Remedial Effects of Tea and Its Phytoconstituents on Central Nervous System

*Manisha Singh, Vandana Tyagi and Shriya Agarwal*

### **Abstract**

Tea in all its forms is one of the commonly consumed beverages globally, after water. Apart from just being a beverage, it also has extensive therapeutic values. The phytoconstituents of tea either in their pure form or as an extract are essential part of traditional as well as modern day medicines. Tea has shown its medicinal benefits in treating, improving and preventing many of the ailments ranging from being potential antimicrobial, antioxidant agent to being central nervous system (CNS) stimulants. This chapter focuses specifically on physiological impacts that each of its constituents have over our nervous system like role of L-theanine to enhance dopamine and serotonin levels, theobromine, and theophylline for stimulating CNS, caffeine to inhibit adenosine receptors, hence, causing increase in brain activity etc. along with many more neuroprotective properties of tea constituents.

**Keywords:** central nervous system (CNS), epigallocatechin-3-gallate (EGCG), epigallocatechin (EGC), epicatechin-3-gallate (ECG), and epicatechin (EC), theaflavin (TF-1), Laminin receptor (67LR)

#### **1. Introduction**

Tea is known as a part of many traditional medicinal practices (Ayurvedic, Chinese etc.) and as a health supplement of daily usage from ancient era. Tea (*Camellia sinensis*) belongs to Theaceae family and is known as a perennial shrub/ tree which reaches up to the height of 30 feet, however it is pruned cropped at a lesser height of around 2–5 feet for cultivation. It is of various types such as black, white, green, oolong varieties. Rooibos or "Red" and Pu-erh tea are produced from tea plant leaves, which are oval and dark green in color, with notched boundaries, and its flowers are usually white, fragrant bunched, together or separately. The tea plant, *C. sinensis*, initially was an indigenous species that belonged to China but later spread to other parts of the world like—Indian subcontinent, Japan, Russia and then to Europe in the late seventeeth century. The various forms of tea (Green, oolong, and black tea) originated from the same plant (*C. sinensis*) but got differentiated, depending on their color display, organoleptic taste, distinctive flavor and their phytochemical content which was eventually a result of different fermentation processes adopted for their production [1].

There are two main varieties of the tea plant, named as *Camellia sinensis* and *Camellia sinensis var. assamica*. The Chinese variant, *Camellia sinensis*, has smaller leaves and is more tolerant to cold weather. It is observed as a perennial plant going up to the height of 3 m in case of *C. var sinensis*, whereas it was up to 10–15 m tall with less branching in *C. var assamica* [2, 3]. But since in tea cultivation practices the plants are usually pruned and are kept at lower height (1–2 m) hence, promoting them to spread their branches horizontally. In the ancient scriptures of China, tea processing and consumption from these two varieties are reported to be practiced from last 4000 years. The second variety, *Camellia sinensis var. assamica*, is a native to the Assam region in India and thrives well in tropical and low elevation areas in the Indian subcontinent. This variety of tea plantation is commonly cultivated in the tropical and subtropical regions of India and apart from its use as a beverage it has been reported for many utilities like—it has high medicinal value, used for extraction of oil (Tea Tree oil). As per the recent global studies conducting in 2016, it was found that Turkey was listed as one of the highest tea devouring country with consumption of approximately 6.96 pounds per year per capita. On the contrary, China was observed with little less annual consumption of around 1.25 pounds per year per person but, it has shown highest tea production globally, followed by India and Kenya at second and third positions respectively.

health benefits exhibited by the tea and its polyphenols, the focus is towards exploring its chemo preventive, hypolipidemic and anti-obesity effects in all sorts of

*Remedial Effects of Tea and Its Phytoconstituents on Central Nervous System*

Tea leaves are either classified on the basis of their consumption and texture it has or on the processing method adopted for their leaves. Hence, the classification, studied commonly for tea is based on its varied fermentation degree process and is comprised of basically three types: non-fermented (green), semi-fermented

(oolong) and entirely fermented (black) [10]. The tea processing starts firstly, from picking up the appropriate and selected tea leaves from shrub or tea tree which undergoes fractional withering. Then roasting the same leaves to inactivate oxidative enzymes, followed by rolling up, drying and sorting the same leaves. The color of the final tea product is usually green tasting slightly constringent. So many countries like China, the taste of green tea is improvised by supplementing aromatic fruits (orange) or flowers (jasmine). Further, the tea processing steps in case of black tea is more complex, as after withering process the tea leaves are subjected for two steps fermentation processes, in the last step of fermentation they have been rolled up and then fermented. Lastly, they are roasted till they become dark-brown or brown black in color imparting a roasting aroma so as to block the activity of enzymes (polyphenol oxidase and glycosidase) along with further, fermentation of the same [5]. Another variant, oolong tea which is partially fermented type usually

Green tea is a non-fermented tea which is largely consumed by the population of china and japan. After cultivation, tea leaves are first withered for the inactivation of enzyme (polyphenol) which is liable for oxidation of tea catechins into their oligomeric forms (thearubigins and theaflavins). To avoid the oxidation and polymerization of tea leaves, they are steamed up and dried at high temperatures [6, 9, 11]. The Chinese traditional dietary system do have another packed form of green tea called "black powder", named after type of leaves processing method. Where these leaves individually are stirred and wrapped into a round pellet looking like explosives. It prevents it from any kind of physical damage and maintains its fragrance and flavor. Polyphenols present in green tea are flavonols (quercetin,

has shorter fermentation time in comparison to the black one.

kaempferol, and rutin), caffeine, phenolic acids, theanine, flavor, and

water-soluble parts of tea comprises of biochemical components like ()

leucoanthocyanins, which show 40% of dry weight of leaves [12, 13]. The highly

epigallocatechin-3-gallate (EGCG), epigallocatechin (EGC), epicatechin-3-gallate (ECG), and epicatechin (EC) (As listed in **Table 1**) [9, 14]. Further, it's also been reported that 1 kg of green tea has around 191 g of the above listed catechins, 36 g of caffeine, and 5.2 g of flavonols [15]. In green tea there are 10–15% of polyphenols present whereas it's lesser in black tea, i.e. around 5%. Dry weight of green tea constitutes about 42% polyphenols which is composed of 26.7% of catechin-gallate components such as ECG (2.25%), EGC (10.32%), Catechins (0.53%), EGCG (11.16%) and Epicatechin (2.45%) [16]. It's been estimated that in one cup of green tea the expected concentration of EGCG is between 2.1–2.4 mg/mL and after testing the effects of both Green tea and EGCG (equivalent of 4–8 cups per day) on human subjects there was no appreciable side effects observed [17, 18]. Epidemiological

possible *in vitro* and *in vivo* model systems [9].

*DOI: http://dx.doi.org/10.5772/intechopen.81521*

**3. Types of tea variants**

**3.1 Green tea**

**23**

Also, on global platform it was estimated that, almost 3.8 billion gallons of tea, in which black tea has 80%, green tea 16% and remaining 4% was oolong, white and dark tea share was consumed in United States in the same year (2016) [4]. These data exhibit the ever-growing popularity of tea consumption among the masses irrespective of their region of cultivation.

### **2. Potential health benefits of tea constituents**

The commonly found and highest content of chemical constituents found in leaves of tea are polyphenols (catechins and flavonoids), inorganic elements (e.g., fluorine, aluminum, and manganese), alkaloids (caffeine, theobromine, theophylline, etc.), amino acids, volatile oils, lipids, polysaccharide, and vitamins. However, the polyphenolic content which is present in the highest concentration, is primarily responsible for its most of the therapeutic benefits. Consequently, flavonoid contents impart its antimicrobial, antioxidant, anti-allergic and anti-inflammatory effects. The phenolic content variants are further elaborated and sub-classified as catechin, gallocatechin, epigallocatechin, epicatechin gallate, epicatechin, and epigallocatechin-gallate (EGCG), the latter being the most active component [2, 5]. Further, the molecular structure of green tea polyphenols exhibits active hydroxyl hydrogen which effectively scavenge free radicals hence, slowing down the detrimental changes in most of the physiological processes existing in human body. Reportedly, tea polyphenols strongly exhibits the movement of glutathione peroxidase and superoxide dismutase causing higher scavenging rate. The phytoconstituents of tea reflects multiple therapeutic benefits on our various diverse physiological systems through various biochemical and pharmacological processes like—antioxidant activities, inhibition of cell proliferation, induction of apoptosis, cell cycle arrest and modulation of carcinogen metabolism [6, 7]. Similarly, in CNS, another constituent in green tea, L-theanine increases the dopamine and serotonin levels resulting in mood elevation and stress reduction. Also, caffeine content in same sources aids in increasing the focus, vigilance, concentration and reasoning ability [8]. Theobromine and theophylline are known as potential CNS stimulants. Numerous studies have shown that most of the tea polyphenols have reactive oxygen and nitrogen species (ROS) scavenging activity along with an ability to chelate down redox-active transition metal ions. Currently, apart from all the listed health benefits exhibited by the tea and its polyphenols, the focus is towards exploring its chemo preventive, hypolipidemic and anti-obesity effects in all sorts of possible *in vitro* and *in vivo* model systems [9].

## **3. Types of tea variants**

leaves and is more tolerant to cold weather. It is observed as a perennial plant going up to the height of 3 m in case of *C. var sinensis*, whereas it was up to 10–15 m tall with less branching in *C. var assamica* [2, 3]. But since in tea cultivation practices the plants are usually pruned and are kept at lower height (1–2 m) hence, promoting them to spread their branches horizontally. In the ancient scriptures of China, tea processing and consumption from these two varieties are reported to be practiced from last 4000 years. The second variety, *Camellia sinensis var. assamica*, is a native to the Assam region in India and thrives well in tropical and low elevation areas in the Indian subcontinent. This variety of tea plantation is commonly cultivated in the tropical and subtropical regions of India and apart from its use as a beverage it has been reported for many utilities like—it has high medicinal value, used for extraction of oil (Tea Tree oil). As per the recent global studies conducting in 2016, it was found that Turkey was listed as one of the highest tea devouring country with consumption of approximately 6.96 pounds per year per capita. On the contrary, China was observed with little less annual consumption of around 1.25 pounds per year per person but, it has shown highest tea production globally, followed by India

Also, on global platform it was estimated that, almost 3.8 billion gallons of tea, in which black tea has 80%, green tea 16% and remaining 4% was oolong, white and dark tea share was consumed in United States in the same year (2016) [4]. These data exhibit the ever-growing popularity of tea consumption among the masses

The commonly found and highest content of chemical constituents found in leaves of tea are polyphenols (catechins and flavonoids), inorganic elements (e.g., fluorine, aluminum, and manganese), alkaloids (caffeine, theobromine, theophylline, etc.), amino acids, volatile oils, lipids, polysaccharide, and vitamins. However, the polyphenolic content which is present in the highest concentration, is primarily responsible for its most of the therapeutic benefits. Consequently, flavonoid contents impart its antimicrobial, antioxidant, anti-allergic and anti-inflammatory effects. The phenolic content variants are further elaborated and sub-classified as catechin, gallocatechin, epigallocatechin, epicatechin gallate, epicatechin, and epigallocatechin-gallate (EGCG), the latter being the most active component [2, 5]. Further, the molecular structure of green tea polyphenols exhibits active hydroxyl hydrogen which effectively scavenge free radicals hence, slowing down the detrimental changes in most of the physiological processes existing in human body. Reportedly, tea polyphenols strongly exhibits the movement of glutathione peroxidase and superoxide dismutase causing higher scavenging rate. The phytoconstituents of tea reflects multiple therapeutic benefits on our various diverse physiological systems through various biochemical and pharmacological processes like—antioxidant activities, inhibition of cell proliferation, induction of apoptosis, cell cycle arrest and modulation of carcinogen metabolism [6, 7]. Similarly, in CNS, another constituent in green tea, L-theanine increases the dopamine and serotonin levels resulting in mood elevation and stress reduction. Also, caffeine content in same sources aids in increasing the focus, vigilance, concentration and reasoning ability [8]. Theobromine and theophylline are known as potential CNS stimulants. Numerous studies have shown that most of the tea polyphenols have reactive oxygen and nitrogen species (ROS) scavenging activity along with an ability to chelate down redox-active transition metal ions. Currently, apart from all the listed

and Kenya at second and third positions respectively.

**2. Potential health benefits of tea constituents**

irrespective of their region of cultivation.

*Tea - Chemistry and Pharmacology*

**22**

Tea leaves are either classified on the basis of their consumption and texture it has or on the processing method adopted for their leaves. Hence, the classification, studied commonly for tea is based on its varied fermentation degree process and is comprised of basically three types: non-fermented (green), semi-fermented (oolong) and entirely fermented (black) [10]. The tea processing starts firstly, from picking up the appropriate and selected tea leaves from shrub or tea tree which undergoes fractional withering. Then roasting the same leaves to inactivate oxidative enzymes, followed by rolling up, drying and sorting the same leaves. The color of the final tea product is usually green tasting slightly constringent. So many countries like China, the taste of green tea is improvised by supplementing aromatic fruits (orange) or flowers (jasmine). Further, the tea processing steps in case of black tea is more complex, as after withering process the tea leaves are subjected for two steps fermentation processes, in the last step of fermentation they have been rolled up and then fermented. Lastly, they are roasted till they become dark-brown or brown black in color imparting a roasting aroma so as to block the activity of enzymes (polyphenol oxidase and glycosidase) along with further, fermentation of the same [5]. Another variant, oolong tea which is partially fermented type usually has shorter fermentation time in comparison to the black one.

