Preface

Tea is one the world's most consumed beverages, either hot or cold, in any number of its forms. Originating in southwestern China as a drink prepared from *Camellia sinensis*, the habit of drinking tea has expanded throughout the world and has also incorporated herbal infusions prepared from a large variety of plants.

The cultural habit of drinking tea has also expanded throughout the world, partially propelled by the many health-promoting effects attributed to the various types of tea. Such effects are a continuous research topic worldwide, and it is well documented that the predominant constituents of tea have the potential to help in therapies addressing a large number of pathological conditions, ranging from inflammation to cancer and neurological disorders.

This book addresses in a succinct way some of the state-of-the-art studies on the chemistry and pharmacology of teas. It starts with some of the reasons why tea is called the elixir of life, and proceeds with a systematic study that establishes the predominant compositions of different types of tea. The effects of tea constituents on health are discussed, and a final chapter discusses some of the potential applications of tea in the food industry.

**II**

**Chapter 8 101**

**Chapter 9 115**

QSPR Prediction of Chromatographic Retention Times of Tea

Tea Polyphenols Chemistry for Pharmaceutical Applications *by Ponnusamy Ponmurugan, Shivaji Kavitha, Mani Suganya* 

Compounds by Bioplastic Evolution *by Francisco Torrens and Gloria Castellano*

*and Balasubramanian Mythili Gnanamangai*

**Gonçalo Justino** Universidade de Lisboa, Lisbon, Portugal

**1**

various types of human cancers [7, 8, 11, 17, 18].

**Chapter 1**

*Gonçalo Justino*

**1. Introduction**

semi-fermentation [1–4].

Introductory Chapter:

Tea - Chemistry and Pharmacology

Tea is one of the two most consumed beverages worldwide, the other being coffee, and the geographic distribution of each is well established—coffee is more abundantly consumed in Europe and the United States, while the rest of the world clearly prefers tea. Tea is prepared from the leaves, stems or buds of various plants of the genus *Camellia*, most commonly from *C. sinensis*, and the final content in polyphenols, minerals, vitamins and other compounds, including caffeine, is strongly dependent on the type of processing. For example, in green tea, the levels of catechins are much higher than in black tea, where tannins dominate. The predominant types of tea, classified with base on their flavour, colour and composition, are green tea, which does not undergo fermentation; black tea, which results from the full fermentation of the plant parts; and oolong tea, which corresponds to

There is a vast body of studies that address the effects on the many types of tea constituents on human health. While initially most studies were focused on the antioxidant effects of polyphenols, nowadays, it is well established that tea is a pleiotropic agent on human health. Catechins and theaflavins are the predominant polyphenols in tea, and their redox activity as metal chelators and reactive species scavengers, well characterized in vitro, was initially pointed as one of the most important tea effects on human health. Continued studies have shown that on top of those modulating properties, tea components also display unique pharmacological properties, in particular enzymatic inhibition and transporter modulation [5, 6]. In general, polyphenol intake is associated with reduced risks of stroke, myocardial infarction and diabetes, and it has been linked to improved blood flow and pressure, improved inflammation response and an overall improved lipid status [1, 5, 7, 8] (**Figure 1**). Among the many polyphenols studied in tea, one that has attracted most attention is quercetin, a flavone with a large number of well-characterized in vitro and in vivo activities, which is a good example of tea chemistry. Quercetin is a powerful metal chelator and radical scavenger, and although it undergoes extensive metabolization upon ingestion, it still retains a good generic antioxidant activity. Due to its role as reactive species modulator, quercetin has the ability to combat their harmful effects that are present in Alzheimer's disease, diabetes, hypertension and agerelated eye degenerative diseases, among many others [8–16]. While most of these effects are linked to the antioxidant properties of quercetin, this flavone is also able to display a pro-oxidant effect in specific situations, like in the presence of high iron content. This pro-oxidant activity has been linked to the pro-apoptotic effect of quercetin on tumour cells, associated with its p53 activation effect in such cells; moreover, quercetin is also a modulator of various cellular cytokines and signal transduction pathways and plays an important role as chemotherapy adjuvant in

