**Author details**

Fernández-Demeneghi Rafael1 , Vargas-Moreno Isidro1 , Acosta-Mesa Héctor-Gabriel<sup>2</sup> , Puga-Olguín Abraham1 , Campos-Uscanga Yolanda3 , Romo-González Tania4 , Guzmán-Gerónimo Rosa-Isela5 , Patraca-Camacho Lorena1 and Herrera-Meza Socorro6 \*

1 Institute of Neuroethology, University of Veracruz, Xalapa, Veracruz, Mexico

2 Artificial Intelligence Research Center, University of Veracruz, Xalapa, Veracruz, Mexico

3 Institute of Public Health, University of Veracruz, Xalapa, Veracruz, Mexico

4 Institute of Biological Research, University of Veracruz, Xalapa, Veracruz, Mexico

5 Basic Sciences Institute, University of Veracruz, Xalapa, Veracruz, Mexico

6 Institute of Psychological Research, University of Veracruz, Xalapa, Veracruz, Mexico

\*Address all correspondence to: soherrera@uv.mx

© 2019 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.

**43**

ffhd.v5i6.183

*Berry Supplementation and Their Beneficial Effects on Some Central Nervous System Disorders*

Pharmaceutical Sciences. 2017;**96**:53-61.

DOI: 10.1016/j.ejps.2016.09.003

[8] McDougall G, Stewart D. The inhibitory effects of berry polyphenols on digestive enzymes. BioFactors. 2006;**27**:189-195. DOI: 10.1002/

[9] Chaves V, Boff L, Vizzotto M,

[10] Lau F, Bielinski D, Joseph J. Inhibitory effects of blueberry extract on the production of inflammatory mediators in lipopolysaccharide‐ activated BV2 microglia. Journal of Neuroscience Research. 2007;**85**:1010-

1017. DOI: 10.1002/jnr.21205

10.1002/mnfr.20120051117

mnfr.201801055

jf071998l

[13] Kalt W, Blumberg J,

McDonald J, Vinqvist-Tymchuk M, Fillmore S, Graf B, et al. Identification of anthocyanins in the liver, eye, and brain of blueberry-fed pigs. Journal of Agricultural and Food Chemistry. 2008;**56**:705-712. DOI: 10.1021/

[14] Bowen-Forbes C, Zhang Y, Muraleedharan N. Anthocyanin

content, antioxidant, anti-inflammatory

[12] Krishna G, Ying Z, Gomez‐ Pinilla F. Blueberry supplementation mitigates altered brain plasticity and behaviour after traumatic brain injury in rats. Molecular Nutrition & Food Research. 2019;**63**:1-8. DOI: 10.1002/

[11] Williamson G. Possible effects of dietary polyphenols on sugar absorption and digestion. Molecular Nutrition & Food Research. 2013;**57**:48-57. DOI:

Calvete E, Reginatto F, Simões C. Berries grown in Brazil: Anthocyanin profiles and biological properties. Journal of Science and Food Agriculture. 2018;**98**:4331-4338. DOI: 10.1002/

biof.5520230403

jsfa.8959

*DOI: http://dx.doi.org/10.5772/intechopen.90428*

[1] Nile S, Park S. Edible berries: Bioactive components and their effect on human health. Nutrition. 2014;**30**:134-144. DOI: 10.1016/j.

[2] Andres-Lacueva C, Shukitt-Hale B, Galli R, Jauregui O, Lamuela-Raventos R,

Joseph J. Anthocyanins in aged blueberry-fed rats are found centrally and may enhance memory. Nutritional Neuroscience. 2005;**8**:111-120. DOI:

10.1080/10284150500078117

DOI: 10.1021/jf050145v

Rodríguez-Landa J,

[4] Fernández-Demeneghi R,

Guzmán-Gerónimo R, Acosta-Mesa H, Meza-Alvarado E, Vargas-Moreno I, et al. Effect of blackberry juice (*Rubus fruticosus* L.) on anxietylike behaviour in Wistar rats.