### **3.1 Green tea**

Green tea is a non-fermented tea which is largely consumed by the population of china and japan. After cultivation, tea leaves are first withered for the inactivation of enzyme (polyphenol) which is liable for oxidation of tea catechins into their oligomeric forms (thearubigins and theaflavins). To avoid the oxidation and polymerization of tea leaves, they are steamed up and dried at high temperatures [6, 9, 11]. The Chinese traditional dietary system do have another packed form of green tea called "black powder", named after type of leaves processing method. Where these leaves individually are stirred and wrapped into a round pellet looking like explosives. It prevents it from any kind of physical damage and maintains its fragrance and flavor. Polyphenols present in green tea are flavonols (quercetin, kaempferol, and rutin), caffeine, phenolic acids, theanine, flavor, and leucoanthocyanins, which show 40% of dry weight of leaves [12, 13]. The highly water-soluble parts of tea comprises of biochemical components like () epigallocatechin-3-gallate (EGCG), epigallocatechin (EGC), epicatechin-3-gallate (ECG), and epicatechin (EC) (As listed in **Table 1**) [9, 14]. Further, it's also been reported that 1 kg of green tea has around 191 g of the above listed catechins, 36 g of caffeine, and 5.2 g of flavonols [15]. In green tea there are 10–15% of polyphenols present whereas it's lesser in black tea, i.e. around 5%. Dry weight of green tea constitutes about 42% polyphenols which is composed of 26.7% of catechin-gallate components such as ECG (2.25%), EGC (10.32%), Catechins (0.53%), EGCG (11.16%) and Epicatechin (2.45%) [16]. It's been estimated that in one cup of green tea the expected concentration of EGCG is between 2.1–2.4 mg/mL and after testing the effects of both Green tea and EGCG (equivalent of 4–8 cups per day) on human subjects there was no appreciable side effects observed [17, 18]. Epidemiological


studies too, have suggested protective and suppressive effects against many types of human cancer (including that of skin, lung, liver, esophagus, and stomach) after tea

*Representing the types and structure of phytocompounds present in the green tea with their therapeutic benefits.*

**Structure of the polyphenols Therapeutic**

*Remedial Effects of Tea and Its Phytoconstituents on Central Nervous System*

**benefit**

Has strong antioxidant and anti-inflammatory activities, induces cell apoptosis by hindering cellular cycles in pancreatic cancer, and decreases autoimmune reactions.

Radical scavengers and Protective effect on lipid peroxidation in phospholipid Bilayers, Antioxidants

This variety of tea is very famous in North America, Europe, and India. Black tea is extracted from the new, soft, firstly appeared leaves of *Camellia sinensis* and is one of the most broadly devoured non-mixed drinks. The flavor, quality and taste of these drinks tends to change with variation in their topographical and climatic conditions [22, 23]. This variety of tea offers, its simple quality parameters, specifically, theaflavins, thearubigins, and caffeine. Theaflavins adds to the abstinence (liveliness) and splendor, while thearubigins adds to the shading and body (mouth

consumption [19–21].

**3.2 Black tea**

**25**

**Table 1.**

**S. No**

6. ()-

Epigallocatechin gallate (EGCG)

**Polyphenols present**

*DOI: http://dx.doi.org/10.5772/intechopen.81521*

5. (+)-Epicatechin gallate (ECG)

#### *Remedial Effects of Tea and Its Phytoconstituents on Central Nervous System DOI: http://dx.doi.org/10.5772/intechopen.81521*

**Table 1.** *Representing the types and structure of phytocompounds present in the green tea with their therapeutic benefits.*

studies too, have suggested protective and suppressive effects against many types of human cancer (including that of skin, lung, liver, esophagus, and stomach) after tea consumption [19–21].

## **3.2 Black tea**

**S. No**

3. ()

Epigallocatechin

4. ()-Catechin gallate (GC)

**24**

**Polyphenols present**

*Tea - Chemistry and Pharmacology*

**Structure of the polyphenols Therapeutic**

1. (+)-Catechin Increases cellular

2. Epicatechin It inhibits lipid

**benefit**

lipid antioxidant activity, act as brain permeable iron chelator

peroxidation in cell membrane and generation of hydrogen peroxide ions in keratinomyocytes. Also, can induce ATF3 (tumor suppressor proteins) through EGR-1activation.

Act as prophylactic agents against *Bordetella pertussis* infection.

Antioxidant

This variety of tea is very famous in North America, Europe, and India. Black tea is extracted from the new, soft, firstly appeared leaves of *Camellia sinensis* and is one of the most broadly devoured non-mixed drinks. The flavor, quality and taste of these drinks tends to change with variation in their topographical and climatic conditions [22, 23]. This variety of tea offers, its simple quality parameters, specifically, theaflavins, thearubigins, and caffeine. Theaflavins adds to the abstinence (liveliness) and splendor, while thearubigins adds to the shading and body (mouth

feel); and caffeine is responsible for stimulatory impact of dark tea. In Black tea, the compound is permitted to act in a way that the leaves are completely aged to give the trademark fragrance and shade of dark tea [24, 25]. Arranged by squashing tea leaves and permitting enzyme mediated oxidation, which leads to the formation of oligomeric flavanols by tea catechins, including theaflavins, thearubigins, and different oligomers [26–28]. Further, the associated compounds like Theaflavins includes, combination of theaflavin (TF-1), theaflavin-3-gallate (TF-2a), theaflavin-30 -gallate9TF-2b), and theaflavin-3, 30 -digallate (TF-3), having lower tea catechin content (3–10% [w/w]), with theaflavins and thearubigins showing around 2–6% (w/w) and 10–20% (w/w) dry weight. Theaflavins, are orange or orange-red colored benzotropolone structure formed due to co-oxidation and oxidative dimerization of catechins (**Table 2**) [29, 30].

**Table 2.**

*Representing the types and structure of phytocompounds present in the black tea with their therapeutic benefits.*

### **3.3 Oolong tea**

Oolong tea is a conventional Chinese tea with a different, unique production method and one of the most popular beverages in china with its Chinese name meaning as "Black dragon tea". It is a semi fermented tea with restricted time of oxidation as compared to black tea and contains phytocompounds of both black and

green tea. It has approximately half of the EGCG from green tea, while double quantity of polymerized polyphenols and theaflavins of black tea. The procyanidins produced in oolong tea are formed due to its unique fermentation process. The

*Representing the types and structure of phytocompounds present in the oolong tea with their therapeutic*

**S. No**

3. ()

Epigallocatechin (EGC)

4. ()-Catechin gallate (GC)

5. (+)-Epicatechin gallate (ECG)

6. ()-

**Table 3.**

*benefits.*

**27**

Epigallocatechin gallate (EGCG)

**Polyphenols present**

*DOI: http://dx.doi.org/10.5772/intechopen.81521*

**Structure of the polyphenols Therapeutic benefit**

activity, act as brain permeable iron

membrane and induces tumor suppressor proteins

It acts as prophylactic agents against *Bordetella pertussis* infection.

Radical scavengers and Protective effect on lipid peroxidation in phospholipid Bilayers, Antioxidants

Has strong antioxidant and antiinflammatory activities, induces cell apoptosis by hindering cellular cycles in pancreatic cancer, and decreases

autoimmune reactions.

chelator

Antioxidant

1. (+)-Catechin Increases cellular lipid antioxidant

*Remedial Effects of Tea and Its Phytoconstituents on Central Nervous System*

2. Epicatechin It inhibits lipid peroxidation of cell


#### *Remedial Effects of Tea and Its Phytoconstituents on Central Nervous System DOI: http://dx.doi.org/10.5772/intechopen.81521*

#### **Table 3.**

feel); and caffeine is responsible for stimulatory impact of dark tea. In Black tea, the compound is permitted to act in a way that the leaves are completely aged to give the trademark fragrance and shade of dark tea [24, 25]. Arranged by squashing tea leaves and permitting enzyme mediated oxidation, which leads to the formation of oligomeric flavanols by tea catechins, including theaflavins, thearubigins, and different oligomers [26–28]. Further, the associated compounds like Theaflavins includes, combination of theaflavin (TF-1), theaflavin-3-gallate (TF-2a),

catechin content (3–10% [w/w]), with theaflavins and thearubigins showing around 2–6% (w/w) and 10–20% (w/w) dry weight. Theaflavins, are orange or orange-red colored benzotropolone structure formed due to co-oxidation and oxi-

1. Thearubigins Shows

2. Theaflavins shows inhibitory

**Structure of the polyphenols Therapeutic**

Oolong tea is a conventional Chinese tea with a different, unique production method and one of the most popular beverages in china with its Chinese name meaning as "Black dragon tea". It is a semi fermented tea with restricted time of oxidation as compared to black tea and contains phytocompounds of both black and

*Representing the types and structure of phytocompounds present in the black tea with their therapeutic benefits.*


**benefit**

antioxidative properties, prevent activity of enzymes participating in enzymatic lipid peroxidation

effect against phytopathogenic bacteria, induce apoptosis, strong antioxidants, prevent free radical generation, show metal chelating abilities


dative dimerization of catechins (**Table 2**) [29, 30].

theaflavin-30

**S. No** **Polyphenols present**

*Tea - Chemistry and Pharmacology*

**3.3 Oolong tea**

**Table 2.**

**26**

*Representing the types and structure of phytocompounds present in the oolong tea with their therapeutic benefits.*

green tea. It has approximately half of the EGCG from green tea, while double quantity of polymerized polyphenols and theaflavins of black tea. The procyanidins produced in oolong tea are formed due to its unique fermentation process. The


products (AGEs) induced neuronal cells injury along with inhibit AGEs—AGE receptor (RAGE) interaction intervened pathways, suggesting a possible therapeutic role of tea catechins for neurodegenerative diseases. Hence, both black and green tea varieties are reported to contribute immensely for the protection against neurodegenerative diseases [34–36]. Also, oxidative variations of cellular components

antioxidative property [37]. The oxidation of these components in aqueous phase is

Moreover, these water soluble tea polyphenols, particularly catechins have effective potential to scavenge free radicals and reduce the versatility of free radicals in the lipid structures too. Polyphenols enters the phospholipids bilayer, coating it with film and, balancing out the impact, by adjusting the lipid pressing ability [38]. They also contain higher amount of chemically dynamic metal particles (iron

Due to the existence of hydroxyl ions on polyphenol ring metal chelation effects

One of the essential pathological cause in Alzheimer's disease (AD) is irregular contact of free chelatable iron which is responsible for the deposition of neocortical amyloid peptide and deposition of metals, phosphorylation of tau and formation of tangles due to production of tau protein from microtubules [45, 46]. Also, the activation of amyloid cascades, which produces amyloid by β-amyloid precursor protein (APP), accumulates in the presence of divalent metal ions into amyloid

Recent studies have reported that the delay in onset or slowdown of the neurodegenerative process along with minimal neural deterioration was observed in the population consuming tea infusions on regular basis [49]. There scientific correlation suggests that the reduction in amyloid beta (Aβ) fibril production in the presence of EC and EGCG is suspected to regulate the amyloid protein precursor (APP) enzyme activity [50]. Additionally, it been also suggested that the regular consumption of tea (green and black) may lead to the acetyl cholinesterase (AChE) activity inhibition, further causing halt in acetylcholine production [51, 52]. Besides this, it was found that there was inhibition of butyrylcholinesterase (BuChE) enzyme deposits in the brain of AD subjects after consuming green tea or black tea for certain time [53]. These research findings advices that active phytocompounds

present in tea can be used to obstruct the development of AD [54].

**5.1 Mechanism of action of EGCG to improve cardiovascular function**

EGCG directly binds to the Laminin receptor (67LR), located on the peptide LR161-170. This receptor shows a high expression only in cancerous cells. This

Tachibana et al. [55] studied the effect of tea polyphenols, and suggested that

such as nucleic acids, lipids, and proteins are prevented by bidirectional

and copper) creating *in-situ* oxygen radicals by Fenton's response [39, 40].

can be observed. Metal Chelating effects by Green and Black Tea additionally, restricts lipid per oxidation and secures the essential lipid structures present in cerebrum leading to reduce oxidative stress [10, 27, 41]. Furthermore, it's been observed in research studies that the phytocompounds of tea (Green/Black) also prevents, the division of mitochondrial layer against iron induced lipid per oxidation and enhanced the survival rate in many *in vivo* models [42, 43]. Hence, it can be concluded from the recent research updates, that the high metal chelating quality of its constituents may provide a unique essential neuroprotection against many

responsible for initiation of membrane lipid peroxidation [35].

*Remedial Effects of Tea and Its Phytoconstituents on Central Nervous System*

*DOI: http://dx.doi.org/10.5772/intechopen.81521*

neurological disorders [44].

fibrils leading to a major cause of AD [47, 48].

**5. Mechanism of tea polyphenols**

**and anticancer activity**

**29**

**Table 4.**

*Comparing the polyphenolic contents of oolong and green tea.*

leaves are first withered, sun dried and then allowed for oxidation before rolling and twisting. *Camellia sinensis* is used for the production of Oolong tea and tastes very different from green and black tea. The tea processing method differs which makes them significantly different from each other, even if they are produced from the same plant [31].