## **Chapter 1**

## Introductory Chapter: Tea - Chemistry and Pharmacology

*Gonçalo Justino*

#### **1. Introduction**

Tea is one of the two most consumed beverages worldwide, the other being coffee, and the geographic distribution of each is well established—coffee is more abundantly consumed in Europe and the United States, while the rest of the world clearly prefers tea. Tea is prepared from the leaves, stems or buds of various plants of the genus *Camellia*, most commonly from *C. sinensis*, and the final content in polyphenols, minerals, vitamins and other compounds, including caffeine, is strongly dependent on the type of processing. For example, in green tea, the levels of catechins are much higher than in black tea, where tannins dominate. The predominant types of tea, classified with base on their flavour, colour and composition, are green tea, which does not undergo fermentation; black tea, which results from the full fermentation of the plant parts; and oolong tea, which corresponds to semi-fermentation [1–4].

There is a vast body of studies that address the effects on the many types of tea constituents on human health. While initially most studies were focused on the antioxidant effects of polyphenols, nowadays, it is well established that tea is a pleiotropic agent on human health. Catechins and theaflavins are the predominant polyphenols in tea, and their redox activity as metal chelators and reactive species scavengers, well characterized in vitro, was initially pointed as one of the most important tea effects on human health. Continued studies have shown that on top of those modulating properties, tea components also display unique pharmacological properties, in particular enzymatic inhibition and transporter modulation [5, 6]. In general, polyphenol intake is associated with reduced risks of stroke, myocardial infarction and diabetes, and it has been linked to improved blood flow and pressure, improved inflammation response and an overall improved lipid status [1, 5, 7, 8] (**Figure 1**).

Among the many polyphenols studied in tea, one that has attracted most attention is quercetin, a flavone with a large number of well-characterized in vitro and in vivo activities, which is a good example of tea chemistry. Quercetin is a powerful metal chelator and radical scavenger, and although it undergoes extensive metabolization upon ingestion, it still retains a good generic antioxidant activity. Due to its role as reactive species modulator, quercetin has the ability to combat their harmful effects that are present in Alzheimer's disease, diabetes, hypertension and agerelated eye degenerative diseases, among many others [8–16]. While most of these effects are linked to the antioxidant properties of quercetin, this flavone is also able to display a pro-oxidant effect in specific situations, like in the presence of high iron content. This pro-oxidant activity has been linked to the pro-apoptotic effect of quercetin on tumour cells, associated with its p53 activation effect in such cells; moreover, quercetin is also a modulator of various cellular cytokines and signal transduction pathways and plays an important role as chemotherapy adjuvant in various types of human cancers [7, 8, 11, 17, 18].

**Figure 1.** *Structure of (A) catechin, (B) quercetin and (C) theaflavin.*

Like quercetin, the effect of tea catechins on human health is also well characterized, not only at the antioxidant/pro-oxidant level but also at the immunomodulatory level and at the central nervous system level. Catechins display a synergistic effect contributing to the inhibition of cerebral Aβ plaque deposition in Alzheimer's and also display a protective role towards α-synuclein, contributing to the prevention and management of Parkinson's [19–22]. The neuroprotective effects of catechins and other polyphenols are not restricted to these two diseases, displaying a widespread protective effect in the nervous system, particularly in dopaminergic neurons, and contributing to the prevention or amelioration of age-related neuronal decay [19, 20, 23]; many of these effects are due to the activation of signalling pathways critical for synaptic plasticity, neuroinflammatory control, cell renewal, cerebrovascular flow and memory decline [24–26].

Although metals are typically associated to oxidative stress, they are also important micronutrients. The most well-known cases are the structural roles of Fe, Cu, Zn and Co ions in biomolecules, and tea is also an important source of these micronutrients. Besides these, higher plants also have specific requirements for other essential elements, namely, B, Cl, Mn, Mo and Ni. Many of these metals are redox-active essential protein cofactors and protein stabilizers and are found in varying amounts in consumed tea. The levels of each metal in the consumed tea depend strongly on the plant growth conditions and partially on the preparation but contribute strongly to the overall micronutrient homeostasis [27, 28].

