-WAX/Agilent J&W, and TRB-WAX/Teknokroma/ 100% polyethylene glycol) and nonpolar (DB-5/Agilent J&W/5% phenyl-methylpolysiloxane) stationary phases.

Monroy-Soto et al. [11] evaluated the volatile composition of Colombian commercial Sacha inchi oil using headspace-solid phase microextraction coupled GC–MS-O. Ramos-Escudero et al. [20] analyzed the Peruvian commercial Sacha inchi by HS-SPME/GC–MS, through which 16 volatile compounds (among them limonene, α-pinene, and sabinene) may have a significant influence upon perceived flavor and odor.


*List of abbreviations: GC-FID, Gas chromatography-flame ionization detector; GC–MS, Gas chromatography– mass spectrometry; HS-SPME, Headspace-solid phase microextraction; GC–MS-O, Gas Chromatography–Mass Spectrometry-Olfactometry. A, authentication; C, characterization; P, cold pressed; S, solvent.*

#### **Table 5.**

*Characterization and authentication of Sacha inchi oil.*

#### **7. Conclusions**

Sacha inchi oil is a product of economic importance that has been characterized according to its chemical composition. At present several classes of chemical compounds have been identified and quantified, and more recently the volatile

**45**

**Author details**

Alexandra Valencia1

**Conflict of interest**

Dayana Barriga-Rodriguez<sup>3</sup>

, Frank L. Romero-Orejon1

1 Unidad de Investigación en Nutrición, Salud, Alimentos Funcionales y

2 Nutrition and Food Chemistry, University of Valencia, Burjassot, Spain

Loyola (ICAN-USIL), Campus Pachacamac, Sección B, Lima, Perú

\*Address all correspondence to: diomedes.fernando@gmail.com

provided the original work is properly cited.

Nutraceúticos, Universidad San Ignacio de Loyola (UNUSAN-USIL), Lima, Perú

3 Facultad de Ciencias de la Salud, Universidad San Ignacio de Loyola, Lima, Perú

4 Instituto de Ciencias de los Alimentos y Nutrición, Universidad San Ignacio de

© 2021 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

, Adriana Viñas-Ospino1,2,

, Ana María Muñoz1,4 and Fernando Ramos-Escudero1,4\*

*Sacha Inchi Seed (*Plukenetia volubilis *L.) Oil: Terpenoids*

The authors declare no conflict of interest.

composition. The volatile organic compounds correspond to notes generated by alcohols, aldehydes, ketones, and terpenoids. The classes of terpenoids found in Sacha inchi oil were monoterpenes, sesquiterpenes, diterpenes, and triterpenes. These compounds provide different sensory properties in the oil. Furthermore, the characterization is conducted mainly by gas chromatography (GC) coupled to flame

ionization detector (FID) and mass spectrometry (MS) detection.

*DOI: http://dx.doi.org/10.5772/intechopen.96690*

*Sacha Inchi Seed (*Plukenetia volubilis *L.) Oil: Terpenoids DOI: http://dx.doi.org/10.5772/intechopen.96690*

composition. The volatile organic compounds correspond to notes generated by alcohols, aldehydes, ketones, and terpenoids. The classes of terpenoids found in Sacha inchi oil were monoterpenes, sesquiterpenes, diterpenes, and triterpenes. These compounds provide different sensory properties in the oil. Furthermore, the characterization is conducted mainly by gas chromatography (GC) coupled to flame ionization detector (FID) and mass spectrometry (MS) detection.

#### **Conflict of interest**

*Terpenes and Terpenoids-Recent Advances*

profiles [18, 19] (**Table 4**).

flavor and odor.

Sterol SAC™-5

Sterol HP-5

Sterol SPB-5

Terpenes DB-WAX

Terpenes ATR-WAX

DB5

(30m x 0.25mm ID)

(30 m x 0.32 mm ID)

(30 m x 0.32 mm ID)

(30 m x 0.25 mm ID)

(30 m x 0.25 mm ID)

(60 m x 0.25 mm ID)

*Characterization and authentication of Sacha inchi oil.*

*trans*-pinocarveol, borneol, 4-terpineol, 3-pinanone, 2-pinen-10-ol, myrtenal, verbenone, α-cubebene, camphor, α-copaene, β-elemene, β-bourbonene, β-selinene, 2-norpinene, aristolen, γ-cadinene, calarene, α-amorphene,

β-bisabolene, δ-cadinene. While the main terpenoids in the following oils were: flaxseed (α-pinene, camphene, verbenene, 2-β-pinene, 3-carene, α-terpinene, DL-limonene, 1,8-cineole, γ-terpinene, and α-terpinolene), rapeseed (*p*-cymene), and sesame seed (2-norpinene). Other vegetable oils have different terpene

**6. Application of chromatographic techniques in Sacha inchi seed oil**

There are few reports about the chemical characterization of the terpenoids in the Sacha inchi oil (**Table 5**). The separation of the different analytes from the sterol fraction was conducted using the following columns: SAC™-5/Merck (Phase: 5% diphenyl/95% dimethyl polysiloxane), HP-5/Agilent J&W (Phase: 5% phenyl-methylpolysiloxane), and SPB-5/Merck (5% diphenyl/95% dimethyl polysiloxane). While the separation of volatile compounds was carried out using columns with high polar (DB-WAX/Agilent J&W, and TRB-WAX/Teknokroma/ 100% polyethylene glycol) and nonpolar (DB-5/Agilent J&W/5% phenyl-methylpolysiloxane) stationary phases. Monroy-Soto et al. [11] evaluated the volatile composition of Colombian commercial Sacha inchi oil using headspace-solid phase microextraction coupled GC–MS-O. Ramos-Escudero et al. [20] analyzed the Peruvian commercial Sacha inchi by HS-SPME/GC–MS, through which 16 volatile compounds (among them limonene, α-pinene, and sabinene) may have a significant influence upon perceived

**Analytes Column Technique Methods Extraction Reference**

HS-SPME-GC– MS-O

HS-SPME/ GC–MS

*List of abbreviations: GC-FID, Gas chromatography-flame ionization detector; GC–MS, Gas chromatography– mass spectrometry; HS-SPME, Headspace-solid phase microextraction; GC–MS-O, Gas Chromatography–Mass* 

*Spectrometry-Olfactometry. A, authentication; C, characterization; P, cold pressed; S, solvent.*

GC-FID C S [61, 62]

GC-FID/MS C, A P [9]

GC-FID C P [8, 63]

C P [11]

C, A P [20]

Sacha inchi oil is a product of economic importance that has been characterized according to its chemical composition. At present several classes of chemical compounds have been identified and quantified, and more recently the volatile

**44**

**7. Conclusions**

**Table 5.**

The authors declare no conflict of interest.

#### **Author details**

Alexandra Valencia1 , Frank L. Romero-Orejon1 , Adriana Viñas-Ospino1,2, Dayana Barriga-Rodriguez<sup>3</sup> , Ana María Muñoz1,4 and Fernando Ramos-Escudero1,4\*

1 Unidad de Investigación en Nutrición, Salud, Alimentos Funcionales y Nutraceúticos, Universidad San Ignacio de Loyola (UNUSAN-USIL), Lima, Perú

2 Nutrition and Food Chemistry, University of Valencia, Burjassot, Spain

3 Facultad de Ciencias de la Salud, Universidad San Ignacio de Loyola, Lima, Perú

4 Instituto de Ciencias de los Alimentos y Nutrición, Universidad San Ignacio de Loyola (ICAN-USIL), Campus Pachacamac, Sección B, Lima, Perú

\*Address all correspondence to: diomedes.fernando@gmail.com

© 2021 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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[20] Ramos-Escudero F, Morales MT, Ramos Escudero M, Muñoz AM, Cancino Chavez K, Asuero AG. Assessment of phenolic and volatile compounds of commercial Sacha inchi oils and sensory evaluation. Food Research International. 2021;140:110022. DOI: 10.1016/j. foodres.2020.110022

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[23] Mishra AP, Devkota HP, Nigam M, Adetunji CO, Srivastava N, Sarla Saklani, Ila Shukla, Lubna Azmi, Mohammad Ali Shariati, Henrique Douglas Melo Coutinho, Amin Mousavi Khaneghah. Combination of essential oils in dairy products: A review of their functions and potential benefits. LWT-Food Science and Technology. 2020;**133**,110116. DOI: 10.1016/j. lwt.2020.110116

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[8] Chasquibol NA, Gómez-Coca RB, Yácono JC, Guinda Á., Moreda W, del Aguila C, Pérez-Camino MC. Markers of quality and genuineness of commercial extra virgin sacha inchi oils. Grasas y Aceites. 2016;**67**:e169. DOI: 10.3989/

[9] Ramos-Escudero F, Muñoz AM,

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gya.0457161

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[3] Sethuraman G, Nizar NMM,

Muhamad FN, Gregory PJ, Azam-Ali S. Nutritional composition of Sacha inchi (*Plukenetia volubikis* L.). International Journal for Innovative Research in Science Technology. 2020;**7**:271-277.

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10.1007/s00425-020-03377-3

DN; 2018. p. 1-24.

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[1] Srichamnong W, Ting P, Pitchakarn P, Nuchuchua O,

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**49**

*Sacha Inchi Seed (*Plukenetia volubilis *L.) Oil: Terpenoids*

Herrera-Ruiz M, Díaz García ER, García JT, Arellano-García J. A cytotoxic and anti-inflammatory campesterol derivative from genetically transformed hairy roots of *Lopezia racemosa* Cav. (Onagraceae). Molecules. 2017;22:118. DOI: 10.3390/molecules22010118

[46] Islam MT, Ali ES, Uddin SJ, Shaw S, Islam MA, Ahmed MI, Chandra Shill M, Karmakar UK, Yarla NS, Khan IN, Billah MM, Pieczynska MD, Zengin G, Malainer C, Nicoletti F, Gulei D, Berindan-Neagoe I, Apostolov A, Banach M, Yeung AWK, El-Demerdash A, Xiao J, Dey P, Yele S, Jóźwik A, Strzałkowska N, Marchewka J, Rengasamy KRR, Horbańczuk J, Kamal MA, Mubarak MS, Mishra SK, Shilpi JA, Atanasov AG. Phytol: A review of biomedical activities. Food and Chemical Toxicology. 2018;121:82-94.

DOI: 10.1016/j.fct.2018.08.032

[47] Alencar MVOB, Islam MT, Ali ES, Santos JVO, Paz MFCJ,

[48] Gutensohn M, Orlova I,

by plastid-generated geranyl diphosphate substrate in transgenic tomato fruits. The Plant Journal. 2013;75:351-363. DOI: 10.1111/tpj.12212

fpls.2020.00589

Sousa JMC, Dantas SMMM, Mishra SK, Cavalcante AACM. Association of phytol with toxic and cytotoxic

activities in an antitumoral perspective: A meta-analysis and systemic review. Anti-Cancer Agents in Medicinal Chemistry. 2018;18:1828-1837. DOI: 10.2 174/1871520618666180821113830

Nguyen TTH, Davidovich-Rikanati R, Ferruzzi MG, Sitrit Y, Lewinsohn E, Pichersky E, Dudareva N. Cytosolic monoterpene biosynthesis is supported

[49] Feng Y, Morgan RML, Fraser PD, Hellgardt K and Nixon PJ. Crystal structure of geranylgeranyl pyrophosphate synthase (CrtE) involved in Cyanobacterial terpenoid biosynthesis. Frontier in Plant Science. 2020;11:589. DOI: 10.3389/

*DOI: http://dx.doi.org/10.5772/intechopen.96690*

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Madrigal-Matute J, Pober JS, Lasunción MA, Wu D, Fernández-Hernando C, Suárez Y. Lanosterol modulates TLR4-mediated innate immune responses in macrophages. Cell Reports. 2017;19: 2743-2755. DOI:

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Reuhl K, Lu W, Luo Z, Yang CS. Intake of stigmasterol and β-sitosterol alters lipid metabolism and alleviates NAFLD in mice fed a high-fat western-style diet. Biochimica et Biophysica Acta-Molecular and Cell Biology of Lipids. 2018;1863:1274-1284. DOI: 10.1016/j.

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[40] Bin Sayeed MS, Ameen SS. Beta-sitosterol: A promising but orphan nutraceutical to fight against cancer. Nutrition and Cancer. 2015;67:1214-1220. DOI: 10.1080/01635581.2015.1087042

[41] Feng S, Dai Z, Liu AB, Huang J, Narsipur N, Guo G, Kong B, Reuhl K, Lu W, Luo Z, Yang CS. Intake of stigmasterol and β-sitosterol alters lipid metabolism and alleviates NAFLD in mice fed a high-fat western-style diet. Biochimica et Biophysica Acta-Molecular and Cell Biology of Lipids. 2018;1863:1274-1284. DOI: 10.1016/j. bbalip.2018.08.004

[42] Yang Q, Yu D, Zhang Y. β-sitosterol attenuates the intracranial aneurysm growth by suppressing TNF-α-mediated mechanism. Pharmacology. 2019;104:303-311. DOI: 10.1159/000502221

[43] Wang S, Wu S, Liu S. Integration of (+)-catechin and β-sitosterol to achieve excellent radical-scavenging activity in emulsions. Food Chemistry. 2019;272:596-603. DOI: 10.1016/j. foodchem.2018.08.098

[44] Antwi AO, Obiri DD, Osafo N. Stigmasterol modulates allergic airway inflammation in guinea pig model of ovalbumin-induced asthma. Mediators of Inflammation. 2017;2017:2953930. DOI: 10.1155/2017/2953930

[45] Moreno-Anzúrez NE, Marquina S, Alvarez L, Zamilpa A, Castillo-España P, Perea-Arango I, Torres PN,

Herrera-Ruiz M, Díaz García ER, García JT, Arellano-García J. A cytotoxic and anti-inflammatory campesterol derivative from genetically transformed hairy roots of *Lopezia racemosa* Cav. (Onagraceae). Molecules. 2017;22:118. DOI: 10.3390/molecules22010118

[46] Islam MT, Ali ES, Uddin SJ, Shaw S, Islam MA, Ahmed MI, Chandra Shill M, Karmakar UK, Yarla NS, Khan IN, Billah MM, Pieczynska MD, Zengin G, Malainer C, Nicoletti F, Gulei D, Berindan-Neagoe I, Apostolov A, Banach M, Yeung AWK, El-Demerdash A, Xiao J, Dey P, Yele S, Jóźwik A, Strzałkowska N, Marchewka J, Rengasamy KRR, Horbańczuk J, Kamal MA, Mubarak MS, Mishra SK, Shilpi JA, Atanasov AG. Phytol: A review of biomedical activities. Food and Chemical Toxicology. 2018;121:82-94. DOI: 10.1016/j.fct.2018.08.032

[47] Alencar MVOB, Islam MT, Ali ES, Santos JVO, Paz MFCJ, Sousa JMC, Dantas SMMM, Mishra SK, Cavalcante AACM. Association of phytol with toxic and cytotoxic activities in an antitumoral perspective: A meta-analysis and systemic review. Anti-Cancer Agents in Medicinal Chemistry. 2018;18:1828-1837. DOI: 10.2 174/1871520618666180821113830

[48] Gutensohn M, Orlova I, Nguyen TTH, Davidovich-Rikanati R, Ferruzzi MG, Sitrit Y, Lewinsohn E, Pichersky E, Dudareva N. Cytosolic monoterpene biosynthesis is supported by plastid-generated geranyl diphosphate substrate in transgenic tomato fruits. The Plant Journal. 2013;75:351-363. DOI: 10.1111/tpj.12212

[49] Feng Y, Morgan RML, Fraser PD, Hellgardt K and Nixon PJ. Crystal structure of geranylgeranyl pyrophosphate synthase (CrtE) involved in Cyanobacterial terpenoid biosynthesis. Frontier in Plant Science. 2020;11:589. DOI: 10.3389/ fpls.2020.00589

[50] Dhar MK, Koul A, Kaul S. Farnesyl pyrophosphate synthase: a key enzyme in isoprenoid biosynthetic pathway and potential molecular target for drug development. New Biotechnology. 2013;30:114-123. DOI: 10.1016/j. nbt.2012.07.001

[51] Bondioli P, Della Bella L, Rettke *P.* Alpha linolenic acid rich oils. Composition of *Plukenetia volubilis* (Sacha Inchi) oil from Perú. Rivista Italiana delle Sostanze Grasse. 2006;83:120-123.

[52] Toyomasu T, Sassa T. Diterpenes. In: Liu HW, Mander L, editors. Comprehensive Natural Products II: Chemistry and Biology. London, UK: Elsevier Ltd; 2010. p. 643-672. DOI: 10.1016/B978-008045382-8.00006-X

[53] Manzano D, Andrade P, Caudepón D, Altabella T, Arró M, Ferrer A. Suppressing farnesyl diphosphate synthase alters chloroplast development and triggers steroldependent induction of jasmonate- and Fe-related responses. Plant Physiology. 2016;172:93-117. DOI: 10.1104/ pp.16.00431

[54] Chirinos R, Pedreschi R, Domínguez G, Campos D. Comparison of the physico-chemical and phytochemical characteristics of the oil of two *Plukenetia* species. Food Chemistry. 2015;173:1203-1206. DOI: 10.1016/j.foodchem.2014.10.120

[55] Scolaro B, de Andrade LFS, Castro IA. Cardiovascular disease prevention: The earlier the better? A review of plant sterol metabolism and implications of childhood supplementation. International Journal of Molecular Science. 2019;21:128. DOI: 10.3390/ijms21010128

[56] Wang C-Y, Chen Y-W, Hou C-Y. Antioxidant and antibacterial activity of seven predominant terpenoids.

International Journal of Food Properties. 2019;22:230-238. DOI: 10.1080/10942912.2019.1582541

[57] Lyu X, Lee J, Chen WN. Potential natural food preservatives and their sustainable production in yeast: Terpenoids and polyphenols. Journal of Agricultural and Food Chemistry. 2019;67:4397-4417. DOI: 10.1021/acs. jafc.8b07141

[58] Ibáñez M.D, Sánchez-Ballester NM, Blázquez MA. Encapsulated limonene: A pleasant lemon-like aroma with promising application in the agrifood industry. A review. Molecules. 2020;25:2598. DOI: 10.3390/ molecules25112598

[59] Gutiérrez L-F, Sanchez-Reinoso Z, Quiñones-Segura Y. Effects of dehulling Sacha inchi (*Plukenetia volubilis* L.) seeds on the physicochemical and sensory properties of oils extracted by means of cold pressing. Journal of the American Oil Chemists' Society. 2019;96:1187-1195. DOI: 10.1002/ aocs.12270

[60] Aguilar-Hernández MG, Sánchez-Bravo P, Hernández F, Carbonell-Barrachina AA, Pastor-Pérez JJ, Legua P. Determination of the volatile profile of Lemon peel oils as affected by rootstock. Foods. 2020;9,241. DOI: 10.3390/foods9020241

[61] Chirinos R, Zuloeta G, Pedreschi R, Mignolet E, Larondelle Y, Campos D. Sacha inchi (*Plukenetia volubilis*): a seed source of polyunsaturated fatty acids, tocopherols, phytosterols, phenolic compounds and antioxidant capacity. Food Chemistry. 2013;141:1732-1739. DOI: 10.1016/j.foodchem.2013.04.078

[62] Chirinos R, Zorrilla D, Aguilar-Galvez A, Pedreschi R, Campos D. Impact of roasting on fatty acids, tocopherols, phytosterols, and phenolic compounds present in *Plukenetia* 

**51**

*Sacha Inchi Seed (*Plukenetia volubilis *L.) Oil: Terpenoids*

*DOI: http://dx.doi.org/10.5772/intechopen.96690*

Gómez-Coca RB, Trujillo D, Moreda W, Pérez-Camino MC. 2019. Glyceridic and unsaponifiable components of microencapsulated Sacha inchi (*Plukenetia huayllabambana* L. and *Plukenetia volubilis* L.) edible oils. Foods. 2019;8:671. DOI: 10.3390/

*huayllabambana* seed. Journal of Chemistry, 2016;2016:6570935.. DOI:

[63] Chasquibol N, Gallardo G,

10.1155/2016/6570935

foods8120671

*Sacha Inchi Seed (*Plukenetia volubilis *L.) Oil: Terpenoids DOI: http://dx.doi.org/10.5772/intechopen.96690*

*huayllabambana* seed. Journal of Chemistry, 2016;2016:6570935.. DOI: 10.1155/2016/6570935

*Terpenes and Terpenoids-Recent Advances*

nbt.2012.07.001

2006;83:120-123.

[51] Bondioli P, Della Bella L,

[53] Manzano D, Andrade P, Caudepón D, Altabella T, Arró M, Ferrer A. Suppressing farnesyl

2016;172:93-117. DOI: 10.1104/

[54] Chirinos R, Pedreschi R,

of the physico-chemical and

[55] Scolaro B, de Andrade LFS, Castro IA. Cardiovascular disease prevention: The earlier the better? A review of plant sterol metabolism and implications of childhood

10.3390/ijms21010128

pp.16.00431

Rettke *P.* Alpha linolenic acid rich oils. Composition of *Plukenetia volubilis* (Sacha Inchi) oil from Perú. Rivista Italiana delle Sostanze Grasse.

[52] Toyomasu T, Sassa T. Diterpenes. In: Liu HW, Mander L, editors. Comprehensive Natural Products II: Chemistry and Biology. London, UK: Elsevier Ltd; 2010. p. 643-672. DOI: 10.1016/B978-008045382-8.00006-X

diphosphate synthase alters chloroplast development and triggers sterol-

dependent induction of jasmonate- and Fe-related responses. Plant Physiology.

Domínguez G, Campos D. Comparison

supplementation. International Journal of Molecular Science. 2019;21:128. DOI:

[56] Wang C-Y, Chen Y-W, Hou C-Y. Antioxidant and antibacterial activity of seven predominant terpenoids.

phytochemical characteristics of the oil of two *Plukenetia* species. Food Chemistry. 2015;173:1203-1206. DOI: 10.1016/j.foodchem.2014.10.120

[50] Dhar MK, Koul A, Kaul S. Farnesyl pyrophosphate synthase: a key enzyme in isoprenoid biosynthetic pathway and potential molecular target for drug development. New Biotechnology. 2013;30:114-123. DOI: 10.1016/j.

International Journal of Food Properties. 2019;22:230-238. DOI: 10.1080/10942912.2019.1582541

jafc.8b07141

[57] Lyu X, Lee J, Chen WN. Potential natural food preservatives and their sustainable production in yeast: Terpenoids and polyphenols. Journal of Agricultural and Food Chemistry. 2019;67:4397-4417. DOI: 10.1021/acs.

[58] Ibáñez M.D, Sánchez-Ballester NM, Blázquez MA. Encapsulated limonene: A pleasant lemon-like aroma with promising application in the agrifood industry. A review. Molecules.

[59] Gutiérrez L-F, Sanchez-Reinoso Z, Quiñones-Segura Y. Effects of dehulling Sacha inchi (*Plukenetia volubilis* L.) seeds on the physicochemical and sensory properties of oils extracted by means of cold pressing. Journal of the American Oil Chemists' Society. 2019;96:1187-1195. DOI: 10.1002/

2020;25:2598. DOI: 10.3390/

[60] Aguilar-Hernández MG, Sánchez-Bravo P, Hernández F,

10.3390/foods9020241

Carbonell-Barrachina AA, Pastor-Pérez JJ, Legua P. Determination of the volatile profile of Lemon peel oils as affected by rootstock. Foods. 2020;9,241. DOI:

[61] Chirinos R, Zuloeta G, Pedreschi R, Mignolet E, Larondelle Y, Campos D. Sacha inchi (*Plukenetia volubilis*): a seed source of polyunsaturated fatty acids, tocopherols, phytosterols, phenolic compounds and antioxidant capacity. Food Chemistry. 2013;141:1732-1739. DOI: 10.1016/j.foodchem.2013.04.078

[62] Chirinos R, Zorrilla D, Aguilar-Galvez A, Pedreschi R, Campos D. Impact of roasting on fatty acids, tocopherols, phytosterols, and phenolic compounds present in *Plukenetia* 

molecules25112598

aocs.12270

**50**

[63] Chasquibol N, Gallardo G, Gómez-Coca RB, Trujillo D, Moreda W, Pérez-Camino MC. 2019. Glyceridic and unsaponifiable components of microencapsulated Sacha inchi (*Plukenetia huayllabambana* L. and *Plukenetia volubilis* L.) edible oils. Foods. 2019;8:671. DOI: 10.3390/ foods8120671

**53**

**Chapter 5**

**Abstract**

**1. Introduction**

plants as food [1].

units [1].

single substrate [4].

lites as they are not essential for viability [5].

Terpenes

*Bechir Baccouri and Imen Rajhi*

Potential Antioxidant Activity of

Terpenes play a key part in the metabolic processes of a wide variety of animals, plants and microorganisms in which they are produced. In nature, terpenoids serve a variety of purposes including defense, signaling and as key agents in metabolic processes. Terpenes have been used in perfumery, cosmetics and medicine for thousands of years and are still extracted from natural sources for these uses. Terpenes antioxidant activities may sometimes explain their capacity to adjust inflammation, immunological effects and neural signal transmission. They offer pertinent protection under oxidative stress situations including renal, liver, cancer, cardiovascular

Terpenes occur widely in nature. They are a large and varied class of hydrocarbons that are produced by varied plants and some animals. Thus, terpenes defend plants against pathogens like bacteria, fungus and can attract pollinating insects or repel herbivores [1]. Numerous plants produce volatile terpenes in order to attract specific insects for pollination or otherwise to expel certain animals using these

They are also abundantly found in fruits and flowers. In plants, they function as infochemicals, attractants or repellents, as they are responsible for the typical perfume of many plants [2]. Last, but not least, terpenes play an important role as signal compounds and growth regulators (phytohormones) of plants, as shown by some studies [1]. Thousands of terpenes have been found across the *plantae*, but only a small percentage of all terpenes have been known. Terpenes are biosynthetically derived from isoprene units with the molecular formula C5H8 [1]. The basic formula of all terpenes is (C5H8)n, where n is the number of linked isoprene

Terpenes presented over 25,000 well defined compounds isolated from all biological kingdoms [3]. The numerous terpene synthases in plants are primarily responsible for terpene diversity; some of them produce different products from a

The nomenclature of terpenes is based on the number of isoprene structures that they contain. Accordingly, these compounds are classified as sesquiterpenes, monoterpenes, diterpenes, triterpenes, tetraterpenes, and polyterpenes [5]. Monoterpenes, sesquiterpenes, and diterpenes are considered secondary metabo-

diseases, neurodegenerative and diabetes as well as in ageing mechanisms.