As all tea leaves are green when they are plucked. Green tea undergoes, heating process in order to inhibit the oxidation of tea leaves. They are rolled up to break the cell structure. While, oolong tea is plucked and kept in optimized condition and allowed for oxidation. Due to difference in its processing method oolong tea tastes different from its sub varieties. It shows a sweet and fruity flavor with striking honey odors to woody and dense with roasted aromas, or even green and fresh with flowery aromas. They are processed by different methods as some are wrappedcurled into small beads and others are rolled into curly leaves. In china, oolong tea is added with flavors like jasmine flowers (**Tables 3** and **4**) [32].

### **4. Therapeutic benefits of tea in CNS health**

As discussed earlier, the health-promoting properties of the tea plants are often credited to their active ingredients including polyphenols. Tea flavanols are a group of natural polyphenols (epicatechins) found in most of the varieties of tea. Their therapeutic benefits although are immense, but they do have contributed exclusively in neural health of living beings. Likewise, the polyphenols of green tea are reported extensively in preventing neuronal degradation by inhibiting neurotoxin formation in cells [33, 34]. Also, in one of the recent study done, with transitional metal (iron and copper) chelating property or EGCG, suggested its possible effective role in treating certain forms of neurodegenerative diseases. Similarly, the antioxidative property of EGCG exhibits protection against advanced glycation end

#### *Remedial Effects of Tea and Its Phytoconstituents on Central Nervous System DOI: http://dx.doi.org/10.5772/intechopen.81521*

products (AGEs) induced neuronal cells injury along with inhibit AGEs—AGE receptor (RAGE) interaction intervened pathways, suggesting a possible therapeutic role of tea catechins for neurodegenerative diseases. Hence, both black and green tea varieties are reported to contribute immensely for the protection against neurodegenerative diseases [34–36]. Also, oxidative variations of cellular components such as nucleic acids, lipids, and proteins are prevented by bidirectional antioxidative property [37]. The oxidation of these components in aqueous phase is responsible for initiation of membrane lipid peroxidation [35].

Moreover, these water soluble tea polyphenols, particularly catechins have effective potential to scavenge free radicals and reduce the versatility of free radicals in the lipid structures too. Polyphenols enters the phospholipids bilayer, coating it with film and, balancing out the impact, by adjusting the lipid pressing ability [38]. They also contain higher amount of chemically dynamic metal particles (iron and copper) creating *in-situ* oxygen radicals by Fenton's response [39, 40].

Due to the existence of hydroxyl ions on polyphenol ring metal chelation effects can be observed. Metal Chelating effects by Green and Black Tea additionally, restricts lipid per oxidation and secures the essential lipid structures present in cerebrum leading to reduce oxidative stress [10, 27, 41]. Furthermore, it's been observed in research studies that the phytocompounds of tea (Green/Black) also prevents, the division of mitochondrial layer against iron induced lipid per oxidation and enhanced the survival rate in many *in vivo* models [42, 43]. Hence, it can be concluded from the recent research updates, that the high metal chelating quality of its constituents may provide a unique essential neuroprotection against many neurological disorders [44].

One of the essential pathological cause in Alzheimer's disease (AD) is irregular contact of free chelatable iron which is responsible for the deposition of neocortical amyloid peptide and deposition of metals, phosphorylation of tau and formation of tangles due to production of tau protein from microtubules [45, 46]. Also, the activation of amyloid cascades, which produces amyloid by β-amyloid precursor protein (APP), accumulates in the presence of divalent metal ions into amyloid fibrils leading to a major cause of AD [47, 48].

Recent studies have reported that the delay in onset or slowdown of the neurodegenerative process along with minimal neural deterioration was observed in the population consuming tea infusions on regular basis [49]. There scientific correlation suggests that the reduction in amyloid beta (Aβ) fibril production in the presence of EC and EGCG is suspected to regulate the amyloid protein precursor (APP) enzyme activity [50]. Additionally, it been also suggested that the regular consumption of tea (green and black) may lead to the acetyl cholinesterase (AChE) activity inhibition, further causing halt in acetylcholine production [51, 52]. Besides this, it was found that there was inhibition of butyrylcholinesterase (BuChE) enzyme deposits in the brain of AD subjects after consuming green tea or black tea for certain time [53]. These research findings advices that active phytocompounds present in tea can be used to obstruct the development of AD [54].

## **5. Mechanism of tea polyphenols**

### **5.1 Mechanism of action of EGCG to improve cardiovascular function and anticancer activity**

Tachibana et al. [55] studied the effect of tea polyphenols, and suggested that EGCG directly binds to the Laminin receptor (67LR), located on the peptide LR161-170. This receptor shows a high expression only in cancerous cells. This

leaves are first withered, sun dried and then allowed for oxidation before rolling and twisting. *Camellia sinensis* is used for the production of Oolong tea and tastes very different from green and black tea. The tea processing method differs which makes them significantly different from each other, even if they are produced from the

**Oolong tea phytocompound concentration (mg/g)**

C22H18O11 14 29

C22H18O11 16 19

C22H18O11 3 6

114 –

Caffeine C8H10N4O2 64 53

Catechin C15H14O6 30 43 Epicatechin C15H14O6 6 25 Gallocatechin C15H14O7 10 5 Epigallocatechin C15H14O7 2 8

Catechin gallate C22H18O10 7 5

**Green tea phytocompound concentration (mg/g)**

As all tea leaves are green when they are plucked. Green tea undergoes, heating process in order to inhibit the oxidation of tea leaves. They are rolled up to break the cell structure. While, oolong tea is plucked and kept in optimized condition and allowed for oxidation. Due to difference in its processing method oolong tea tastes different from its sub varieties. It shows a sweet and fruity flavor with striking honey odors to woody and dense with roasted aromas, or even green and fresh with flowery aromas. They are processed by different methods as some are wrappedcurled into small beads and others are rolled into curly leaves. In china, oolong tea is

As discussed earlier, the health-promoting properties of the tea plants are often credited to their active ingredients including polyphenols. Tea flavanols are a group of natural polyphenols (epicatechins) found in most of the varieties of tea. Their therapeutic benefits although are immense, but they do have contributed exclusively in neural health of living beings. Likewise, the polyphenols of green tea are reported extensively in preventing neuronal degradation by inhibiting neurotoxin formation in cells [33, 34]. Also, in one of the recent study done, with transitional metal (iron and copper) chelating property or EGCG, suggested its possible effective role in treating certain forms of neurodegenerative diseases. Similarly, the antioxidative property of EGCG exhibits protection against advanced glycation end

added with flavors like jasmine flowers (**Tables 3** and **4**) [32].

**4. Therapeutic benefits of tea in CNS health**

*Comparing the polyphenolic contents of oolong and green tea.*

same plant [31].

**Polyphenols Chemical**

*Tea - Chemistry and Pharmacology*

**Flavanol with galloyl moiety**

**Flavanol without galloyl moiety**

Epigallocatechin gallate

Gallocatechin gallate

Epicatechin gallate

**Table 4.**

**28**

**Oolong tea polymerized polyphenols (OTPP)**

**structure**

suggests that EGCG specifically binds to the cancer cells and binding of EGCG with 67LR receptor activate the enzyme protein kinase B which further activate ENOS pathway leading to vasodilation that contributes to the improvement of cardiovascular function of cell [16, 55]. It also elevates the activity of CGMP that activate the PKC/Acidic sphingomyelinases that induces the apoptosis in cancerous cells.

content, Aluminum presence and the effects of tea polyphenols on iron bioavailability [59, 60]. In the study done by Lin et al. [31], it was been reported that the caffeine content in tea is available in following order: black tea > oolong tea > green tea > fresh tea leaf. Similarly, Cabrera et al. also studied the caffeine content and its

It can be concluded in the review that tea polyphenols with other constituents have a very high therapeutic potential including the potency to decrease the threat of diseases such as cancer, cardiovascular, diabetes and neurodegenerative diseases. It has proven to be a strong antioxidant agent that shows a therapeutic effect of tea. To evaluate the efficacy of tea many experiments are being conducted which shows a promising data from many trials and other ongoing trials are conducted to study the therapeutic effect of tea. Because less information is available about bioavailability of tea polyphenols after intake of tea, studies of bioavailability polyphenols

Department of Biotechnology, Jaypee Institute of Information Technology, Noida,

© 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,

of tea is needed on animals and humans to evaluate its protective role.

Manisha Singh\*, Vandana Tyagi and Shriya Agarwal

provided the original work is properly cited.

\*Address all correspondence to: manishasingh1295@gmail.com

after effects in 45 samples of tea and determined that black tea has the high concentration of caffeine (41.5–67.4 mg/g), whereas oolong and green tea samples have less amount of caffeine content of 32.5 and 29.2 mg/g, respectively [61]. The harmful effects of caffeine content in tea are listed as—vomiting, sleep disorder, nervousness, tachycardia, and epigastric pain etc. [62]. Hence, tea intake is strictly restricted in patients suffering from cardiovascular problems. Breastfeeding and pregnant women should avoid over-consumption of green tea because it do causes tachycardia in them giving rise to higher health risks to fetus [63, 64]. The presence of aluminum in black and green teas also suggested increased accumulation of the same inside the body affecting the neural well-being and causing neurological

*Remedial Effects of Tea and Its Phytoconstituents on Central Nervous System*

*DOI: http://dx.doi.org/10.5772/intechopen.81521*

disorders [65].

**6. Conclusion**

**Author details**

UP, India

**31**

#### **5.2 Antagonistic actions of theanine on glutamate receptors**

Nozawa et al. [56] discovered the death of 50% of neurons at higher concentration of glutamate but when pre-treated with theanine, the possibility of death was significantly decreased. Many more recent updates suggested that increased glutamate level in cell may lead to massive influx of Ca+ ions and increases the formation of ROS which leads to the death of neuronal cells. In order to avoid the toxicity of glutamate, the glutamate receptors binds with theanine. Theanine has same structure as glutamate so in presence of theanine it shows a competitive inhibition and inhibit the binding of glutamate to its receptor. Furthermore, Kakuda et al. [57] studies the inhibiting effect of glutamate receptors by theanine that suggests the neuroprotective role of theanine. It shows the specific binding of theanine to NMDA receptor to inhibit the glutamate binding affinity. Theanine has an antagonistic effect to glutamate receptors. Glutamine, derived from glutamate, is synthesized by glutamine synthetase. Theanine can inhibit the transport of glutamine and regulate the glutamate-glutamine cycle in the neurons and, thus, shows the neuroprotective effect of tea (**Figure 1**) [58].

**Figure 1.** *Schematic representation. Inhibition effect of theanine on glutamate receptor.*

#### **5.3 Therapeutic limitations of tea compounds**

Although being therapeutically crucial compound tea phytocompounds do have certain harmful side effects, if over consumed or overdosed like—higher Caffeine

*Remedial Effects of Tea and Its Phytoconstituents on Central Nervous System DOI: http://dx.doi.org/10.5772/intechopen.81521*

content, Aluminum presence and the effects of tea polyphenols on iron bioavailability [59, 60]. In the study done by Lin et al. [31], it was been reported that the caffeine content in tea is available in following order: black tea > oolong tea > green tea > fresh tea leaf. Similarly, Cabrera et al. also studied the caffeine content and its after effects in 45 samples of tea and determined that black tea has the high concentration of caffeine (41.5–67.4 mg/g), whereas oolong and green tea samples have less amount of caffeine content of 32.5 and 29.2 mg/g, respectively [61]. The harmful effects of caffeine content in tea are listed as—vomiting, sleep disorder, nervousness, tachycardia, and epigastric pain etc. [62]. Hence, tea intake is strictly restricted in patients suffering from cardiovascular problems. Breastfeeding and pregnant women should avoid over-consumption of green tea because it do causes tachycardia in them giving rise to higher health risks to fetus [63, 64]. The presence of aluminum in black and green teas also suggested increased accumulation of the same inside the body affecting the neural well-being and causing neurological disorders [65].

### **6. Conclusion**

suggests that EGCG specifically binds to the cancer cells and binding of EGCG with 67LR receptor activate the enzyme protein kinase B which further activate ENOS pathway leading to vasodilation that contributes to the improvement of cardiovascular function of cell [16, 55]. It also elevates the activity of CGMP that activate the PKC/Acidic sphingomyelinases that induces the apoptosis in cancerous cells.

Nozawa et al. [56] discovered the death of 50% of neurons at higher concentration of glutamate but when pre-treated with theanine, the possibility of death was significantly decreased. Many more recent updates suggested that increased glutamate level in cell may lead to massive influx of Ca+ ions and increases the formation of ROS which leads to the death of neuronal cells. In order to avoid the toxicity of glutamate, the glutamate receptors binds with theanine. Theanine has same structure as glutamate so in presence of theanine it shows a competitive inhibition and inhibit the binding of glutamate to its receptor. Furthermore, Kakuda et al. [57] studies the inhibiting effect of glutamate receptors by theanine that suggests the neuroprotective role of theanine. It shows the specific binding of theanine to NMDA receptor to inhibit the glutamate binding affinity. Theanine has an antagonistic effect to glutamate receptors. Glutamine, derived from glutamate, is synthesized by glutamine synthetase. Theanine can inhibit the transport of glutamine and

regulate the glutamate-glutamine cycle in the neurons and, thus, shows the

neuroprotective effect of tea (**Figure 1**) [58].