International Journal of Food Sciences and Nutrition. 2019;**70**:1-12. DOI: 10.1080/09637486.2019.1580680

[5] Casadesus G, Shukitt-Hale B, Stellwagen H, Zhu X, Lee H, Smith M, et al. Modulation of hippocampal plasticity and cognitive behavior by short-term blueberry supplementation

Neuroscience. 2004;**7**:309-316. DOI: 10.1080/10284150400020482

[6] Martirosyan D, Singh J. A new definition of functional food by FFC: What makes a new definition unique. FFHD. 2015;**5**:209-223. DOI: 10.31989/

[7] Santini A, Tenore G, Novellino E. Nutraceuticals: A paradigm of proactive

medicine. European Journal of

in aged rats. Nutritional

[3] Talavéra S, Felgines C, Texier O, Besson C, Gil-Izquierdo A, Lamaison J, et al. Anthocyanin metabolism in rats and their distribution to digestive area, kidney, and brain. Journal of Agricultural and Food Chemistry. 2005;**53**:3902-3908.

nut.2013.04.007

**References**

*Berry Supplementation and Their Beneficial Effects on Some Central Nervous System Disorders DOI: http://dx.doi.org/10.5772/intechopen.90428*

## **References**

*Behavioral Pharmacology - From Basic to Clinical Research*

(Scholarship no. 592714, 628503, 297410, 713495).

The authors declare no conflict of interest.

**Acknowledgements**

**Conflict of interest**

**42**

**Author details**

Mexico

Mexico

Fernández-Demeneghi Rafael1

Acosta-Mesa Héctor-Gabriel<sup>2</sup>

and Herrera-Meza Socorro6

Romo-González Tania4

, Vargas-Moreno Isidro1

, Puga-Olguín Abraham1

The authors gratefully acknowledge the financial support from CONACyT

, Guzmán-Gerónimo Rosa-Isela5

1 Institute of Neuroethology, University of Veracruz, Xalapa, Veracruz, Mexico

3 Institute of Public Health, University of Veracruz, Xalapa, Veracruz, Mexico

5 Basic Sciences Institute, University of Veracruz, Xalapa, Veracruz, Mexico

6 Institute of Psychological Research, University of Veracruz, Xalapa, Veracruz,

© 2019 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 Artificial Intelligence Research Center, University of Veracruz, Xalapa, Veracruz,

4 Institute of Biological Research, University of Veracruz, Xalapa, Veracruz, Mexico

\*

\*Address all correspondence to: soherrera@uv.mx

provided the original work is properly cited.

,

, Campos-Uscanga Yolanda3

, Patraca-Camacho Lorena1

,

[1] Nile S, Park S. Edible berries: Bioactive components and their effect on human health. Nutrition. 2014;**30**:134-144. DOI: 10.1016/j. nut.2013.04.007

[2] Andres-Lacueva C, Shukitt-Hale B, Galli R, Jauregui O, Lamuela-Raventos R, Joseph J. Anthocyanins in aged blueberry-fed rats are found centrally and may enhance memory. Nutritional Neuroscience. 2005;**8**:111-120. DOI: 10.1080/10284150500078117

[3] Talavéra S, Felgines C, Texier O, Besson C, Gil-Izquierdo A, Lamaison J, et al. Anthocyanin metabolism in rats and their distribution to digestive area, kidney, and brain. Journal of Agricultural and Food Chemistry. 2005;**53**:3902-3908. DOI: 10.1021/jf050145v

[4] Fernández-Demeneghi R, Rodríguez-Landa J, Guzmán-Gerónimo R, Acosta-Mesa H, Meza-Alvarado E, Vargas-Moreno I, et al. Effect of blackberry juice (*Rubus fruticosus* L.) on anxietylike behaviour in Wistar rats. International Journal of Food Sciences and Nutrition. 2019;**70**:1-12. DOI: 10.1080/09637486.2019.1580680

[5] Casadesus G, Shukitt-Hale B, Stellwagen H, Zhu X, Lee H, Smith M, et al. Modulation of hippocampal plasticity and cognitive behavior by short-term blueberry supplementation in aged rats. Nutritional Neuroscience. 2004;**7**:309-316. DOI: 10.1080/10284150400020482