**Keywords:** terpenes, terpenoids, antioxydant, ROS, health

#### **Chapter 5**

## Potential Antioxidant Activity of Terpenes

*Bechir Baccouri and Imen Rajhi*

#### **Abstract**

Terpenes play a key part in the metabolic processes of a wide variety of animals, plants and microorganisms in which they are produced. In nature, terpenoids serve a variety of purposes including defense, signaling and as key agents in metabolic processes. Terpenes have been used in perfumery, cosmetics and medicine for thousands of years and are still extracted from natural sources for these uses. Terpenes antioxidant activities may sometimes explain their capacity to adjust inflammation, immunological effects and neural signal transmission. They offer pertinent protection under oxidative stress situations including renal, liver, cancer, cardiovascular diseases, neurodegenerative and diabetes as well as in ageing mechanisms.

**Keywords:** terpenes, terpenoids, antioxydant, ROS, health

#### **1. Introduction**

Terpenes occur widely in nature. They are a large and varied class of hydrocarbons that are produced by varied plants and some animals. Thus, terpenes defend plants against pathogens like bacteria, fungus and can attract pollinating insects or repel herbivores [1]. Numerous plants produce volatile terpenes in order to attract specific insects for pollination or otherwise to expel certain animals using these plants as food [1].

They are also abundantly found in fruits and flowers. In plants, they function as infochemicals, attractants or repellents, as they are responsible for the typical perfume of many plants [2]. Last, but not least, terpenes play an important role as signal compounds and growth regulators (phytohormones) of plants, as shown by some studies [1]. Thousands of terpenes have been found across the *plantae*, but only a small percentage of all terpenes have been known. Terpenes are biosynthetically derived from isoprene units with the molecular formula C5H8 [1]. The basic formula of all terpenes is (C5H8)n, where n is the number of linked isoprene units [1].

Terpenes presented over 25,000 well defined compounds isolated from all biological kingdoms [3]. The numerous terpene synthases in plants are primarily responsible for terpene diversity; some of them produce different products from a single substrate [4].

The nomenclature of terpenes is based on the number of isoprene structures that they contain. Accordingly, these compounds are classified as sesquiterpenes, monoterpenes, diterpenes, triterpenes, tetraterpenes, and polyterpenes [5]. Monoterpenes, sesquiterpenes, and diterpenes are considered secondary metabolites as they are not essential for viability [5].

Including neurodegenerative diseases (Alzheimer's and Parkinson's diseases), cancer, cardiovascular diseases, liver diseases, diabetes, and other diseases; oxidative stress is involved in the pathological development of many diseases. Antioxidant therapy, via direct and indirect mechanisms, has become one of the main and promising strategies to face oxidative stress-induced cellular damage [1, 6]. Studies have shown that both natural terpenes and their synthetic derivatives enjoy diverse pharmacological properties, including antioxidant, antifungal, anti-inflammatory, antiviral, anticancer, antibacterial, antinociceptive, antiarrhythmic, antispasmodic, antiaggregating, local anesthetic and antihistaminic activities [6, 7]. These interesting characteristics were used in pharmaceuticals and cosmetic industries. In this context, the search for antioxidant compounds among natural terpene products has significantly increased in the last recent years. As shown throughout this chapter, terpenes can function as antioxidant compounds through modulating the endogenous antioxidant system and direct ROS scavenging pathway.

#### **2. Oxidative stress**

Reactive oxygen species (ROS) comprise a series of chemical molecules derived from molecular oxygen whose reactivity is much greater than that of this element in its basal state [8]. Intracellular ROS can oxydize lipids, proteins and DNA thus damaging many cellular components and even causing genetic damage and cell death, mainly by apoptosis [1, 8, 9]. These species include oxygen ions as atomic oxygen (O), ozone (O3) and singlet oxygen (1O2) free radicals such as superoxide radical (O2• -), hydroxyl radical (OH •), the alkoxy radical (RO •) and peroxyl radical (ROO •), and peroxides such as hydrogen peroxide (H2O2) and peroxynitrite (ONOO-) [1, 8].

Molecules such as, ascorbic acid (vitamin C), α tocoferol (vitamin E), bilirubin, selenium and glutathione, between many others, proceed as ROS scavengers, preventing oxidative cellular damage [10, 11]. Among these, glutathione, the antioxidant compound, plays an important role in protecting vital functions [8, 11].

In addition to nonenzymatic compounds, during the antioxidant enzymes action including superoxyde dismutase (SOD), catalase (CAT), glutathione peroxydase (GPx) and heme oxygenase-1 (HO-1), ROS can be detoxyfied or converted into nontoxic forms [8]. Catalase, located principally in peroxisomes, efficiently converts hydrogen peroxide to water and oxygen [12]. The efficiency of this enzyme is such that one CAT molecule is able to turn 6 million of hydrogen peroxide molecules into water and oxygen per minute. In addition, this enzyme cannot be saturated at any hydrogen peroxide concentration [13]. Superoxyde dismutase produces molecular oxygen and hydrogen peroxide through dismutation of superoxide anion and this reaction is over 4 times faster than the non-enzymatic reaction [12]. GPx reduces hydroperoxides using glutathione (GSH) as substrate. The resulting GSSG is reduced back to GSH by the action of GR. The gene expression of all of these antioxidant proteins is regulated by nuclear factor erythroid-2 (Nrf2), through its binding to a specific DNA sequence called antioxidant response element (ARE) [14].

Nevertheless, under various pathological conditions, this endogenous cellular antioxyant defense system cannot remove excessive amounts of ROS, resulting in an oxidant-antioxidant imbalance called oxidative stress [1].

#### **3. Terpenes antioxidants potential**

The main triterpenes present in EVOO are two hydroxyl pentacyclic triterpene acids (oleanolic and maslinic acid) and two dialcohols (uvaol and erythrodiol)

**55**

**Figure 1.**

*Chemical structure of EVOO triterpenes.*

*Potential Antioxidant Activity of Terpenes DOI: http://dx.doi.org/10.5772/intechopen.96638*

respectively [16, 17].

act as antioxidant compounds [19].

(**Figure 1**), whose concentrations oscillate between 8.90 and 112.36 mg kg−1 [15]. Terpenes compounds are mostly found in the epicarp, then, pomace olive oil gener-

In the incessant search for new bioactive natural products against oxidation and inflammation, terpenes are emerging as a rich source of these compounds. Some monoterpenes possess both anti-inflammatory and antioxidant properties [16, 17]. (+)-limonene, and 1,8-cineole demonstrated strong antioxidant, anti-inflammatory and anticancer properties in assays using DPPH method, pleural cell migration, and U251, UACC-62, MCF-7, NCI-ADR/RES, OVCAR-3 human cancer cell lines,

Menthol is present in the aroma oil of numerous species of mint plants, such as cornmint oil from *M. arvensis* (wild mint) and peppermint oil derived from *Mentha piperita* (peppermint). Menthol and 1,8-Cineole ([11] had antioxidant characteristics in the ABTS-radical caption scavenging assay [18]. Cornmint and peppermint oils contain 70 and 50%, respectively, of menthol. Menthol can be extracted from other essential oils, such as citronella, eucalyptus and Indian turpentine oils.

Previous works have demonstrated that the antioxidant and prooxidant behaviour

Ruberto and Baratta [20] studied the antioxidant activity of monoterpene and sesquiterpene compounds found abundantly in essential oils Two lipid model systems were used: one for evaluating the formation of thiobarbituric acid reactive species (TBARS), utilizing egg yolk as lipid oxydable substrate and the other one for evaluating the peroxides that are formed during linoleic acid oxydation in a micellar system. Among monoterpene hydrocarbons, such as terpinolene, α-terpinene, γ-terpinene and sabinene were the most active [19]. Among oxygenated monoterpenes the order of antioxidant activity effectiveness was monoterpene phenols (thymol and carvacrol > allylic alcoholes (nerol), perillyl alcohol, geraniol and cisverbenol > monoterpenes aldehydes and ketones. Concerning the sesquiterpene group [1], the radical

of a particular terpene depend most of all on it amount: at high concentrations, terpenes can act as a prooxidant compounds whereas at low concentrations, they can

ally contains 10-fold elevated concentrations than EVOO [15].

#### *Potential Antioxidant Activity of Terpenes DOI: http://dx.doi.org/10.5772/intechopen.96638*

*Terpenes and Terpenoids-Recent Advances*

**2. Oxidative stress**

Including neurodegenerative diseases (Alzheimer's and Parkinson's diseases), cancer, cardiovascular diseases, liver diseases, diabetes, and other diseases; oxidative stress is involved in the pathological development of many diseases. Antioxidant therapy, via direct and indirect mechanisms, has become one of the main and promising strategies to face oxidative stress-induced cellular damage [1, 6]. Studies have shown that both natural terpenes and their synthetic derivatives enjoy diverse pharmacological properties, including antioxidant, antifungal, anti-inflammatory, antiviral, anticancer, antibacterial, antinociceptive, antiarrhythmic, antispasmodic, antiaggregating, local anesthetic and antihistaminic activities [6, 7]. These interesting characteristics were used in pharmaceuticals and cosmetic industries. In this context, the search for antioxidant compounds among natural terpene products has significantly increased in the last recent years. As shown throughout this chapter, terpenes can function as antioxidant compounds through modulating the endog-

Reactive oxygen species (ROS) comprise a series of chemical molecules derived from molecular oxygen whose reactivity is much greater than that of this element in its basal state [8]. Intracellular ROS can oxydize lipids, proteins and DNA thus damaging many cellular components and even causing genetic damage and cell death, mainly by apoptosis [1, 8, 9]. These species include oxygen ions as atomic oxygen (O), ozone (O3) and singlet oxygen (1O2) free radicals such as superoxide radical (O2• -), hydroxyl radical (OH •), the alkoxy radical (RO •) and peroxyl radical (ROO •), and peroxides

Molecules such as, ascorbic acid (vitamin C), α tocoferol (vitamin E), bilirubin, selenium and glutathione, between many others, proceed as ROS scavengers, preventing oxidative cellular damage [10, 11]. Among these, glutathione, the antioxidant compound, plays an important role in protecting vital functions [8, 11].

In addition to nonenzymatic compounds, during the antioxidant enzymes action including superoxyde dismutase (SOD), catalase (CAT), glutathione peroxydase (GPx) and heme oxygenase-1 (HO-1), ROS can be detoxyfied or converted into nontoxic forms [8]. Catalase, located principally in peroxisomes, efficiently converts hydrogen peroxide to water and oxygen [12]. The efficiency of this enzyme is such that one CAT molecule is able to turn 6 million of hydrogen peroxide molecules into water and oxygen per minute. In addition, this enzyme cannot be saturated at any hydrogen peroxide concentration [13]. Superoxyde dismutase produces molecular oxygen and hydrogen peroxide through dismutation of superoxide anion and this reaction is over 4 times faster than the non-enzymatic reaction [12]. GPx reduces hydroperoxides using glutathione (GSH) as substrate. The resulting GSSG is reduced back to GSH by the action of GR. The gene expression of all of these antioxidant proteins is regulated by nuclear factor erythroid-2 (Nrf2), through its binding to a

enous antioxidant system and direct ROS scavenging pathway.

such as hydrogen peroxide (H2O2) and peroxynitrite (ONOO-) [1, 8].

specific DNA sequence called antioxidant response element (ARE) [14].

oxidant-antioxidant imbalance called oxidative stress [1].

**3. Terpenes antioxidants potential**

Nevertheless, under various pathological conditions, this endogenous cellular antioxyant defense system cannot remove excessive amounts of ROS, resulting in an

The main triterpenes present in EVOO are two hydroxyl pentacyclic triterpene acids (oleanolic and maslinic acid) and two dialcohols (uvaol and erythrodiol)

**54**

(**Figure 1**), whose concentrations oscillate between 8.90 and 112.36 mg kg−1 [15]. Terpenes compounds are mostly found in the epicarp, then, pomace olive oil generally contains 10-fold elevated concentrations than EVOO [15].

In the incessant search for new bioactive natural products against oxidation and inflammation, terpenes are emerging as a rich source of these compounds. Some monoterpenes possess both anti-inflammatory and antioxidant properties [16, 17]. (+)-limonene, and 1,8-cineole demonstrated strong antioxidant, anti-inflammatory and anticancer properties in assays using DPPH method, pleural cell migration, and U251, UACC-62, MCF-7, NCI-ADR/RES, OVCAR-3 human cancer cell lines, respectively [16, 17].

Menthol is present in the aroma oil of numerous species of mint plants, such as cornmint oil from *M. arvensis* (wild mint) and peppermint oil derived from *Mentha piperita* (peppermint). Menthol and 1,8-Cineole ([11] had antioxidant characteristics in the ABTS-radical caption scavenging assay [18]. Cornmint and peppermint oils contain 70 and 50%, respectively, of menthol. Menthol can be extracted from other essential oils, such as citronella, eucalyptus and Indian turpentine oils.

Previous works have demonstrated that the antioxidant and prooxidant behaviour of a particular terpene depend most of all on it amount: at high concentrations, terpenes can act as a prooxidant compounds whereas at low concentrations, they can act as antioxidant compounds [19].

Ruberto and Baratta [20] studied the antioxidant activity of monoterpene and sesquiterpene compounds found abundantly in essential oils Two lipid model systems were used: one for evaluating the formation of thiobarbituric acid reactive species (TBARS), utilizing egg yolk as lipid oxydable substrate and the other one for evaluating the peroxides that are formed during linoleic acid oxydation in a micellar system. Among monoterpene hydrocarbons, such as terpinolene, α-terpinene, γ-terpinene and sabinene were the most active [19]. Among oxygenated monoterpenes the order of antioxidant activity effectiveness was monoterpene phenols (thymol and carvacrol > allylic alcoholes (nerol), perillyl alcohol, geraniol and cisverbenol > monoterpenes aldehydes and ketones. Concerning the sesquiterpene group [1], the radical

**Figure 1.** *Chemical structure of EVOO triterpenes.*

scavenging properties of the hydrocarbons-type were quite low and lower than that of the monoterpene hydrocarbons cluster, but between the oxygenated type, mainly allylic alcohols (i.e. farnesol, guaiol, (+)-8- (15)-cedren-9-ol showed good scavenging properties, similar to those of oxygenated monoterpenes [1, 19].

Several terpenes display also a protective effect against the oxidative stress induced by heavy metals. Pretreatments with the triterpene arjunolic acid recovered almost completely from reduced antioxidant protection (SOD, CAT, GR, GPx GST, GSH) and increased oxidative damage (lipid peroxydation and protein carbonyl content), mainly via radical scavenging, in murine brain treated with arsenic. El-Missiry and Shalaby [21] indicated that treatments with the ß-carotene (tetraterpene) protected against cadmium oxidative stress in brain with an associated increase in SOD, GST and non-enzymatic (GSH) antioxidant status [1], a decline in LDH activity and lipid peroxydation and an rise of ATPase activity [1, 22].

The oxidative pathway is also one of the described mechanisms to clarify glutamate toxicity. This excitatory neurotransmitter depletes intracellular GSH, produces ROS and augments lipid peroxydation levels. Koo et al. [23] identified the diterpene 15- methoxypinusolidic acid, obtained from the leaves of *Biota orientalis* L., as protective neuroagent with antioxidant activity in primary cultured cortical rat cells. Moreover, the monoterpenes from *Scrophularia buergeriana* Miq. were capable to ameliorate the antioxidant defense system in primary cultures of rat cerebral cortical cells in glutamate-mediated oxidative stress conditions [1].

Kim et al. [22] focused on the search for antioxidant compounds that delay or prevent oxidant/antioxidant imbalances and its harmful consequences, since oxidative stress is associated with Parkinson's disease pathology. The monoterpene catalpol, isolated from the roots of *Rehmannia glutinosa*, has demonstrated to protect cultured mesencephalic neurons against MPP+-induced toxicity by preventing the inhibition of the mitochondrial complex I, and thus avoiding mitochondrial dysfunction, and by diminishing the level of MDA content and increasing the activity of the antioxidant enzymes (SOD and GPx) [22]. The exogenous neurotoxins 1-methyl-4- phenylpyridinium (MPP+) and 6-hydroxydopamine (6-OHDA) are frequently used in experimental Parkinson models since these chemical compounds induce selectively oxidative stress in nigrostriatal dopaminergic neurons [24].

Its beneficial effects may be partly due to ROS scavenging and enhancement of endogenous antioxidants. Concerning fungi-derived terpenes, the labdane diterpenes, obtained from the fruiting body of the parasitic fungus *Antrodia camphorate* [24]*.* On the other hand, the carotene astaxanthin resulted to be a potent mitochondria-targeted antioxidant in dopaminergic SH-SY5Y cells treated with 6-OHDA [25].

Naval and Gómez-Serranillos [26] reviewed the neuroprotective activity of ginseng constituents, based on their antioxidant activities. Herein, we highlight some examples. *In vitro* studies concerning the neuroprotective activity of the isolated ginsenosides Rb1, Rb2, Rc, Rd., Re and Rg1 under hydrogen peroxideinduced oxidative stress in astrocytes revealed that the triterpene compound Re was the most effective among all tested ones since this compound could decrease cell death, improve SOD, GR and GPx activities and inhibit ROS production [27]. In addition, oxidative stress markers such as high ROS and MDA levels, low amounts of GHS and decreased antioxidant enzyme (SOD, CATand GPx) activity have been detected during oxygen–glucose privation and reoxygenation processes on hippocampal neurons. The ginsenoside Rd. lets return all these oxidant parameters to basal levels [27, 28].

Pretreatments with arjunolic acid isolated from the bark of *Terminalia arjuna* (Roxb.). Wight and Arn. prevented cardiac tissues from arsenic-induced oxidative

**57**

pathway [1, 35].

*Potential Antioxidant Activity of Terpenes DOI: http://dx.doi.org/10.5772/intechopen.96638*

among others [29].

(smoke and alcohol) [30].

ability [30].

(Burm.f.).

stress by restoring antioxidant status and inhibiting lipid peroxydation and protein carbonyl accumulation. There is evidence supporting a link between oxidative stress and cardiovascular tissue injury. Some studies have been conducted on the cardioprotective impacts of terpenes in response to cardiovascular pathological situations oxidative stress-related including hypertension and atherosclerosis,

Moreover, antihypertensive beneficial effects through antioxidant actions have been also observed for astaxanthin. In another study, the endothelial function of resistance of arteries was improved in those experimental animals that had been during eight weeks on an astaxanthinenriched diet. Astaxanthin decreased NADPH enhanced O2·- production by direct ROS scavenging and improved NO bioavail-

As it has been previously demonstrated, excessive cigarette smoking and alcohol

Additionally, Bansal et al. [31] confirmed that the carotenoid lycopene acts as a myocardial protective agent for the prevention of oxidative stress caused after ischemia reperfusion in the heart of rats through lipid peroxydation reduction and antioxiydant capacity enhancement [31]*.* Through antioxidant mechanisms, particularly scavenging of oxygen free radicals, prevention of lipid peroxydation and upregulation of the Bcl-2/Bax ratio, the diterpene tanshinone IIA also exhibited

ROS formation and subsequent oxidative stress events are one of the mechanisms of liver injury with hepatotoxic chemicals injury [32]. Several terpenes have shown hepatoprotective activity against this toxic chemical compound [27]. The kaurane diterpenes kahweol and cafestol, found in coffee beans, inhibited the production of superoxide anion radicals, reduced the level of the lipid peroxydation product malondialdehyde (MDA) and prevented the depletion of intracellular glutathione (GSH) injury [27, 32]. The labdane diterpenes neoandrographolide and andrographiside isolated from the plant species *Andrographis paniculata*

Moroever, *in vivo* studies demonstrated an increase in the concentration of reduced glutathione (GSH) in the liver of those rats after chronic alcohol consump-

Several environmental pollutants are able to induce oxidative stress, liver being the organ mostly affected [30]. Also, the ß-carotene (tetraterpene), behaving as an antioxidant, protected from liver damage associated with oxidative stress caused by

Among the monoterpene class, catalpol may hold promising protective actions

Moreover, the protective effect of terpenes as antioxidants against excessive ROS production, it is worth to indicate the role of these compounds as chemoprotective agents against tumor cells. Many papers have demonstrated that terpenes could have a very efficient activity in different cancer types [1]. Anticancer therapy of terpenes targeting the apoptotic pathway rather than the antioxidant

The protective effect of carotenoids was attributed to its capacity to inhibit lipid peroxydation, restore GSH levels and improve the activities of the enzymes super-

drinking are both risk factors for triggering atherosclerosis. In a randomized double-bind placebo-controlled study undertaken in over 100 habitual cigarette smokers and alcohol consumers, men 22–57-aged, the possible protective effect of lycopene against heart disease was evaluated in these oxidative stress conditions

a protective role on cardiomyocytes against ischemic injury [32].

tion but fed with a diet containing the carotenoid ß-carotene [33].

bile acid or as a side effect of chemotherapy with methotrexate [34].

oxide dismutase, catalase and glutathione S-transferase (**Figure 2**) [36].

against encephalopathy under hyperglycemic conditions [22].

#### *Potential Antioxidant Activity of Terpenes DOI: http://dx.doi.org/10.5772/intechopen.96638*

*Terpenes and Terpenoids-Recent Advances*

scavenging properties of the hydrocarbons-type were quite low and lower than that of the monoterpene hydrocarbons cluster, but between the oxygenated type, mainly allylic alcohols (i.e. farnesol, guaiol, (+)-8- (15)-cedren-9-ol showed good scavenging

Several terpenes display also a protective effect against the oxidative stress induced by heavy metals. Pretreatments with the triterpene arjunolic acid recovered almost completely from reduced antioxidant protection (SOD, CAT, GR, GPx GST, GSH) and increased oxidative damage (lipid peroxydation and protein carbonyl content), mainly via radical scavenging, in murine brain treated with arsenic. El-Missiry and Shalaby [21] indicated that treatments with the ß-carotene (tetraterpene) protected against cadmium oxidative stress in brain with an associated increase in SOD, GST and non-enzymatic (GSH) antioxidant status [1], a decline in

LDH activity and lipid peroxydation and an rise of ATPase activity [1, 22].

cortical cells in glutamate-mediated oxidative stress conditions [1].

The oxidative pathway is also one of the described mechanisms to clarify glutamate toxicity. This excitatory neurotransmitter depletes intracellular GSH, produces ROS and augments lipid peroxydation levels. Koo et al. [23] identified the diterpene 15- methoxypinusolidic acid, obtained from the leaves of *Biota orientalis* L., as protective neuroagent with antioxidant activity in primary cultured cortical rat cells. Moreover, the monoterpenes from *Scrophularia buergeriana* Miq. were capable to ameliorate the antioxidant defense system in primary cultures of rat cerebral

Kim et al. [22] focused on the search for antioxidant compounds that delay or prevent oxidant/antioxidant imbalances and its harmful consequences, since oxidative stress is associated with Parkinson's disease pathology. The monoterpene catalpol, isolated from the roots of *Rehmannia glutinosa*, has demonstrated to protect cultured mesencephalic neurons against MPP+-induced toxicity by preventing the inhibition of the mitochondrial complex I, and thus avoiding mitochondrial dysfunction, and by diminishing the level of MDA content and increasing the activity of the antioxidant enzymes (SOD and GPx) [22]. The exogenous neurotoxins 1-methyl-4- phenylpyridinium (MPP+) and 6-hydroxydopamine (6-OHDA) are frequently used in experimental Parkinson models since these chemical compounds induce selectively oxidative stress in nigrostriatal dopaminergic neurons [24]. Its beneficial effects may be partly due to ROS scavenging and enhancement of endogenous antioxidants. Concerning fungi-derived terpenes, the labdane diterpenes, obtained from the fruiting body of the parasitic fungus *Antrodia* 

*camphorate* [24]*.* On the other hand, the carotene astaxanthin resulted to be a potent mitochondria-targeted antioxidant in dopaminergic SH-SY5Y cells treated with

Naval and Gómez-Serranillos [26] reviewed the neuroprotective activity of ginseng constituents, based on their antioxidant activities. Herein, we highlight some examples. *In vitro* studies concerning the neuroprotective activity of the isolated ginsenosides Rb1, Rb2, Rc, Rd., Re and Rg1 under hydrogen peroxideinduced oxidative stress in astrocytes revealed that the triterpene compound Re was the most effective among all tested ones since this compound could decrease cell death, improve SOD, GR and GPx activities and inhibit ROS production [27]. In addition, oxidative stress markers such as high ROS and MDA levels, low amounts of GHS and decreased antioxidant enzyme (SOD, CATand GPx) activity have been detected during oxygen–glucose privation and reoxygenation processes on hippocampal neurons. The ginsenoside Rd. lets return all these oxidant parameters to

Pretreatments with arjunolic acid isolated from the bark of *Terminalia arjuna* (Roxb.). Wight and Arn. prevented cardiac tissues from arsenic-induced oxidative

properties, similar to those of oxygenated monoterpenes [1, 19].

**56**

6-OHDA [25].

basal levels [27, 28].

stress by restoring antioxidant status and inhibiting lipid peroxydation and protein carbonyl accumulation. There is evidence supporting a link between oxidative stress and cardiovascular tissue injury. Some studies have been conducted on the cardioprotective impacts of terpenes in response to cardiovascular pathological situations oxidative stress-related including hypertension and atherosclerosis, among others [29].

Moreover, antihypertensive beneficial effects through antioxidant actions have been also observed for astaxanthin. In another study, the endothelial function of resistance of arteries was improved in those experimental animals that had been during eight weeks on an astaxanthinenriched diet. Astaxanthin decreased NADPH enhanced O2·- production by direct ROS scavenging and improved NO bioavailability [30].

As it has been previously demonstrated, excessive cigarette smoking and alcohol drinking are both risk factors for triggering atherosclerosis. In a randomized double-bind placebo-controlled study undertaken in over 100 habitual cigarette smokers and alcohol consumers, men 22–57-aged, the possible protective effect of lycopene against heart disease was evaluated in these oxidative stress conditions (smoke and alcohol) [30].