*Tea - Chemistry and Pharmacology*

**5.3 Therapeutic limitations of tea compounds**

*Schematic representation. Inhibition effect of theanine on glutamate receptor.*

**Figure 1.**

**30**

Although being therapeutically crucial compound tea phytocompounds do have certain harmful side effects, if over consumed or overdosed like—higher Caffeine

**5.2 Antagonistic actions of theanine on glutamate receptors**

It can be concluded in the review that tea polyphenols with other constituents have a very high therapeutic potential including the potency to decrease the threat of diseases such as cancer, cardiovascular, diabetes and neurodegenerative diseases. It has proven to be a strong antioxidant agent that shows a therapeutic effect of tea. To evaluate the efficacy of tea many experiments are being conducted which shows a promising data from many trials and other ongoing trials are conducted to study the therapeutic effect of tea. Because less information is available about bioavailability of tea polyphenols after intake of tea, studies of bioavailability polyphenols of tea is needed on animals and humans to evaluate its protective role.

## **Author details**

Manisha Singh\*, Vandana Tyagi and Shriya Agarwal Department of Biotechnology, Jaypee Institute of Information Technology, Noida, UP, India

\*Address all correspondence to: manishasingh1295@gmail.com

© 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.

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[64] Bedrood Z, Rameshrad M,

Phytotherapy Research. 2018

and Biology. 2003;**17**(3):159

[65] Hamdaoui MH, Chabchoub S, Hédhili A. Iron bioavailability and weight gains to iron-deficient rats fed a commonly consumed Tunisian meal 'bean seeds ragout' with or without beef and with green or black tea decoction. Journal of Trace Elements in Medicine

Hosseinzadeh H. Toxicological effects of Camellia sinensis (green tea): A review.

Regulatory Toxicology and Pharmocology. 2017;**89**:165-185

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10701-10707

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[52] Chakrabarti S, Sinha M, Thakurta IG, Banerjee P, Chattopadhyay M. Oxidative stress and amyloid beta toxicity in Alzheimer's disease:

Intervention in a complex relationship by antioxidants. Current Medicinal Chemistry. 2013;**20**(37):4648-4664

[53] Harada M, Kan Y, Naoki H, Fukui Y, Kageyama N, Nakai M, et al. Identification of the major

antioxidative metabolites in biological fluids of the rat with ingested (+) catechin and ()-epicatechin. Bioscience, Biotechnology, and Biochemistry. 1999;**63**(6):973-977

[54] Skrzydlewska E, Ostrowska J, Farbiszewski R, Michalak K. Protective

[55] Fujimura Y, Sumida M, Sugihara K, Tsukamoto S, Yamada K, Tachibana H. Green tea polyphenol EGCG sensing motif on the 67-kDa laminin receptor.

[56] Kakuda T, Nozawa A, Sugimoto A, Niino H. Inhibition by theanine of binding of [3H] AMPA, [3H] kainate, and [3H] MDL 105,519 to glutamate receptors. Bioscience, Biotechnology, and Biochemistry. 2002;**66**(12):

effect of green tea against lipid peroxidation in the rat liver, blood serum and the brain. Phytomedicine.

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2683-2686

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[43] Sutherland BA, Rahman RM, Appleton I. Mechanisms of action of green tea catechins, with a focus on ischemia-induced neurodegeneration. The Journal of Nutritional Biochemistry. 2006;**17**(5):291-306

[44] Lardner AL. Neurobiological effects of the green tea constituent theanine and its potential role in the treatment of psychiatric and neurodegenerative disorders. Nutritional Neuroscience. 2014;**17**(4):145-155

[45] Weinreb O, Amit T, Mandel S, Youdim MB. Neuroprotective molecular mechanisms of ()-epigallocatechin-3-gallate: A reflective outcome of its antioxidant, iron chelating and neuritogenic properties. Genes & Nutrition. 2009;**4**(4):283

[46] Yang CS, Hong J. Prevention of chronic diseases by tea: Possible mechanisms and human relevance. Annual Review of Nutrition. 2013;**33**: 161-181

[47] Weinreb O, Mandel S, Amit T, Youdim MB. Neurological mechanisms of green tea polyphenols in Alzheimer's and Parkinson's diseases. The Journal of Nutritional Biochemistry. 2004;**15**(9): 506-516

[48] Bush AI. The metallobiology of Alzheimer's disease. Trends in Neurosciences. 2003;**26**:207-214

[49] Rezai-Zadeh K, Arendash GW, Hou H, Fernandez F, Jensen M, Runfeldt M, et al. Green tea epigallocatechin-3-gallate (EGCG) reduces β-amyloid mediated cognitive impairment and modulates tau pathology in Alzheimer transgenic mice. Brain Research. 2008; **1214**:177-187

*Remedial Effects of Tea and Its Phytoconstituents on Central Nervous System DOI: http://dx.doi.org/10.5772/intechopen.81521*

[50] Checkoway H, Powers K, Smith-Weller T, Franklin GM, Longstreth WT Jr, Swanson PD. Parkinson's disease risks associated with cigarette smoking, alcohol consumption, and caffeine intake. American Journal of Epidemiology. 2002;**155**(8):732-738

esters against beta-amyloid-induced toxicity. The European Journal of Neuroscience. 2006;**23**(1):55-64

*Tea - Chemistry and Pharmacology*

paraquat-induced microsomal lipid peroxidation—A mechanism of protective effects of EGCg against paraquat toxicity. Toxicology. 2003;**183**

[43] Sutherland BA, Rahman RM, Appleton I. Mechanisms of action of green tea catechins, with a focus on ischemia-induced neurodegeneration. The Journal of Nutritional Biochemistry.

[44] Lardner AL. Neurobiological effects of the green tea constituent theanine and its potential role in the treatment of psychiatric and neurodegenerative disorders. Nutritional Neuroscience.

[45] Weinreb O, Amit T, Mandel S, Youdim MB. Neuroprotective molecular mechanisms of ()-epigallocatechin-3-gallate: A reflective outcome of its antioxidant, iron chelating and neuritogenic properties. Genes &

[46] Yang CS, Hong J. Prevention of chronic diseases by tea: Possible mechanisms and human relevance. Annual Review of Nutrition. 2013;**33**:

[47] Weinreb O, Mandel S, Amit T, Youdim MB. Neurological mechanisms of green tea polyphenols in Alzheimer's and Parkinson's diseases. The Journal of Nutritional Biochemistry. 2004;**15**(9):

[48] Bush AI. The metallobiology of Alzheimer's disease. Trends in Neurosciences. 2003;**26**:207-214

[49] Rezai-Zadeh K, Arendash GW, Hou H, Fernandez F, Jensen M, Runfeldt M, et al. Green tea epigallocatechin-3-gallate (EGCG) reduces β-amyloid mediated cognitive impairment and modulates tau pathology in Alzheimer transgenic mice. Brain Research. 2008;

(1–3):143-149

2006;**17**(5):291-306

2014;**17**(4):145-155

Nutrition. 2009;**4**(4):283

161-181

506-516

**1214**:177-187

[36] Oboh G, Rocha JB. Antioxidant and neuroprotective properties of sour tea (Hibiscus sabdariffa, calyx) and green tea (Camellia sinensis) on some prooxidant-induced lipid peroxidation in brain in vitro. Food Biophysics. 2008

[37] Reznichenko L, Amit T, Youdim MB, Mandel S. Green tea polyphenol ()-epigallocatechin-3-gallate induces neurorescue of long-term serumdeprived PC12 cells and promotes neurite outgrowth. Journal of

Neurochemistry. 2005;**93**(5):1157-1167

[38] Seeram NP, Henning SM, Niu Y, Lee R, Scheuller HS, Heber D. Catechin and caffeine content of green tea dietary supplements and correlation with antioxidant capacity. Journal of

Agricultural and Food Chemistry. 2006;

[39] Lorenz M. Cellular targets for the beneficial actions of tea polyphenols. The American Journal of Clinical Nutrition. 2013;**98**(6):1642S-1650S

[40] Swomley AM, Förster S, Keeney JT, Triplett J, Zhang Z, Sultana R, et al. Abeta, oxidative stress in Alzheimer disease: Evidence based on proteomics studies. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease. 2014;

[41] Rodrigues MJ, Neves V, Martins A, Rauter AP, Neng NR, Nogueira JM, et al.

inflammatory properties of Limonium algarvense flowers' infusions and decoctions: A comparison with green tea (*Camellia sinensis*). Food Chemistry.

[42] Higuchi A, Yonemitsu K, Koreeda A, Tsunenari S. Inhibitory activity of epigallocatechin gallate (EGCg) in

In vitro antioxidant and anti-

Dec 1;**3**(4):382

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**1842**(8):1248-1257

2016;**200**:322-329

**34**

[51] Wei CC, Yu CW, Yen PL, Lin HY, Chang ST, Hsu FL, et al. Antioxidant activity, delayed aging, and reduced amyloid-β toxicity of methanol extracts of tea seed pomace from Camellia tenuifolia. Journal of Agricultural and Food Chemistry. 2014;**62**(44): 10701-10707

[52] Chakrabarti S, Sinha M, Thakurta IG, Banerjee P, Chattopadhyay M. Oxidative stress and amyloid beta toxicity in Alzheimer's disease: Intervention in a complex relationship by antioxidants. Current Medicinal Chemistry. 2013;**20**(37):4648-4664

[53] Harada M, Kan Y, Naoki H, Fukui Y, Kageyama N, Nakai M, et al. Identification of the major antioxidative metabolites in biological fluids of the rat with ingested (+) catechin and ()-epicatechin. Bioscience, Biotechnology, and Biochemistry. 1999;**63**(6):973-977

[54] Skrzydlewska E, Ostrowska J, Farbiszewski R, Michalak K. Protective effect of green tea against lipid peroxidation in the rat liver, blood serum and the brain. Phytomedicine. 2002;**9**(3):232-238

[55] Fujimura Y, Sumida M, Sugihara K, Tsukamoto S, Yamada K, Tachibana H. Green tea polyphenol EGCG sensing motif on the 67-kDa laminin receptor. PLoS One. 2012;**7**(5):e37942

[56] Kakuda T, Nozawa A, Sugimoto A, Niino H. Inhibition by theanine of binding of [3H] AMPA, [3H] kainate, and [3H] MDL 105,519 to glutamate receptors. Bioscience, Biotechnology, and Biochemistry. 2002;**66**(12): 2683-2686

[57] Kakuda T. Neuroprotective effects of theanine and its preventive effects on cognitive dysfunction. Pharmacological Research. 2011;**64**(2):162-168

[58] Kakuda T, Hinoi E, Abe A, Nozawa A, Ogura M, Yoneda Y. Theanine, an ingredient of green tea, inhibits [3H] glutamine transport in neurons and astroglia in rat brain. Journal of Neuroscience Research. 2008;**86**(8): 1846-1856

[59] Jain A, Manghani C, Kohli S, Nigam D, Rani V. Tea and human health: The dark shadows. Toxicology Letters. 2013 Jun 20;**220**(1):82-87

[60] Ruchi V. An overview on tea. International Journal of Pharmaceutical Research. 2013;**3**(3):36

[61] Hayat K, Iqbal H, Malik U, Bilal U, Mushtaq S. Tea and its consumption: Benefits and risks. Critical Reviews in Food Science and Nutrition. 2015;**55**(7): 939-954

[62] Turnbull D, Rodricks JV, Mariano GF, Chowdhury F. Pharmacology. Caffeine and cardiovascular health. Regulatory Toxicology and Pharmocology. 2017;**89**:165-185

[63] Lu JH, He JR, Shen SY, Wei XL, Chen NN, Yuan MY, et al. Does tea consumption during early pregnancy have an adverse effect on birth outcomes? Birth. 2017;**44**(3):281-289

[64] Bedrood Z, Rameshrad M, Hosseinzadeh H. Toxicological effects of Camellia sinensis (green tea): A review. Phytotherapy Research. 2018

[65] Hamdaoui MH, Chabchoub S, Hédhili A. Iron bioavailability and weight gains to iron-deficient rats fed a commonly consumed Tunisian meal 'bean seeds ragout' with or without beef and with green or black tea decoction. Journal of Trace Elements in Medicine and Biology. 2003;**17**(3):159

**37**

**Chapter 4**

**Abstract**

of oral carcinoma.

**1. Introduction**

gingivitis, periodontitis

disease has struck [2].

There are six different types of tea produced [4]:

Tea and Oral Health

Tea consumption as a beverage is very common in various parts of the world. It has attained a worldwide liking and measure of social status in many parts. Tea contains various chemicals which have positive effects on health from heart to skin. It has been associated with the cure of aging to potent anticancer agent also. Considering these facts an attempt was made to establish a relation between tea and oral health. Tea has its effects on oral microorganisms, anticariogenic properties, and reduction of gingivitis as well as periodontitis. A cup of tea immediately after lunch had reduced dental caries in children and rinsing with 0.2% Chinese green tea decreased plaque and the gingival index significantly. Tea has been found to be effective against oral cancer, precancerous lesions and conditions as well. Hence tea has been rightly said as a functional food for health. Green tea has shown to have bactericidal effects on *Porphyromonas gingivalis* and Prevotella species. The gingival inflammation is reduced and a marked reduction in pocket size has been noticed. Tea selectively induces p57 and apoptosis as well as inhibits the growth and invasion

**Keywords:** tea, oral cancer, antimicrobial properties, catechins, EGCG,

Ancient Chinese and Japanese medicines have emphasized the fact that green tea consumption could heal wounds and cure diseases. In 2737 BC Chinese had a belief on tea for its healing powers. Lu Yu who was a scholar in China, who had written a treatise in AD 780, entitled *Cha Ching*, states that 'tea tempers the spirits, harmonizes the mind, dispels the lassitude, relieves fatigues, awakens thought, prevents drowsiness, refreshes the body and clears the perspective faculties' [1]. In the ancient system of Medicine, Ayurveda had listed tea in the group of medicaments as 'rasayanas' that bring about positive health, resistance to diseases and assured full lifespan of quality living, unlike drugs that cure after

Tea has been considered a desired drink worldwide. The world consumed 2.9 million tones of tea in 2016 which was more when compared to 1.6 in 2002 and this may shoot to 3.3 million tones in 2021 (Euromonitor data). More than half of tea is contributed by Asia and the top three markets by per capita consumption of tea are Turkey, Ireland and UAE [3]. Different forms of tea are obtainable in the market claiming varied health benefits. These categories are based on the oxidation process.