More recently, a strong link between phytochemicals and oral health has been established, based on the role these compounds display in microbes. Tea, in particular green tea, has been linked to lower incidence of periodontal disease, dental caries and halitosis, as well as to a lower smoke-dependent inflammation. These effects are greatly dependent on the capacity of tea polyphenols to inhibit or diminish dental biofilm formation but also to inhibit bacterial ATPases, interfering with bacterial energy metabolism and bacterial enzymes involved in DNA synthesis, interfering with bacterial replication [29–38].

This plethora of health-promoting effects of tea constituents is at the origin of the functional food approach to tea, in which tea, in its native drink form, or as supplement, is marketed as an unsurmountable supplement, contributing to a healthier lifestyle. Also, tea and its constituents are also used in the food industry, in particular as antioxidants, preventing and retarding food breakdown, and as food supplements [39–42]. However, and in spite of all the advantages associated with tea, functional supplements must be carefully considered—although tea extracts

**3**

**Author details**

Gonçalo Justino

Universidade de Lisboa, Lisbon, Portugal

provided the original work is properly cited.

\*Address all correspondence to: goncalo.justino@tecnico.ulisboa.pt

© 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,

*Introductory Chapter: Tea - Chemistry and Pharmacology*

have been shown to promote health, with no observed counter-indications or side effects in most studies, highly purified supplements have been linked to toxic events from gastrointestinal irritation to hepatic injuries, depending not only on the type of supplement but also on the type of intake, in fasting vs. after meals or in pills vs.

*DOI: http://dx.doi.org/10.5772/intechopen.90838*

infusion [43, 44].

*Introductory Chapter: Tea - Chemistry and Pharmacology DOI: http://dx.doi.org/10.5772/intechopen.90838*

*Tea - Chemistry and Pharmacology*

**Figure 1.**

Like quercetin, the effect of tea catechins on human health is also well characterized, not only at the antioxidant/pro-oxidant level but also at the immunomodulatory level and at the central nervous system level. Catechins display a synergistic effect contributing to the inhibition of cerebral Aβ plaque deposition in Alzheimer's and also display a protective role towards α-synuclein, contributing to the prevention and management of Parkinson's [19–22]. The neuroprotective effects of catechins and other polyphenols are not restricted to these two diseases, displaying a widespread protective effect in the nervous system, particularly in dopaminergic neurons, and contributing to the prevention or amelioration of age-related neuronal decay [19, 20, 23]; many of these effects are due to the activation of signalling pathways critical for synaptic plasticity, neuroinflammatory control, cell renewal,

Although metals are typically associated to oxidative stress, they are also important micronutrients. The most well-known cases are the structural roles of Fe, Cu, Zn and Co ions in biomolecules, and tea is also an important source of these micronutrients. Besides these, higher plants also have specific requirements for other essential elements, namely, B, Cl, Mn, Mo and Ni. Many of these metals are redox-active essential protein cofactors and protein stabilizers and are found in varying amounts in consumed tea. The levels of each metal in the consumed tea depend strongly on the plant growth conditions and partially on the preparation but

More recently, a strong link between phytochemicals and oral health has been established, based on the role these compounds display in microbes. Tea, in particular green tea, has been linked to lower incidence of periodontal disease, dental caries and halitosis, as well as to a lower smoke-dependent inflammation. These effects are greatly dependent on the capacity of tea polyphenols to inhibit or diminish dental biofilm formation but also to inhibit bacterial ATPases, interfering with bacterial energy metabolism and bacterial enzymes involved in DNA synthesis,

This plethora of health-promoting effects of tea constituents is at the origin of the functional food approach to tea, in which tea, in its native drink form, or as supplement, is marketed as an unsurmountable supplement, contributing to a healthier lifestyle. Also, tea and its constituents are also used in the food industry, in particular as antioxidants, preventing and retarding food breakdown, and as food supplements [39–42]. However, and in spite of all the advantages associated with tea, functional supplements must be carefully considered—although tea extracts

contribute strongly to the overall micronutrient homeostasis [27, 28].

cerebrovascular flow and memory decline [24–26].

*Structure of (A) catechin, (B) quercetin and (C) theaflavin.*

interfering with bacterial replication [29–38].