Additionally, Bansal et al. [31] confirmed that the carotenoid lycopene acts as a myocardial protective agent for the prevention of oxidative stress caused after ischemia reperfusion in the heart of rats through lipid peroxydation reduction and antioxiydant capacity enhancement [31]*.* Through antioxidant mechanisms, particularly scavenging of oxygen free radicals, prevention of lipid peroxydation and upregulation of the Bcl-2/Bax ratio, the diterpene tanshinone IIA also exhibited a protective role on cardiomyocytes against ischemic injury [32].

ROS formation and subsequent oxidative stress events are one of the mechanisms of liver injury with hepatotoxic chemicals injury [32]. Several terpenes have shown hepatoprotective activity against this toxic chemical compound [27]. The kaurane diterpenes kahweol and cafestol, found in coffee beans, inhibited the production of superoxide anion radicals, reduced the level of the lipid peroxydation product malondialdehyde (MDA) and prevented the depletion of intracellular glutathione (GSH) injury [27, 32]. The labdane diterpenes neoandrographolide and andrographiside isolated from the plant species *Andrographis paniculata* (Burm.f.).

Moroever, *in vivo* studies demonstrated an increase in the concentration of reduced glutathione (GSH) in the liver of those rats after chronic alcohol consumption but fed with a diet containing the carotenoid ß-carotene [33].

Several environmental pollutants are able to induce oxidative stress, liver being the organ mostly affected [30]. Also, the ß-carotene (tetraterpene), behaving as an antioxidant, protected from liver damage associated with oxidative stress caused by bile acid or as a side effect of chemotherapy with methotrexate [34].

Among the monoterpene class, catalpol may hold promising protective actions against encephalopathy under hyperglycemic conditions [22].

Moreover, the protective effect of terpenes as antioxidants against excessive ROS production, it is worth to indicate the role of these compounds as chemoprotective agents against tumor cells. Many papers have demonstrated that terpenes could have a very efficient activity in different cancer types [1]. Anticancer therapy of terpenes targeting the apoptotic pathway rather than the antioxidant pathway [1, 35].

The protective effect of carotenoids was attributed to its capacity to inhibit lipid peroxydation, restore GSH levels and improve the activities of the enzymes superoxide dismutase, catalase and glutathione S-transferase (**Figure 2**) [36].

**Figure 2.** *Interaction of zeaxanthin With ROS.*

#### **4. Conclusions**

Concerning the number of *in vivo* and *in vitro* studies that have evaluated the terpenes antioxidant activities it is relatively little when compared to the enormous number of identified Terpenes in nature. They have a ample biological activities including anti-inflammatory, anticancer, antimicrobial, antioxidant etc.. Several other as yet undiscovered compounds can exist with immense antioxidant potentials.

#### **Conflict of interest**

The authors declare that they have no conflict of interests.

"Reviewed by Pr. Mokhtar Zarrouk, Centre of Biotechnology of Borj Cédria, Tunisia".

**59**

**Author details**

Bechir Baccouri1

Tunisia

\* and Imen Rajhi2

\*Address all correspondence to: bechirbaccouri@yahoo.fr

provided the original work is properly cited.

1 Laboratory of Olive Biotechnology, Center of Biotechnology of Borj-Cédria,

© 2021 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

2 Laboratory of Legumes Center of Biotechnology of Borj-Cédria, Tunisia

*Potential Antioxidant Activity of Terpenes DOI: http://dx.doi.org/10.5772/intechopen.96638* *Potential Antioxidant Activity of Terpenes DOI: http://dx.doi.org/10.5772/intechopen.96638*

*Terpenes and Terpenoids-Recent Advances*

**58**

**4. Conclusions**

*Interaction of zeaxanthin With ROS.*

**Figure 2.**

potentials.

Tunisia".

**Conflict of interest**

Concerning the number of *in vivo* and *in vitro* studies that have evaluated the terpenes antioxidant activities it is relatively little when compared to the enormous number of identified Terpenes in nature. They have a ample biological activities including anti-inflammatory, anticancer, antimicrobial, antioxidant etc.. Several other as yet undiscovered compounds can exist with immense antioxidant

"Reviewed by Pr. Mokhtar Zarrouk, Centre of Biotechnology of Borj Cédria,

The authors declare that they have no conflict of interests.

### **Author details**

Bechir Baccouri1 \* and Imen Rajhi2

1 Laboratory of Olive Biotechnology, Center of Biotechnology of Borj-Cédria, Tunisia

2 Laboratory of Legumes Center of Biotechnology of Borj-Cédria, Tunisia

\*Address all correspondence to: bechirbaccouri@yahoo.fr

© 2021 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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[23] Koo, K.A.; Kim, S.H.; Lee, M.K.; Kim, Y.C. 15-Methoxypinusolidic acid from *Biota orientalis* attenuates glutamate-induced neurotoxicity in primary cultured rat cortical cells. Toxicol. In Vitro. 2006, *20*, 936-941.

[24] Tian, Y.Y.; Jiang, B.; An, L.J.; Bao, Y.M. Neuroprotective effect of catalpol against MPP(+)-induced oxidative stress in mesencephalic neurons. Eur. J.

Pharmacol.*,* 2007, *568*, 142-148.

[26] Naval-López, M.V.; Gómez-Serranillos, M.P. In: Ginseng research

[25] Liu, X.; Osawa, T. Astaxanthin protects neuronal cells against oxidative damage and is a potent candidate for brain food. Forum Nutr., 2009, *61*,

*33*, 641-646.

334-335.

167-174.

*74*, 948-955.

*Potential Antioxidant Activity of Terpenes DOI: http://dx.doi.org/10.5772/intechopen.96638*

[18] Qiu, L.H.; Xie, X.J.; Zhang, B.Q. Astragaloside IV improves homocysteineinduced acute phase endothelial dysfunction via antioxidation. Biol. Pharm. Bull., 2010, *33*, 641-646.

[19] Maleknia, S.D.; Adams, M.A. Reactions of oxygen-containing terpenes with peptides and proteins. *Proc. 4th Intl. Peptide Symp*., 2007, 334-335.

[20] Ruberto, G.; Baratta, M.T. Antioxidant activity of selected essential oil components in two lipid model systems. Food Chem., 2000, *69*, 167-174.

[21] El-Missiry, M.A.; Shalaby, F. Role of beta-carotene in ameliorating the cadmium-induced oxidative stress in rat brain and testis. J. Biochem. Mol. Toxicol., 2000, *14*, 238-243.

[22] Kim, S.R.; Koo, K.A.; Sung, S.H.; Ma, C.J.; Yoon, J.S.; Kim, Y.C. Iridoids from *Scrophularia buergeriana* attenuate glutamate-induced neurotoxicity in rat cortical cultures. *J. Neurosci. Re*s., 2003, *74*, 948-955.

[23] Koo, K.A.; Kim, S.H.; Lee, M.K.; Kim, Y.C. 15-Methoxypinusolidic acid from *Biota orientalis* attenuates glutamate-induced neurotoxicity in primary cultured rat cortical cells. Toxicol. In Vitro. 2006, *20*, 936-941.

[24] Tian, Y.Y.; Jiang, B.; An, L.J.; Bao, Y.M. Neuroprotective effect of catalpol against MPP(+)-induced oxidative stress in mesencephalic neurons. Eur. J. Pharmacol.*,* 2007, *568*, 142-148.

[25] Liu, X.; Osawa, T. Astaxanthin protects neuronal cells against oxidative damage and is a potent candidate for brain food. Forum Nutr., 2009, *61*, 129-135.

[26] Naval-López, M.V.; Gómez-Serranillos, M.P. In: Ginseng research in the era of systems biology; Yan J, Ed; Int. J. Curr. Biomed. Pharmaceut. Res., 2012, pp. 1-10.

[27] López, M.V.; Cuadrado, M.P.; Ruiz-Poveda, O.M.; Del Fresno, A.M.; Accame, M.E. Neuroprotective effect of individual ginsenosides on astrocytes primary culture. Biochim. Biophys. Acta. 2007, *1770*, 1308-1316.

[28] Ye, R.; Li, N.; Han, J.; Kong, X.; Cao, R.; Rao, Z.; Zhao, G. Neuroprotective effects of ginsenoside Rd against oxygen-glucose deprivation in cultured hippocampal neurons. Neurosci. Res., 2009, *64*, 306-310.

[29] Lakshmi, S.V.; Padmaja, G.; Kuppusamy, P.; Kutala, V.K. Oxidative stress in cardiovascular disease. Indian J. Biochem. Biophys., 2009, *46*, 421-440.

[30] Sudhahar, V.; Kumar, S.A.; Varalakshmi, P. Role of lupeol and lupeol linoleate on lipemicoxidative stress in experimental hypercholesterolemia. Life Sci., 2006, *78*, 1329-1335.

[31] Bansal, P.; Gupta, S.K.; Ojha, S.K.; Nandave, M.; Mittal, R.; Kumari, S.; Arya, D.S. Cardioprotective effect of lycopene in the experimental model of myocardial ischemia-reperfusion injury. Mol. Cell. Biochem., 2006, *289*, 1-9.

[32] Fu, J.; Huang, H.; Liu, J.; Pi, R.; Chen, J.; Liu, P. Tanshinone IIA protects cardiac myocytes against oxidative stress-triggered damage and apoptosis. Eur. J. Pharmacol., 2007, *568*, 213-221.

[33] Lin, W.T.; Huang, C.C.; Lin, T.J.; Chen, J.R.; Shieh, M.J.; Peng, H.C.; Yang, S.C., Huang, C.Y. Effects of betacarotene on antioxidant status in rats with chronic alcohol consumption. Cell Biochem. Funct.*,* 2009, 27, 344-350.

[34] Vardi, N.; Parlakpinar, H.; Cetin, A.; Erdogan, A.; Cetin Ozturk, I. Protective effect of beta-carotene on

**60**

*Terpenes and Terpenoids-Recent Advances*

[1] Wang, S.Y.; Wu, J.H.; Shyur, L.F.; Kuo, Y.H.; Chang, S. Antioxidant activity of abietane-type diterpenes from heartwood of *Taiwania* 

Antioxidatns & Redox Signaling, 2003,

[10] Li, Y.; Cao, Z.; Zhu, H. Upregulation

of endogenous antioxidants and phase 2 enzymes by the red wine polyphenol, resveratrol in cultured and aortic smooth muscle cells leads to cytoprotection against oxidative and electrophilic stress. Pharmacol. Res.,

[11] Townsend, D.M.; Tew, K.D.; Tapiero, H. The importance of

Interact., 2006, *160*, 1-40.

Toxicol., 2000, *153*, 83-104.

Crops Prod. 120, 11-15.

[14] Lee, J.M.; Johnson, J.A. An important role of Nrf2-ARE pathway in the cellular defense mechanism. J. Biochem. Mol. Biol., 2004, *37*, 139-143.

[15] Baccouri, B., Manaia, H., Casas, J.S., Osorio, E. & Zarrouk, M., (2018). Tunisian wild olive (Olea europaea L. subsp. oleaster) oils: Sterolic and triterpenic dialcohol compounds. Ind.

[16] Luis, J.C.; Johnson, C.B. Seasonal variations of rosmarinic and carnosic acids in rosemary extracts. Analysis of their *in vitro* antiradical activity. *Spanish J. Agr. Res*., 2005a, *3*, 106.

[17] Sinha, M.; Manna, P.; Sil, P.C. Protective effect of arjunolic acid against arsenic-induced oxidative stress in mouse brain. J Biochem. Mol.

Toxicol., 2008, *22*, 15-26.

glutathione in human disease. Biomed. Pharmacother., 2003, *57*, 145-155.

[12] Valko, M.; Rhodes, C. J.; Moncol, J., Izakovic, M.; Mazur, M. Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem. Biol.

[13] Mates, M. Effects of antioxidant enzymes in the molecular control of reactive oxygen species toxicology.

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*cryptomerioides* Hayata. Holzforschung,

[2] Schulz, G.E.; Schirmer, R.H.; Sachsenheimer, W.; Pai, E.F. The structure of the flavoenzyme glutathione reductase. Nature. 1978,

[3] Buckingham, J. *Dictionary of natural products on CD-ROM*, version 6.1; Chapman & Hall: London, 1998. antioxidant polyoxygenated triterpenes from *Salsola baryosma*, by 1D and 2D

[4] Ruzlcka, L. The isoprene rule and the biogenesis of terpenic compounds.

[5] Flesh, G.; Rohmer, M. Prokaryotic hopanoids: the biosynthesis of the bacteriohopane skeleton. Formation of isoprenic units from two distinct acetate pools and a novel type of carbon/ carbon linkage between a triterpene and Dribose. Eur. J. Biochem., 1988, *175*,

[6] Avery, S.V. Molecular targets of oxidative stress. Biochem. J., 2011, *434*,

[7] Valko, M.; Morris, H.; Cronin, M.T. Metals, toxicity and oxidative stress. Curr. Med. Chem., 2005, *12*, 1161-1208.

[8] D'Autreaux, B.; Toledano, M.B. ROS as signalling molecules: mechanisms that generate specificity in ROS homeostasis. Nat. Rev. Mol. Cell Biol.,

[9] Stadtman, E.R.; Moskovitz, J.; Levine, R.L. Forum Mini Review, Oxidation of methionine residues of proteins: Biological consequences.

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NMR spectroscopy.

405-411.

201-210.

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methotrexate-induced oxidative liver damage. *Toxicol. Pathol*., 2010, *38*, 592- 597.Vqrdi et al., 2010.

[35] Aune, D., Chan, D.S., Vieira, A.R., Navarro Rosenblatt, D.A., Vieira, R., Greenwood, D.C., Norat, T. Dietary compared with blood concentrations of carotenoids and breast cancer risk: a systematic review and meta-analysis of prospective studies. Am. J. Clin. Nutr. 2012, *96*, 356-373.

[36] Gupta, S.K.; Trivedi, D.; Srivastava, S.; Joshi, S.; Halder, N.; Verma, S.D. Lycopene attenuates oxidative stress induced experimental cataract development: an *in vitro* and *in vivo* study. Nutrition. 2003, *19*, 794-799.

**63**

discovery.

**Chapter 6**

**Abstract**

**1. Introduction**

Therapy

Algal Terpenoids: A Potential

*Umme Tamanna Ferdous and Zetty Norhana Balia Yusof*

In cancer treatment, increase in drug resistance and decrease in new chemotherapeutic drugs have become a pressing problem. Hence, searching for novel anticancer agents with less toxicity and high sensitivity is expanding gradually. Many preclinical and clinical studies indicate that natural antioxidants can help combating carcinogenicity and reduce the adverse effects on cancer therapy, when used alone or as adjuvant in chemotherapy. Consequently, marine algae pave the way for exploring more potential antioxidant compounds which have pharmaceutical importance. Algal terpenoids comprise a large group of bioactive compounds that have excellent antioxidative property and can be used as source of antioxidant in cancer therapy. This chapter summarizes the potential role of terpenoids from algal sources in inhibiting cancer cells, blocking cell cycle,

hindering angiogenesis and metastasis as well as in inducing apoptosis.

**Keywords:** algal terpenoids, antioxidant, cancer, chemotherapy, marine algae

Though cancer is the prime reason for the premature death and responsible for more than nine million death globally in 2018, cancer treatments are still facing challenges in terms of their potency and safety [1]. Over fifty percent of the existing cancer drugs are from natural origin, therefore, exploration of cancer therapeutics from natural reservoir has been escalated currently [2]. In accordance with this natural anti-cancer drug discovery, natural antioxidants can be considered as an alternative source of cancer therapeutics. Many antioxidants, for instance, vitamins, carotenoids, genistein, curcumin, resveratrol, gingerol etc. exhibited promising outcomes in preclinical and clinical studies [3]. Currently, researchers are looking for more novel phytochemicals that can be further used as cancer drug

Terpenoids are the broadest class of diverse phytochemicals which are widely available in marine algae. These secondary metabolites have excellent antioxidative property and exerted *in vitro* as well as *in vivo* anticancer activity [4]. Algal terpenoids mainly comprised of mono-, di-, tri-, tetra-, mero- and sesquiterpenoids. Tetraterpenoid which is mostly carotenoid, is widely studied algal terpenoid. Carotenoids isolated from macro- and microalgae have been used widely in healthrelated industries and they have been reported to display strong anticancer activity

Source of Antioxidants for Cancer

#### **Chapter 6**

*Terpenes and Terpenoids-Recent Advances*

methotrexate-induced oxidative liver damage. *Toxicol. Pathol*., 2010, *38*, 592-

[35] Aune, D., Chan, D.S., Vieira, A.R., Navarro Rosenblatt, D.A., Vieira, R., Greenwood, D.C., Norat, T. Dietary compared with blood concentrations of carotenoids and breast cancer risk: a systematic review and meta-analysis of prospective studies. Am. J. Clin. Nutr.

[36] Gupta, S.K.; Trivedi, D.; Srivastava,

S.; Joshi, S.; Halder, N.; Verma, S.D. Lycopene attenuates oxidative stress induced experimental cataract development: an *in vitro* and *in vivo* study. Nutrition. 2003, *19*, 794-799.

597.Vqrdi et al., 2010.

2012, *96*, 356-373.

**62**

## Algal Terpenoids: A Potential Source of Antioxidants for Cancer Therapy

*Umme Tamanna Ferdous and Zetty Norhana Balia Yusof*

#### **Abstract**

In cancer treatment, increase in drug resistance and decrease in new chemotherapeutic drugs have become a pressing problem. Hence, searching for novel anticancer agents with less toxicity and high sensitivity is expanding gradually. Many preclinical and clinical studies indicate that natural antioxidants can help combating carcinogenicity and reduce the adverse effects on cancer therapy, when used alone or as adjuvant in chemotherapy. Consequently, marine algae pave the way for exploring more potential antioxidant compounds which have pharmaceutical importance. Algal terpenoids comprise a large group of bioactive compounds that have excellent antioxidative property and can be used as source of antioxidant in cancer therapy. This chapter summarizes the potential role of terpenoids from algal sources in inhibiting cancer cells, blocking cell cycle, hindering angiogenesis and metastasis as well as in inducing apoptosis.

**Keywords:** algal terpenoids, antioxidant, cancer, chemotherapy, marine algae

#### **1. Introduction**

Though cancer is the prime reason for the premature death and responsible for more than nine million death globally in 2018, cancer treatments are still facing challenges in terms of their potency and safety [1]. Over fifty percent of the existing cancer drugs are from natural origin, therefore, exploration of cancer therapeutics from natural reservoir has been escalated currently [2]. In accordance with this natural anti-cancer drug discovery, natural antioxidants can be considered as an alternative source of cancer therapeutics. Many antioxidants, for instance, vitamins, carotenoids, genistein, curcumin, resveratrol, gingerol etc. exhibited promising outcomes in preclinical and clinical studies [3]. Currently, researchers are looking for more novel phytochemicals that can be further used as cancer drug discovery.

Terpenoids are the broadest class of diverse phytochemicals which are widely available in marine algae. These secondary metabolites have excellent antioxidative property and exerted *in vitro* as well as *in vivo* anticancer activity [4]. Algal terpenoids mainly comprised of mono-, di-, tri-, tetra-, mero- and sesquiterpenoids. Tetraterpenoid which is mostly carotenoid, is widely studied algal terpenoid. Carotenoids isolated from macro- and microalgae have been used widely in healthrelated industries and they have been reported to display strong anticancer activity against different cancer cells [5]. Besides these tetraterpenoids, other terpenes and terpenoids have also significant anticancer property. This chapter focus on the usage of antioxidants in cancer therapy, presenting the anticancer property of algal terpenoids with their mechanism of action in cancer cells.

#### **2. Role of antioxidant in cancer therapy**

Antioxidants are molecules which can detoxify the reactive species (reactive oxygen species (ROS), reactive nitrogen species (RNS), reactive sulfur species (RSS), reactive carbonyl species (RCS) and reactive selenium species (RSeS)), that are generated through body's normal metabolism or can be obtained from environment [6]. These reactive species give rise to oxidative stress which is of two types, oxidative eustress and oxidative distress. Oxidative eustress is considered as good stress, which under basal intensity, maintains redox homeostasis, responsible for controlled cell growth and reversible oxidative modification which ensure normal physiology. On the other hand, oxidative distress is known as bad stress, that in higher intensity, damage biomolecules and consequently disrupt redox signaling and give rise to different diseases, e.g. cancer [7].

Antioxidants protect cellular damage from free radicles through their organized defense mechanism (**Figure 1**), where they either inhibit new free radicle formation or scavenge the formed free radicles. They can also repair the damaged DNA and biomolecules [8]. In cancer cells, ROS level is excessively high which helps in protumorigenic cell signaling while prolonging the cell death. Some chemotherapeutic agents also can induce production of high amount of ROS, which is often considered as one of the main reasons for chemotherapeutic treatment side effects. However, antioxidants, when used in therapeutic dose in adjuvant chemotherapy, can hinder this high production of ROS and thus, potentiate the efficacy of cancer treatments, reduce the adverse effects of the therapy and improves the overall health status of the cancer patients. Antioxidants can inhibit cancer proliferation, angiogenesis and metastasis [9]. Dietary antioxidants supplements are frequently in cancer treatment. About 20–80% of the cancer patients use antioxidant supplements after cancer diagnosis [10]. The efficacy of using antioxidants in adjuvant chemotherapy has been assessed in many clinical trials. The clinical studies of antioxidant administration, especially vitamin, glutathione, melatonin, Coenzyme Q10, during chemotherapy have been revealed the reduction of chemotherapy induced toxicity and improvement of patient health [11].

**65**

*Algal Terpenoids: A Potential Source of Antioxidants for Cancer Therapy*

**3. Algal terpenoids as prospective candidate in cancer therapy**

Seaweed are more studied, in terms of their terpenoid profile, compared to marine microalgae. Though the anticancer activity of tetraterpenoids from marine microalgae has been reported broadly, brown macroalgae are good source of carotenoids. Anticancer activity of carotenoids (zeaxanthin, lutein, β-carotene, violaxanthin) was reported in Malaysian green and brown macroalgae [12].

Monoterpenoids, found in different plant parts, like in bark, root, seeds or leaves, have antioxidant and anticancer activity. For instance, carvacrol, thymol, linalool as well as eugenol are good antioxidant and at the same time, exert antitumor activity against liver, prostate and breast cancer cells [13, 14]. Limonene and perillyl alcohol were subjected to phase I clinical trials in cancer

*Plocamium cartilagineum,* a red alga, produces halogenated monoterpenes like furoplocamioid C, prefuroplocamioid, pirene and cyclohexane which have selective cytotoxicity against human melanoma, human and murine colon cancer cells as well as HeLa cells [16]. Similarly, *Plocamium sp.* from Namibia possesses halogenated monoterpene that have better antioxidant property than that of standard antioxidant [17]. *Sargassum ringgoldianum,* Korean brown seaweed, showed antioxidative activity through monoterpene lactone, that also gave protection against

A new diterpenoid has been isolated from green alga *Gracilaria Salicornia*, which displays antioxidant activity equivalent to α-tocopherol [19]. Brown alga *Bifurcaria bifurcate* has been reported to produce diterpenes, namely eleganolone and eleganonal which have better antioxidant activity in comparison to standard antioxidant, as well as exert neuroprotective effect on neuroblastoma [20]. Likewise, diterpenes from brown seaweed *Dictyota dichotoma* has good antioxidant capacity and shows cytotoxicity to liver and breast cancer cell lines [21]. Rodrigues et al., isolated a new diterpene sphaerodactylomelol from *Sphaerococcus coronopifolius* which blocked proliferation of human liver cancer cells at an IC50 of 280 μM, while killed the cancer

However, diterpenoids can induce apoptosis in cancer cells through downregulating Bcl2 and regulatory pathways like, JAK2/STAT3, PI3K/Akt and NF-κB. They can arrest cell cycle at G1 and G2-M checkpoint. Besides, diterpenoids can also inhibit metastasis and angiogenesis by hindering PI3K/Akt/mTOR and VEGFR-2

Triterpenoid (benzene dicarboxylic acid, diisooctyl ester) from the dichloromethane extract of *Sargassum wightii* displayed excellent radical scavenging and reducing activity [24]. Similarly, triterpenoids from the methanolic extracts of *Sargassum sp.* and *Eucheuma cottonii* could be responsible for their strong antioxidant activity [25]. Methanolic extract of *Gracilaria salicornia*, isolated from Persian Gulf, has inhibited human colon cancer cells at an IC50 of 58.6 μg/mL and also has good antioxidant property. Phytochemical analysis has been revealed that

*DOI: http://dx.doi.org/10.5772/intechopen.94122*

H2O2-induced damage in Vero cells [18].

**3.1 Monoterpenoids**

patients [15].

**3.2 Diterpenoids**

cells at IC50 of 720 μM [22].

signaling pathways [23].

**3.3 Triterpenoids**

**Figure 1.** *Three lines of defense system of antioxidant in cell.*

#### **3. Algal terpenoids as prospective candidate in cancer therapy**

Seaweed are more studied, in terms of their terpenoid profile, compared to marine microalgae. Though the anticancer activity of tetraterpenoids from marine microalgae has been reported broadly, brown macroalgae are good source of carotenoids. Anticancer activity of carotenoids (zeaxanthin, lutein, β-carotene, violaxanthin) was reported in Malaysian green and brown macroalgae [12].

#### **3.1 Monoterpenoids**

*Terpenes and Terpenoids-Recent Advances*

against different cancer cells [5]. Besides these tetraterpenoids, other terpenes and terpenoids have also significant anticancer property. This chapter focus on the usage of antioxidants in cancer therapy, presenting the anticancer property of algal

Antioxidants are molecules which can detoxify the reactive species (reactive oxygen species (ROS), reactive nitrogen species (RNS), reactive sulfur species (RSS), reactive carbonyl species (RCS) and reactive selenium species (RSeS)), that are generated through body's normal metabolism or can be obtained from environment [6]. These reactive species give rise to oxidative stress which is of two types, oxidative eustress and oxidative distress. Oxidative eustress is considered as good stress, which under basal intensity, maintains redox homeostasis, responsible for controlled cell growth and reversible oxidative modification which ensure normal physiology. On the other hand, oxidative distress is known as bad stress, that in higher intensity, damage biomolecules and consequently disrupt redox signaling

Antioxidants protect cellular damage from free radicles through their organized defense mechanism (**Figure 1**), where they either inhibit new free radicle formation or scavenge the formed free radicles. They can also repair the damaged DNA and biomolecules [8]. In cancer cells, ROS level is excessively high which helps in protumorigenic cell signaling while prolonging the cell death. Some chemotherapeutic agents also can induce production of high amount of ROS, which is often considered as one of the main reasons for chemotherapeutic treatment side effects. However, antioxidants, when used in therapeutic dose in adjuvant chemotherapy, can hinder this high production of ROS and thus, potentiate the efficacy of cancer treatments, reduce the adverse effects of the therapy and improves the overall health status of the cancer patients. Antioxidants can inhibit cancer proliferation, angiogenesis and metastasis [9]. Dietary antioxidants supplements are frequently in cancer treatment. About 20–80% of the cancer patients use antioxidant supplements after cancer diagnosis [10]. The efficacy of using antioxidants in adjuvant chemotherapy has been assessed in many clinical trials. The clinical studies of antioxidant administration, especially vitamin, glutathione, melatonin, Coenzyme Q10, during chemotherapy have been revealed the reduction of chemotherapy induced toxicity

terpenoids with their mechanism of action in cancer cells.