*Aswini Y. Balappanavar*

## **Chapter 4** Tea and Oral Health

*Aswini Y. Balappanavar*

## **Abstract**

Tea consumption as a beverage is very common in various parts of the world. It has attained a worldwide liking and measure of social status in many parts. Tea contains various chemicals which have positive effects on health from heart to skin. It has been associated with the cure of aging to potent anticancer agent also. Considering these facts an attempt was made to establish a relation between tea and oral health. Tea has its effects on oral microorganisms, anticariogenic properties, and reduction of gingivitis as well as periodontitis. A cup of tea immediately after lunch had reduced dental caries in children and rinsing with 0.2% Chinese green tea decreased plaque and the gingival index significantly. Tea has been found to be effective against oral cancer, precancerous lesions and conditions as well. Hence tea has been rightly said as a functional food for health. Green tea has shown to have bactericidal effects on *Porphyromonas gingivalis* and Prevotella species. The gingival inflammation is reduced and a marked reduction in pocket size has been noticed. Tea selectively induces p57 and apoptosis as well as inhibits the growth and invasion of oral carcinoma.

**Keywords:** tea, oral cancer, antimicrobial properties, catechins, EGCG, gingivitis, periodontitis

## **1. Introduction**

Ancient Chinese and Japanese medicines have emphasized the fact that green tea consumption could heal wounds and cure diseases. In 2737 BC Chinese had a belief on tea for its healing powers. Lu Yu who was a scholar in China, who had written a treatise in AD 780, entitled *Cha Ching*, states that 'tea tempers the spirits, harmonizes the mind, dispels the lassitude, relieves fatigues, awakens thought, prevents drowsiness, refreshes the body and clears the perspective faculties' [1]. In the ancient system of Medicine, Ayurveda had listed tea in the group of medicaments as 'rasayanas' that bring about positive health, resistance to diseases and assured full lifespan of quality living, unlike drugs that cure after disease has struck [2].

Tea has been considered a desired drink worldwide. The world consumed 2.9 million tones of tea in 2016 which was more when compared to 1.6 in 2002 and this may shoot to 3.3 million tones in 2021 (Euromonitor data). More than half of tea is contributed by Asia and the top three markets by per capita consumption of tea are Turkey, Ireland and UAE [3]. Different forms of tea are obtainable in the market claiming varied health benefits. These categories are based on the oxidation process. There are six different types of tea produced [4]:


Tea has shown to have various benefits on Health and oral health. Tea reduces the risk of several major life style related diseases which include cancer, arteriosclerosis and cardiovascular diseases, neural and obesity problems, diabetes, diseases of the kidneys and liver, pulmonary ailments, flu, SARS and even AIDS. The impact on oral health though less researched has been beneficial.

### **2. Tea and oral health**

Oral/dental diseases are a costly burden to health care services, accounting for between 5 and 10% of total health care expenditures and exceeding the cost of treating cardiovascular disease, cancer and osteoporosis in industrialized countries [5]. In low-income countries, the cost of traditional restorative treatment of dental disease would probably exceed the available resources for health care. Dental health promotion and preventive strategies are clearly more affordable and sustainable. Although not life-threatening, dental diseases have a detrimental effect on quality of life in childhood through to old age, having an impact on self-esteem, eating ability, nutrition and health.

Oral health is related to diet in many ways, for example, through nutritional influences on craniofacial development, oral cancer and oral infectious diseases [6]. Both animal studies and experimental investigations in humans have shown that black tea extract increases plaque fluoride concentration and reduces the cariogenicity of a sugar rich diet. The protection against the causative organisms of dental caries is well documented by Banerjee in 1990 [7]. Sava et al. showed that the melanin-like pigment from black tea has immunostimulant activity [8].

#### **2.1 Anticariogenic effects**

Dental caries is a transmissible microbial disease affecting the hard tissues of teeth caused by acids from bacterial metabolism leading to demineralization and dissolution of enamel and dentin. The bacteria responsible of producing organic acids as a by-product of their metabolism of fermentable carbohydrates. The caries process is a continuum in the oral cavity resulting from many cycles of demineralization and remineralization [9].

The studies of cariostatic effects of tea were started in the 1940s and 1950s showing fluoride to be the active component [10]. Reports by many researchers have showed that the tea consumption leads to reduction in dental caries in humans and experimental animals, that tannins and fluoride were the reason for this inhibitory effect [11–14]. Despite the positive animal data supporting the positive relationship between tea and dental caries prevention, relatively little attention has

**39**

*Tea and Oral Health*

*DOI: http://dx.doi.org/10.5772/intechopen.80998*

been given to this field of research. Green tea extracts, or polyphenols, have been reported to inhibit *in vitro* growth, acid production and water insoluble glucan synthesis by glucosyltransferase enzyme of *Streptococcuss mutans* [12, 15–18]. Similar findings have been reported for oolong tea by Nakahara et al., in 1993 and Ooshima et al., in 1993 [18, 19]. Taiwanese green, black and oolong teas have also been shown to inhibit *in vitro* growth of selected cariogenic and periodontal pathogens [20, 21]. In an adult human study by Wu et al. [22] rinsing with black tea ten times a day for 7 days resulted in significantly less pronounced pH fall, a lower plaque index (P < 0.05) and lower numbers of mutans streptococci and total oral streptococci in plaque but not in saliva. Fluoride concentrations in plaque and saliva increased, reaching a maximum at day 7. Black tea and its polyphenols may benefit human oral

health by inhibition of dental plaque, acidity and cariogenic microflora.

ase enzyme activity of Mutans Streptococci and dental plaque bacteria.

also calculated the total F intake from tea consumption.

Tea is a source of fluoride (F) as well as many other dietary trace elements. The caries-preventive effect of teas was first believed to be due to its fluoride content. More recent studies, however, have pointed out that the polyphenol contents of tea may affect plaque formation and metabolism as well [31]. The commercial tea plant, *Camellia sinensis*, takes up F from the soil by passive diffusion and concentrates it in the leaves by transpiration [32]. Due to differing soils, types of tea leaves, infusion times and methods of analysis, a great deal of variation in tea content has been found. Coupled with the various drinking habits among different people, it is very difficult to calculate the contribution of tea to total fluoride intake. A recent animal study showed that rats consuming black tea (prepared from fluoride-free water) over a 2-week period had a significantly lower rate of caries than those consuming non-fluoridated water. Furthermore, the caries scores in the group receiving tea were significantly greater than those in the group receiving fluoridated water. The authors suggested that black tea consumption attenuates the development of caries in young, caries-prone rats [14]. Wei et al. found a 15-min infusion to result in a mean fluoride concentration of 1.75 p.p.m. for 15 Chinese teas, 1.24 p.p.m. for 11 Ceylon/Indian teas and a negligible F amount for six herbal teas [32]. The bioavailability of fluoride in tea has been said to be approximately 85%. A review by Kavanagh and Renehan lists over 10 papers that measured the fluoride content of various teas [33]. Several studies have

Animal studies have shown that specific pathogen-free (SPF) rats infected with *S. mutans* and then fed a cariogenic diet containing green tea polyphenols demonstrated significantly lowered caries scores [17]. Supplementing drinking water of rats with 0.1% green tea polyphenol along with a cariogenic diet also significantly reduced total fissure caries lesions [23]. Animal studies using oolong tea gave similar results and it was suggested that active substances may affect bacterial virulence factors other than the glucosyltransferase enzymes [24]. Caries were found to be significantly lower among children who drank a cup of tea immediately after lunch and the tea polyphenols, rather than fluoride, were found to be responsible for the anticariogenic effects [25]. Another study reported that rinsing with 0.2% Chinese green tea while brushing decreased plaque and the gingival index significantly [26]. Tea drinking has been attributed as one of the factors in the declining prevalence of caries in Tunisia [27]. Tea extracts have also been shown to inhibit human salivary amylase and tea consumption may reduce the cariogenic potential of starch-containing foods, such as biscuits and cakes, because tea may reduce the tendency for these foods to serve as slow-release sources of fermentable carbohydrate [28]. It is likely that cariogenic challenge in a cariogenic diet may be overcome by the simultaneous presence of green tea in the diet. An anticariogenic potential of black tea has been suggested in various *in vitro* studies. [20, 29, 30]. Black tea and its polyphenols inhibited growth, acid production, metabolism and glucosyltransfer*Tea - Chemistry and Pharmacology*

Chinese culture

**2. Tea and oral health**

**2.1 Anticariogenic effects**

ization and remineralization [9].

in Chinese culture"

• White: wilted and unoxidized

• Green: unwilted and unoxidized

• Yellow: unwilted and unoxidized but allowed to yellow

• Black: wilted, sometime crushed, and fully oxidized which is called red tea in

• Post fermented: green tea that has been allowed to ferment/compost "black tea

Tea has shown to have various benefits on Health and oral health. Tea reduces the risk of several major life style related diseases which include cancer, arteriosclerosis and cardiovascular diseases, neural and obesity problems, diabetes, diseases of the kidneys and liver, pulmonary ailments, flu, SARS and even AIDS. The impact on

Oral/dental diseases are a costly burden to health care services, accounting for between 5 and 10% of total health care expenditures and exceeding the cost of treating cardiovascular disease, cancer and osteoporosis in industrialized countries [5]. In low-income countries, the cost of traditional restorative treatment of dental disease would probably exceed the available resources for health care. Dental health promotion and preventive strategies are clearly more affordable and sustainable. Although not life-threatening, dental diseases have a detrimental effect on quality of life in childhood through to old age, having an impact on self-esteem, eating ability, nutrition and health. Oral health is related to diet in many ways, for example, through nutritional influences on craniofacial development, oral cancer and oral infectious diseases [6]. Both animal studies and experimental investigations in humans have shown that black tea extract increases plaque fluoride concentration and reduces the cariogenicity of a sugar rich diet. The protection against the causative organisms of dental caries is well documented by Banerjee in 1990 [7]. Sava et al. showed that the melanin-like pigment from black tea has immunostimulant activity [8].

Dental caries is a transmissible microbial disease affecting the hard tissues of teeth caused by acids from bacterial metabolism leading to demineralization and dissolution of enamel and dentin. The bacteria responsible of producing organic acids as a by-product of their metabolism of fermentable carbohydrates. The caries process is a continuum in the oral cavity resulting from many cycles of demineral-

The studies of cariostatic effects of tea were started in the 1940s and 1950s showing fluoride to be the active component [10]. Reports by many researchers have showed that the tea consumption leads to reduction in dental caries in humans and experimental animals, that tannins and fluoride were the reason for this inhibitory effect [11–14]. Despite the positive animal data supporting the positive relationship between tea and dental caries prevention, relatively little attention has

• Oolong: wilted, bruised and partially oxidized

oral health though less researched has been beneficial.

**38**

been given to this field of research. Green tea extracts, or polyphenols, have been reported to inhibit *in vitro* growth, acid production and water insoluble glucan synthesis by glucosyltransferase enzyme of *Streptococcuss mutans* [12, 15–18]. Similar findings have been reported for oolong tea by Nakahara et al., in 1993 and Ooshima et al., in 1993 [18, 19]. Taiwanese green, black and oolong teas have also been shown to inhibit *in vitro* growth of selected cariogenic and periodontal pathogens [20, 21]. In an adult human study by Wu et al. [22] rinsing with black tea ten times a day for 7 days resulted in significantly less pronounced pH fall, a lower plaque index (P < 0.05) and lower numbers of mutans streptococci and total oral streptococci in plaque but not in saliva. Fluoride concentrations in plaque and saliva increased, reaching a maximum at day 7. Black tea and its polyphenols may benefit human oral health by inhibition of dental plaque, acidity and cariogenic microflora.

Animal studies have shown that specific pathogen-free (SPF) rats infected with *S. mutans* and then fed a cariogenic diet containing green tea polyphenols demonstrated significantly lowered caries scores [17]. Supplementing drinking water of rats with 0.1% green tea polyphenol along with a cariogenic diet also significantly reduced total fissure caries lesions [23]. Animal studies using oolong tea gave similar results and it was suggested that active substances may affect bacterial virulence factors other than the glucosyltransferase enzymes [24]. Caries were found to be significantly lower among children who drank a cup of tea immediately after lunch and the tea polyphenols, rather than fluoride, were found to be responsible for the anticariogenic effects [25]. Another study reported that rinsing with 0.2% Chinese green tea while brushing decreased plaque and the gingival index significantly [26].