[6] Martirosyan D, Singh J. A new definition of functional food by FFC: What makes a new definition unique. FFHD. 2015;**5**:209-223. DOI: 10.31989/ ffhd.v5i6.183

[7] Santini A, Tenore G, Novellino E. Nutraceuticals: A paradigm of proactive medicine. European Journal of

Pharmaceutical Sciences. 2017;**96**:53-61. DOI: 10.1016/j.ejps.2016.09.003

[8] McDougall G, Stewart D. The inhibitory effects of berry polyphenols on digestive enzymes. BioFactors. 2006;**27**:189-195. DOI: 10.1002/ biof.5520230403

[9] Chaves V, Boff L, Vizzotto M, Calvete E, Reginatto F, Simões C. Berries grown in Brazil: Anthocyanin profiles and biological properties. Journal of Science and Food Agriculture. 2018;**98**:4331-4338. DOI: 10.1002/ jsfa.8959

[10] Lau F, Bielinski D, Joseph J. Inhibitory effects of blueberry extract on the production of inflammatory mediators in lipopolysaccharide‐ activated BV2 microglia. Journal of Neuroscience Research. 2007;**85**:1010- 1017. DOI: 10.1002/jnr.21205

[11] Williamson G. Possible effects of dietary polyphenols on sugar absorption and digestion. Molecular Nutrition & Food Research. 2013;**57**:48-57. DOI: 10.1002/mnfr.20120051117

[12] Krishna G, Ying Z, Gomez‐ Pinilla F. Blueberry supplementation mitigates altered brain plasticity and behaviour after traumatic brain injury in rats. Molecular Nutrition & Food Research. 2019;**63**:1-8. DOI: 10.1002/ mnfr.201801055

[13] Kalt W, Blumberg J, McDonald J, Vinqvist-Tymchuk M, Fillmore S, Graf B, et al. Identification of anthocyanins in the liver, eye, and brain of blueberry-fed pigs. Journal of Agricultural and Food Chemistry. 2008;**56**:705-712. DOI: 10.1021/ jf071998l

[14] Bowen-Forbes C, Zhang Y, Muraleedharan N. Anthocyanin content, antioxidant, anti-inflammatory and anticancer properties of blackberry and raspeberry fruits. Journal of Food Composition and Analysis. 2010;**23**: 554-560. DOI: 10.1016/j.jfca.2009.08.012

[15] Hampto S, Isherwood C, Kirkpatrick V, Lynne-Smith A, Griffin B. The influence of alcohol consumed with a meal on endothelial function in healthy individuals. Journal of Human Nutrition and Dietetics. 2010;**23**: 120-125. DOI: 10.1111/j.1365-277X.2009. 01021.x

[16] Zhao M, Liu X, Luo Y, Guo H, Hu X, Chen F. Evaluation of protective effect of freeze‐dried strawberry, grape, and blueberry powder on acrylamide toxicity in mice. Journal of Food Science. 2015;**80**:869-874. DOI: 10.1111/1750-3841.12815

[17] Shukitt-Hale B, Bielinski D, Lau F, Willis L, Carey A, Joseph J. The beneficial effects of berries on cognition, motor behaviour and neuronal function in ageing. British Journal of Nutrition. 2015;**114**:1542-1549. DOI: 10.1017/ S0007114515003451

[18] Dohadwala M, Holbrook M, Hamburg N, Shenouda S, Chun W, Titas M, et al. Effects of cranberry juice consumption on vascular function in patients with coronary artery disease. The American Journal of Clinical Nutrition. 2011;**93**:934-940. DOI: 10.3945/ajcn.110.004242

[19] Barros D, Amaral B, Izquierdo I, Geracitano L, Raseira M, Henriques A, et al. Behavioral and genoprotective effects of Vaccinium berries intake in mice. Pharmacology Biochemistry & Behavior. 2006;**84**:229-234. DOI: 10.1016/j.pbb.2006.05.001