**2**

have been shown to promote health, with no observed counter-indications or side effects in most studies, highly purified supplements have been linked to toxic events from gastrointestinal irritation to hepatic injuries, depending not only on the type of supplement but also on the type of intake, in fasting vs. after meals or in pills vs. infusion [43, 44].

## **Author details**

Gonçalo Justino Universidade de Lisboa, Lisbon, Portugal

\*Address all correspondence to: goncalo.justino@tecnico.ulisboa.pt

© 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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[3] Grigg D. The worlds of tea and coffee: Patterns of consumption. GeoJournal. 2002;**57**(4):283-294

[4] Reyes CM, Cornelis MC. Caffeine in the diet: Country-level consumption and guidelines. Nutrients. 2018;**10**(11):1772

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[6] Babich H, Gottesman RT, Liebling EJ, Schuck AG. Theaflavin-3-gallate and theaflavin-3′-gallate, polyphenols in black tea with prooxidant properties. Basic & Clinical Pharmacology & Toxicology. 2008;**103**(1):66-74

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[16] Bule M, Abdurahman A, Nikfar S, Abdollahi M, Amini M. Antidiabetic effect of quercetin: A systematic review and meta-analysis of animal studies. Food and Chemical Toxicology: An International Journal. 2019;**125**:494-502

**5**

*Introductory Chapter: Tea - Chemistry and Pharmacology*

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*DOI: http://dx.doi.org/10.5772/intechopen.90838*

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microenvironment: Friends or foes? International Journal of Molecular

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2019;**67**(4):1029-1043

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tea. Nutrients. 2018;**10**(5):655

Ma YX, Zhang W, Lu JL, Liang YR, et al. Neuroprotective effects and

[23] Chen LW, Wang YQ, Wei LC, Shi M, Chan YS. Chinese herbs and herbal extracts for neuroprotection of dopaminergic neurons and potential therapeutic treatment of Parkinson's disease. CNS & Neurological Disorders Drug Targets. 2007;**6**(4):273-281

[24] Vauzour D, Martinsen A,

Laye S. Neuroinflammatory processes in cognitive disorders: Is there a role

mechanisms of tea bioactive components in neurodegenerative diseases. Molecules (Basel, Switzerland). 2018;**23**(3):512

[22] Chen SQ, Wang ZS,

of triple-negative breast cancers.

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compounds in the tumor

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*Introductory Chapter: Tea - Chemistry and Pharmacology DOI: http://dx.doi.org/10.5772/intechopen.90838*

[17] Varghese E, Samuel SM, Abotaleb M, Cheema S, Mamtani R, Busselberg D. The "Yin and Yang" of natural compounds in anticancer therapy of triple-negative breast cancers. Cancers. 2018;**10**(10):346

[18] Focaccetti C, Izzi V, Benvenuto M, Fazi S, Ciuffa S, Giganti MG, et al. Polyphenols as immunomodulatory compounds in the tumor microenvironment: Friends or foes? International Journal of Molecular Sciences. 2019;**20**(7)

[19] Pervin M, Unno K, Ohishi T, Tanabe H, Miyoshi N, Nakamura Y. Beneficial effects of green tea catechins on neurodegenerative diseases. Molecules (Basel, Switzerland). 2018;**23**(6):1297

[20] Xing L, Zhang H, Qi R, Tsao R, Mine Y. Recent advances in the understanding of the health benefits and molecular mechanisms associated with green tea polyphenols. Journal of Agricultural and Food Chemistry. 2019;**67**(4):1029-1043

[21] Polito CA, Cai ZY, Shi YL, Li XM, Yang R, Shi M, et al. Association of tea consumption with risk of Alzheimer's disease and anti-beta-amyloid effects of tea. Nutrients. 2018;**10**(5):655

[22] Chen SQ, Wang ZS, Ma YX, Zhang W, Lu JL, Liang YR, et al. Neuroprotective effects and mechanisms of tea bioactive components in neurodegenerative diseases. Molecules (Basel, Switzerland). 2018;**23**(3):512

[23] Chen LW, Wang YQ, Wei LC, Shi M, Chan YS. Chinese herbs and herbal extracts for neuroprotection of dopaminergic neurons and potential therapeutic treatment of Parkinson's disease. CNS & Neurological Disorders Drug Targets. 2007;**6**(4):273-281