Tea drinking has been attributed as one of the factors in the declining prevalence of caries in Tunisia [27]. Tea extracts have also been shown to inhibit human salivary amylase and tea consumption may reduce the cariogenic potential of starch-containing foods, such as biscuits and cakes, because tea may reduce the tendency for these foods to serve as slow-release sources of fermentable carbohydrate [28]. It is likely that cariogenic challenge in a cariogenic diet may be overcome by the simultaneous presence of green tea in the diet. An anticariogenic potential of black tea has been suggested in various *in vitro* studies. [20, 29, 30]. Black tea and its polyphenols inhibited growth, acid production, metabolism and glucosyltransferase enzyme activity of Mutans Streptococci and dental plaque bacteria.

Tea is a source of fluoride (F) as well as many other dietary trace elements. The caries-preventive effect of teas was first believed to be due to its fluoride content. More recent studies, however, have pointed out that the polyphenol contents of tea may affect plaque formation and metabolism as well [31]. The commercial tea plant, *Camellia sinensis*, takes up F from the soil by passive diffusion and concentrates it in the leaves by transpiration [32]. Due to differing soils, types of tea leaves, infusion times and methods of analysis, a great deal of variation in tea content has been found. Coupled with the various drinking habits among different people, it is very difficult to calculate the contribution of tea to total fluoride intake. A recent animal study showed that rats consuming black tea (prepared from fluoride-free water) over a 2-week period had a significantly lower rate of caries than those consuming non-fluoridated water. Furthermore, the caries scores in the group receiving tea were significantly greater than those in the group receiving fluoridated water. The authors suggested that black tea consumption attenuates the development of caries in young, caries-prone rats [14]. Wei et al. found a 15-min infusion to result in a mean fluoride concentration of 1.75 p.p.m. for 15 Chinese teas, 1.24 p.p.m. for 11 Ceylon/Indian teas and a negligible F amount for six herbal teas [32]. The bioavailability of fluoride in tea has been said to be approximately 85%. A review by Kavanagh and Renehan lists over 10 papers that measured the fluoride content of various teas [33]. Several studies have also calculated the total F intake from tea consumption.

#### *Tea - Chemistry and Pharmacology*

When using the assumptions of 2.5 cups/day, 150 ml per cup and 2.2 p.p.m. F diluted in half with milk for children, an ingested range of 0.1 mg to 1.08 mg was found. Wei et al. estimated a daily F intake at a level of 1.05 mg [32]. As well as teas are unlikely to cause fluorosis by themselves, but they may be significant contributors to the total fluoride intake of children.

#### **2.2 Tea and gingivitis/periodontal disease**

Periodontal disease (PD) is one of the most omnipresent diseases of mankind, which is also second most common oral disease worldwide, after dental caries. This is a chronic condition in which a multiple and complex group of inflammatory diseases are affecting the periodontal complex i.e., tissue that surround and support the teeth (Periodontium, bone, gingival fibers). Negligence towards this condition may show further deterioration of periodontium leading to progressive loss of the alveolar bone around the teeth and subsequent loss of teeth. In fact, PD remains the most common cause of tooth loss in the world today; in the United States, it has a prevalence of 30–50% of the population and can affect up to 90% of the population worldwide [34].

Researchers have observed that for every one cup of green tea consumed per day, there was a decrease in the indicators of gingival inflammation, in turn reducing the periodontal disease. Green tea catechin has been shown to be bactericidal against *Porphyromonas gingivalis* and Prevotella species *in vitro*. A local slow delivery system of green catechin along with mechanical treatment was found to be effective in improving periodontal status. There was a reduction pocket size and the suppression of peptidase activities in the gingival crevicular fluid [35]. Tea catechins containing the galloyl radical (Epicatechin Gallate [ECG] and Epigallocatechin Gallate [EGCG]) possess the ability to inhibit both eukaryotic and prokaryotic cell-derived collagenase, an enzyme that plays an important role in the disruption of the collagen component in the gingival tissues of patients with periodontal disease [36–38]. Catechin derivatives have been reported to inhibit certain proteases and toxic metabolites of *P. gingivalis* and may reduce periodontal breakdown [39, 40]. Green tea catechins EGCG have also been shown to inhibit protein tyrosine phosphatase in Prevotella intermedia [41]. Zhu et al. have shown that purified tea polyphenols inhibited *in vitro* growth and H2S production of *P. gingivalis* and *Fusobacterium nucleatum* associated with human halitosis [42].

The molecular and cellular effects of green tea on oral cells of smokers were researched [43]. A recent human study investigated the effect of tea polyphenols in the form of chew candies on gingival inflammation over a 4-week period [44]. The approximal plaque index (API) and sulcus bleeding index (SBI) were determined at the end of day 7 and day 28. These authors suggested that tea polyphenols might exert a positive influence on gingival inflammation.

#### **2.3 Oral cancer**

Oral cancer is a global public health problem and relevant to dentists due to proximity of this area to the work carried out by them. It is located within the top 10 ranking incidence of cancers and despite the progress in research and therapy, survival has not improved significantly in the last years, representing a continuing challenge for biomedical science. Oral cancer is a malignant neoplasia, which arises on the lip or oral cavity. It was traditionally defined as a squamous cell carcinoma (OSCC), as 90% of cancers are histologically originated in the squamous cells in the oral cavity [45].

The influence of tea on oral cancer as well as various studies has been summarized in **Tables 1–3** [44, 46–75]. Green tea polyphenols are found to induce

**41**

**Sl no. Author**

1.

The Indian-US Head and Neck Cancer Cooperative Group, 1997

Population based chemo preventive experimental trial—6 months

2. 3. 4. 5. 6.

Li N, Han C, Chen J,

*In vivo* animal experimental

trial—hamsters

Randomized control trial—human—

36

1999

7. 8.

Masuda M, Suzui M,

*In vitro* experimental trial

Weinstein IB, 2001

9. 10. 11. 12.

Lee MJ et al., 2004

*In vivo* cross over

Clinical trial—human

Masuda M et al., 2003

*In vitro* experimental trial

Li N et al., 2002

18 months

*In vivo* experimental trial—hamsters

Hsu SD et al., 2002

*In vitro* experimental trial

Li N et al., 1998

6 months

Li N et al., 1999

Double blind randomized controlled human clinical trial— 6 months

64

China

Tea—3 g/day 1.5% green tea, 0.1% tea pigments,

and 0.5% mixed tea

Mixed tea—3 g/day oral and 0.1%

topical

Egcg—10 microg/ml

Tea extracts, green tea polyphenols,

Selectively induce apoptosis only in oral carcinoma cells, EGCG inhibit

the growth and invasion of oral carcinoma cells

Decreased the number of visible tumors and the tumor volume.

Suppression of cell proliferation, induction of apoptosis, and inhibition

(−)-epigallo-catechin


0.6% green tea powder, 0.6% green

tea powder + 10 mumol curcumin

10 or 30 microg of EGCG

2 g of black tea, 2 g of green tea

of angiogenesis

50% inhibition of growth of carcinoma cells

Concen-trations of catechins (C(max) =

131.0–2.2 micro M) and theaflavins (C(max) =

1.8–0.6 micro M) were observed in saliva in the 1st hour

growth inhibition (P < 0.001)

Yang CS, Lee MJ, Chen L., 1999

*In vivo* experimental trial—human

 6

Khafif A, et al., 1998

*In vitro* experimental trial—mice

EGCG [(−)- epigallocatechin


Green tea

Khafif A et al., 1998

*In vitro* experimental trial

**Type of study**

**Sample**

64

India

Green—3.6 g per day and 5.4 g per day

(−)-epigallocatechin

 -3-gallate (EGCG) from green tea

A reduction of 4.4–8.5-fold in cell cycle of cancer cells

Inhibited cancer cells growth

Increase in (−)-epigallo-catechin (EGC; 11.7–43.9 microg/ml), EGC-

3-gallate (EGCG; 4.8–22 microg/ml), and (−)-epicatechin (EC; 1.8–7.5 microg/ml) levels in saliva

Reduction in size in 37.9% of leckoplakic patients

Reduced buccal pouch tumor burden and the incidence of dysplasia

and oral carcinoma (P < 0.01)

Significant decrease in micronuclei (P < 0.001)

**Country**

**Intervention**

**Outcome**

Feasible

*Tea and Oral Health*

*DOI: http://dx.doi.org/10.5772/intechopen.80998*


#### *Tea and Oral Health DOI: http://dx.doi.org/10.5772/intechopen.80998*

*Tea - Chemistry and Pharmacology*

worldwide [34].

tors to the total fluoride intake of children.

**2.2 Tea and gingivitis/periodontal disease**

*nucleatum* associated with human halitosis [42].

exert a positive influence on gingival inflammation.

When using the assumptions of 2.5 cups/day, 150 ml per cup and 2.2 p.p.m. F diluted in half with milk for children, an ingested range of 0.1 mg to 1.08 mg was found. Wei et al. estimated a daily F intake at a level of 1.05 mg [32]. As well as teas are unlikely to cause fluorosis by themselves, but they may be significant contribu-

Periodontal disease (PD) is one of the most omnipresent diseases of mankind, which is also second most common oral disease worldwide, after dental caries. This is a chronic condition in which a multiple and complex group of inflammatory diseases are affecting the periodontal complex i.e., tissue that surround and support the teeth (Periodontium, bone, gingival fibers). Negligence towards this condition may show further deterioration of periodontium leading to progressive loss of the alveolar bone around the teeth and subsequent loss of teeth. In fact, PD remains the most common cause of tooth loss in the world today; in the United States, it has a prevalence of 30–50% of the population and can affect up to 90% of the population

Researchers have observed that for every one cup of green tea consumed per day, there was a decrease in the indicators of gingival inflammation, in turn reducing the periodontal disease. Green tea catechin has been shown to be bactericidal against *Porphyromonas gingivalis* and Prevotella species *in vitro*. A local slow delivery system of green catechin along with mechanical treatment was found to be effective in improving periodontal status. There was a reduction pocket size and the suppression of peptidase activities in the gingival crevicular fluid [35]. Tea catechins containing the galloyl radical (Epicatechin Gallate [ECG] and Epigallocatechin Gallate [EGCG]) possess the ability to inhibit both eukaryotic and prokaryotic cell-derived collagenase, an enzyme that plays an important role in the disruption of the collagen component in the gingival tissues of patients with periodontal disease [36–38]. Catechin derivatives have been reported to inhibit certain proteases and toxic metabolites of *P. gingivalis* and may reduce periodontal breakdown [39, 40]. Green tea catechins EGCG have also been shown to inhibit protein tyrosine phosphatase in Prevotella intermedia [41]. Zhu et al. have shown that purified tea polyphenols inhibited *in vitro* growth and H2S production of *P. gingivalis* and *Fusobacterium* 

The molecular and cellular effects of green tea on oral cells of smokers were researched [43]. A recent human study investigated the effect of tea polyphenols in the form of chew candies on gingival inflammation over a 4-week period [44]. The approximal plaque index (API) and sulcus bleeding index (SBI) were determined at the end of day 7 and day 28. These authors suggested that tea polyphenols might

Oral cancer is a global public health problem and relevant to dentists due to proximity of this area to the work carried out by them. It is located within the top 10 ranking incidence of cancers and despite the progress in research and therapy, survival has not improved significantly in the last years, representing a continuing challenge for biomedical science. Oral cancer is a malignant neoplasia, which arises on the lip or oral cavity. It was traditionally defined as a squamous cell carcinoma (OSCC), as 90% of cancers are histologically originated in the squamous cells in the oral cavity [45]. The influence of tea on oral cancer as well as various studies has been summarized in **Tables 1–3** [44, 46–75]. Green tea polyphenols are found to induce

**40**

**2.3 Oral cancer**


**43**

**Table 3.** *Review.*

*Tea and Oral Health*

1. Bundgaard T, et al., 1995

2. Ariyawardana A et al., 2007

3. Ide R et al., 2007

of green tea as well as (

*Descriptive studies of tea and oral cancer.*

**Sl no. Author Type of** 

Herzog CR, Yang YM,

6. Boehm K et al., 2009 Systematic

1. Weisburger JH, Chung FL, 2002

2. Chung FL, Schwartz J,

2003

cycle regulator.

**Table 2.**

*DOI: http://dx.doi.org/10.5772/intechopen.80998*

Case control study

Longitudinal study— 10.3 years

apoptosis (programmed cell death) in many types of tumor cells, including oral cancer cells. However, how the normal cells escape the apoptotic effect has not still been understood by the researchers. The effect of extracts and polyphenols

**Sl no. Author Type of study Risk Sample Country Outcome**

HR—0.51 0.60 0.31

OR = 0.45 561

Cases—161 Controls—400

Cross sectional 12,716 Srilanka 46.1 per 1000 for

Denmark Squamous cell

50,221 Japan 37 oral cancer

carcinoma occurence

cases. Did not suggest a prominent inverse association of green tea consumption with oral cancer, although there was a tendency for a reduced risk in women

leukoplakia and 16.4 per 1000 for oral submucous fibrosis

potent green tea polyphenol on normal human keratinocytes and oral carcinoma cells were assessed through assays for cell growth, invasion, combined with apoptosis. It was shown that the green tea and its constituents selectively induce apoptosis, whereas EGCG usually inhibits the growth and invasion of oral car

cinoma cells. This difference in the identification of normal cells and malignant cells by green tea and its constituents was attributed to the induction of p57, a cell

**study**

3. Lodi G et al., 2004 Review Tea Leukoplakia 4. Wu CD, Wei GX, 2007 Review Tea Reduced oral cancer 5. Klass CM, Shin DM Review Green tea Premalignant lesions

review

7. Yang CS et al., 2008 Review Tea and tea

−)-epigallocatechin-3-gallate (EGCG) which is the most

**Input Outcome**

Review Tea Chemo preventive effects of

Tea Reduced oral cancer

Review Tea Cancer

polyphenols

tea and mechanisms

Reduced carcinogenesis



*Tea and Oral Health DOI: http://dx.doi.org/10.5772/intechopen.80998*

#### **Table 2.**

*Tea - Chemistry and Pharmacology*

**42**

**Sl no. Author**

13.