[20] Miller M, Shukitt-Hale B. Berry fruit enhances beneficial signaling in the brain. Journal of Agricultural and Food Chemistry. 2012;**60**:5709-5715. DOI: 10.1021/jf2036033

[21] Baby B, Antony P, Vijayan R. Antioxidant and anticancer properties of berries. Critical Reviews in Food Science and Nutrition. 2018;**58**:2491-2507. DOI: 10.1080/10408398.2017.1329198

[22] Diaconeasa Z, Leopold L, Rugină D, Ayvaz H, Socaciu C. Antiproliferative and antioxidant properties of anthocyanin rich extracts from blueberry and blackcurrant juice. International Journal of Molecular Sciences. 2015;**16**:2352-2365. DOI: 10.3390/ijms16022352

[23] Pantelidis G, Vasilakakis M, Manganaris G, Diamantidis G. Antioxidant capacity, phenol, anthocyanin and ascorbic acid contents in raspberries, blackberries, red currants, gooseberries and cornelian cherries. Food Chemistry. 2007;**102**:777-783. DOI: 10.1016/j. foodchem.2006.06.021

[24] Lorenzo J, Pateiro M, Domínguez R, Barba F, Putnik P, Kovačević D, et al. Berries extracts as natural antioxidants in meat products: A review. Food Research International. 2018;**106**:1095- 1104. DOI: 10.1016/j.foodres.2017.12.005

[25] Wang S, Lin H. Antioxidant activity in fruits and leaves of blackberry, raspberry, and strawberry varies with cultivar and developmental stage. Journal of Agricultural and Food Chemistry. 2010;**48**:140-146. DOI: 10.1021/jf9908345I

[26] Lee S, Vance T, Nam T, Kim D, Koo S, Chun O. Contribution of anthocyanin composition to total antioxidant capacity of berries. Plant Food for Human Nutrition. 2015;**70**:427- 432. DOI: 10.1007/s11130-015-0514-5

[27] Rabassa M, Trespalacios M, Urpi-Sarda M, Llorach R, Tulípani S, Zamora-Ros M, et al. Polifenoles como antioxidantes. In: Álvarez E, González A, De la Rosa L, Ayala J, editors. Antioxidantes en Alimentos y Salud.

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[36] Jäger A, Saaby L. Flavonoids and the CNS. Molecules. 2011;**16**:1471-1485. DOI: 10.3390/molecules16021471

[37] Cho S, Han D, Yang H, Jeon Y, Lee C, Jin Y, et al. Phlorotannins of the edible brown seaweed Ecklonia cava Kjellman induce sleep via positive allosteric modulation of gamma-aminobutyric acid type A–benzodiazepine receptor: A novel neurological activity of

seaweed polyphenols. Food Chemistry. 2012;**132**:1133-1142. DOI: 10.1016/j.

Pharmacological Reports. 2009;**61**:7-75. DOI: 10.1016/S1734-1140(09)70008-8

foodchem.2011.08.040

[38] Perez-Vizcaino F, Duarte J, Jimenez R, Santos-Buelga C, Osuna A. Antihypertensive effects

of the flavonoid quercetin.

[39] Quiñones M, Miguel M, Aleixandre A. Los polifenoles, compuestos de origen natural con efectos saludables sobre el sistema cardiovascular. Nutrición Hospitalaria.

2012;**77**:76-89. DOI: 10.3305/

[40] Ferraro F, Balota D, Connor L. Implicit memory and the formation of new associations in nondemented Parkinson's disease individuals and individuals with senile dementia of the Alzheimer type: A serial reaction time (SRT) investigation. Brain and Cognition. 1993;**21**:163-180. DOI:

[41] Narayana K, Reddy M, Chaluvadi M, Krishna D. Bioflavonoids classification, pharmacological, biochemical effects and therapeutic potential. Indian Journal of Pharmacology. 2001;**33**:2-16

nh.2012.27.1.5418

10.1006/brcg.1993.1013

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[28] Estrada-Reyes R, Ubaldo-Suárez D, Araujo-Escalona A. Los flavonoides y el sistema nervioso central. Salud Mental.