[24] Vauzour D, Martinsen A, Laye S. Neuroinflammatory processes in cognitive disorders: Is there a role

for flavonoids and n-3 polyunsaturated fatty acids in counteracting their detrimental effects? Neurochemistry International. 2015;**89**:63-74

[25] Spencer JP. The impact of fruit flavonoids on memory and cognition. The British Journal of Nutrition. 2010;**104**(Suppl 3):S40-S47

[26] Vauzour D. Effect of flavonoids on learning, memory and neurocognitive performance: Relevance and potential implications for Alzheimer's disease pathophysiology. Journal of the Science of Food and Agriculture. 2014;**94**(6):1042-1056

[27] Karak T, Kutu FR, Nath JR, Sonar I, Paul RK, Boruah RK, et al. Micronutrients (B, Co, Cu, Fe, Mn, Mo, and Zn) content in made tea (*Camellia sinensis* L.) and tea infusion with health prospect: A critical review. Critical Reviews in Food Science and Nutrition. 2017;**57**(14):2996-3034

[28] Hänsch R, Mendel RR. Physiological functions of mineral micronutrients (Cu, Zn, Mn, Fe, Ni, Mo, B, Cl). Current Opinion in Plant Biology. 2009;**12**(3):259-266

[29] Khurshid Z, Zafar MS, Zohaib S, Najeeb S, Naseem M. Green tea (*Camellia sinensis*): Chemistry and oral health. The Open Dentistry Journal. 2016;**10**:166-173

[30] Islam B, Khan SN, Khan AU. Dental caries: From infection to prevention. Medical Science Monitor: International Medical Journal of Experimental and Clinical Research. 2007;**13**(11):Ra196-Ra203

[31] Abachi S, Lee S, Rupasinghe HP. Molecular mechanisms of inhibition of *Streptococcus* species by phytochemicals. Molecules (Basel, Switzerland). 2016;**21**(2):215

[32] Chen L, Mo H, Zhao L, Gao W, Wang S, Cromie MM, et al. Therapeutic

**4**

*Tea - Chemistry and Pharmacology*

2014;**68**(3):501-506. 95-9

**References**

Nutrients. 2019;**11**(2):474

and guidelines. Nutrients.

2017;**174**(11):1195-1208

2019;**10**(2):514-528

2018;**10**(11):1772

[1] Wierzejska R. Tea and health—A review of the current state of

[2] Prasanth MI, Sivamaruthi BS, Chaiyasut C, Tencomnao T. A review of the role of green tea (*Camellia sinensis*) in antiphotoaging, stress resistance, neuroprotection, and autophagy.

[3] Grigg D. The worlds of tea and coffee: Patterns of consumption. GeoJournal. 2002;**57**(4):283-294

[4] Reyes CM, Cornelis MC. Caffeine in the diet: Country-level consumption

[5] Peluso I, Serafini M. Antioxidants from black and green tea: From dietary modulation of oxidative stress to pharmacological mechanisms. British Journal of Pharmacology.

[6] Babich H, Gottesman RT, Liebling EJ, Schuck AG. Theaflavin-3-gallate and theaflavin-3′-gallate, polyphenols in black tea with prooxidant properties. Basic & Clinical Pharmacology & Toxicology. 2008;**103**(1):66-74

[7] Fraga CG, Croft KD, Kennedy DO, Tomás-Barberán FA. The effects of polyphenols and other bioactives on human health. Food & Function.

[8] Zaplatic E, Bule M, Shah SZA, Uddin MS, Niaz K. Molecular

mechanisms underlying protective role of quercetin in attenuating Alzheimer's disease. Life Sciences. 2019;**224**:109-119

[9] Justino GC, Santos MR, Canário S, Borges C, Florêncio MH, Mira L. Plasma quercetin metabolites: Structure– antioxidant activity relationships.

knowledge. Przeglad Epidemiologiczny.