**2. Role of antioxidant in cancer therapy**

and give rise to different diseases, e.g. cancer [7].

and improvement of patient health [11].

*Three lines of defense system of antioxidant in cell.*

**64**

**Figure 1.**

Monoterpenoids, found in different plant parts, like in bark, root, seeds or leaves, have antioxidant and anticancer activity. For instance, carvacrol, thymol, linalool as well as eugenol are good antioxidant and at the same time, exert antitumor activity against liver, prostate and breast cancer cells [13, 14]. Limonene and perillyl alcohol were subjected to phase I clinical trials in cancer patients [15].

*Plocamium cartilagineum,* a red alga, produces halogenated monoterpenes like furoplocamioid C, prefuroplocamioid, pirene and cyclohexane which have selective cytotoxicity against human melanoma, human and murine colon cancer cells as well as HeLa cells [16]. Similarly, *Plocamium sp.* from Namibia possesses halogenated monoterpene that have better antioxidant property than that of standard antioxidant [17]. *Sargassum ringgoldianum,* Korean brown seaweed, showed antioxidative activity through monoterpene lactone, that also gave protection against H2O2-induced damage in Vero cells [18].

#### **3.2 Diterpenoids**

A new diterpenoid has been isolated from green alga *Gracilaria Salicornia*, which displays antioxidant activity equivalent to α-tocopherol [19]. Brown alga *Bifurcaria bifurcate* has been reported to produce diterpenes, namely eleganolone and eleganonal which have better antioxidant activity in comparison to standard antioxidant, as well as exert neuroprotective effect on neuroblastoma [20]. Likewise, diterpenes from brown seaweed *Dictyota dichotoma* has good antioxidant capacity and shows cytotoxicity to liver and breast cancer cell lines [21]. Rodrigues et al., isolated a new diterpene sphaerodactylomelol from *Sphaerococcus coronopifolius* which blocked proliferation of human liver cancer cells at an IC50 of 280 μM, while killed the cancer cells at IC50 of 720 μM [22].

However, diterpenoids can induce apoptosis in cancer cells through downregulating Bcl2 and regulatory pathways like, JAK2/STAT3, PI3K/Akt and NF-κB. They can arrest cell cycle at G1 and G2-M checkpoint. Besides, diterpenoids can also inhibit metastasis and angiogenesis by hindering PI3K/Akt/mTOR and VEGFR-2 signaling pathways [23].

#### **3.3 Triterpenoids**

Triterpenoid (benzene dicarboxylic acid, diisooctyl ester) from the dichloromethane extract of *Sargassum wightii* displayed excellent radical scavenging and reducing activity [24]. Similarly, triterpenoids from the methanolic extracts of *Sargassum sp.* and *Eucheuma cottonii* could be responsible for their strong antioxidant activity [25]. Methanolic extract of *Gracilaria salicornia*, isolated from Persian Gulf, has inhibited human colon cancer cells at an IC50 of 58.6 μg/mL and also has good antioxidant property. Phytochemical analysis has been revealed that triterpenes are present in ample amount in that extract which could be attributed for these activities [26]. On the other hand, Indonesian seaweed *Eucheuma cottonii* contains triterpenoid which exhibited cytotoxicity against lung cancer cells at an IC50 of 251.73 μg/mL [27]. *Padina boergesenii* has been reported to produce triterpenes that have antiangiogenic activity against renal carcinoma [28]. Ethanolic extract of edible seaweed *Kjellmaniella crassifolia* has been reported to contain three terpenoids, namely dihydrocimicifugenol, 3-epicyclomusalenol and cyclosadol with chemo-preventive property [29]. Anti-cancerous triterpenoids can also be found in *Laurencia mariannensis*, *L. viridis* and *L. obtuse* [30].

#### **3.4 Tetraterpenoids**

Algal tetraterpenoids mainly consist of carotenoids, namely, β-carotene, lutein, fucoxanthin, astaxanthin, canthaxanthin, zeaxanthin, cryptoxanthin, violaxanthin, neoxanthin and siphonaxanthin (**Figure 2**). Theses carotenoids have both antioxidative and anticancer activity with other pharmaceutical importance.

#### *3.4.1 Lutein*

Lutein from *Botryococcus braunii* has been reported to exhibit both *in vitro* and *in vivo* antioxidant activity [31].

#### *3.4.2* β*-carotene*

β-Carotene from *Dunaliella salina* is responsible for apoptotic cell death in human prostate carcinoma [32].

#### *3.4.3 Fucoxanthin*

*Phaeodactylum tricornutum*, *Odontella aurita*, *I. galbana, C. calcitrans, D. salina, C. gracilis, Navicula sp., Thalassiosira sp., Pavlova lutheri, Cylindrotheca closterium* can produce ample amount of fucoxanthin with antioxidative property [33–36]. *P. tricornutum* and *C. calcitrans* possess fucoxanthin which exhibits strong anticancer activity [33, 37]. Fucoxanthin, obtained from brown macroalgae *Padina tetrastromatica,* exhibited cytoprotective effect against oxidative damage [38].

#### *3.4.4 Zeaxanthin*

Zeaxanthin separated from *Nannochloropsis oculata, Scenedesmus obliquus, Porphyridium aerugineum* has showed antioxidative property [39, 40]. Zeaxanthin from *Porphyridium purpureum* induced apoptosis human melanoma. Moreover, ZX from this *P. purpureum* potentiates the efficacy of chemotherapeutic drug, vemurafenib towards human melanoma [41].

#### *3.4.5 Violaxanthin*

Violaxanthin with antioxidative and anti-inflammatory activities has been isolated from *Chlorella vulgaris*, *N. oceanica*, *Dunaniella salina*, *Tetraselmis spp*., *Isochrysis galbana*, *Pavlova lutheri*, *P. salina* and *Chaetoceros spp*. *Eustigmatos cf. polyphem* [42–46]. Violaxanthin from *Dunaliella tertiolecta* and *Chlorella ellipsoidea* inhibited breast and colon carcinoma, respectively [47].

**67**

**Figure 2.**

*Chemical structure of some algal tetraterpenoids.*

*Algal Terpenoids: A Potential Source of Antioxidants for Cancer Therapy*

*DOI: http://dx.doi.org/10.5772/intechopen.94122*

*Terpenes and Terpenoids-Recent Advances*

and *in vivo* antioxidant activity [31].

human prostate carcinoma [32].

rafenib towards human melanoma [41].

inhibited breast and colon carcinoma, respectively [47].

**3.4 Tetraterpenoids**

importance.

*3.4.1 Lutein*

*3.4.2* β*-carotene*

*3.4.3 Fucoxanthin*

damage [38].

*3.4.4 Zeaxanthin*

*3.4.5 Violaxanthin*

*Laurencia mariannensis*, *L. viridis* and *L. obtuse* [30].

triterpenes are present in ample amount in that extract which could be attributed for these activities [26]. On the other hand, Indonesian seaweed *Eucheuma cottonii* contains triterpenoid which exhibited cytotoxicity against lung cancer cells at an IC50 of 251.73 μg/mL [27]. *Padina boergesenii* has been reported to produce triterpenes that have antiangiogenic activity against renal carcinoma [28]. Ethanolic extract of edible seaweed *Kjellmaniella crassifolia* has been reported to contain three terpenoids, namely dihydrocimicifugenol, 3-epicyclomusalenol and cyclosadol with chemo-preventive property [29]. Anti-cancerous triterpenoids can also be found in

Algal tetraterpenoids mainly consist of carotenoids, namely, β-carotene, lutein, fucoxanthin, astaxanthin, canthaxanthin, zeaxanthin, cryptoxanthin, violaxanthin, neoxanthin and siphonaxanthin (**Figure 2**). Theses carotenoids have both antioxidative and anticancer activity with other pharmaceutical

Lutein from *Botryococcus braunii* has been reported to exhibit both *in vitro*

β-Carotene from *Dunaliella salina* is responsible for apoptotic cell death in

*Phaeodactylum tricornutum*, *Odontella aurita*, *I. galbana, C. calcitrans, D. salina, C. gracilis, Navicula sp., Thalassiosira sp., Pavlova lutheri, Cylindrotheca closterium* can produce ample amount of fucoxanthin with antioxidative property [33–36]. *P. tricornutum* and *C. calcitrans* possess fucoxanthin which exhibits strong anticancer activity [33, 37]. Fucoxanthin, obtained from brown macroalgae *Padina tetrastromatica,* exhibited cytoprotective effect against oxidative

Zeaxanthin separated from *Nannochloropsis oculata, Scenedesmus obliquus, Porphyridium aerugineum* has showed antioxidative property [39, 40]. Zeaxanthin from *Porphyridium purpureum* induced apoptosis human melanoma. Moreover, ZX from this *P. purpureum* potentiates the efficacy of chemotherapeutic drug, vemu-

Violaxanthin with antioxidative and anti-inflammatory activities has been isolated from *Chlorella vulgaris*, *N. oceanica*, *Dunaniella salina*, *Tetraselmis spp*., *Isochrysis galbana*, *Pavlova lutheri*, *P. salina* and *Chaetoceros spp*. *Eustigmatos cf. polyphem* [42–46]. Violaxanthin from *Dunaliella tertiolecta* and *Chlorella ellipsoidea*

**66**

**Figure 2.** *Chemical structure of some algal tetraterpenoids.*

#### *3.4.6 Neoxanthin*

The antioxidative property of neoxanthin was found in *Scenedesmus sp., Chlorella sp.* and *Tetraselmis suecica* [48, 49].

#### *3.4.7 Astaxanthin*

Astaxanthin from *H. pluvialis* inhibits the oxidative stress inside the cells [50].

#### *3.4.8* β*-Cryptoxanthin*

*β-*Cryptoxanthin obtained from *Cyanophora paradoxa* exerted cytotoxicity against human skin, breast and lung cancer cells [51].

#### *3.4.9 Siphonaxanthin*

Siphonaxanthin from green microalgae *Codium fragile* exhibited apoptosis in human leukemia cells through TRAIL induction with the augmentation of GADD45a and DR5 expression and reduced Bcl-2 and thus, showed more effective anticancer property compared to FX [52].

#### **3.5 Sesquiterpenoids**

Sesquiterpenoids have also high antioxidative and anticancer properties. Green seaweed *Ulva fasciata*, isolated from south Indian rocky shore, produced five sesquiterpenoids with radical scavenging activity and among them, 3,4,5,5-tetramethyl-4-(30-oxopentyl)-2-cyclohexen-1-one was revealed as one of the most potent radical scavengers [53]. Isozonarol, a sesquiterpenoid, has been identified from *Dictyopteris undulata* that can scavenge DPPH with an EC50 of 71 μM which is similar to α-tocopherol [54].

Sesquiterpenoids from *Laurencia composita* Yamada, namely compositacin D and G, as well as cycloelatanene A and B inhibited the growth of lung cancer cells at IC50 values ranging from 48.6 to 85.2 μM [55]. *Laurencia spp.* are good sources of anti-cancer sesquiterpenoids [56]. For instance, *Laurencia okamurai* produced laurinterol which inhibited melanoma cells by causing apoptosis via p53-dependent pathway and caspase activation [57]. Likewise, teuhetenone from *Laurencia obtuse* has been reported to display anticancer property against breast cancer cell line with an IC50 of 22 μM which is more effective in inhibiting breast cancer cells compared to chemotherapeutic drug, cisplatin (59 μM) [58]. Another major sesquiterpene, caulerpenyne was separated from *Caulerpa taxifolia,* that hindered human neuroblastoma cells (IC50 = 10 μM), while blocked cell cycle at G2/M phase [59].

#### **3.6 Meroterpenoids**

*Cystoseira usneoides*, brown macroalgae, is a rich source of meroterpenoids. Eight meroterpenoids have been isolated from this seaweed which have anti-colon and anti-lung cancer activity. These meroterpenoids can hinder growth and migration of colon cancer cells by suppressing ERK/JNK/AKT pathways, as well as can arrest cells at G2/M phase [60]. Similarly, these meroterpenoids displayed anticancer effect against lung carcinoma, while blocks lung cancer cells at G2/M and S phases [61]. Another brown seaweed *Stypopodium flabelliforme* produced meroterpenoids, namely epitaondiol, epitaondiol monoacetate and stypotriol triacetate which exhibited anticancer property against human colon and brain carcinoma [62].

**69**

**Author details**

**4. Conclusion**

Umme Tamanna Ferdous2

43400 UPM Serdang, Selangor, Malaysia

provided the original work is properly cited.

\*Address all correspondence to: zettynorhana@upm.edu.my

and Zetty Norhana Balia Yusof1,2,3\*

1 Department of Biochemistry, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia

2 Aquatic Animal Health and Therapeutics Laboratory (AquaHealth), Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia

3 Bioprocessing and Biomanufacturing Research Center, Universiti Putra Malaysia,

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

*Algal Terpenoids: A Potential Source of Antioxidants for Cancer Therapy*

*Sargassum muticum* can produce tetraprenyltoluquinol meroterpenoid that has antioxidant activity and can give protection against oxidative damage [63]. Likewise, highly oxygenated meroterpenoids with antioxidant property have been found from *Kappaphycus alvarezii*, a red macroalgae [64]. *Hypnea musciformis* has meroterpenoid like 2-(tetrahydro-5-(4-hydroxyphenyl)-4-pentylfuran-3-yl) ethyl-4-hydroxy benzoate which shows antioxidative properties comparable to gallic acid [65]. Meroterpenoids from ethanolic extract of *Sargassum serratifolium* have the capability to protect liver from the oxidative damage generated from pro-

The investigation on the anticancer properties of algal terpenoids is still in its infancy, albeit the anticancer efficacy of these phytochemicals is quite persuasive. Marine algae contain a wide array of promising terpenes and terpenoids that can strongly inhibit the proliferation of cancer cells. Extensive research on these algal terpenoids regarding their mechanism of action in the cancer cells and more clinical

studies will open the door to develop novel drugs for treating cancer.

*DOI: http://dx.doi.org/10.5772/intechopen.94122*

oxidant tert-butyl hydroperoxide [66].

*Algal Terpenoids: A Potential Source of Antioxidants for Cancer Therapy DOI: http://dx.doi.org/10.5772/intechopen.94122*

*Sargassum muticum* can produce tetraprenyltoluquinol meroterpenoid that has antioxidant activity and can give protection against oxidative damage [63]. Likewise, highly oxygenated meroterpenoids with antioxidant property have been found from *Kappaphycus alvarezii*, a red macroalgae [64]. *Hypnea musciformis* has meroterpenoid like 2-(tetrahydro-5-(4-hydroxyphenyl)-4-pentylfuran-3-yl) ethyl-4-hydroxy benzoate which shows antioxidative properties comparable to gallic acid [65]. Meroterpenoids from ethanolic extract of *Sargassum serratifolium* have the capability to protect liver from the oxidative damage generated from prooxidant tert-butyl hydroperoxide [66].

#### **4. Conclusion**

*Terpenes and Terpenoids-Recent Advances*

*Chlorella sp.* and *Tetraselmis suecica* [48, 49].

against human skin, breast and lung cancer cells [51].

anticancer property compared to FX [52].

The antioxidative property of neoxanthin was found in *Scenedesmus sp.,* 

Astaxanthin from *H. pluvialis* inhibits the oxidative stress inside the cells [50].

*β-*Cryptoxanthin obtained from *Cyanophora paradoxa* exerted cytotoxicity

Siphonaxanthin from green microalgae *Codium fragile* exhibited apoptosis in human leukemia cells through TRAIL induction with the augmentation of GADD45a and DR5 expression and reduced Bcl-2 and thus, showed more effective

Sesquiterpenoids have also high antioxidative and anticancer properties. Green

Sesquiterpenoids from *Laurencia composita* Yamada, namely compositacin D and G, as well as cycloelatanene A and B inhibited the growth of lung cancer cells at IC50 values ranging from 48.6 to 85.2 μM [55]. *Laurencia spp.* are good sources of anti-cancer sesquiterpenoids [56]. For instance, *Laurencia okamurai* produced laurinterol which inhibited melanoma cells by causing apoptosis via p53-dependent pathway and caspase activation [57]. Likewise, teuhetenone from *Laurencia obtuse* has been reported to display anticancer property against breast cancer cell line with an IC50 of 22 μM which is more effective in inhibiting breast cancer cells compared to chemotherapeutic drug, cisplatin (59 μM) [58]. Another major sesquiterpene, caulerpenyne was separated from *Caulerpa taxifolia,* that hindered human neuro-

blastoma cells (IC50 = 10 μM), while blocked cell cycle at G2/M phase [59].

*Cystoseira usneoides*, brown macroalgae, is a rich source of meroterpenoids. Eight meroterpenoids have been isolated from this seaweed which have anti-colon and anti-lung cancer activity. These meroterpenoids can hinder growth and migration of colon cancer cells by suppressing ERK/JNK/AKT pathways, as well as can arrest cells at G2/M phase [60]. Similarly, these meroterpenoids displayed anticancer effect against lung carcinoma, while blocks lung cancer cells at G2/M and S phases [61]. Another brown seaweed *Stypopodium flabelliforme* produced meroterpenoids, namely epitaondiol, epitaondiol monoacetate and stypotriol triacetate which exhibited anticancer property against human colon and brain carcinoma [62].

seaweed *Ulva fasciata*, isolated from south Indian rocky shore, produced five sesquiterpenoids with radical scavenging activity and among them, 3,4,5,5-tetramethyl-4-(30-oxopentyl)-2-cyclohexen-1-one was revealed as one of the most potent radical scavengers [53]. Isozonarol, a sesquiterpenoid, has been identified from *Dictyopteris undulata* that can scavenge DPPH with an EC50 of 71 μM which is

*3.4.6 Neoxanthin*

*3.4.7 Astaxanthin*

*3.4.8* β*-Cryptoxanthin*

*3.4.9 Siphonaxanthin*

**3.5 Sesquiterpenoids**

similar to α-tocopherol [54].

**3.6 Meroterpenoids**

**68**

The investigation on the anticancer properties of algal terpenoids is still in its infancy, albeit the anticancer efficacy of these phytochemicals is quite persuasive. Marine algae contain a wide array of promising terpenes and terpenoids that can strongly inhibit the proliferation of cancer cells. Extensive research on these algal terpenoids regarding their mechanism of action in the cancer cells and more clinical studies will open the door to develop novel drugs for treating cancer.

#### **Author details**

Umme Tamanna Ferdous2 and Zetty Norhana Balia Yusof1,2,3\*

1 Department of Biochemistry, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia

2 Aquatic Animal Health and Therapeutics Laboratory (AquaHealth), Institute of Bioscience, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia

3 Bioprocessing and Biomanufacturing Research Center, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia

\*Address all correspondence to: zettynorhana@upm.edu.my

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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nuz027

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[32] Jayappriyan KR, Rajkumar R, Venkatakrishnan V, Nagaraj S, Rengasamy R. In vitro anticancer activity of natural β-carotene from Dunaliella salina EU5891199 in PC-3 cells. *Biomedicine and Preventive Nutrition*. 2013;*3*(2):99-105. DOI: 10.1016/j.bionut.2012.08.003

[33] Neumann U, Derwenskus F, Flister VF, Schmid-Staiger U, Hirth T, Bischoff SC. Fucoxanthin, a carotenoid derived from Phaeodactylum tricornutum exerts antiproliferative and antioxidant activities in vitro. *Antioxidants*. 2019;*8*(6):1-11. DOI: 10.3390/antiox8060183

[34] Peraman M, Nachimuthu S. Bioautography-based Identification of Antioxidant Metabolites of Solanum nigrum L. and Exploration Its Hepatoprotective Potential agChester, K. et al. (2017) 'Bioautographybased Identification of Antioxidant Metabolites of Solanum nigrum L. and Explorati. *Pharmacognosy Magazine*. 2019;*15*:S243-S249. DOI: 10.4103/pm.pm

[35] Rijstenbil JW. Effects of UVB radiation and salt stress on growth, pigments and antioxidative defence of the marine diatom Cylindrotheca closterium. *Marine Ecology Progress Series*. 2003;*254*(June 2003):37-48. DOI: 10.3354/meps254037

[36] Xia S, Wang K, Wan L, Li A, Hu Q, Zhang C. Production, characterization, and antioxidant activity of fucoxanthin from the marine diatom odontella aurita. *Marine Drugs*. 2013;*11*(7):2667- 2681. DOI: 10.3390/md11072667

[37] Foo SC, Yusoff FM, Imam MU, Foo JB, Ismail N, Azmi NH, et al. Increased fucoxanthin in Chaetoceros calcitrans extract exacerbates apoptosis in liver cancer cells via multiple targeted cellular pathways. *Biotechnology Reports*. 2018;*20*(e00296). DOI: 10.1016/j. btre.2018.e00296

[38] Raguraman VLSA,

MubarakAli D, Narendrakumar G, Thirugnanasambandam R, Kirubagaran R, Thajuddin N. Unraveling rapid extraction of fucoxanthin from Padina tetrastromatica: Purification, characterization and biomedical application. *Process Biochemistry*. 2018;*73*:211-219. DOI: 10.1016/j. procbio.2018.08.006

[39] Banskota AH, Sperker S, Stefanova R, McGinn PJ, O'Leary SJB. Antioxidant properties and lipid composition of selected microalgae. *Journal of Applied Phycology*. 2019;*31*(1):309-318. DOI: 10.1007/ s10811-018-1523-1

**73**

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*and Pharmaceutical Bulletin*.

[46] Wang F, Huang L, Gao B, Zhang C. Optimum production

from microalga eustigmatos cf.

*Drugs*. 2018;*16*(6). DOI: 10.3390/

[47] Pasquet V, Morisset P,

831. DOI: 10.3390/md9050819

[48] Patias LD, Fernandes AS, Petry FC, Mercadante AZ,

profile of three microalgae/

10.1016/j.foodres.2017.06.069

10.1038/srep41215

md13052857

[50] Régnier P, Bastias J,

[51] Baudelet PH, Gagez AL, Bérard JB, Juin C, Bridiau N,

Jacob-Lopes E, Zepka LQ. Carotenoid

cyanobacteria species with peroxyl radical scavenger capacity. *Food Research International*. 2017;*100*:260-266. DOI:

[49] Sansone C, Galasso C, Orefice I, Nuzzo G, Luongo E, Cutignano A, et al. The green microalga Tetraselmis suecica reduces oxidative stress and induces repairing mechanisms in human cells. *Scientific Reports*. 2017;*7*(December 2015):1-12. DOI:

Rodriguez-Ruiz V, Caballero-Casero N, Caballo C, Sicilia D, et al. Astaxanthin from Haematococcus pluvialis prevents oxidative stress on human endothelial cells without toxicity. *Marine Drugs*. 2015;*13*(5):2857-2874. DOI: 10.3390/

Kaas R, et al. Antiproliferative activity of Cyanophora paradoxa pigments in melanoma, breast and lung cancer cells.

bpb.b12-00187

md16060190

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conditions, purification, identification, and antioxidant activity of violaxanthin

Polyphem (eustigmatophyceae). *Marine* 

Ihammouine S, Chepied A, Aumailley L, Berard JB, et al. Antiproliferative activity of violaxanthin isolated from bioguided fractionation of Dunaliella tertiolecta extracts. *Marine Drugs*. 2011;*9*(5):819-

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[40] Cho YC, Cheng JH, Hsu SL, Hong SE, Lee TM, Chang CMJ. Supercritical carbon dioxide antisolvent precipitation of anti-oxidative zeaxanthin highly recovered by elution chromatography from Nannochloropsis oculata. *Separation and Purification Technology*. 2011;*78*(3):274-280. DOI:

10.1016/j.seppur.2011.02.017

[41] Juin, C., Oliveira Junior, R. G. de, Fleury, A., Oudinet, C., Pytowski, L., Bérard, J. B., … Picot, L. (2018). Zeaxanthin from Porphyridium purpureum induces apoptosis in human melanoma cells expressing the oncogenic BRAF V600E mutation and sensitizes them to the BRAF

inhibitor vemurafenib. *Brazilian Journal of Pharmacognosy*, *28*(4), 457-467. doi:10.1016/j.bjp.2018.05.009

[42] Ahmed F, Fanning K, Netzel M, Turner W, Li Y, Schenk PM. Profiling of carotenoids and antioxidant capacity of microalgae from subtropical coastal and brackish waters. *Food Chemistry*. 2014;*165*:300-306. DOI: 10.1016/j.

foodchem.2014.05.107

php.13030

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[43] Kim HM, Jung JH, Kim JY, Heo J, Cho DH, Kim HS, et al. The Protective Effect of Violaxanthin from Nannochloropsis oceanica against Ultraviolet B-Induced Damage in Normal Human Dermal Fibroblasts. *Photochemistry and Photobiology*. 2019;*95*(2):595-604. DOI: 10.1111/

[44] Kim J, Kim M, Lee S, Jin ES. Development of a Chlorella vulgaris mutant by chemical mutagenesis as a producer for natural violaxanthin. *Algal Research*. 2020;*46*(September 2019):101790. DOI: 10.1016/j.