Srinivasan P, Sabitha

*In vivo* experimental trial—rats

KE, Shyamaladevi CS.

1 month

2004

14. 15.

Gonzalez de Mejia E

*In vitro* controlled experimental

et al., 2005

16. 17. 18. 19. 20. **Table 1.**

*Experimental studies for tea and oral cancer.*

Tsao AS et al., 2009

Randomized control human

trial—12 weeks

Ko SY et al., 2007

*In vivo* experimental trial—hamsters

Green tea

Hua Y et al., 2006

*In vitro* experimental trial

Tea polyphenols

Halder A et al., 2005

*In vivo* human experimental

82

India

Black tea

trial—1 year

Hsu S et al., 2005

*In vitro* experimental study

Egcg

study

Babich H et al., 2005

*In vitro* experimental trial

**Type of study**

**Sample**

**Country**

**Intervention** Green tea polyphenols (GTP)

Enhances the cellular thiol status thereby mitigate oral cancer

(200 mg/kg)

Catechin gallate (CG),

Reduced carcinoma HSC-2 cells of oral cavity

epigallocatechin gallate (EGCG),

epigallocatechin (EGC), catechin

(C) and epicatechin (EC)

Yerba mate tea products

Inhibition of topoisomerase II (cancer cell proliferation)

p21WAF1 is involved in EGCG-induced growth arrest of OSC2 cells

Significant decrease in the micronuclei frequency and chromosomal

aberrations, which correlated with the clinical improvement

The human telomerase reverse transcriptase (hTERT) gene in the Tca8113

cancerous cell line was less (0.1 g/l, TP 0.05 g/l)when compared to

controls (0.32 ± 0.05, 0.41 ± 0.04 and 0.72 ± 0.05, respectively) (P < 0.05)

Amyloid precursor protein (APP) expression was also significantly

increased in MBN-induced HBP carcinomas but was significantly reduced

The OPL clinical response rate was higher in all GTE arms (n = 28; 50%)

versus placebo (n = 11; 18.2%; P = 0.09) However, the two higher-dose

GTE arms [58.8% (750 and 1000 mg/m2), 36.4% (500 mg/m2), and 18.2%

(placebo); P = 0.03] had higher responses, improved histology (21.4%

versus 9.1%; P = 0.65)

by tea intake (P < 0.0001)

Green tea extracts at 500, 750, or

1000 mg/m2 or placebo thrice daily

**Outcome**

*Descriptive studies of tea and oral cancer.*

apoptosis (programmed cell death) in many types of tumor cells, including oral cancer cells. However, how the normal cells escape the apoptotic effect has not still been understood by the researchers. The effect of extracts and polyphenols of green tea as well as (−)-epigallocatechin-3-gallate (EGCG) which is the most potent green tea polyphenol on normal human keratinocytes and oral carcinoma cells were assessed through assays for cell growth, invasion, combined with apoptosis. It was shown that the green tea and its constituents selectively induce apoptosis, whereas EGCG usually inhibits the growth and invasion of oral carcinoma cells. This difference in the identification of normal cells and malignant cells by green tea and its constituents was attributed to the induction of p57, a cell cycle regulator.


#### **Figure 1.** *The effect of tea on cancer.*

p57 mediated survival pathway in normal epithelial cells is the reason for the chemopreventive effects of green tea polyphenols in normal cells, while oral carcinoma cells undergo an apoptotic pathway. Regular consumption of green tea has favorable effects in the prevention of oral cancer. The oxidative stress and inflammation in the oral cavity may be reduced in the presence of green tea polyphenols (**Figure 1**). Green tea prevents the transformation of healthy cells to malignant cells and locally facilitates the induction of apoptosis in oral cancer cells.

### **3. Conclusions: tea—a multi edged sword**

Tea is rich in the beneficial polyphenols and similar components that can supplement the recommended 5–10 vegetables and fruits per day. Tea is not a drug. It is a health food, akin to *Rasayanas* known to the ancient Indians. It has shown its effect on various diseases and oral diseases.

The above review also leads us to conclude that this popular beverage can regress tumors directly by inhibiting tumor angiogenesis, blocking metastasis and inducing apoptosis in cancer cells. Thus, tea, previously considered only as a popular beverage, can now emerge as a 'multiedged sword' against the various diseases.

Although there has been a substantial amount of research related to the study of teas and their health benefits, it has been difficult to compare data between laboratories due to the lack of standardization in experimental procedures. Teas used in studies often differed in their types, sources, method of manufacture and procedures for extraction. Analytical data of tea preparations were often not specified or provided, making the comparison of *in vitro* or *in vivo* data difficult among laboratories. Improvement in this aspect and encouragement in designing new multidisciplinary research approaches will strengthen our knowledge concerning this ancient beverage with its many health attributes.

At present, the use of tea in clinical application is still a long way from reality, and further controlled clinical trials in humans are warranted. Furthermore, consumption of tea may have added oral health benefits by controlling 'through prevention' the most prevalent infectious disease of humankind, namely caries considering the Indian scenario. With the added dental health implication among many other bioregulatory functions, tea can be considered as a functional food for oral health.

**45**

**Author details**

New Delhi, India

Aswini Y. Balappanavar

*Tea and Oral Health*

information.

**Acknowledgements**

**Conflict of interest**

No conflict of interest.

*DOI: http://dx.doi.org/10.5772/intechopen.80998*

I acknowledge the various resources from which I have gathered the

provided the original work is properly cited.

\*Address all correspondence to: phdaswini@gmail.com

© 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,

Department of Public Health Dentistry, Maulana Azad Institute of Dental Sciences,

*Tea and Oral Health DOI: http://dx.doi.org/10.5772/intechopen.80998*

## **Acknowledgements**

*Tea - Chemistry and Pharmacology*

**Figure 1.**

*The effect of tea on cancer.*

p57 mediated survival pathway in normal epithelial cells is the reason for the chemopreventive effects of green tea polyphenols in normal cells, while oral carcinoma cells undergo an apoptotic pathway. Regular consumption of green tea has favorable effects in the prevention of oral cancer. The oxidative stress and inflammation in the oral cavity may be reduced in the presence of green tea polyphenols (**Figure 1**). Green tea prevents the transformation of healthy cells to malignant cells

Tea is rich in the beneficial polyphenols and similar components that can supplement the recommended 5–10 vegetables and fruits per day. Tea is not a drug. It is a health food, akin to *Rasayanas* known to the ancient Indians. It has shown its effect

The above review also leads us to conclude that this popular beverage can regress tumors directly by inhibiting tumor angiogenesis, blocking metastasis and inducing apoptosis in cancer cells. Thus, tea, previously considered only as a popular bever-

Although there has been a substantial amount of research related to the study of teas and their health benefits, it has been difficult to compare data between laboratories due to the lack of standardization in experimental procedures. Teas used in studies often differed in their types, sources, method of manufacture and procedures for extraction. Analytical data of tea preparations were often not specified or provided, making the comparison of *in vitro* or *in vivo* data difficult among laboratories. Improvement in this aspect and encouragement in designing new multidisciplinary research approaches will strengthen our knowledge concerning

At present, the use of tea in clinical application is still a long way from reality, and further controlled clinical trials in humans are warranted. Furthermore, consumption of tea may have added oral health benefits by controlling 'through prevention' the most prevalent infectious disease of humankind, namely caries considering the Indian scenario. With the added dental health implication among many other bioregulatory functions, tea can be considered as a functional food for oral health.

age, can now emerge as a 'multiedged sword' against the various diseases.

and locally facilitates the induction of apoptosis in oral cancer cells.

**3. Conclusions: tea—a multi edged sword**

this ancient beverage with its many health attributes.

on various diseases and oral diseases.

**44**

I acknowledge the various resources from which I have gathered the information.

## **Conflict of interest**

No conflict of interest.

## **Author details**

Aswini Y. Balappanavar Department of Public Health Dentistry, Maulana Azad Institute of Dental Sciences, New Delhi, India

\*Address all correspondence to: phdaswini@gmail.com

© 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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[30] Sarkar S, Sett P, Chowdhury T, Ganguly DK. Effect of black tea on teeth. Journal of the Indian Society of Pedodontics and Preventive Dentistry. 2000;**18**:139-140

[31] Yu H, Oho T, Xu LX. Effects of several tea components on acid resistance of human tooth enamel. Journal of Dentistry. 1995;**13**:s101-s105

[32] Wei SHY, Hattab FN, Mellberg JR. Concentration of fluoride and selected other elements in teas. Nutrition. 1989;**5**:237-240

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**46**

*Tea - Chemistry and Pharmacology*

[1] Shukla Y. Tea and cancer

Prevention. 2007;**8**:155-166

[Accessed: 27 July 2018]

137 p. ISBN 7-5085-0835-1

2009;**83**(9):641-720

2010;**38**(2):136-144

chemoprevention. A comprehensive review. Asian Pacific Journal of Cancer [11] Elvin-Lewis M, Steelman R. The anticariogenic effects of tea drinking among Dallas children. Journal of Dental Research. 1968;**65**:198

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[13] Smullen J, Koutsou GA, Foster HA, Zumbé A, Storey DM. The antibacterial activity of plant extracts containing polyphenols against *Streptococcus mutans*. Caries Research.

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**49**

*Tea and Oral Health*

1998;**20**(6):528-534

*DOI: http://dx.doi.org/10.5772/intechopen.80998*

causation by nutritional factors and tobacco products and their prevention by tea polyphenols. Food and Chemical Toxicology. 2002;**40**(8):1145-1154

[61] Li N, Chen X, Han C, Chen J. Chemopreventive effect of tea and curcumin on DMBA-induced oral carcinogenesis in hamsters. Wei Sheng

[62] Masuda M, Suzui M, Lim JT,

inhibits activation of HER-2/neu and downstream signaling pathways in human head and neck and breast carcinoma cells. Clinical Cancer Research. 2003;**15**(9):3486-3491

[63] Chung FL, Schwartz J, Herzog CR, Yang YM. Tea and cancer prevention: Studies in animals and humans. The Journal of Nutrition.

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Biomarkers & Prevention.

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[66] Babich H, Krupka ME, Nissim HA, Zuckerbraun HL. Differential in vitro cytotoxicity of (−)-epicatechin gallate (EPICATECHIN GALLATE (ECG)) to cancer and normal cells from the human oral cavity. Toxicology In Vitro.

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Weinstein IB. Epigallocatechin-3-gallate

Yan Jiu. 2002;**31**(5):354-357

malignant human oral epithelial cells. Carcinogenesis. 1998;**19**(3):419-424

[53] Khafif A, Schantz SP, Al-Rawi M, Edelstein D, Sacks PG. Green tea regulates cell cycle progression in oral leukoplakia. Head & Neck.

[54] Yang CS, Lee MJ, Chen L. Human salivary tea catechin levels and catechin esterase activities: Implication in human cancer prevention studies. Cancer Epidemiology, Biomarkers &

[55] Li N, Sun Z, Han C, Chen J. The chemopreventive effects of tea on human oral precancerous mucosa lesions. Proceedings of the Society for Experimental Biology and Medicine.

Prevention. 1999;**8**(1):83-89

1999;**220**(4):218-224

1998;**27**(3):173-174

[56] Li N, Han C, Chen J. Tea

preparations protect against DMBAinduced oral carcinogenesis in hamsters. Nutrition and Cancer. 1999;**35**(1):73-79

[57] Li N, Sun Z, Liu Z, Han C. Study on the preventive effect of tea on DNA damage of the buccal mucosa cells in oral leukoplakias induce by cigarette smoking. Wei Sheng Yan Jiu.

[58] Masuda M, Suzui M, Weinstein IB. Effects of epigallocatechin-3-gallate on growth, epidermal growth factor receptor signaling pathways, gene expression, and chemosensitivity in human head and neck squamous cell carcinoma cell lines. Clinical Cancer Research. 2001;**7**(12):4220-4229

[59] Hsu SD, Singh BB, Lewis JB, Borke JL, Dickinson DP, Drake L, et al. Chemoprevention of oral cancer by green tea. General Dentistry.

[60] Weisburger JH, Chung FL. Mechanisms of chronic disease

2002;**50**(2):140-146

#### *Tea and Oral Health DOI: http://dx.doi.org/10.5772/intechopen.80998*

*Tea - Chemistry and Pharmacology*

Acta. 2000;**1478**(1):51-60

2003;**51**:1858-1863

2004;**19**:118-120

[37] Demeule M, Brossard M, Page M, Gingras D, Beliveau R. Matrix metalloproteinase inhibition by green tea catechins. Biochimica et Biophysica [44] Krahwinkel T, Willershausen B. The effect of sugar-free green tea chew candies on the degree of inflammation of the gingiva. European Journal of Medical Research. 2000;**5**:463-467

[45] Rivera C. Essentials of oral cancer. International Journal of Clinical and Experimental Pathology.