Archives of Biochemistry and Biophysics. 2004;**432**(1):109-121

Free Radical Research. 2002;**36**(11):1219-1227

[11] Rauf A, Imran M, Khan IA,

[12] Pandey MK, Gupta SC,

as backbone for bone health. Biotechnology Advances. 2018;**36**(6):1633-1648

[13] Amor S, Chalons P, Aires V,

[15] Yousefian M, Shakour N, Hosseinzadeh H, Hayes AW,

Hadizadeh F, Karimi G. The natural phenolic compounds as modulators of NADPH oxidases in hypertension. Phytomedicine: International Journal of Phytotherapy and Phytopharmacology.

[16] Bule M, Abdurahman A, Nikfar S, Abdollahi M, Amini M. Antidiabetic effect of quercetin: A systematic review and meta-analysis of animal studies. Food and Chemical Toxicology: An International Journal. 2019;**125**:494-502

2018;**6**(4):106

2019;**55**:200-213

Delmas D. Polyphenol extracts from red wine and grapevine: Potential effects on cancers. Diseases (Basel, Switzerland).

[14] Bungau S, Abdel-Daim MM, Tit DM, Ghanem E, Sato S, Maruyama-Inoue M, et al. Health benefits of polyphenols and carotenoids in age-related eye diseases. Oxidative Medicine and Cellular Longevity. 2019;**2019**:9783429

Ur-Rehman M, Gilani SA, Mehmood Z, et al. Anticancer potential of quercetin: A comprehensive review. Phytotherapy Research. 2018;**32**(11):2109-2130

Karelia D, Gilhooley PJ, Shakibaei M, Aggarwal BB. Dietary nutraceuticals

[10] Silva MM, Santos MR, Caroco G, Rocha R, Justino G, Mira L. Structureantioxidant activity relationships of flavonoids: A re-examination.

properties of green tea against environmental insults. The Journal of Nutritional Biochemistry. 2017;**40**:1-13

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**7**

green tea [9].

**Chapter 2**

**Abstract**

of human beings.

**1. Introduction**

Tea Is an Elixer of Life

**Keywords:** green tea, catechins, EGCG, elixir of life, tea

*and Shanmugam Thangapandiyan*

*Tamilselvan Hema, Mathan Ramesh, Selvaraj Miltonprabu* 

Green tea is a commonly consumed beverage in the world and it is a rich source of polyphenolic compounds, which are known as the tea flavonoids. Polyphenolic compounds are effective against oxidative damage in various pathological conditions. Many herbal medicines are used in traditional medicine for their protective and therapeutic properties against various diseases. Among their bioactive components, tea catechins have been found to be active against all kind of diseases including cancer. Extensive report is available that green tea displays a wide range of healthy properties, such as antioxidative, anti-inflammatory, anti-apoptotic and chemopreventors against reactive oxygen and nitrogen species. This review aims to critically analyze the available literature regarding the effects of green tea or tea catechins with special emphasis on its phytoremediation against various health disorders elicited by different chemical compounds. Overall, data in literature show tea catechins appear to be a promising elixir to recover the illness

Tea is the second most frequently consumed daily beverage in the world [1]. The tea plant, *Camellia sinensis,* is a member of Theaceae family, and is produced from its leaves. It is an evergreen shrub or tree [2]. The origins of tea drinking date back to 2737 BC [3]. It is legendarily attributed to the Chinese emperor Shen Nung, the divine cultivator who also apparently invented agriculture and herbal medicine [4]. Since tea is important to human life, a vast number of researchers have investigated the function of tea. It has been found that tea has beneficial effect on both physical health and cognition [5–7]. All tea is produced from the leaves of *Camellia sinensis*, but differences in processing result in different types of tea. In the processing of green tea, fresh tea leaves are steamed or heated immediately after harvest, resulting in minimal oxidation of the naturally occurring polyphenols in the tea leaves. On the other hand, in the processing of black tea, the tea leaves are dried and crushed upon harvesting to encourage oxidation, which converts indigenous tea polyphenols (primarily catechins and gallatecatechins) to other polyphenols (mainly theaflavins and thearubigins). Finally, partially oxidized tea leaves yield oolong tea [8]. Among all of these, however, the most significant effects on human health have been observed with the consumption of

## **Chapter 2**

*Tea - Chemistry and Pharmacology*

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