[45] Soontornchaiboon W, Joo SS, Kim SM. Anti-inflammatory effects of violaxanthin isolated from microalga Chlorella ellipsoidea in RAW 264.7 macrophages. *Biological* 

*Algal Terpenoids: A Potential Source of Antioxidants for Cancer Therapy DOI: http://dx.doi.org/10.5772/intechopen.94122*

[40] Cho YC, Cheng JH, Hsu SL, Hong SE, Lee TM, Chang CMJ. Supercritical carbon dioxide antisolvent precipitation of anti-oxidative zeaxanthin highly recovered by elution chromatography from Nannochloropsis oculata. *Separation and Purification Technology*. 2011;*78*(3):274-280. DOI: 10.1016/j.seppur.2011.02.017

*Terpenes and Terpenoids-Recent Advances*

[34] Peraman M, Nachimuthu S. Bioautography-based Identification of Antioxidant Metabolites of Solanum nigrum L. and Exploration Its

Hepatoprotective Potential agChester, K. et al. (2017) 'Bioautographybased Identification of Antioxidant Metabolites of Solanum nigrum L. and Explorati. *Pharmacognosy Magazine*. 2019;*15*:S243-S249. DOI: 10.4103/pm.pm

[35] Rijstenbil JW. Effects of UVB radiation and salt stress on growth, pigments and antioxidative defence of the marine diatom Cylindrotheca closterium. *Marine Ecology Progress Series*. 2003;*254*(June 2003):37-48. DOI:

[36] Xia S, Wang K, Wan L, Li A, Hu Q, Zhang C. Production, characterization, and antioxidant activity of fucoxanthin from the marine diatom odontella aurita. *Marine Drugs*. 2013;*11*(7):2667- 2681. DOI: 10.3390/md11072667

[37] Foo SC, Yusoff FM, Imam MU, Foo JB, Ismail N, Azmi NH, et al. Increased fucoxanthin in Chaetoceros calcitrans extract exacerbates apoptosis in liver cancer cells via multiple targeted cellular pathways. *Biotechnology Reports*. 2018;*20*(e00296). DOI: 10.1016/j.

MubarakAli D, Narendrakumar G, Thirugnanasambandam R, Kirubagaran R,

Thajuddin N. Unraveling rapid extraction of fucoxanthin from Padina tetrastromatica: Purification, characterization and biomedical application. *Process Biochemistry*. 2018;*73*:211-219. DOI: 10.1016/j.

10.3354/meps254037

btre.2018.e00296

[38] Raguraman VLSA,

procbio.2018.08.006

s10811-018-1523-1

[39] Banskota AH, Sperker S,

*Journal of Applied Phycology*. 2019;*31*(1):309-318. DOI: 10.1007/

Stefanova R, McGinn PJ, O'Leary SJB. Antioxidant properties and lipid composition of selected microalgae.

Activity and Cell Line Study of Marine Red Macroalgae Eucheuma cottonii on Lung A-549 Cancer Cells. *Pharmacognosy Journal*. 2020;*12*(2):276-

281. DOI: 10.5530/pj.2020.12.43

10.1016/j.lwt.2018.04.010

[29] Wu ZH, Liu T, Gu CX,

[30] Li YX, Himaya SWA,

molecules18077886

Kim SK. Triterpenoids of marine origin as anti-cancer agents. *Molecules*. 2013;*18*(7):7886-7909. DOI: 10.3390/

[31] Rao AR, Sarada R, Baskaran V, Ravishankar GA. Antioxidant activity of Botryococcus braunii extract elucidated in vitro models. *Journal of Agricultural and Food Chemistry*. 2006;*54*(13):4593-

4599. DOI: 10.1021/jf060799j

[32] Jayappriyan KR, Rajkumar R, Venkatakrishnan V, Nagaraj S, Rengasamy R. In vitro anticancer activity of natural β-carotene from Dunaliella salina EU5891199 in PC-3 cells. *Biomedicine and Preventive Nutrition*. 2013;*3*(2):99-105. DOI: 10.1016/j.bionut.2012.08.003

[33] Neumann U, Derwenskus F, Flister VF, Schmid-Staiger U, Hirth T, Bischoff SC. Fucoxanthin, a carotenoid

derived from Phaeodactylum tricornutum exerts antiproliferative and antioxidant activities in vitro. *Antioxidants*. 2019;*8*(6):1-11. DOI:

10.3390/antiox8060183

Shao CL, Zhou J, Wang CY. Steroids and triterpenoids from the brown alga Kjellmaniella crassifolia. *Chemistry of Natural Compounds*. 2012;*48*(1):158- 160. DOI: 10.1007/s10600-012-0190-8

[28] Rajamani K, Balasubramanian T, Thirugnanasambandan SS. Bioassayguided isolation of triterpene from brown alga Padina boergesenii possess anti-inflammatory and anti-angiogenic potential with kinetic inhibition of β-carotene linoleate system. *LWT - Food Science and Technology*. 2018. DOI:

**72**

[41] Juin, C., Oliveira Junior, R. G. de, Fleury, A., Oudinet, C., Pytowski, L., Bérard, J. B., … Picot, L. (2018). Zeaxanthin from Porphyridium purpureum induces apoptosis in human melanoma cells expressing the oncogenic BRAF V600E mutation and sensitizes them to the BRAF inhibitor vemurafenib. *Brazilian Journal of Pharmacognosy*, *28*(4), 457-467. doi:10.1016/j.bjp.2018.05.009

[42] Ahmed F, Fanning K, Netzel M, Turner W, Li Y, Schenk PM. Profiling of carotenoids and antioxidant capacity of microalgae from subtropical coastal and brackish waters. *Food Chemistry*. 2014;*165*:300-306. DOI: 10.1016/j. foodchem.2014.05.107

[43] Kim HM, Jung JH, Kim JY, Heo J, Cho DH, Kim HS, et al. The Protective Effect of Violaxanthin from Nannochloropsis oceanica against Ultraviolet B-Induced Damage in Normal Human Dermal Fibroblasts. *Photochemistry and Photobiology*. 2019;*95*(2):595-604. DOI: 10.1111/ php.13030

[44] Kim J, Kim M, Lee S, Jin ES. Development of a Chlorella vulgaris mutant by chemical mutagenesis as a producer for natural violaxanthin. *Algal Research*. 2020;*46*(September 2019):101790. DOI: 10.1016/j. algal.2020.101790

[45] Soontornchaiboon W, Joo SS, Kim SM. Anti-inflammatory effects of violaxanthin isolated from microalga Chlorella ellipsoidea in RAW 264.7 macrophages. *Biological* 

*and Pharmaceutical Bulletin*. 2012;*35*(7):1137-1144. DOI: 10.1248/ bpb.b12-00187

[46] Wang F, Huang L, Gao B, Zhang C. Optimum production conditions, purification, identification, and antioxidant activity of violaxanthin from microalga eustigmatos cf. Polyphem (eustigmatophyceae). *Marine Drugs*. 2018;*16*(6). DOI: 10.3390/ md16060190

[47] Pasquet V, Morisset P, Ihammouine S, Chepied A, Aumailley L, Berard JB, et al. Antiproliferative activity of violaxanthin isolated from bioguided fractionation of Dunaliella tertiolecta extracts. *Marine Drugs*. 2011;*9*(5):819- 831. DOI: 10.3390/md9050819

[48] Patias LD, Fernandes AS, Petry FC, Mercadante AZ, Jacob-Lopes E, Zepka LQ. Carotenoid profile of three microalgae/ cyanobacteria species with peroxyl radical scavenger capacity. *Food Research International*. 2017;*100*:260-266. DOI: 10.1016/j.foodres.2017.06.069

[49] Sansone C, Galasso C, Orefice I, Nuzzo G, Luongo E, Cutignano A, et al. The green microalga Tetraselmis suecica reduces oxidative stress and induces repairing mechanisms in human cells. *Scientific Reports*. 2017;*7*(December 2015):1-12. DOI: 10.1038/srep41215

[50] Régnier P, Bastias J, Rodriguez-Ruiz V, Caballero-Casero N, Caballo C, Sicilia D, et al. Astaxanthin from Haematococcus pluvialis prevents oxidative stress on human endothelial cells without toxicity. *Marine Drugs*. 2015;*13*(5):2857-2874. DOI: 10.3390/ md13052857

[51] Baudelet PH, Gagez AL, Bérard JB, Juin C, Bridiau N, Kaas R, et al. Antiproliferative activity of Cyanophora paradoxa pigments in melanoma, breast and lung cancer cells. *Marine Drugs*. 2013;*11*(11):4390-4406. DOI: 10.3390/md11114390

[52] Ganesan P, Noda K, Manabe Y, Ohkubo T, Tanaka Y, Maoka T, et al. Siphonaxanthin, a marine carotenoid from green algae, effectively induces apoptosis in human leukemia (HL-60) cells. *Biochimica et Biophysica Acta - General Subjects*. 2011;*1810*(5):497-503. DOI: 10.1016/j.bbagen.2011.02.008

[53] Chakraborty K, Paulraj R. Sesquiterpenoids with free-radicalscavenging properties from marine macroalga Ulva fasciata Delile. *Food Chemistry*. 2010;*122*(1):31-41. DOI: 10.1016/j.foodchem.2010.02.012

[54] Kumagai M, Nishikawa K, Matsuura H, Umezawa T, Matsuda F, Okino T. Antioxidants from the brown alga dictyopteris undulata. *Molecules*. 2018;*23*(5):1-8. DOI: 10.3390/ molecules23051214

[55] Yu XQ, Jiang CS, Zhang Y, Sun P, Kurtán T, Mándi A, et al. Compositacins A–K: Bioactive chamigrane-type halosesquiterpenoids from the red alga Laurencia composita Yamada. *Phytochemistry*. 2017;*136*:81-93. DOI: 10.1016/j.phytochem.2017.01.007

[56] Rocha DHA, Seca AML, Pinto DCGA. Seaweed secondary metabolites in vitro and in vivo anticancer activity. *Marine Drugs*. 2018;*16*(11):1-27. DOI: 10.3390/ md16110410

[57] Kim MM, Mendis E, Kim SK. Laurencia okamurai extract containing laurinterol induces apoptosis in melanoma cells. *Journal of Medicinal Food*. 2008;*11*(2):260-266. DOI: 10.1089/ jmf.2007.575

[58] Alarif WM, Al-Footy KO, Zubair MS, Halid Ph M, Ghandourah MA, Basaif SA, et al. The role of new eudesmane-type sesquiterpenoid and known eudesmane derivatives from the red alga Laurencia obtusa as potential antifungalantitumour agents. *Natural Product Research*. 2016;*30*(10):1150-1155. DOI: 10.1080/14786419.2015.1046378

[59] Barbier P, Guise S, Huitorel P, Amade P, Pesando D, Briand C, et al. Caulerpenyne from Caulerpa taxifolia has an antiproliferative activity on tumor cell line SK-N-SH and modifies the microtubule network. *Life Sciences*. 2001;*70*(4):415-429. DOI: 10.1016/ S0024-3205(01)01396-0

[60] Zbakh H, Zubía E, de Los Reyes C, Calderón-Montaño JM, Motilva V. Anticancer Activities of Meroterpenoids Isolated from the Brown Alga Cystoseira usneoides against the Human Colon Cancer Cells HT-29. *Foods*. 2020b;*9*:300. DOI: 10.3390/foods9030300

[61] Zbakh H, Zubía E, de los Reyes C, Calderón-Montaño JM, López-Lázaro M, Motilva V. Meroterpenoids from the brown alga cystoseira usneoides as potential anti-inflammatory and lung anticancer agents. *Marine Drugs*. 2020a;*18*(4). DOI: 10.3390/md18040207

[62] Pereira DM, Cheel J, Areche C, San-Martin A, Rovirosa J, Silva LR, et al. Anti-proliferative activity of meroditerpenoids isolated from the brown alga Stypopodium flabelliforme against several cancer cell lines. *Marine Drugs*. 2011;*9*(5):852-862. DOI: 10.3390/ md9050852

[63] Balboa EM, Li YX, Ahn BN, Eom SH, Domínguez H, Jiménez C, et al. Photodamage attenuation effect by a tetraprenyltoluquinol chromane meroterpenoid isolated from Sargassum muticum. *Journal of Photochemistry and Photobiology B: Biology*. 2015;*148*:51-58. DOI: 10.1016/j.jphotobiol.2015.03.026

[64] Makkar F, Chakraborty K. Antioxidant and anti-inflammatory oxygenated meroterpenoids from the

**75**

*Algal Terpenoids: A Potential Source of Antioxidants for Cancer Therapy*

*DOI: http://dx.doi.org/10.5772/intechopen.94122*

thalli of red seaweed Kappaphycus alvarezii. *Medicinal Chemistry Research*. 2018;*27*(8):2016-2026. DOI: 10.1007/

[65] Chakraborty K, Joseph D, Joy M, Raola VK. Characterization of substituted aryl meroterpenoids from red seaweed Hypnea musciformis as potential antioxidants. *Food Chemistry*. 2016;*212*:778-788. DOI: 10.1016/j.

[66] Lim S, Kwon M, Joung EJ, Shin T, Oh CW, Choi JS, et al. Meroterpenoid-Rich fraction of the ethanolic extract from sargassum serratifolium suppressed oxidative stress induced by tert-butyl hydroperoxide in HepG2 cells. *Marine Drugs*. 2018;*16*(10). DOI:

s00044-018-2210-0

foodchem.2016.06.039

10.3390/md16100374

*Algal Terpenoids: A Potential Source of Antioxidants for Cancer Therapy DOI: http://dx.doi.org/10.5772/intechopen.94122*

thalli of red seaweed Kappaphycus alvarezii. *Medicinal Chemistry Research*. 2018;*27*(8):2016-2026. DOI: 10.1007/ s00044-018-2210-0

*Terpenes and Terpenoids-Recent Advances*

[52] Ganesan P, Noda K, Manabe Y, Ohkubo T, Tanaka Y, Maoka T, et al. Siphonaxanthin, a marine carotenoid from green algae, effectively induces apoptosis in human leukemia (HL-60) cells. *Biochimica et Biophysica Acta - General Subjects*. 2011;*1810*(5):497-503. DOI: 10.1016/j.bbagen.2011.02.008

[53] Chakraborty K, Paulraj R. Sesquiterpenoids with free-radicalscavenging properties from marine macroalga Ulva fasciata Delile. *Food Chemistry*. 2010;*122*(1):31-41. DOI: 10.1016/j.foodchem.2010.02.012

[54] Kumagai M, Nishikawa K, Matsuura H, Umezawa T, Matsuda F, Okino T. Antioxidants from the brown alga dictyopteris undulata. *Molecules*.

2018;*23*(5):1-8. DOI: 10.3390/

[55] Yu XQ, Jiang CS, Zhang Y, Sun P, Kurtán T, Mándi A, et al. Compositacins

A–K: Bioactive chamigrane-type halosesquiterpenoids from the red alga Laurencia composita Yamada. *Phytochemistry*. 2017;*136*:81-93. DOI: 10.1016/j.phytochem.2017.01.007

[56] Rocha DHA, Seca AML, Pinto DCGA. Seaweed secondary metabolites in vitro and in vivo anticancer activity. *Marine Drugs*. 2018;*16*(11):1-27. DOI: 10.3390/

[57] Kim MM, Mendis E, Kim SK. Laurencia okamurai extract containing

laurinterol induces apoptosis in melanoma cells. *Journal of Medicinal Food*. 2008;*11*(2):260-266. DOI: 10.1089/

[58] Alarif WM, Al-Footy KO, Zubair MS, Halid Ph M,

Ghandourah MA, Basaif SA, et al. The role of new eudesmane-type sesquiterpenoid and known eudesmane

md16110410

jmf.2007.575

molecules23051214

DOI: 10.3390/md11114390

*Marine Drugs*. 2013;*11*(11):4390-4406.

derivatives from the red alga Laurencia

obtusa as potential antifungalantitumour agents. *Natural Product Research*. 2016;*30*(10):1150-1155. DOI: 10.1080/14786419.2015.1046378

[59] Barbier P, Guise S, Huitorel P, Amade P, Pesando D, Briand C, et al. Caulerpenyne from Caulerpa taxifolia has an antiproliferative activity on tumor cell line SK-N-SH and modifies the microtubule network. *Life Sciences*. 2001;*70*(4):415-429. DOI: 10.1016/

[60] Zbakh H, Zubía E, de Los Reyes C, Calderón-Montaño JM, Motilva V. Anticancer Activities of Meroterpenoids Isolated from the Brown Alga Cystoseira usneoides against the Human Colon Cancer Cells HT-29. *Foods*. 2020b;*9*:300.

S0024-3205(01)01396-0

DOI: 10.3390/foods9030300

[61] Zbakh H, Zubía E, de los Reyes C, Calderón-Montaño JM, López-Lázaro M, Motilva V.

10.3390/md18040207

md9050852

Meroterpenoids from the brown alga cystoseira usneoides as potential anti-inflammatory and lung anticancer agents. *Marine Drugs*. 2020a;*18*(4). DOI:

[62] Pereira DM, Cheel J, Areche C, San-Martin A, Rovirosa J, Silva LR, et al. Anti-proliferative activity of meroditerpenoids isolated from the brown alga Stypopodium flabelliforme against several cancer cell lines. *Marine Drugs*. 2011;*9*(5):852-862. DOI: 10.3390/

[63] Balboa EM, Li YX, Ahn BN, Eom SH, Domínguez H, Jiménez C, et al. Photodamage attenuation effect by a tetraprenyltoluquinol chromane meroterpenoid isolated from Sargassum muticum. *Journal of Photochemistry and Photobiology B: Biology*. 2015;*148*:51-58. DOI: 10.1016/j.jphotobiol.2015.03.026

[64] Makkar F, Chakraborty K. Antioxidant and anti-inflammatory oxygenated meroterpenoids from the

**74**

[65] Chakraborty K, Joseph D, Joy M, Raola VK. Characterization of substituted aryl meroterpenoids from red seaweed Hypnea musciformis as potential antioxidants. *Food Chemistry*. 2016;*212*:778-788. DOI: 10.1016/j. foodchem.2016.06.039

[66] Lim S, Kwon M, Joung EJ, Shin T, Oh CW, Choi JS, et al. Meroterpenoid-Rich fraction of the ethanolic extract from sargassum serratifolium suppressed oxidative stress induced by tert-butyl hydroperoxide in HepG2 cells. *Marine Drugs*. 2018;*16*(10). DOI: 10.3390/md16100374

**Chapter 7**

**Abstract**

been discussed.

**1. Introduction**

**77**

*and Yoshiaki Takaya*

Sesquiterpene from Myanmar

*Khun Nay Win Tun, Nanik Siti Aminah,*

*Alfinda Novi Kristanti, Hnin Thanda Aung*

Medicinal Plant (*Curcuma comosa*)

*Curcuma comosa* (Zingiberaceae) is widely grown in tropical and subtropical areas of Asia, like Thailand, Indonesia, Malaysia, and Myanmar. In Myanmar, the rhizome of *Curcuma comosa* is called Sa-nwin-ga, and local people had used it as a traditional medicine for stomach ache, diabetes mellitus, and hypertension. This species produces secondary metabolites of phenolic and nonphenolic groups. Phenolic groups like diarylheptanoids and flavonoids. While nonphenolics are terpenoids, especially sesqui- and monoterpenes. In this chapter, the group of sesquiterpene compounds from *Curcuma comosa* starts from the isolation technique, followed by the elucidation of the molecular structure, and their activity tests have

**Keywords:** *Curcuma comosa*, Myanmar, sesquiterpenes, Zingiberaceae, Sa-nwin-ga

Terpenes are formally derived from the carbon backbone of isoprene and based on the polymers of the active building blocks head-to-tail and tail-to-tail. Virtually all parts of the plant, especially flowers, leaves, fruits, and roots, contain different quantities of terpenes and terpenoids which are separated by means of methods such as distillation, extraction and other techniques. More than 30,000 terpenes and terpenoids are known to date. Their role in nature is still unknown and undergoes further research. Essential oils play an important role in defense and signaling as a product of plant secondary metabolism. Today, herbs and spices have an important role to play in disease prevention. In vitro trials have shown that terpenes can inhibit or sometimes induce pathways that regulating cell division, cell proliferation and detoxification [1]. *Curcuma comosa* (Zingiberaceae), widely grown in tropical and subtropical area of Asia, like Thailand, Indonesia, Malaysia, and Taunggyi (Shan State of Myanmar). It is popularly known for its beneficial effect in human health, being traditionally used in folk medicine in Asian countries, including Myanmar, Malaysia, Indonesia, and Thailand. In Taunggyi, the rhizome of *Curcuma comosa* is called **Sa-nwin-ga** and local people had used as a traditional medicine for stomach ache, diabetes mellitus and hypertension. In Thailand, the

#### **Chapter 7**

## Sesquiterpene from Myanmar Medicinal Plant (*Curcuma comosa*)

*Khun Nay Win Tun, Nanik Siti Aminah, Alfinda Novi Kristanti, Hnin Thanda Aung and Yoshiaki Takaya*

#### **Abstract**

*Curcuma comosa* (Zingiberaceae) is widely grown in tropical and subtropical areas of Asia, like Thailand, Indonesia, Malaysia, and Myanmar. In Myanmar, the rhizome of *Curcuma comosa* is called Sa-nwin-ga, and local people had used it as a traditional medicine for stomach ache, diabetes mellitus, and hypertension. This species produces secondary metabolites of phenolic and nonphenolic groups. Phenolic groups like diarylheptanoids and flavonoids. While nonphenolics are terpenoids, especially sesqui- and monoterpenes. In this chapter, the group of sesquiterpene compounds from *Curcuma comosa* starts from the isolation technique, followed by the elucidation of the molecular structure, and their activity tests have been discussed.

**Keywords:** *Curcuma comosa*, Myanmar, sesquiterpenes, Zingiberaceae, Sa-nwin-ga

#### **1. Introduction**

Terpenes are formally derived from the carbon backbone of isoprene and based on the polymers of the active building blocks head-to-tail and tail-to-tail. Virtually all parts of the plant, especially flowers, leaves, fruits, and roots, contain different quantities of terpenes and terpenoids which are separated by means of methods such as distillation, extraction and other techniques. More than 30,000 terpenes and terpenoids are known to date. Their role in nature is still unknown and undergoes further research. Essential oils play an important role in defense and signaling as a product of plant secondary metabolism. Today, herbs and spices have an important role to play in disease prevention. In vitro trials have shown that terpenes can inhibit or sometimes induce pathways that regulating cell division, cell proliferation and detoxification [1]. *Curcuma comosa* (Zingiberaceae), widely grown in tropical and subtropical area of Asia, like Thailand, Indonesia, Malaysia, and Taunggyi (Shan State of Myanmar). It is popularly known for its beneficial effect in human health, being traditionally used in folk medicine in Asian countries, including Myanmar, Malaysia, Indonesia, and Thailand. In Taunggyi, the rhizome of *Curcuma comosa* is called **Sa-nwin-ga** and local people had used as a traditional medicine for stomach ache, diabetes mellitus and hypertension. In Thailand, the

rhizome of *Curcuma comosa* is called **Waamchak mod luuk** and had been used for the treatment of reproductive disorders in women, and for relief of unpleasant menopausal symptoms among postmenopausal women. Phytochemical investigations of this plant led to the isolation of several compounds. Two major groups of structures reported constituents include sesquiterpenes and diarylheptanoids [2, 3].

#### **2. Classification of terpenes**

Terpenes are typically classified according to the number of biogenetically derived isoprene units (**Figure 1**). (i) Hemiterpenes: They are made up of C5 unit or 1 residues of isoprene. (ii) Monoterpenes: They are made up of C10 unit or 2 residues of isoprene. (iii) Sesquiterpenes: They are made up of C15 unit or 3 residues of isoprene. (iv) Diterpenes: They are made up of C20unit or 4 residues of isoprene. (v) Sesterterpenes: They are made up of C25 unit or 5 residues of isoprene. (vi) Triterpenes: They are made up of C30 unit or 6 residues of isoprene. (vii) Tetraterpenes: They are made up of C40 unit or 8 residues of isoprene [4, 5].

#### **2.1 Sesquiterpenes**

Sesquiterpenes can be classified into five sub-groups (**Figure 2**): (i) germacranetype sesquiterpenes, (ii) guaiane-type sesquiterpenes, (iii) bisaborane-type sesquiterpenes, (iv) carabrane-type sesquiterpenes, and (v) eudesmane-type sesquiterpenes [6].

**Figure 2.**

**79**

*Sesquiterpenes (1-48) from* Curcuma comosa *[6, 18–20].*

*Sesquiterpene from Myanmar Medicinal Plant (*Curcuma comosa*)*

*DOI: http://dx.doi.org/10.5772/intechopen.93794*

**Figure 1.** *Classification of terpenes [4].*

*Sesquiterpene from Myanmar Medicinal Plant (*Curcuma comosa*) DOI: http://dx.doi.org/10.5772/intechopen.93794*

rhizome of *Curcuma comosa* is called **Waamchak mod luuk** and had been used

unpleasant menopausal symptoms among postmenopausal women. Phytochemical investigations of this plant led to the isolation of several compounds. Two major

Terpenes are typically classified according to the number of biogenetically derived isoprene units (**Figure 1**). (i) Hemiterpenes: They are made up of C5 unit or 1 residues of isoprene. (ii) Monoterpenes: They are made up of C10 unit or 2 residues of isoprene. (iii) Sesquiterpenes: They are made up of C15 unit or 3 residues of isoprene. (iv) Diterpenes: They are made up of C20unit or 4 residues of isoprene. (v) Sesterterpenes: They are made up of C25 unit or 5 residues of isoprene. (vi) Triterpenes: They are made up of C30 unit or 6 residues of isoprene. (vii) Tetraterpenes: They are made up of C40 unit or 8 residues of

Sesquiterpenes can be classified into five sub-groups (**Figure 2**): (i) germacrane-

type sesquiterpenes, (ii) guaiane-type sesquiterpenes, (iii) bisaborane-type sesquiterpenes, (iv) carabrane-type sesquiterpenes, and (v) eudesmane-type

for the treatment of reproductive disorders in women, and for relief of

groups of structures reported constituents include sesquiterpenes and

diarylheptanoids [2, 3].

isoprene [4, 5].

**2.1 Sesquiterpenes**

sesquiterpenes [6].

**Figure 1.**

**78**

*Classification of terpenes [4].*

**2. Classification of terpenes**

*Terpenes and Terpenoids-Recent Advances*

**Figure 2.** *Sesquiterpenes (1-48) from* Curcuma comosa *[6, 18–20].*

#### **3. Sample collection and preparation**

Plant material may be obtained from fresh or dried plant parts such as leaves, barks, stem barks, roots, rhizomes, fruits, and flowers. The plant materials were dried at room temperature. These were cut into small pieces. The air-dried samples were kept in a covered glass container to protect them from humidity and light prior to extraction.