[46] Bundgaard T, Wildt J, Frydenberg M, Elbrønd O. Case-control study of squamous cell cancer of the oral cavity in Denmark. Cancer Causes & Control.

[47] Ariyawardana A, Sitheeque MA, Ranasinghe AW, Perera I, Tilakaratne WM, Amaratunga EA, et al. Prevalence of oral cancer and pre-cancer and associated risk factors among tea estate workers in the central Sri Lanka. Journal of Oral Pathology & Medicine.

[48] Ide R, Fujino Y, Hoshiyama Y, Mizoue T, Kubo T, Pham TM, et al. A prospective study of green tea consumption and oral cancer incidence in Japan. Annals of Epidemiology. 2007;**17**(10):821-826 Epub 2007 Jul 2

[49] Lodi G, Sardella A, Bez C, Demarosi F, Carrassi A. Interventions for treating oral leukoplakia. Cochrane Database of Systematic Reviews. 2004;**3**:CD001829

[50] Wu CD, Wei GX. Tea as a functional

food for oral health. Nutrition.

[51] Green tea and leukoplakia. The Indian-US Head and Neck Cancer Cooperative Group. American Journal of Surgery. 1997;**174**(5):552-555

[52] Khafif A, Schantz SP, Chou TC, Edelstein D, Sacks PG. Quantitation of chemopreventive synergism

between (−)-epigallocatechin-3-gallate and in normal, premalignant and

2002;**18**(5):443-444

2015;**8**(9):11884-11894

1995;**6**(1):57-67

2007;**36**(10):581-587

[38] Maeda-Yamamoto M, Suzuki N, Sawai Y, Miyase T, Sano M, Hashimoto-Ohta A, et al. Association of suppression of extracellular signal-regulated kinase phosphorylation by epigallocatechin gallate with the reduction of matrix metalloproteinase activites in human fibrosarcoma HT1080 cells. Journal of Agricultural and Food Chemistry.

[39] Okamoto M, Sugimoto A, Leung KP, Nakayama K, Maeda N. Inhibitory effect of green tea catechins on cysteine proteinases in *Porphyromonas gingivalis*. Oral Microbiology and Immunology.

[40] Sakanaka S, Okada Y. Inhibitory effects of green tea polyphenols on the production of a virulence factor of the periodontal-disease-causing anaerobic bacterium *Porphyromonas gingivalis*. Journal of Agricultural and Food Chemistry. 2004;**52**:1688-1692

[41] Okamoto M, Leung KP, Ansai T, Sugimoto A, Maeda N. Inhibitory effects of green tea catechins on protein tyrosine phosphatase in *Prevotella intermedia*. Oral Microbiology and Immunology. 2003;**18**:192-195

[42] Zhu M, Wei GX, Wu CD. Effect of tea polyphelonls on growth and H2S production of halitosis causing bacteria. In: Presented at American Society for Microbiology 103rd General Meeting;

[43] Schwartz JL, Baker V, Larios E, Chung FL. Molecular and cellular effects of green tea on oral cells of smokers: A pilot study. Molecular Nutrition Food Research. 2005;**49**:43-51

Washington, DC. 2003

**48**

malignant human oral epithelial cells. Carcinogenesis. 1998;**19**(3):419-424

[53] Khafif A, Schantz SP, Al-Rawi M, Edelstein D, Sacks PG. Green tea regulates cell cycle progression in oral leukoplakia. Head & Neck. 1998;**20**(6):528-534

[54] Yang CS, Lee MJ, Chen L. Human salivary tea catechin levels and catechin esterase activities: Implication in human cancer prevention studies. Cancer Epidemiology, Biomarkers & Prevention. 1999;**8**(1):83-89

[55] Li N, Sun Z, Han C, Chen J. The chemopreventive effects of tea on human oral precancerous mucosa lesions. Proceedings of the Society for Experimental Biology and Medicine. 1999;**220**(4):218-224

[56] Li N, Han C, Chen J. Tea preparations protect against DMBAinduced oral carcinogenesis in hamsters. Nutrition and Cancer. 1999;**35**(1):73-79

[57] Li N, Sun Z, Liu Z, Han C. Study on the preventive effect of tea on DNA damage of the buccal mucosa cells in oral leukoplakias induce by cigarette smoking. Wei Sheng Yan Jiu. 1998;**27**(3):173-174

[58] Masuda M, Suzui M, Weinstein IB. Effects of epigallocatechin-3-gallate on growth, epidermal growth factor receptor signaling pathways, gene expression, and chemosensitivity in human head and neck squamous cell carcinoma cell lines. Clinical Cancer Research. 2001;**7**(12):4220-4229

[59] Hsu SD, Singh BB, Lewis JB, Borke JL, Dickinson DP, Drake L, et al. Chemoprevention of oral cancer by green tea. General Dentistry. 2002;**50**(2):140-146

[60] Weisburger JH, Chung FL. Mechanisms of chronic disease causation by nutritional factors and tobacco products and their prevention by tea polyphenols. Food and Chemical Toxicology. 2002;**40**(8):1145-1154

[61] Li N, Chen X, Han C, Chen J. Chemopreventive effect of tea and curcumin on DMBA-induced oral carcinogenesis in hamsters. Wei Sheng Yan Jiu. 2002;**31**(5):354-357

[62] Masuda M, Suzui M, Lim JT, Weinstein IB. Epigallocatechin-3-gallate inhibits activation of HER-2/neu and downstream signaling pathways in human head and neck and breast carcinoma cells. Clinical Cancer Research. 2003;**15**(9):3486-3491

[63] Chung FL, Schwartz J, Herzog CR, Yang YM. Tea and cancer prevention: Studies in animals and humans. The Journal of Nutrition. 2003;**133**(10):3268S-3274S

[64] Lee MJ, Lambert JD, Prabhu S, Meng X, Lu H, Maliakal P, et al. Delivery of tea polyphenols to the oral cavity by green tea leaves and black tea extract. Cancer Epidemiology, Biomarkers & Prevention. 2004;**13**(1):132-137

[65] Srinivasan P, Sabitha KE, Shyamaladevi CS. Therapeutic efficacy of green tea polyphenols on cellular thiols in 4-nitroquinoline 1-oxide-induced oral carcinogenesis. Chemico-Biological Interactions. 2004;**149**(2-3):81-87

[66] Babich H, Krupka ME, Nissim HA, Zuckerbraun HL. Differential in vitro cytotoxicity of (−)-epicatechin gallate (EPICATECHIN GALLATE (ECG)) to cancer and normal cells from the human oral cavity. Toxicology In Vitro. 2005;**19**(2):231-242

[67] Gonzalez de Mejia E, Song YS, Ramirez-Mares MV, Kobayashi H. Effect of yerba mate (*Ilex paraguariensis*) tea

on topoisomerase inhibition and oral carcinoma cell proliferation. Journal of Agricultural and Food Chemistry. 2005;**53**(6):1966-1973

[68] Hsu S et al. Role of p21WAF1 in green tea polyphenol-induced growth arrest and apoptosis of oral carcinoma cells. Anticancer Research. 2005;**25**(1A):63-67

[69] Halder A, Raychowdhury R, Ghosh A, De M. Black tea (*Camellia sinensis*) as a chemopreventive agent in oral precancerous lesions. Journal of Environmental Pathology, Toxicology and Oncology. 2005;**24**(2):141-144

[70] Hua Y, Jianhua L, Qiuliang W, Jun F, Zhi C. Effects of tea polyphenols on telomerase activity of a tongue cancer cell line: A preliminary study. International Journal of Oral and Maxillofacial Surgery. 2006;**35**(4):352- 355. Epub 2005 Nov 8

[71] Ko SY, Chang KW, Lin SC, Hsu HC, Liu TY. The repressive effect of green tea ingredients on amyloid precursor protein (APP) expression in oral carcinoma cells in vitro and in vivo. Cancer Letters. 2007;**245**(1-2):81-89. Epub 2006 Feb 3

[72] Klass CM, Shin DM. Current status and future perspectives of chemoprevention in head and neck cancer. Current Cancer Drug Targets. 2007;**7**(7):623-632

[73] Yang CS, Ju J, Lu G, Xiao H, Hao X, Sang S, et al. Cancer prevention by tea and tea polyphenols. Asia Pacific Journal of Clinical Nutrition. 2008;**17**(Suppl 1): 245-248

[74] Tsao AS, Liu D, Martin J, Tang XM, Lee JJ, El-Naggar AK, et al. Phase II randomized, placebo-controlled trial of green tea extract in patients with highrisk oral premalignant lesions. Cancer Prevention Research (Philadelphia, Pa.). 2009;**2**(11):931-941

[75] Boehm K, Borrelli F, Ernst E, Habacher G, Hung SK, Milazzo S, et al. Green tea (*Camellia sinensis*) for the prevention of cancer. Cochrane Database of Systematic Reviews. 2009;**3**:CD005004

**51**

**1.1 Theaflavins**

**Chapter 5**

**Abstract**

Black Tea: Chemical and

Pharmacological Appraisal

*Rabia Shabir Ahmed, Muhammad Haseeb Ahmad,* 

*Muhammad Asif Khan and Muhammad Shahbaz*

the black tea chemistry for elucidating its pharmacological worth.

**1. Chemical illustration of black tea**

**Keywords:** black tea, catechins, theaflavins, oxidative stress, metabolic syndromes

Black tea is manufactured by the fermentation of green tea involving two steps; oxidation and polymerization [1, 2]. The oxidation involves enzymatic catalysis of polyphenol while the polymerization, involves a nucleophilic addition and further oxidized by oxygen or hydrogen peroxide, Black tea polyphenols consist of 2–6% theaflavins, 12–18% thearubigins, 5–10% catechins, 6–9%flavonols, 10–12% phenolic acids, 12–14% proteins, 8–12% methylxanthines, 15–20% fiber, 2–5% alkaloids [3].

Theaflavin is an important antioxidant and metal chelating polyphenol present in black tea due to the presence of hydroxy groups and gallic acid moiety [3]. The structures of theaflavins possess benzotropolone nucleus that are formed through the co-oxidation of selected catechin pairs, one with a vic-trihydroxyphenyl structure, and the other with an ortho-dihydroxyphenyl moiety [4, 5]. Theaflavins including theaflavin, theaflavin-3-gallate, theaflavin-3-gallate, and theaflavin-3,3-digallate,

*Ali Imran, Muhammad Umair Arshad, Ghulam Hussain,* 

*Bilal Rasool, Muhammad Imran, Qasim Ali, Jazia Naseem,* 

*Darosham Sohail, Sara Ishtiaq, Neelam Faiza, Usman Naeem,* 

Medicinal plants are gaining popularity as folk medicine due to future demand to get rid of synthetic health promoting medicines. Nowadays, black tea is gaining interest as the most frequently consumed therapeutic drink after the water. The importance of black tea is due to existence of flavonoids such as (Thearubigins (TRs) and theaflavins (TFs) and catechins) that are the main therapeutic agents and are more bio-direct and stable compounds compared to those exist in other herbal plants alongside some other promising compounds which enhance is credentials as therapeutic drug. Numerous scientific explorations have elucidated the biological worth of these bioactive moieties against plethora of ailments with special reference to metabolic disorder. The mandate of current chapter is to discuss

## **Chapter 5**

*Tea - Chemistry and Pharmacology*

2005;**53**(6):1966-1973

2005;**25**(1A):63-67

355. Epub 2005 Nov 8

Epub 2006 Feb 3

2007;**7**(7):623-632

2009;**2**(11):931-941

245-248

on topoisomerase inhibition and oral carcinoma cell proliferation. Journal of Agricultural and Food Chemistry.

[75] Boehm K, Borrelli F, Ernst E, Habacher G, Hung SK, Milazzo S, et al. Green tea (*Camellia sinensis*) for the prevention of cancer. Cochrane Database of Systematic Reviews.

2009;**3**:CD005004

[68] Hsu S et al. Role of p21WAF1 in green tea polyphenol-induced growth arrest and apoptosis of oral carcinoma cells. Anticancer Research.

[69] Halder A, Raychowdhury R, Ghosh A, De M. Black tea (*Camellia sinensis*) as a chemopreventive agent in oral precancerous lesions. Journal of Environmental Pathology, Toxicology and Oncology. 2005;**24**(2):141-144

[70] Hua Y, Jianhua L, Qiuliang W, Jun F, Zhi C. Effects of tea polyphenols on telomerase activity of a tongue cancer cell line: A preliminary study. International Journal of Oral and Maxillofacial Surgery. 2006;**35**(4):352-

[71] Ko SY, Chang KW, Lin SC, Hsu HC, Liu TY. The repressive effect of green tea ingredients on amyloid precursor protein (APP) expression in oral carcinoma cells in vitro and in vivo. Cancer Letters. 2007;**245**(1-2):81-89.

[72] Klass CM, Shin DM. Current status and future perspectives of chemoprevention in head and neck cancer. Current Cancer Drug Targets.

[73] Yang CS, Ju J, Lu G, Xiao H, Hao X, Sang S, et al. Cancer prevention by tea and tea polyphenols. Asia Pacific Journal of Clinical Nutrition. 2008;**17**(Suppl 1):

[74] Tsao AS, Liu D, Martin J, Tang XM, Lee JJ, El-Naggar AK, et al. Phase II randomized, placebo-controlled trial of green tea extract in patients with highrisk oral premalignant lesions. Cancer Prevention Research (Philadelphia, Pa.).

**50**