[29] Ono K, Yoshiike Y, Takashima A, Hasegawa K, Naiki H, Yamada M. Potent

destabilizing effects of polyphenols in vitro: Implications for the prevention and therapeutics of Alzheimer's disease. Journal of Neurochemistry. 2003;**87**: 172-181. DOI: 10.1046/j.1471-4159.

[30] Sellappan S, Akoh C, Krewer G. Phenolic compounds and antioxidant capacity of Georgia-grown blueberries and blackberries. Journal of Agricultural and Food Chemistry. 2012;**50**:2432- 2438. DOI: 10.1021/jf011097r

[31] Vignes M, Maurice T, Lanté F, Nedjar M, Thethi K, Guiramand J, et al. Anxiolytic properties of green tea polyphenol (−)-epigallocatechin gallate (EGCG). Brain Research. 2006;**1110**:102-115. DOI: 10.1016/j.

[32] De la Peña J, Kim C, Lee H, Yoon S, Kim H, Hong E, et al. Luteolin mediates the antidepressant-like effects of Cirsium japonicum in mice, possibly through modulation of the GABAA receptor. Archives of Pharmacal Research. 2014;**37**:263-269. DOI: 10.1007/s12272-013-0229-9

[33] Johnston G. GABAA receptor channel pharmacology. Current Pharmaceutical Design. 2005;**11**:1867- 1885. DOI: 10.2174/1381612054021024

Johnston G. Interactions of flavonoids with ionotropic GABA receptors. Advances in Pharmacology. 2015;**72**:189- 200. DOI: 10.1016/bs.apha.2014.10.007

[34] Hanrahan J, Chebib M,

brainres.2006.06.062

anti‐amyloidogenic and fibril‐

1st ed. Ameditores: Cdmx; 2012.

pp. 155-200

2012;**35**:375-384

2003.01976.x

*Berry Supplementation and Their Beneficial Effects on Some Central Nervous System Disorders DOI: http://dx.doi.org/10.5772/intechopen.90428*

1st ed. Ameditores: Cdmx; 2012. pp. 155-200

*Behavioral Pharmacology - From Basic to Clinical Research*

[21] Baby B, Antony P, Vijayan R. Antioxidant and anticancer properties

[22] Diaconeasa Z, Leopold L, Rugină D, Ayvaz H, Socaciu C. Antiproliferative

of berries. Critical Reviews in Food Science and Nutrition. 2018;**58**:2491-2507. DOI: 10.1080/10408398.2017.1329198

and antioxidant properties of anthocyanin rich extracts from blueberry and blackcurrant juice. International Journal of Molecular Sciences. 2015;**16**:2352-2365. DOI:

[23] Pantelidis G, Vasilakakis M,

Manganaris G, Diamantidis G. Antioxidant capacity, phenol, anthocyanin and ascorbic acid contents in raspberries, blackberries, red currants, gooseberries and cornelian cherries. Food Chemistry. 2007;**102**:777-783. DOI: 10.1016/j.

[24] Lorenzo J, Pateiro M, Domínguez R, Barba F, Putnik P, Kovačević D, et al. Berries extracts as natural antioxidants in meat products: A review. Food Research International. 2018;**106**:1095- 1104. DOI: 10.1016/j.foodres.2017.12.005

[25] Wang S, Lin H. Antioxidant activity in fruits and leaves of blackberry, raspberry, and strawberry varies with cultivar and developmental stage. Journal of Agricultural and Food Chemistry. 2010;**48**:140-146. DOI:

10.3390/ijms16022352

foodchem.2006.06.021

10.1021/jf9908345I

[26] Lee S, Vance T, Nam T,

Kim D, Koo S, Chun O. Contribution of anthocyanin composition to total antioxidant capacity of berries. Plant Food for Human Nutrition. 2015;**70**:427- 432. DOI: 10.1007/s11130-015-0514-5

[27] Rabassa M, Trespalacios M, Urpi-Sarda M, Llorach R, Tulípani S, Zamora-Ros M, et al. Polifenoles como

antioxidantes. In: Álvarez E,

González A, De la Rosa L, Ayala J, editors. Antioxidantes en Alimentos y Salud.

and anticancer properties of blackberry and raspeberry fruits. Journal of Food Composition and Analysis. 2010;**23**: 554-560. DOI: 10.1016/j.jfca.2009.08.012

Kirkpatrick V, Lynne-Smith A, Griffin B. The influence of alcohol consumed with a meal on endothelial function in healthy individuals. Journal of Human Nutrition and Dietetics. 2010;**23**:

120-125. DOI: 10.1111/j.1365-277X.2009.