**3.5 Structure elucidation**

*DOI: http://dx.doi.org/10.5772/intechopen.93794*

copy (TOCSY) [13–16].

**5. Biological activities**

for various diseases **Table 2**.

**6. Conclusion**

**81**

**4. Sesquiterpenes from** *C. comosa*

A mixture of physical (melting point, CD and alpha-D) and spectroscopic (UV, IR, 1D-, 2D- NMR, and HR-MS) techniques have typically used to characterize the structures of the isolated pure sesquiterpenes. UV–Vis spectroscopy is widely used in analytical chemistry for the measurement of various analyze, such as strongly multiple bonds or aromatic conjugation within molecules, bioprocess, and fermentation of food production. Fourier-transform infrared (FTIR) spectroscopy is an effective method to classify the functional groups found in the sesquiterpenes compound. Nuclear magnetic resonance (NMR) may be the capable spectroscopy that gives complete data on atomic structure and is well appropriate for the identification of simple molecules. NMR spectroscopy is primarily partitioned into one dimensional (1D-NMR) and two-dimensional techniques (2D-NMR). The <sup>1</sup>

*Sesquiterpene from Myanmar Medicinal Plant (*Curcuma comosa*)*

and 13C-NMR one-dimension techniques provide information about the numbers and types of protons and carbon atoms in the sesquiterpenes compound. There are five 2D-NMR techniques commonly used to determine the sesquiterpenes structure, double quantum filtered correlated spectroscopy (DQF-COSY), nuclear Overhauser enhancement spectroscopy (NOESY), heteronuclear multiple-bond correlation (HMBC), heteronuclear single-quantum correlation spectroscopy (HSQC)/heteronuclear multiple-quantum coherence (HMQC), rotating frame Overhauser enhancement spectroscopy (ROESY), and total correlation spectros-

Xu et al., isolated six new sesquiterpenes (**1-6**) from the EtOAc soluble portion

Several studies have reported that *Curcuma comosa* have been successfully used

Work on natural products has recently experienced rapid expansion due to improvement in isolation techniques and the design of synthesis methods and also for the identification of a wide range of biological properties of these compounds. In

high-performance-liquid-chromatography (HPLC) [17]. Qu et al., also isolated 26 known compounds (**7-32**) from the EtOAc soluble layer of the methanol rhizomes extract of *C. comosa* by using silica gel column chromatography, octa decyl silica (ODS) column chromatography, and high-performance-liquid-chromatography (HPLC) [18]. Khine isolated 25 sesquiterpenes (**7**, **15**, **24-28**, and **30-47**) from the hexane extract and *n*-butanol fraction of *C. comosa* by using different chromatographic techniques [6]. In our previous work, 3 known sesquiterpenes (**25**, **36**, and **48**) were isolated from the MeOH soluble fraction of *C. comosa* by using vacuumliquid chromatography and successive repeated column chromatography [19]. The physical and spectroscopic data of the isolated compounds are depicted in **Table 1**.

of the methanol rhizomes extract of *C. comosa* by using silica gel column chromatography, octa decyl silica (ODS) column chromatography, and

H-NMR

#### **3.1 Extraction**

Plant materials are an immensely complicated system containing a broad range of natural compounds. The most relevant techniques can effortlessly be used for especially selective and reliable extraction of specific components found in complex matrices. These techniques comprise maceration, percolation, decoction, reflux extraction, soxhlet extraction, pressurized liquid extraction, ultrasonic extraction, (sonication), microwave-assisted extraction (MAE), accelerated solvent extraction (ASE), supercritical fluid extraction (SFE), pulsed electric field extraction, enzyme assisted extraction, hydro distillation, and steam distillation. The point of the method for extraction is to optimize the number of goal compounds and to realize most biological activity [7, 8].

#### **3.2 Examination of the crude extract**

Analytical TLC was used to examine the composition of the unrefined extracts. The visualizations were assisted either by the UV detection of the TLC or by anisaldehyde dipping, accompanied by warming at 100°C. The TLC has been changed more than once by altering solvent processes to achieve the best separation [9].

#### **3.3 Fractionation**

Fractionation is the method of classification by physical or chemical characteristics of a specific sample of an analyte or group of analytes. Raw extracts can contain thousands of compounds in a complicated mix. It would not be possible to produce a single compound from crude extract with a single separation procedure. It is therefore also important to divide the crude extract into different fractions that contain a similar group of polarities or molecular compounds [10].

#### **3.4 Isolation and purification**

Solvent extraction and partition accompanied by column chromatography (CC), vacuum-liquid chromatography (VLC), thin-layer chromatography (TLC), highperformance liquid chromatography (HPLC), and gas chromatography–mass spectrometry (GCMS) are the prevalent separation techniques for sesquiterpenes. Resembling extraction, the most significant factor to be considered before choosing an isolation protocol is the nature of the goal compound(s) present in the crude extracts or fractions. Chromatography is a technique that allows qualitative and quantitative analysis to separate, identify and purify the mixture of a compound. Chromatography is based on the concept under which the mixed molecules deposited on or in the solid and fluid stationary phases are separated with the aid of a mobile phase. The stationary phase normally employed is silica gel with the mobile the solvent(s) of choice to fractionate or extract bioactive compounds [11–13].

#### **3.5 Structure elucidation**

**3. Sample collection and preparation**

*Terpenes and Terpenoids-Recent Advances*

prior to extraction.

most biological activity [7, 8].

**3.4 Isolation and purification**

**3.2 Examination of the crude extract**

**3.1 Extraction**

separation [9].

**80**

**3.3 Fractionation**

Plant material may be obtained from fresh or dried plant parts such as leaves, barks, stem barks, roots, rhizomes, fruits, and flowers. The plant materials were dried at room temperature. These were cut into small pieces. The air-dried samples were kept in a covered glass container to protect them from humidity and light

Plant materials are an immensely complicated system containing a broad range of natural compounds. The most relevant techniques can effortlessly be used for especially selective and reliable extraction of specific components found in complex matrices. These techniques comprise maceration, percolation, decoction, reflux extraction, soxhlet extraction, pressurized liquid extraction, ultrasonic extraction, (sonication), microwave-assisted extraction (MAE), accelerated solvent extraction (ASE), supercritical fluid extraction (SFE), pulsed electric field extraction, enzyme assisted extraction, hydro distillation, and steam distillation. The point of the method for extraction is to optimize the number of goal compounds and to realize

Analytical TLC was used to examine the composition of the unrefined extracts.

Fractionation is the method of classification by physical or chemical character-

Solvent extraction and partition accompanied by column chromatography (CC), vacuum-liquid chromatography (VLC), thin-layer chromatography (TLC), highperformance liquid chromatography (HPLC), and gas chromatography–mass spectrometry (GCMS) are the prevalent separation techniques for sesquiterpenes. Resembling extraction, the most significant factor to be considered before choosing an isolation protocol is the nature of the goal compound(s) present in the crude extracts or fractions. Chromatography is a technique that allows qualitative and quantitative analysis to separate, identify and purify the mixture of a compound. Chromatography is based on the concept under which the mixed molecules deposited on or in the solid and fluid stationary phases are separated with the aid of a mobile phase. The stationary phase normally employed is silica gel with the mobile the solvent(s) of choice to fractionate or extract bioactive compounds [11–13].

istics of a specific sample of an analyte or group of analytes. Raw extracts can contain thousands of compounds in a complicated mix. It would not be possible to produce a single compound from crude extract with a single separation procedure. It is therefore also important to divide the crude extract into different fractions that

contain a similar group of polarities or molecular compounds [10].

The visualizations were assisted either by the UV detection of the TLC or by anisaldehyde dipping, accompanied by warming at 100°C. The TLC has been changed more than once by altering solvent processes to achieve the best

A mixture of physical (melting point, CD and alpha-D) and spectroscopic (UV, IR, 1D-, 2D- NMR, and HR-MS) techniques have typically used to characterize the structures of the isolated pure sesquiterpenes. UV–Vis spectroscopy is widely used in analytical chemistry for the measurement of various analyze, such as strongly multiple bonds or aromatic conjugation within molecules, bioprocess, and fermentation of food production. Fourier-transform infrared (FTIR) spectroscopy is an effective method to classify the functional groups found in the sesquiterpenes compound. Nuclear magnetic resonance (NMR) may be the capable spectroscopy that gives complete data on atomic structure and is well appropriate for the identification of simple molecules. NMR spectroscopy is primarily partitioned into one dimensional (1D-NMR) and two-dimensional techniques (2D-NMR). The <sup>1</sup> H-NMR and 13C-NMR one-dimension techniques provide information about the numbers and types of protons and carbon atoms in the sesquiterpenes compound. There are five 2D-NMR techniques commonly used to determine the sesquiterpenes structure, double quantum filtered correlated spectroscopy (DQF-COSY), nuclear Overhauser enhancement spectroscopy (NOESY), heteronuclear multiple-bond correlation (HMBC), heteronuclear single-quantum correlation spectroscopy (HSQC)/heteronuclear multiple-quantum coherence (HMQC), rotating frame Overhauser enhancement spectroscopy (ROESY), and total correlation spectroscopy (TOCSY) [13–16].

#### **4. Sesquiterpenes from** *C. comosa*

Xu et al., isolated six new sesquiterpenes (**1-6**) from the EtOAc soluble portion of the methanol rhizomes extract of *C. comosa* by using silica gel column chromatography, octa decyl silica (ODS) column chromatography, and high-performance-liquid-chromatography (HPLC) [17]. Qu et al., also isolated 26 known compounds (**7-32**) from the EtOAc soluble layer of the methanol rhizomes extract of *C. comosa* by using silica gel column chromatography, octa decyl silica (ODS) column chromatography, and high-performance-liquid-chromatography (HPLC) [18]. Khine isolated 25 sesquiterpenes (**7**, **15**, **24-28**, and **30-47**) from the hexane extract and *n*-butanol fraction of *C. comosa* by using different chromatographic techniques [6]. In our previous work, 3 known sesquiterpenes (**25**, **36**, and **48**) were isolated from the MeOH soluble fraction of *C. comosa* by using vacuumliquid chromatography and successive repeated column chromatography [19]. The physical and spectroscopic data of the isolated compounds are depicted in **Table 1**.

#### **5. Biological activities**

Several studies have reported that *Curcuma comosa* have been successfully used for various diseases **Table 2**.

#### **6. Conclusion**

Work on natural products has recently experienced rapid expansion due to improvement in isolation techniques and the design of synthesis methods and also for the identification of a wide range of biological properties of these compounds. In


*DOI: http://dx.doi.org/10.5772/intechopen.93794*

*Sesquiterpene from Myanmar Medicinal Plant (*Curcuma comosa*)*

Dimethoxycurcumenone (**6**)

[17]

**83**

280.1674).

A colorless oil; ½ � <sup>α</sup> <sup>25</sup>

C17H28O3: 280.2038). Zederone (**7**) [20, 21] Colorless plates; melting point: 153 � 154°C; ½ � <sup>α</sup> <sup>20</sup>

) 1662. <sup>1</sup>

15.8 (C-15). MS m/z: 246 (M<sup>+</sup>

EI-MS: 262 (18.2, Mþ), 43 (100,C3H<sup>þ</sup>

Furanodienone (**9**) [23, 24] Colorless prisms; melting point 87 � 88°C. UV λmax (EtOH) nm (ε): 241 (9150), 269 (6800). IR (cm�<sup>1</sup>

Isofuranodienone (**10**) [24, 25] Needles; melting point: 70-71°C; .½ � α <sup>D</sup> �0°145º (*c* = 10.0). UV λmax

m/z: 230 (M+

(cm�<sup>1</sup>

Zederone epoxide (**8**) [22] White amorphous powder;½ � <sup>α</sup> <sup>25</sup>

(log ε): 255 (3.59). IR (cm�<sup>1</sup>

(C-15), 57.7 (C-16). EI-MS m/z: 280 [M<sup>+</sup>

[M - 141]+ (100). HR-EI-MS m/z: 280.1676 (Calcd for C16H24O4:

NMR (600 MHz, CDCl3) δH: 0.47, 0.66 (1H each, both m, H-1, 5), 1.13, 1.23, 1.79, 2.10 (3H each, all s, H3-14, 15, 13, 12), 1.34, 1.65 (2H each, both m, H2-2, 3), 2.51, 2.56 (1H each, both d, *J* = 15.6 Hz, H2-9), 2.83 (2H, br s, H2-6), 3.15, 3.15 (3H each, both s, OCH3-4). 13C NMR (150 MHz, CDCl3) <sup>δ</sup>C: 24.7 (C-1), 23.9 (C-2), 36.7(C-3), 101.3 (C-4), 24.1 (C-5), 28.0 (C-6), 128.2 (C-7), 201.7 (C-8), 49.0 (C-9), 20.0 (C-10), 147.0 (C-11), 23.4 (C-12), 23.4 (C-13), 19.1 (C-14), 20.9 (C-15), 48.0 (C-16), 48.0 (C-17). EI-MS m/z: 280 [M+

(3), 85 [M – 195]<sup>+</sup> (100). HR-EI-MS m/z: 280.2046 (Calcd for

CHCl3). UV λmax (MeOH) nm (log ε): 232 (5010), 285 (2450). IR

1.30 (3H, s, H3-14), 2.07 (3H, s, H3-13), 7.04 (1H, br.s, H-12), 3.66, 3.70 (2H, m, H2-9), 3.77 (1H, s, H-5), 1.24, 2.27 (2H, m, H2-3), 2.24, 2.46 (2H, m, H2-2), 5.46 (1H, d, J = 11.8 Hz, H-1). 13C NMR (100 MHz, CDCl3) δC: 131.2 (C-1), 24.7 (C-2), 38.0 (C-3), 64.0 (C-4), 66.6 (C-5), 192.2 (C-6), 123.2 (C-7), 157.2 (C-8), 41.9 (C-9), 131.1 (C-10), 122.2 (C-11), 138.1 (C-12), 10.3 (C-13), 15.2 (C-14),

(500 MHz, CDCl3) δH: 7.08 (1H, br. s, H-12), 3.78 (1H, s, H-5), 3.68 (1H, d, *J* = 17.0 Hz, H-9a), 2.93 (1H, br. d, *J* = 10.0 Hz, H-1), 2.82 (d, J = 17.0 Hz, H-9b); 2.41 (1H, br. d, J = 11.0 Hz, H-3a), 2.21 (1H, br d, J = 14.0 Hz, H-2a), 2.16 (3H, s, H3-13), 1.52 (1H, m, H-2b), 1.47 (1H, m, H-3b), 1.32 (3H, s, H3-14), 1.15 (3H, s, H3-15). 13C NMR (125 MHz, CDCl3): 189.8 (C-6), 156.1 (C-8), 138.4 (C-12), 123.4 (C-11), 122.6 (C-7), 69.0 (C-1), 63.6 (C-4), 63.2 (C-5), 57.9 (C-10), 39.5 (C-9), 36.1 (C-3), 23.8 (C-2), 16.8 (C-14), 15.3 (C-15), 10.5 (C-13).

<sup>7</sup> ).

NMR (400 MHz, CDCl3) δH: 5.15 (1H, dd, *J* = 11.4, 4.1 Hz, H-1), 2.16 (1H, td, *J* = 12.4, 3.5 Hz, H-2α), 2.30 (1H, td, *J* = 12.4, 4.1 Hz, H-2β), 1.85 (1H, td, *J* = 11.4, 4.1 Hz, H-3α), 2.44 (1H, ddd, *J* = 11.4, 6.9, 3.4 Hz, H-3β), 5.78 (1H, br s, H-5), 3.66 (1H, br d, *J* = 14.5 Hz, H-9α), 3.70 (1H, br d, *J* = 14.5 Hz, H-9β), 7.05 (1H, br s, H-12), 2.11 (3H, s, H3-13), 1.97 (3H, s, H3-14), 1.28 (3H, s, H3-15). 13C NMR (100 MHz, CDCl3) δC: 130.5 (C-1), 26.4 (C-2), 40.6 (C-3), 145.8 (C-4), 132.4 (C-5), 190.0 (C-6), 123.9 (C-7), 156.5 (C-8), 41.7 (C-9), 135.4 (C-10), 122.0 (C-11), 138.0 (C-12), 9.5 (C-13), 18.9 (C-14), 15.7 (C-15). MS

, 47%), 150 (50), 122 (100), 94 (26), 81 (48).

NMR (CDCl3, 400 MHz), δH: 5.25 (1H, br t, *J* = 8.6 Hz, H-1), 1.78 (1H, m, H-2α), 2.09 (1H, m, H-2β), 2.20 (1H, m, H-3α), 2.25 (1H, m, H-3β), 5.84 (1H, br s, H-5), 3.03 (1H, d, *J* = 14.5 Hz, H-9α), 3.57 (1H, d, *J* = 14.5 Hz, H-9β), 7.05 (3H, br s, H-12), 2.16 (3H, br s, H3- 13), 1.73 (3H, s, H3-14), 1.63 (3H, s, H3-15). 13C NMR (CDCl3, 100 MHz), δC: 123.9 (C-1), 26.1 (C-2), 36.3 (C-3), 141.1 (C-4), 129.0 (C-5), 193.8 (C-6), 123.9 (C-7), 161.5 (C-8), 32.8 (C-9), 134.0

(EtOH) nm (ε): 223 (4.17), 248 (3.95). IR (KBr) cm�<sup>1</sup>

(50), 43 (27). HR-TOF-MS m/z: 247.0889 (C15H18O3).

H NMR (400 MHz, CDCl3) δH: 1.56 (3H, br.s, H3-15),

, 18%), 188 (15), 175 (100), 161, 119

) 1664, 1608, 1231, 1013, 755. <sup>1</sup>

<sup>D</sup> +38.3° (*<sup>c</sup>* = 0.3, MeOH). <sup>1</sup>

<sup>D</sup> �10.1° (*c* = 1.4, MeOH). UV λmax (MeOH) nm

): 1682, 1601, 1458, 1375, 1055, 853. <sup>1</sup>

] (2), 265[M - Me]<sup>+</sup> (3), 139

H

]

<sup>D</sup> +220° (*c* = 0.10,

H NMR

H

: 1667. <sup>1</sup> H


*Sesquiterpene from Myanmar Medicinal Plant (*Curcuma comosa*) DOI: http://dx.doi.org/10.5772/intechopen.93794*

1655, 1541, 754. <sup>1</sup>

(C15). EI-MS m/z: 236 [M<sup>+</sup>

1655, 1541, 754. <sup>1</sup>

15). EI-MS *m*/*z*: 236 [M<sup>+</sup>

(log ε): 221 (3.78). IR (cm�<sup>1</sup>

(C-15). EI-MS m/z: 234 (M+

(log ε): 237 (3.77). IR (cm�<sup>1</sup>

234.1620).

236.1771 (Calcd for C15H24O2: 236.1776).

m/z: 236.1771 (Calcd for C15H24O2: 236.1776).

<sup>D</sup> +34.7° (*<sup>c</sup>* = 0.2, CHCl3); IR (cm�<sup>1</sup>

<sup>D</sup> �34.7° (*<sup>c</sup>* = 0.2, CHCl3); IR (cm�<sup>1</sup>

both s, H3-14, 13), 1.16, 1.99 (1H each, both m, H2-10), 1.59, 1.82 (1H each, both m, H2-3), 1.73 (1H, br d, *J* = *ca.* 12 Hz, H-6), [1.88 (1H, dd, J = 13.0, 11.7 Hz), 2.53 (1H, br d, *J* = *ca.* 13 Hz), H2-7], [1.94 (1H, dd like, *J* = 13.7 Hz), 2.67 (1H, br d, *J* = *ca.* 14 Hz), H2-9], 2.10, 2.32 (1H each, both m, H2-4), 3.39 (1H, dd, *J* = 11.6, 4.1 Hz, H-2), 4.16 (2H, s, H2-12), 4.57, 4.82 (1H each, both br s, H2-15). 13C NMR (150 MHz, CDCl3) δC: 40.5 (C-1), 79.1 (C-2), 31.4 (C-3), 34.1 (C-4), 148.8 (C-5), 48.1 (C-6), 28.1 (C-7), 136.5 (C-8), 25.0 (C-9), 38.3 (C-10), 125.4 (C-11), 63.4 (C-12), 16.4 (C-13), 9.8 (C-14), 107.0 (C-

(600 MHz, CDCl3) δH: 1.22, 1.74 (1H each, both m, H2-2), 1.34, 1.65, 1.92, 1.92 (3H each, all s, H3-14, 15, 12, 13), 1.92 (2H, m, H2-3), 1.96 (1H, m, H-1), 2.35 (1H, dd, *J* = 18.3, 1.6 Hz, H-9b), 2.50 (1H, d, J = 18.3 Hz, H-9a), 3.74, 5.33 (1H each, both br s, H-6, 5). 13C NMR (150 MHz, CDCl3) δC: 43.9 (C-1), 23.5 (C-2), 29.6 (C-3), 134.8 (C-4), 121.6 (C-5), 36.0 (C-6), 134.3 (C-7), 203.4 (C-8), 51.5 (C-9), 72.9 (C-10), 141.6 (C-11), 22.4 (C-12) 22.5 (C-13), 27.6 (C-14), 23.7

191) (100). HR-EI-MS m/z: 234.1616 (Calcd for C15H22O2:

13), 20.8 (C-14), 23.5 (C-15). EI-MS m/z: 216 (M+

MS m/z: 216.1509 (Calcd for C15H20O: 216.1514).

NMR (600 MHz, CDCl3) δH: 1.58, 1.87, 1.93, 2.06 (3H each, all s, H3- 15, 13, 14, 12), 1.82 (2H, m, H2-3), 1.83, 2.20 (1H each, both m, H2- 2), 2.75 (1H, m, H-1), 3.76 (1H, br s, H-6), 4.92 (1H, br s, H-5), 5.90 (1H, s, H-9). 13C NMR (150 MHz, CDCl3) δC: 38.3 (C-1), 25.3 (C-2), 26.0 (C-3), 135.1 (C-4), 122.0 (C-5), 39.8 (C-6), 1333.5 (C-7), 191.8 (C-8), 130.8 (C-9), 158.6 (C-10), 141.8 (C-11), 23.0 (C-12), 21.9 (C-

<sup>D</sup> +23.9° (*<sup>c</sup>* = 0.5, MeOH). IR (cm�<sup>1</sup>

H NMR (600 MHz, CDCl3) δH: 0.79 (1H, ddd, *J* = 8.1, 5.4, 5.4 Hz, H-1), 1.13 (1H, t like, *J* = *ca*. 5 Hz, H-5), 1.18, 1.21, 1.39, 2.17 (3H each, all s, H3-12, 14, 13, 15), 1.64, 1.76 (1H each, both m, H2-2), 2.56 (2H, t, *J* = 7.6 Hz, H2-3), 2.68, 2.77 (1H each, both d, *J* = 19.9 Hz, H2- 9), 3.43 (3H, s, OCH3-6), 3.88 (1H, d, *J* = 4.1 Hz, H-6). 13C NMR (150 MHz, CDCl3) δC: 25.9 (C-1), 23.09 (C-2), 43.3 (C-3), 208.0 (C-4), 30.4 (C-5), 79.3 (C-6), 69.9 (C-7), 204.9 (C-8), 47.2 (C-9), 18.8 (C-10), 62.6 (C-11), 19.4 (C-12), 20.8 (C-13), 19.3 (C-14), 30.0

s H3-14, 13), 1.16, 1.99 (1H each, both m, H2-10), 1.59, 1.82 (1H each, both m, H2-3), 1.73 (1H, br d, J = *ca*. 12 Hz, H-6), [1.88 (1H, dd, J = 13.0, 11.7 Hz), 2.53 (1H, br d, J = *ca*. 13 Hz), H2-7], [1.94 (1H, dd like, J = 13.7 Hz), 2.67 (1H, br d, J = ca. 14 Hz), H2-9], 2.10, 2.32 (1H each, both m, H2-4), 3.39 (1H, dd, J = 11.6, 4.1 Hz, H-2), 4.16 (2H, s, H2-12), 4.57, 4.82 (1H each, both br s, H2-15). 13C NMR (150 MHz, CDCl3) δC: 40.5 (C-1), 79.1 (C-2), 31.4 (C-3), 34.1 (C-4), 148.8 (C-5), 48.1 (C-6), 28.1 (C-7), 136.5 (C-8), 25.0 (C-9), 38.3 (C-10), 125.4 (C-11), 63.4 (C-12), 16.4 (C-13), 9.8 (C-14), 107.0

H NMR (600 MHz, CDCl3) δΗ: 0.80, 1.79 (each 3H,

] (6), 218 [M -H2O]+ (100). HR-EI-MS

] (6), 218 [M - H2O]<sup>+</sup> (100). HR-EI-MS *m*/*z*:

) (28), 216 (M - H2O)+ (30), 43 (M -

): 1665, 1651, 1515, 1439, 1379, 754. <sup>1</sup>

<sup>D</sup> +10.1° (*c* = 0.70, MeOH). UV λmax (MeOH) nm

<sup>D</sup> +15.4° (*c* = 0.80, MeOH). UV λmax (MeOH) nm

): 3420, 2936, 1655, 1541, 754. <sup>1</sup>

H NMR (600 MHz, CDCl3) δH: 0.80, 1.79 (3H each,

): 3420, 2936,

): 3420, 2936,

H NMR

H

) (100). HR-EI-

): 1713, 1092.

(+)-Comosol (**1**) [17] A colorless oil; ½ � <sup>α</sup> <sup>23</sup>

*Terpenes and Terpenoids-Recent Advances*

(�)-Comosol (**2**) [17] A colorless oil; ½ � <sup>α</sup> <sup>22</sup>

Comosone I (**3**) [17] A colorless oil; ½ � <sup>α</sup> <sup>25</sup>

Comosone II (**4**) [17] A colorless oil; ½ � <sup>α</sup> <sup>27</sup>

Comosone III (**5**) [17] A colorless oil; ½ � <sup>α</sup> <sup>24</sup>

**82**

1


*DOI: http://dx.doi.org/10.5772/intechopen.93794*

*Sesquiterpene from Myanmar Medicinal Plant (*Curcuma comosa*)*

+

234.

M = 230).

264.1362).

alismol:½ � <sup>α</sup> <sup>25</sup>

Alismol (**23**) [33, 34] Colorless oil; (+)-alismol:½ � <sup>α</sup> <sup>25</sup>

Curcolonol (**22**) [32] Colorless prisms (acetone); melting point 183-184°C;½ � <sup>α</sup> <sup>25</sup>

(*c* = 2.0, EtOH). IR (cm�<sup>1</sup>

1381, 1275, 1126, 1067, 1040, 922, 742. <sup>1</sup>

<sup>D</sup> <sup>=</sup> �38.6° (*<sup>c</sup>* = 0.80, CHCl3). <sup>1</sup>

106.5 (C-15). MS: m/z %: 220 [M<sup>+</sup>

(16), 43 (87), 41 (38).

CDCl3) δH: 0.99 (3H, d, J = 6.9 Hz), 1.00 (3H, d, *J* = 6.9 Hz), 1.25 (3H, s), 1.72 -1.80 (2H, m), 1.92 (1H, m), 1.99-2.08 (1H, m), 2.02-2.09 (1H, m), 2.19-2.25 (1H, m), 2.25-2.28 (1H, m), 2.03 (2H, m), 2.51 (1H, m), 4.71 (1H, s), 4.77 (1H, s), 5.55 (1H, s). 13C NMR (400 MHz, CDC13) δC: 47.3 (C-1), 24.7 (C-2), 40.2 (C-3), 80.7 (C-4), 55.0 (C-5), 121.3 (C-6), 149.8 (C-7), 30.0 (C-8), 37.1 (C-9), 153.9 (C-10), 37.4 (C-11), 21.5, 21.3 (C-12 and C-13), 24.1 (C-14),

177 (18), 162 (53), 159 (52), 149 (18), 147 (37), 145 (16), 134 (25), 131 (23), 119 (100), 117 (30), 107 (39), 105 (47), 93 (48), 91 (76), 85 (9), 81 (15), 79 (36), 77 (28), 71 (15), 69 (14), 67 (16), 55 (25),53

13-hydroxygermacrone (**20**)

[29]

**85**

) (C15H22O).

Colorless oil (CHCl3); IR (KBr) cm�<sup>1</sup>

Curzerenone (**21**) [30, 31] Yellowish oil. 1H-NMR (400 MHz, CDCl3) δ: 7.07 (1H, brs, H-11),

Germacrone (**19**) [20, 27] Colorless prisms; melting point: 53-54°C (MeOH). IR (cm�<sup>1</sup>

1665, 1445, 1294, 1135. <sup>1</sup>

): 1679,

H NMR (400 MHz, CDCl3) δH: 1.62 (3H, s,

: 3452, 1679. <sup>1</sup>

H NMR

<sup>D</sup> = 0°

): 3420, 2934, 2872, 1723, 1653, 1562, 1426,

<sup>D</sup> = +38.8° (*c* = 0.80, CHCl3,), (�)-

H NMR (600 MHz,

](6), 205 (12), 202 (10), 187 (16),

H NMR (500 MHz,

H3-15), 1.43 (3H, s, H3-14), 1.76 (3H, s, H3-13), 1.73 (1H, s, H-12), 3.42, 2.95 (2H, dd, *J* = 11, 3.68 Hz, H2-9), 2.86 (2H, m, H2-6), 4.71 (1H, d, *J* = 11 Hz, H-5), 2.15 (2H, m, H2-3), 2.08, 2.35 (2H, m, H2-2), 4.94 (1H, d, J = 11.8 Hz, H-1). 13C NMR (100 MHz, CDCl3) δC: 132.8 (C-1), 24.0 (C-2), 38.1 (C-3), 126.0 (C-4), 125.4 (C-5), 29.3 (C-6), 129.0 (C-7), 208.0 (C-8), 56.0 (C-9), 135.1 (C-10), 137.0 (C-11), 20.0 (C-12), 22.4 (C-13), 15.6 (C-14), 16.8 (C-15). MS m/z: 218 (M

(400 MHz, CDCl3) δH: 4.95 (1H, br. d, *J* = 10.8 Hz, H-1), 4.63 (1H, dd, *J* = 10.0, 3.2 Hz, H-5), 4.25 (1H, d, J = 12.4 Hz, H-13a), 4.13 (1H, d, *J* = 12.4 Hz, H-13b), 3.40 (1H, d, *J* = 10.4 Hz, H-9a), 2.95 (1H, d, *J* = 10.4 Hz, H-9b), 2.92 (2H, overapped, H2-6), 2.33 (1H, m, H-2a), 2.14 (1H, m, H-3a), 2.04 (1H, m, H-3b), 1.89 (1H, m, H-2b), 1.78 (3H, s, H3-12), 1.59 (3H, s, H3-15), 1.40 (3H, s, H3- 14). 13C NMR (100 MHz, CDCl3) δC: 133.08 (C-1), 24.03 (C-2), 38.02 (C-3), 135.70 (C-4), 124.94 (C-5), 28.55 (C-6), 131.43 (C-7), 207.32 (C-8), 55.48 (C-9), 126.20 (C-10), 139.80 (C-11), 17.73 (C-12), 62.65 (C13), 15.56 (C-14), 16.60 (C-15). EI-MS m/z:

5.81 (1H, brs, H-5), 5.18 (1H, t, *J* = 7.5 Hz, H-1), 3.72 (2H, ABsystem, *J* = 15 Hz, H-9a, 9b), 2.20 (3H, d, *J* = 1.5 Hz, H3-13), 1.76 (3H, d, *J* = 1.5 Hz, H3-14), 1.31 (3H, s, H3-15), 1.60–2.48 (4H, m, H2- 2 and H2-3). 13C-NMR (100 MHz, CDCl3) δ: 130.5 (C-1), 26.4 (C-2), 41.6 (C-3), 145.7 (C-4), 132.4 (C-5), 189.7 (C-6), 122.2 (C-7), 156.5 (C-8), 40.6 (C-9), 135.4 (C-10), 138.1 (C-11), 123.7 (C-12), 9.5 (C-13), 18.9 (C-14), 15.7 (C-15). ESI-MS m/z: 231 [M + H]+ (C15H18O2,

Acetone-*d*6) δH: 3.69 (1H, m, H-1), 1.73 (1H, m, H-2 eq), 1.63 (1H, m, H-2ax), 1.58 (2H, m, H2-3), 2.61 (1H, s, H-5), 3.03 (d, *J* = 17 Hz, H-9 eq), 2.84 (d, *J* = 17 Hz, H-9ax), 7.29 (1H, br s, H-11), 2.14 (3H, d, *J* = 1.3 Hz, H3-13), 1.40 (3H, s, H3-14), 0.97 (3H, s, H3-15). 13C NMR (50 MHz, Acetone-*d*6) δC: 77.9 (C-1), 28.8 (C-2), 39.3 (C-3), 71.5 (C-4), 62.8 (C-5), 198.4 (C-6), 119.8 (C-7), 167.6 (C-8), 40.3 (C-9), 45.4 (C-10), 140.6 (C-11), 119.6 (C-12), 9.1 (C-13), 25.0 (C-14), 15.0 (C-15). EIMS m/z (rel int) 264 [m] + (13, 249 (29), 246 (15), 231 (5), 228 (5), 213 (12), 163 (100), 135 (35), 122 (37), 107 (31), 94 (14); HR-EI-MS m/z: 264.1354 (calcd for C15H20O4,

*Sesquiterpene from Myanmar Medicinal Plant (*Curcuma comosa*) DOI: http://dx.doi.org/10.5772/intechopen.93794*

1(10)Z,4Z-furanodiene-6-one

Glechomanolide (**12**) No data

*Terpenes and Terpenoids-Recent Advances*

(**11**)

(C-15). MS m/z: 230 [M<sup>+</sup>

No data

Dehydrocurdione (**13**) [26, 27] Colorless needles; melting point 40-42°C.½ � <sup>α</sup> <sup>23</sup>

(CHCl3) cm�<sup>1</sup>

Neocurdione (14) [27] Colorless needles; melting point 45-47°C (hexane). .½ � <sup>α</sup> <sup>23</sup>

Curdione (**15**) [23, 27, 28] Colorless prisms; melting point 53-54°C (MeOH).½ � <sup>α</sup> <sup>23</sup>

MS m/z 236[M<sup>+</sup>

(KBr) cm�<sup>1</sup>

7α-hydroxyneocurdione (**16**) No data 7β-hydroxycurdione (**17**) No data

Germacrone-1(**10**),4-diepoxide

(**18**) [6]

**84**

1

[M <sup>+</sup>

(C-10), 122.1 (C-11), 138.4 (C-12), 9.5 (C-13), 22.6 (C-14), 19.1

], 122 (100%).

MeOH): ½ � *θ* <sup>303</sup> +13,671. UV λmax (EtOH) nm (ε): 207 (1.16). IR

CDCl3) δH: 5.13 (1H, t, *J* = 8.24 Hz, H-1), 2.10 (2H, m, H2-2), 2.0 (2H, m, H2-3), 2.38 (1H, m, H-4), 3.21/3.29 (each 1H, dd, *J* = 16.48 Hz, H2-6), 3.06/3.23 (each 1H, dd, *J* = 11.44 Hz, H2-9), 1.76 (3H, s, H3-12), 1.73 (3H, s, H3-13), 1.01 (3H, d, *J* = 6.88 Hz, H3-14), 1.3 (3H, s, H3-15). 13C NMR (100 MHz, CDCl3) δC: 133.0 (C-1), 26.4 (C-2), 34.2(C-3), 46.4(C-4), 211.1(C-5), 43.4(C-6), 129.3(C-7), 207.2(C-8), 57.0(C-9), 129.9(C-10), 137.0(C-11), 21.0(C-12), 22.1

(*c* = 2.1, CHCl3): CD (*c* = 0.022, MeOH): ½ � *θ* <sup>301</sup> �29,230. UV λmax

H NMR (CDCl3): 0.92 (3H, d, *J* = 6.6 Hz, H3-14), 0.98 (3H, d, *J* = 6.8 Hz, H3-12 or �13), 1.03 (3H, d, J = 6.8 Hz, H3-13 or �12), 1.67 (3H, s, H3-15), 5.18 (1H, br t, *J* = 7.0 Hz, H-1). 13C NMR (CDCl3) δC: 131.1 (C-1), 25.5 (C-2), 32.8 (C-3), 45.8 (C-4), 210.2 (C-5), 42.4 (C-6), 52.6 (C-7), 212.5 (C-8), 55.3 (C-9), 129.1 (C-10), 30.9 (C-11), 20.2 (C-12), 21.1 (C-13), 18.2 (C-14), 18.2 (C-15). MS m/z: 236.1763

MeOH). CD (*<sup>c</sup>* = 0.0033, CHCl3) ½ � *<sup>θ</sup>* <sup>309</sup> +26,655. IR (KBr) cm�<sup>1</sup>

(1H, br s, H-1), 2.08-2.13 (2H, m, H2-2), 1.56 (1H, m, H-3α), 2.08-2.13 (1H, m, H-3β), 2.30 (1H, br s, H-4), 2.37 (1H, dd, *J* = 16.4, 1.5 Hz, H-6α), 2.65 (1H, m, H-6β), 2.88 (1H, ddd, *J* = 16.4, 8.5, 7.8 Hz, H-7), 2.91 (1H, d, *J* = 10.7 Hz, H-9α), 3.04 (1H, d, J = 10.7 Hz, H-9β), 1.85 (1H, m, H-11), 0.85 (3H, d, J = 6.5 Hz, H3- 12), 0.92 (3H, d, J = 6.5 Hz, H3-13), 0.95 (3H, d, *J* = 6.9 Hz, H3-14), 1.62 (3H, s, H3-15).13C NMR (CDCl3, 100 MHz) δC: 131.5 (C-1), 26.3 (C-2), 34.0 (C-3), 46.7 (C-4), 214.6 (C-5), 44.2 (C-6), 53.5 (C-7), 211.1 (C-8), 55.8 (C-9), 129.2 (C-10), 29.9 (C-11), 21.1 (C-12), 19.8 (C-13), 18.5 (C-14), 16.5 (C-15). EI-MS m/z (rel. Int.): 236 (2), 208 (1), 180 (33), 167 (28), 109 (52), 95 (23), 83 (13), 69 (100), 55 (76).

White powder; melting point 84-86°C.½ � α <sup>D</sup> = +71.17° (*c* = 0.14, MeOH). UV (MeOH) λmax nm (log ε): 256 (4.22), 315 (2.30). IR

s, H3-14), 1.26-1.32 (1H, m, H-3b), 1.444 (3H, s, H3-15), 1.45-1.50 (1H, m, H-2b), 1.794 (3H, s, H3-12), 1.862 (3H, s,H3-13), 2.02-2.08 (1H, m, H-2a), 2.19-2.24 (1H, m, H-3a), 2.260 (1H, dd, *J* = 14.2/ 10.8 Hz, H-6b), 2.644 (1H, d, *J* = 10.8 Hz, H-9b), 2.652 (1H, dd, *J* = 10.9/2.2 Hz H-5), 2.855 (1H, dd, *J* = 14.2/2.2 Hz, H-6a), 2.918 (1H, d, *J* = 10.8 Hz, H-1), 3.007 (1H, *J* = 10.8 Hz, H-9a). EI-MS m/z: 124.9 (100), 122 (80). 13C NMR (500 MHz, CDCl3) δC: 61.3 (C-1), 22.8 (C-2), 35.7 (C-3), 60.1 (C-4), 64.0 (C-5), 29.2 (C-6), 134.3 (C-7), 207.2 (C-8), 54.5 (C-9), 58.4 (C-10), 137.8 (C-11), 22.9 (C-12), 20.8 (C-13), 15.5 (C-14), 17.3 (C-15). HR-ESI-MS: C15H22O3Na[M + Na]<sup>+</sup> calcd. 273.14611 found 273.14575.

: 1742, 2934, 1680, 1453, 1375. <sup>1</sup>

(C-13), 18.4(C-14), 16.3(C-15). MS m/z: 234 (M+

(EtOH) nm (ε): 203 (3.73). IR (KBr) cm�<sup>1</sup>

] (Calcd for C15H24O2 236.1777).

] C15H24O2.

. 1678, 1645. <sup>1</sup>

1690, 1460, 1420, 1170, 1060. <sup>1</sup>

<sup>D</sup> +145° (*c* = 1.1,

H NMR (400 MHz,

) (C15H22O2).

: 1696, 1682, 1395, 1282.

H NMR (CDCl3, 400 MHz), δ: 5.14

H NMR (400 MHz, CDCl3) δH: 1.143 (3H,

<sup>D</sup> �190°

<sup>D</sup> +214° (*c* = 1.6,

:



*DOI: http://dx.doi.org/10.5772/intechopen.93794*

*Sesquiterpene from Myanmar Medicinal Plant (*Curcuma comosa*)*

HR-MS, found: [M-H2O]+

(log ε): 205(1.28). <sup>1</sup>

MS: RT 28.9, 234(M<sup>+</sup>

for C15H22O2: 234.1620).

14), 17.3 (C-15).

½ � *<sup>α</sup> <sup>D</sup>* +35.2° (*<sup>c</sup>* = 0.15, MeOH). <sup>1</sup>

9.2 (C-13), 18.6 (C-14), 16.0 (C-15).

207 (1.16). <sup>1</sup>

1

1

(37), 107(32), 91(29), 68(91), 67(75), 43(100).

Curcumadione (**32**) [38] Colorless oil; ½ � *α <sup>D</sup>* +63.3° (*c* = 0.15, MeOH). UV λmax (EtOH) nm (ε):

262.1205.

Curcumenone (**31**) [26] Colorless oil. IR (CHCl3) cm�<sup>1</sup>

(1S, 10S), (4S, 5S)-Germacrone-1(10), 4(5)-diepoxide (**33**) [6]

3,6,10-trimethyl-7,8,11,11 atetrahydrocyclodeca[b]furan-2,5(4H,6H)-dione (**34**) [6]

11a-hydroxy-3,6,10-trimethyl-7,8,11,11a-tetrahydrocyclodeca [b]furan-2,5(4H,6H)-dione-

methane (**35**) [6]

**87**

13.1 Hz, H-2α), 3.10 (1H, ddd, *J* = 2.0, 9.0, 13.1 Hz, H-2β), 2.15 (1H, ddd, *J* = 2.0, 8.0, 11.5 Hz, H-3α), 2.41 (1H, ddd, *J* = 9.0, 11.5, 11.5 Hz, H-3β), 3.35 (1H, dd, *J* = 3.0, 12.8 Hz, H-5), 3.21 (1H, ddd, *J* = 1.5, 12.8, 17.4 Hz, H-6α), 3.08 (1H, ddd, *J* = 1.5, 3.0, 17.4 Hz, H-6β), 6.09 (1H, s, H-9), 1.71 (3H, d, *J* = 1.5, H3-13), 1.75 (3H, br s, H3-14), 1.90 (3H, s, H3-15), 7.12 (s, 1-OH), 6.22 (s, 4-OH), 6.02 (s, 10-OH). 13C NMR (125 MHz, pyridine-*d*5) δH: 75.1 (C-1), 35.7(C-2), 41.5(C-3), 79.5(C-4), 50.3 (C-5), 22.0 (C-6), 151.2 (C-7), 148.5 (C-8), 118.8 (C-9), 82.7 (C-10), 125.8 (C-11), 170.2 (C-12), 8.4 (C-13), 23.7(C-14), 26.1 (C-15). EIMS m/z: [M]<sup>+</sup> absent, 262 [M – H2O]+ (13), 244 [M – 2H2O]+ (33), 226 [M – 3H2O]+ (100), 211 [ M – 3H2O – CH3]

<sup>+</sup> (66).

) (calcd

,

, 262.1195. C15H18O4 requires [M – H2O]<sup>+</sup>

: 1679, 1715. UV (MeOH) λmax nm

H NMR (400 MHz, CDCl3) δH: 0.43 (1H, dt,

, 13.5), 176(78), 163(29), 161(48), 149 (43), 133

H NMR (500 MHz, CDCl3) δH: 4.92

H NMR (400 MHz, CDCl3) δH: 1.07 (3H, d, *J* = 6.8 Hz,

H3-15), 1.80, 1.99 (3H each, s, H3-12, �13), 2.14 (3H, s, H3-14), 5.52 (1H, t, *J* = 6.6 Hz, H-5). 13C NMR (100 MHz, CDCl3) δC: 140.0 (C-1), 27.8(C-2), 42.6(C-3), 208.1(C-4), 121.1(C-5), 30.2(C-6), 134.7 (C-7), 205.1(C-8), 48.6(C-9), 35.0(C-10), 143.7(C-11), 19.1(C-12), 22.6(C-13), 22.2(C-14), 19.1(C-15). MS m/z: 234.1625 (M+

H NMR (500 MHz, CDCl3) δH: 2.92 (1H, d, J = 10.8 Hz, H-1), 2.06, 1.46 (m, H2-2), 2.21, 1.28 (2H, m, H2-3), 2.65 (1H, dd, J = 10.9, 2.2 Hz, H-5), 2.86 (dd, J = 14.2, 2.2 Hz, H-6a), 2.26 (dd, J = 14.2, 10.8 Hz, H-6b), 3.01 (d, J = 10.8 Hz, H-9a), 2.64 (d, J = 10.8 Hz, H-9b), 1.79 (s, H3-12), 1.86 (s, H3-13), 1.14 (s, H3-14), 1.44 (s, H3-15). 13C NMR (500 MHz, CDCl3) <sup>δ</sup>C: 61.3 (C-1), 22.8 (C-2), 35.7 (C-3), 60.1 (C-4), 64.0 (C-5), 29.2 (C-6), 134.3 (C-7), 207.2 (C-8), 54.5 (C-9), 58.4 (C-10), 137.8 (C-11), 22.9 (C-12), 20.8 (C-13), 15.5 (C-

(1H, br s, H-1), 2.06, 2.20 (2H, m, H2-2), 1.72, 2.04 (2H, m, H2-3), 2.44 (1H, m, H-4), 3.36 (2H, m, H2-6), 4.92 (1H, br s, H-8), 2.04, 2.94 (m, H2-9), 1.85 (3H, s, H3-13), 1.09 (3H, d, J = 6.7 Hz, H3-14), 1.82 (3H, s, H3-15). 13C NMR (500 MHz, CDCl3) δC: 133.4 (C-1), 27.3 (C-2), 35.9 (C-3), 48.0 (C-4), 208.2 (C-5), 41.6 (C-6), 155.2 (C-7), 79.7 (C-8), 46.1 (C-9), 128.9 (C-10), 128.9 (C-11), 173.5 (C-12),

H NMR (500 MHz, CDCl3) δH: 4.88 (1H, d, J = 10.7 Hz, H-1), 2.00, 2.20 (2H, m, H2-2), 1.65, 2.10 (2H, m, H2-3), 2.45 1H, (m, H-4), 3.58 (d, J = 15.4 Hz, H-6a), 3.30 (d, J = 15.7 Hz, H-6b), 2.93 (1H, d, J = 13.4 Hz, H-9a), 2.31 (1H, d, J = 13.4 Hz, H-9b), 1.86 (3H, s, H3- 13), 1.06 (3H, d, J = 6.8 Hz, H3-14), 1.93 (3H, s, H3-15). 13C NMR (500 MHz, CDCl3) δC: 133.8 (C-1), 27.2 (C-2), 36.0 (C-3), 47.8 (C-4), 209.6 (C-5), 40.2 (C-6), 154.6 (C-7), 106.9 (C-8), 49.7 (C-9), 130.5 (C-10), 129.9 (C-11), 172.3 (C-12), 9.2 (C-13), 18.4 (C-14),

*J* = 4.56, 7.32 Hz, H-1), 1.64 (2H, q, *J* = 7.32 Hz, H2-2), 2.47 (2H, t, *J* = 7.36 Hz, H2-3), 0.67 (1H, q, *J* = 4.56 Hz, H-5), 2.8 (2H, m, H2-6), 2.52 (2H, d, *J* = 15.6 Hz, H2-9), 2.07 (3H, s, H3-12), 1.77 (3H, s, H3- 13), 2.12 (3H, s, H3-14), 1.10 (3H, s, H3-15). 13C NMR (100 MHz, CDCl3) δC: 24.1 (C-1), 23.4(C-2), 44.0(C-3), 209.0(C-4), 24.2(C-5), 28.0(C-6), 128.1(C-7), 201.9(C-8), 49.0(C-9), 20.2(C-10), 147.6(C-11), 23.5(C-12), 23.5(C-13), 30.1(C-14), 19.1(C-15). C15H22O2. GC

*Terpenes and Terpenoids-Recent Advances*

Alismoxide(**24**) [33, 35] Colorless crystals, mp 138–141°C;½ � <sup>α</sup> <sup>20</sup>

(24).

Zedoarondiol (**25**) [27] Colorless needles; melting point 134°C (CHCl3);½ � <sup>α</sup> <sup>23</sup>

m/z: 252 (M+

isozedoarondiol (**26**) [27] Colorless needles; melting point 150-156°C.½ � <sup>α</sup> <sup>23</sup>

H, 9.52.

m/z: 235 [M + H]+

cm�<sup>1</sup>

1

Procurcumenol (**27**) [26, 36] Viscous oil;½ � <sup>α</sup> <sup>24</sup>

Aerugidiol (**29**) No data

**86**

λmax nm (log ε): 258 (3.86). IR (cm�<sup>1</sup>

) (C15H24O3).

(log ε):248 (3.90), 275 (3.75). IR (cm�<sup>1</sup>

158(35), 121(84), 105(100), 93(60), 43(79).

6.08), 158(35), 121(84), 105(100), 93(60), 43(79).