[16] Zhao M, Liu X, Luo Y, Guo H, Hu X, Chen F. Evaluation of protective effect of freeze‐dried strawberry, grape, and blueberry powder on acrylamide toxicity in mice. Journal of Food Science. 2015;**80**:869-874. DOI:

[17] Shukitt-Hale B, Bielinski D, Lau F, Willis L, Carey A, Joseph J. The beneficial effects of berries on cognition, motor behaviour and neuronal function in ageing. British Journal of Nutrition. 2015;**114**:1542-1549. DOI: 10.1017/

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10.1111/1750-3841.12815

S0007114515003451

10.3945/ajcn.110.004242

DOI: 10.1021/jf2036033

[19] Barros D, Amaral B, Izquierdo I, Geracitano L, Raseira M, Henriques A, et al. Behavioral and genoprotective effects of Vaccinium berries intake in mice. Pharmacology Biochemistry & Behavior. 2006;**84**:229-234. DOI: 10.1016/j.pbb.2006.05.001

[20] Miller M, Shukitt-Hale B. Berry fruit enhances beneficial signaling in the brain. Journal of Agricultural and Food Chemistry. 2012;**60**:5709-5715.

[15] Hampto S, Isherwood C,

01021.x

**44**

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[32] De la Peña J, Kim C, Lee H, Yoon S, Kim H, Hong E, et al. Luteolin mediates the antidepressant-like effects of Cirsium japonicum in mice, possibly through modulation of the GABAA receptor. Archives of Pharmacal Research. 2014;**37**:263-269. DOI: 10.1007/s12272-013-0229-9

[33] Johnston G. GABAA receptor channel pharmacology. Current Pharmaceutical Design. 2005;**11**:1867- 1885. DOI: 10.2174/1381612054021024

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**55**

**1. Introduction**

**Chapter 4**

**Abstract**

Pharmaceutical and Botanical

with Psychopathology: A

Narrative Review

*Minerva Hernández Lozano,* 

*Marcos Fernando Ocaña Sánchez,* 

*Libna Sulem Gallardo Beatriz,* 

*Ibrahim Guillermo Castro Torres,* 

*Gabriela Josefina Mendoza Rangel* 

*and Tania Monserrat Camacho Márquez*

Management of Pain Associated

*Rosa Virginia García Rodríguez, Van Dan Castro Gerónimo,* 

*María Gabriela Alcántara López, Julio César González Ortiz,* 

Generally, pain can be described as an unpleasant sensory or emotional experience associated with tissue damage. Chronic pain has become a public health problem because among 35 and 75% of the world population has shown the symptom. In particular, neuropathic pain has shown high comorbidity disorders such as anxiety and depression. Conventional therapies for treating pain include nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, tricyclic antidepressants, anticonvulsants, and opioids, which usually cause some side effects such as gastritis, headache, liver and kidney toxicity, and drug dependence. Conventional pharmaceuticals also tend to be expensive, and they cannot be easily afforded in developing countries, which have led to the use of natural products as an alternative treatment. In this chapter, we reviewed the current research of natural products for pain treatment. We also describe preclinical studies that assess the effect of some natural products on pain therapy, phytochemistry research, toxicity, adverse effects, and biosecurity. We also describe how conventional pain is managed and the possible use of compounds obtained from vegetable species for pain treatment.

**Keywords:** pain, analgesic, anti-inflammatory, herbal medicine, phytopharmaceuticals

Over the course of history, the pain has been manifested in a wide range of forms, and it has not been treated properly. It is estimated that approximately 116 million