Isoprocurcumenol (**28**) [26] Colorless oil; UV (MeOH) λmax nm (log ε): 205 (1.83). IR (CHCl3)

Zedoalactone B (**30**) [37] Oil; ½ � *α <sup>D</sup>* +177.7° (*c* = 0.4, MeOH). UV (MeOH) λmax nm (log ε): 273 (4.33). IR (KBr) cm�<sup>1</sup>

: 3450, 1674, 1610. <sup>1</sup>

(log ε): 258 (3.86). IR (cm�<sup>1</sup>

<sup>D</sup> = +9.3 (c 0.9 CHCl3,). <sup>1</sup>

<sup>D</sup> = �44°

<sup>D</sup> = �147.2° (*c* = 0.8,

H NMR (CDCl3)

H NMR

, 6.08),

,

H NMR

): 3420, 1662, 1604. <sup>1</sup>

NMR (400 MHz, CDCl3) δH: 5.44 (1H, br d, J = 3.0 Hz, H-6), 0.98, 1.0 (3H each, d, *J* = 6.9 Hz, H3-12, �13), 1.25, 128 (3H each, s, H3-14, �15). 13C NMR (100 MHz, CDCl3): <sup>δ</sup>C: 50.5 (C-1), 21.4 (C-2), 40.3 (C-3), 80.0 (C-4), 50.1 (C-5), 121.3 (C-6), 149.4(C-7), 25.0 (C-8), 42.5 (C-9), 75.2 (C-10), 37.2 (C-11), 21.1 (C-12), 21.2 (C-13), 22.4 (C-14), 21.3 (C-15). MS: m/z (%): 220 (M+ -H2O)(7), 205 (9), 202 (4), 187 (9), 177 (12), 162 (66), 159 (28), 149 (20), 147 (38), 134 (34), 121 (23), 119 (53), 107 (34), 105 (24), 93 (42), 91 (30), 85 (12), 81 (14), 79 (28), 77 (16), 71 (12), 69 (12), 55 (20), 43 (100), 41

(*c* = 1.0, MeOH). CD (*c* = 0.03, MeOH): ½ � *θ* <sup>321</sup>� 6468. UV (MeOH)

(CDCl3) δH: 1.18 (3H, s, H3-14 or �15), 1.20 (3H, s, H3-15 or �14), 1.84 (3H, s, H3-12, or �13), 1.94 (3H, s, H3-13 or �12), 2.60 (1H, d, *J* = 13.0 Hz, H-9β), 2.98 (1H, d, *J* = 13.0 Hz, H-9α). 13C NMR (CDCl3) δC: 55.9 (C-1), 22.9 (C-2), 28.5 (C-3), 79.9 (C-4), 52.0 (C-5), 39.7 (C-6), 134.6 (C-7), 202.9 (C-8), 59.8 (C-9), 72.7 (C-10), 142.1 (C-11), 21.9 (C-12), 22.2 (C-13), 22.7 (C-14), 20.6 (C-15). MS

MeOH). CD (*c* = 0.003, MeOH): ½ � *θ* <sup>313</sup> �6323. UV (MeOH) λmax nm

δH: 1.23 (3H, s, H3-14), 1.42 (3H, s, H3-15), 1.86 (3H, s, H3-12 or �13), 2.03 (3H, s, H3-13 or �12), 2.42 (H, d, *J* = 16.0 Hz, H-9β), 3.21 (H, d, *J* = 16.0 Hz, H-9α). 53.4 (C-1), 25.2 (C-2), 27.4 (C-3), 82.4 (C-4), 51.7 (C-5), 37.0 (C-6), 134.0 (C-7), 203.0 (C-8), 50.2 (C-9), 73.2 (C-10), 143.7 (C-11), 22.1 (C-12), 22.8 (C-13), 25.0 (C-14), 32.2 (C-15). MS: *Anal*. Calcd for C15H24O3: C, 71.39; H, 9.59. Found: C, 71.65:

(500 MHz, CDCl3) δH: 1.24 (3H, s, H3-14), 1.75 (3H, s, H3-13), 1.78 (3H, s, H3-12), 1.88 (3H, s, H3-15), 2.18 (1H, dd, *J* = 16.0, 13.0 Hz, H-6α), 2.38 (1H, ddd, J = 10.5, 10.0 Hz, H-1), 2.61 (1H, br d, J = 16.0 Hz, H-6β), 5.88 (1H, br s, H-9). 13C NMR (100 MHz, CDCl3) δC: 50.5 (C-1), 26.9(C-2), 39.9 (C-3), 80.3 (C-4), 53.9 (C-5), 28.6 (C-6), 136.9 (C-7), 199.2(C-8), 129.2 (C-9), 155.1(C-10), 136.3 (C-11), 21.3 (C-12), 22.4(C-13), 23.4 (C-14), 24.3 (C-15). ESI-MS

*J* = 14.68 Hz, H-1), 1.21 (2H, m, H2-2), 1.39 (2H, m, H2-3), 1.40 (1H, m, H-5), 2.81 (2H, d, *J* = 14.2 Hz, H2-6), 2.16 (2H, s, H2-9), 1.92 (3H, s, H3-12), 1.82 (3H, s, H3-13), 1.24 (3H, s, H3-14), 4.90 (2H, br S, H2-15). 13C NMR (100 MHz, CDCl3) δC: 51.2 (C-1), 24.7(C-2), 28.2 (C-3), 77.4 (C-4), 58.9 (C-5), 39.8 (C-6), 134.5 (C-7), 203.0 (C-8), 53.8 (C-9), 141.3 (C-10), 143.9 (C-11), 21.9 (C-12), 22.8 (C-13), 24.4 (C-14), 111.6 (C-15). C15H20O2. GC mS: RT 29.36 min, 234 (M+

H NMR (500 MHz, pyridine-*d*5) δH: 2.06 (1H, ddd, *J* = 8.0, 11.5,

): 3420, 1662, 1604. <sup>1</sup>

<sup>D</sup> = +218.5° (*c* = 0.15, MeOH). UV (MeOH) λmax nm

. C15H20O2. GC MS: RT 29.36 min, 234(M<sup>+</sup>

): 3430, 1646. <sup>1</sup>

H NMR (400 MHz, CDCl3) δH: 3.22 (1H, q,

: 3400, 2970, 2940, 2880, 1740, 1660, 1630.

H



*DOI: http://dx.doi.org/10.5772/intechopen.93794*

*Sesquiterpene from Myanmar Medicinal Plant (*Curcuma comosa*)*

1

4a,8,9,9a-Tetrahydroxy-3,5,8 trimethyl-4a,5,6,7,7a,8,9,9aoctahydroazuleno[6,5-b]-furan-

7-(1-hydroxy-1-methylethyl)- 1,4-dimethyl-1,2,3,3a,4,5,8,8aoctahydroazulene-1,4-diol (**44**)

Gajutsulactone B (**45**) [6] <sup>1</sup>

7-isopropenyl-1,4a-

1,4-diol (**47**) [6]

(**48**) [19]

**Table 1.**

**89**

dimethyldecahydronaphthalene-

(1S,4S,5S,10R)-isozedoarondiol

*Physical and spectral data of sesquiterpenes.*

2(4H)-one (**43**) [6]

[6]

(C-14), 32.5 (C-15).

H2O + Na]<sup>+</sup>

26.3 (C-14), 31.6 (C-15).

(C-13), 25.2 (C-14), 19.9 (C-15). Bisacumol (**46**) [6] 13C NMR (300 MHz, CDCl3) δC: 144.2 (C-1), 127.2 (C-2), 129.3

(C-14), 21.3 (C-15).

Yellow oil. IR (cm<sup>1</sup>

1

1

13C NMR (400 MHz, C5D5N) δC: 53.1 (C-1), 25.3 (C-2), 38.2 (C-3), 80.7 (C-4), 52.4 (C-5), 24.6 (C-6), 161.5 (C-7), 106.9 (C-8), 44.0 (C-9), 72.1 (C-10), 122.7 (C-11), 173.7 (C-12), 8.0 (C-13), 25.6

H NMR (400 MHz, C5D5N) δH: 3.74 (1H, dd, J = 5.0, 3.8 Hz, H-1), 1.77 (2H, m, H2-2), 2.36 (1H, dddd, J = 11.4, 11.4, 10.7, 6.8 Hz, H-3a), 1.43 (1H, m, H-3a), 2.05 (1H, qd, J = 7.3, 6.8 Hz, H-4), 3.28 (1H, d, J = 15.6 Hz, H-6a), 2.87 (1H, dq, J = 15.6, 1.7, H-6b), 3.99 (1H, s, H-9), 1.87 (3H, d, J = 1.7 Hz, H3-13), 0.71 (3H, d, J = 7.3 Hz, H3-14), 1.47 (3H, s, H3-15). 13C NMR (400 MHz, C5D5N) δC: 43.3 (C-1), 25.0 (C-2), 33.2 (C-3), 42.9 (C-4), 92.2 (C-5), 32.2 (C-6), 158.8 (C-7), 108.6 (C-8), 81.1 (C-9), 82.0 (C-10), 126.9 (C-11), 172.4 (C-12), 8.7 (C-13), 14.2 (C-14), 19.7 (C-15). MS: m/z 303.12047, [M –

H NMR (400 MHz, C5D5N) δH: 3.48 (m, H-1), 1.96 (1H, m, H-2a), 1.78 (1H, m, H-2b), 2.02 (1H, m, H-3a), 1.85 (1H, m, H-3b), 2.41 (dd, J = 12.8, 4.9 Hz, H-5), 2.52 (1H, d, J = 13.9 Hz, H-6a), 2.15 (1H, dd, J = 13.9, 12.8 Hz, H-6b), 6.16 (1H, br dd, J = 8.4, 5.2 Hz, H-8), 2.78 (91H, J = 14.2, 5.2 Hz, H-9a), 2.27 (1H, dd, J = 14.2, 8.4 Hz, H-9b), 1.57 (3H, s, H3-12), 1.57 (3H, s, H3-13), 1.62 (3H, s, H3-14), 1.36 (3H, s, H3-15). 13C NMR (400 MHz, C5D5N) δC: 54.2 (C-1), 25.5 (C-2), 37.5 (C-3), 80.9 (C-4), 49.4 (C-5), 26.2 (C-6), 150.9 (C-7), 118.8 (C-8), 35.4 (C-9), 70.6 (C-10), 72.7 (C-11), 29.2 (C-12), 29.4 (C-13),

H NMR (300 MHz, CDCl3) δH: 2.88 (ddd, 6.4, 6.4, 9.8 Hz, H-1), 2.06 (1H, m, H-2a), 1.86 (1H, m, H-2b), 1.90 (m, H-3), 2.30 (m, H-5), 2.50 (d, H-6a), 2.24 (d, H-6b), 5.01 (br s, H-9a), 4.84 (br s, H-9b), 2.18 (3H, s, H-12), 1.86 (3H, s, H-13), 1.78 (3H, s, H-14), 1.22 (3H, s, H-15). 13C NMR (300 MHz, CDCl3) δC: 42.4 (C-1), 26.2 (C-2), 38.0 (C-3), 85.3 (C-4), 45.7 (C-5), 25.7 (C-6), 120.4 (C-7), 167.5 (C-8), 111.9 (C-9), 145.2 (C-10), 151.8 (C-11), 23.3 (C-12), 23.5

(C-3), 135.7 (C-4), 129.3 (C-5), 127.2 (C-6), 36.1 (C-7), 46.1 (C-8), 67.1 (C-9), 128.6 (C-10), 135.0 (C-11), 18.4 (C-12), 26.0 (C-13), 23.3

H NMR (500 MHz, CDCl3) δH: 3.27 (1H, dd, 12.7, 4.2 Hz, H-1), 1.87 (1H, m, H-2a), 1.62 (1H, m, H-2b), 1.72 (1H, m, H-3a), 1.5 (1H, ddd, J = 14.1, 14.1, 4.5 Hz, H-3b), 1.07 (1H, dd, 12.4, 2.6 Hz, H-5), 1.68 (1H, m, H-6a), 1.94 (1H, m, H-6b), 1.62 (1H, m, H-8a), 1.45 (1H, m, H-8b), 1.87 (1H, m, H-9a), 1.11 (1H, dd, J = 13.2, 3.7 Hz, H-9b),1.76 (3H, s, H3-12), 4.74 1H, (H-13, Z), 4.71 (1H, H-13, E), 1.16 (3H, s, H3-14), 1.05 (3H, s, H3-15). 13C NMR (500 MHz, CDCl3) δC: 79.7 (C-1), 26.8 (C-2), 39.4 (C-3), 71.4 (C-4), 50.4 (C-5), 25.6 (C-6), 46.1 (C-7), 26.4 (C-8), 39.3 (C-9), 38.9 (C-10), 150.5 (C-11), 20.7

): 3394, 1701, 1665, 1612. <sup>1</sup>

CDCl3) δH: 2.79 (1H, m, H-1), 1.63 (2H, m, H2-2), 1.73 (2H, m, H2- 3), 2.02(1H, d, J = 12.9 Hz, H-5), 2.52, 1.91 (each, 1H, d, J = 13.9 Hz, H2-6), 2.30 (1H, dd, J = 16.1, 1.2 hz, H-9a), 3.34 (d, J = 16.1 Hz, H-9b), 1.97 (3H, s, H3-12), 1.88 (3H, s, H3-13), 1.39 (3H, d, J = 6.4 Hz, H-14), 1.19 (3H, s, H-15).13C NMR (151 MHz, methanol-*d4*) δC: 51.2 (C-1), 24.6 (C-2), 36.0 (C-3), 81.7 (C-4), 52.6 (C-5), 27.0 (C-6), 134.0 (C-7), 204.7 (C-8), 49.9 (C-9), 72.5 (C-10), 143.0 (C-11), 20.9

H NMR (600 MHz,

(C-12), 108.6 (C-13), 30.0 (C-14), 12.6 (C-15).

(C-12), 21.8 (C-13), 23.4 (C-14), 31.3 (C-15).

. HR-MS 303.12047 C15H22O6.

*Terpenes and Terpenoids-Recent Advances*

1,4-dihydroxy-1,4-dimethyl-7- (1-methylethylidene) octahydroazulen-6(1H)-one-

Zedoalactone A (**39**) [6] <sup>1</sup>

5,8-dihydroxy-3,5,8-trimethyl-

octahydroazuleno[6,5-b]furan-2

5,8-dihydroxy-3,5,8-trimethyl-

octahydroazuleno[6,5-b]-furan-

Zedoarolide B (**42**) [6] <sup>1</sup>

4a,5,6,7,7a,8,9,9a-

(4H)-one (**40**) [6]

4a,5,6,7,7a,8,9,9a-

2(4H)-one (**41**) [6]

**88**

methane (**38**) [6]

16.5 (C-15). HR-ESI-MS: 287.12547[M + Na]<sup>+</sup>

C15H20O4Na 287.1253802. Curcumenol (**36**) [19] Colorless crystals; melting point: 98-100°C. IR (cm<sup>1</sup>

11.8 (C-14), 20.9 (C-15). Isocurcumenol (**37**) [6] 13C NMR (400 MHz, CDCl3) δC: 53.0 (C-1), 28.6 (C-2), 31.0 (C-3),

(C-14), 112.5 (C-15).

30.0 (C-15).

31.8 (C-15).

(C-14), 24.0 (C-15).

1

1

(C-15).

1

1695, 1658, 1274. <sup>1</sup>

, calcd. For

H NMR (600 MHz, CDCl3) δH: 1.95 (1H, m, H-1),

1.96 2H, (m, H2-2), 1.90 (2H, m, H2-3), 1.93 (1H, m, H-4), 2.11, 2.66 (each, 1H, d, J = 16.9 Hz, H2-6), 5.77 (1H, s, H-9), 1.60 (3H, s, H3- 12), 1.82 (3H, s, H3-13), 1.03 (3H, d, J = 6.4 Hz, H-14), 1.67 (3H, s, H-15).13C NMR (151 MHz, CDCl3) δC: 51.3 (C-1), 27.6 (C-2), 31.2 (C-3), 40.4 (C-4), 85.7 (C-5), 37.3 (C-6), 137.4 (C-7), 101.5 (C-8), 125.6 (C-9), 139.2 (C-10), 122.2 (C-11), 22.3 (C-12), 18.9 (C-13),

41.9 (C-4), 87.4 (C-5), 39.2 (C-6), 134.1 (C-7), 104.0 (C-8),36.4 (C-9), 145.4 (C-10), 127.2 (C-11), 22.8 (C-12), 19.2 (C-13), 12.7

H NMR (400 MHz, CDCl3) δH: 1.16 (s), 1.26 (s), 1.81 (s), 1.89 (s), 1.50-1.80 (m), 2.51 (d, J = 11.7), 2.83 (d, J = 15.6), 2.92 (d, J 11.7). 13C NMR (400 MHz, CDCl3) δC: 54.7 (C-1), 21.4 (C-2), 28.0 (C-3), 80.4 (C-4), 50.1 (C-5), 39.9 (C-6), 135.8 (C-7), 205.6 (C-8), 57.3 (C-9), 71.5 (C-10), 140.0 (C-11), 22.0 (C-12), 22.9 (C-13), 22.0 (C-14),

H NMR (500 MHz, CDCl3) δH: 2.71 (1H, m, H-1), 1.85 (1H, m, H-2a), 1.49 (1H, m, H-2b), 1.80 (2H, m, H2-3), 2.00 (1H, ddd, J = 13.3, 6.6, 3.7 Hz, H-5), 2.71 (1H, m, H-6a), 1.85 (1H, m, H-6b), 4.92 (1H, ddq, J = 6.9, 2.6, 2.0 Hz, H-8), 2.33 (1H, dd, 16.0, 6.9 Hz, H-9a), 2.09 (1H, ddd, J = 16.0, 2.6, 0.7 Hz, H-9b), 1.83 (3H, d, J = 2.0 Hz, H3-13), 1.34 (3H, s, H3-14), 1.24 (3H, s, H3-15). 13C NMR (500 MHz, CDCl3) δC: 51.5 (C-1), 24.5 (C-2), 37.1 (C-3), 816 (C-4), 50.8 (C-5), 24.9 (C-6), 161.4 (C-7), 80.8 (C-8), 35.7 (C-9), 73.5 (C-10), 122.5 (C-11), 175.5 (C-12), 8.0 (C-13), 25.0 (C-14),

H NMR (500 MHz, CDCl3) δH: 1.97 (1H, m, H-1), 1.82 (m, H-2a), 1.70 (m, H-2b), 1.70 (2H, m, H2-3), 1.58 (1H, ddd, J = 13.0, 9.0, 2.8 Hz, H-5), 2.30 (1H, dd, J = 15.7, 2.8 Hz, H-6a), 2.06 (1H, dd, J = 14.7 13.3 Hz, H-6b), 5.13 (1H, d, J = 11.2 Hz, H-8), 2.31 (1H, dd, 14.7, 2.7 Hz, H-9a), 1.76 (1H, dd, J = 14.7, 11.3 Hz, H-9b), 1.81 (3H, dd, J = 1.7, 1.7 Hz, H3-13), 1.28 (3H, s, H3-14), 1.25 (3H, s, H3-15). 13C NMR (500 MHz, CDCl3) <sup>δ</sup>C: 53.2 (C-1), 23.5 (C-2), 41.2 (C-3), 80.4 (C-4), 48.1 (C-5), 29.8 (C-6), 162.4 (C-7), 79.0 (C-8), 46.3 (C-9), 72.6 (C-10), 122.2 (C-11), 174.2 (C-12), 8.7 (C-13), 23.5

H NMR (500 MHz, CDCl3) δH: 2.86 (1H, dddd, J = 12.3, 7.9, 5.1, 1.4 Hz, H-1), 1.81 (m, H-2a), 1.34 (m, H-2b), 1.72 (2H, m, H2-3), 2.23 (1H, m, H-5), 2.72 (1H, m, H-6a), 2.23 (1H, m H-6b), 5.28 (1H, dqd, 11.7, 1.8, 1.7 Hz, H-8), 2.28 (1H, ddd, J = 13.7, 3.4, 1.7 Hz, H-9a), 1.68 (1H, dd, 13.7, 11.7 Hz, H-9b), 1.79 (3H, dd, 1.8, 1.4 Hz, H3-13), 1.40 (3H, s, H3-14), 1.32 (3H, s, H3-15). 13C NMR (500 MHz, C5D5N) δC: 53.1 (C-1), 24.9 (C-2), 37.8 (C-3), 80.7 (C-4), 48.4 (C-5), 24.9 (C-6), 165.4 (C-7), 79.8 (C-8), 41.2 (C-9), 71.2 (C-10), 121.3 (C-11), 174.9 (C-12), 8.8 (C-13), 25.8 (C-14), 32.4

H NMR (400 MHz, C5D5N) δH: 3.38 (1H, ddd, 3.7, 7.6, 7.6 Hz, H-1), 1.98 (1H, m, H-2a), 1,79 (1H, m, H-2b), 2.08 (1H, m, H-3a), 1.97 (1H, m, H-3b), 2.64 (1H, ddd, J = 3.7, 3.7, 12.8 Hz, H-5), 2.82 (1H, dd, J = 3.7, 12.8 Hz, H-6a), 2.43 (1H, dd, J = 12.8, 12.8 Hz, H-6b), 2.86 (1H, Abq, J = 15.5 Hz, H-9a), 2.80 (1H, Abq, J = 15.5 Hz, H-9b), 1.81 (3H, s, H-13), 1.44 (3H, s, H-14), 1.58 (3H, s, H-15).

): 3371, 3321,


**Table 1.** *Physical and spectral data of sesquiterpenes.*


**References**

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Distribution of phytoestrogenic diarylheptanoids and sesquiterpenoids components in *Curcuma comosa*

[3] Matsumoto T, Nakamura S, Fujimoto K, Ohta T, Ogawa K, Yoshikawa M, et al. Structure of diarylheptanoids with antiallergic activity from the rhizomes of *Curcuma comosa*. Journal of Natural Medicines. 2014;**69**(1):142-147. DOI: 10.1007/

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Villar AM. Terpenoids: sources, structure elucidation and therapeutic potential in inflammation. Current Topics in Medicinal Chemistry. 2003;

**3**(2):171-185. DOI: 10.2174/

[6] Khine MM. Isolation and

Fakultät (mathematisch-

**91**

characterization of phytoconstituents from Myanmar medicinal plants [Dissertation]. Mathematisch-Naturwissenschaftlich-Technischen

naturwissenschaftlicher Bereich) der Martin-Luther-Universität Halle-Wittenberg. Germany; 2006

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s11418-014-0870-8

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*Sesquiterpene from Myanmar Medicinal Plant (*Curcuma comosa*)*

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Netherlands: Elsevier; 2015. pp. 267-309. DOI: 10.1016/bs.

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Mandrekar VK. Analytical methods for natural products isolation. In: Advances in Biological Science Research. Elsevier; 2019. pp. 395-409. DOI: 10.1016/ b978-0-12-817497-5.00024-0

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of Organic Compounds. 7th ed. Hoboken, New Jersey: John Wiley and

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Sons, Inc; 2005. p. 512

coac.2015.09.009

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10.14744/nci.2016.32757

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04000100017

rhizomes and its related species. Revista Brasileira de Farmacognosia. 2017;**27**(3): 290-296. DOI: 10.1016/j.bjp.2016.12.003

1934578X1000500927

#### **Table 2.**

*Biological activities of extracts and compounds from* Curcuma comosa*.*

this chapter, the extraction, isolation, and spectroscopic data of sesquiterpenes from *Curcuma comosa* have been discussed.

#### **Author details**

Khun Nay Win Tun1,2, Nanik Siti Aminah1 \*, Alfinda Novi Kristanti<sup>1</sup> , Hnin Thanda Aung<sup>3</sup> and Yoshiaki Takaya<sup>4</sup>

1 Department of Chemistry, Faculty of Science and Technology, Universitas Airlangga, Komplek Kampus C UNAIR, JL. Mulyorejo, Surabaya, Indonesia

2 Department of Chemistry, Pathein University, Pathein, Myanmar

3 Department of Chemistry, Mandalay University, Mandalay, Myanmar

4 Faculty of Pharmacy, Meijo University, Tempaku, Nagoya, Japan

\*Address all correspondence to: nanik-s-a@fst.unair.ac.id

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

*Sesquiterpene from Myanmar Medicinal Plant (*Curcuma comosa*) DOI: http://dx.doi.org/10.5772/intechopen.93794*

#### **References**

this chapter, the extraction, isolation, and spectroscopic data of sesquiterpenes from

**Sample/extract Biological activity References** Hexand and DCM Nematocidal [39] EtOAc Choleretic [40] Crude protein Antioxidant [41] EtOH Antibacterial [42] Hexane and EtOH Anti-inflammatory [43] Hexane, EtOAc, and *n*-butanol Antifungal [6] Zedoarondiol (**25**) Cytotoxic [19] (1S, 10S), (4S, 5S)-Germacrone-1(10), 4(5)-diepoxide (**33**) Cellular viability [6] Curcumenol (**36**) Cytotoxic [19] (1S,4S,5S,10R)-isozedoarondiol (**48**) Cytotoxic [19]

1 Department of Chemistry, Faculty of Science and Technology, Universitas Airlangga, Komplek Kampus C UNAIR, JL. Mulyorejo, Surabaya, Indonesia

2 Department of Chemistry, Pathein University, Pathein, Myanmar

4 Faculty of Pharmacy, Meijo University, Tempaku, Nagoya, Japan

\*Address all correspondence to: nanik-s-a@fst.unair.ac.id

3 Department of Chemistry, Mandalay University, Mandalay, Myanmar

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

\*, Alfinda Novi Kristanti<sup>1</sup>

,

*Curcuma comosa* have been discussed.

*Terpenes and Terpenoids-Recent Advances*

*Biological activities of extracts and compounds from* Curcuma comosa*.*

Khun Nay Win Tun1,2, Nanik Siti Aminah1

Hnin Thanda Aung<sup>3</sup> and Yoshiaki Takaya<sup>4</sup>

provided the original work is properly cited.

**Author details**

**90**

**Table 2.**

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[13] Majik MS, Gawas UB, Mandrekar VK. Analytical methods for natural products isolation. In: Advances in Biological Science Research. Elsevier; 2019. pp. 395-409. DOI: 10.1016/ b978-0-12-817497-5.00024-0

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Complementary and Alternative Medicine. 2018;**2018**:2812908. DOI: 10.1155/2018/2812908

**Chapter 8**

**Abstract**

**95**

Effects of Terpenes and

in Essential Oils on Vascular

Studies and Perspective of

Therapeutic Use

*Levy Gabriel de Freitas Brito,*

*and José Henrique Leal-Cardoso*

*Andrelina Noronha Coelho-de-Souza*

Terpenoids of Natural Occurrence

Smooth Muscle and on Systemic

Blood Pressure: Pharmacological

*Ana Carolina Cardoso-Teixeira, Klausen Oliveira-Abreu,*

Terpenes are a class of chemical compounds with carbon and hydrogen atoms in their structure. They can be classified into several classes according to the quantity of isoprene units present in its structure. Terpenes can have their structure modified by the addition of various chemical radicals. When these molecules are modified by the addition of atoms other than carbon and hydrogen, they become terpenoids. Terpenes and terpenoids come from the secondary metabolism of several plants. They can be found in the leaves, fruits, stem, flowers, and roots. The concentration of terpenes and terpenoids in these organs can vary according to several factors such as the season, collection method, and time of the day. Several biological activities and physiological actions are attributed to terpenes and terpenoids. Studies in the literature demonstrate that these molecules have antioxidant,

anticarcinogenic, anti-inflammatory, antinociceptive, antispasmodic, and

has been reported. Studies also have shown that some monoterpenes and

gated calcium channels. It can also be observed that monoterpenes and

reported. Among the most prominent activities of monoterpenes and

antidiabetogenic activities. Additionally, repellent and gastroprotective activity is

monoterpenoids are those on the cardiovascular system. Reports on literature reveal the potential effect of monoterpenes and monoterpenoids on systemic blood pressure. Studies show that these substances have a hypotensive and bradycardic effect. In addition, the inotropic activity, both positive and negative, of these compounds

monoterpenoids also have a vasorelaxing activity on several vascular beds. These effects are attributed, in many cases to the blocking of ion channels, such as voltage-

[43] Sodsai A, Piyachaturawat P, Sophasan S, Suksamrarn A, Vongsakul M. Suppression by *Curcuma comosa* Roxb. of pro-inflammatory cytokine secretion in phorbol-12 myristate-13-acetate stimulated human mononuclear cells. International Immunopharmacology. 2007;**7**(4): 524-531. DOI: 10.1016/j.intimp. 2006.12.013

### **Chapter 8**

Complementary and Alternative Medicine. 2018;**2018**:2812908. DOI:

*Terpenes and Terpenoids-Recent Advances*

[43] Sodsai A, Piyachaturawat P, Sophasan S, Suksamrarn A,

Vongsakul M. Suppression by *Curcuma comosa* Roxb. of pro-inflammatory cytokine secretion in phorbol-12 myristate-13-acetate stimulated human mononuclear cells. International Immunopharmacology. 2007;**7**(4): 524-531. DOI: 10.1016/j.intimp.

10.1155/2018/2812908

2006.12.013

**94**
