EVIDENCE-BASED HEALTH BENEFITS OF MULTIFACETED PLANT GREEN TEA: A REVIEW

EVIDENCE-BASED HEALTH BENEFITS OF MULTIFACETED PLANT GREEN TEA: A REVIEW

Aakriti Thakur *, Shweta Aggarwal and Aakrshan Kumar

L. R. Institute of Pharmacy, Solan, Himachal Pradesh, India.

ABSTRACT: In response to the increasing popularity and greater demand for medicinal plants, several conservation groups recommend cultivating wild medicinal plants. Green Tea is among the most ancient and popular therapeutic beverages worldwide. This product is made from the plant leaf called “Camellia sinensis.” It can be prepared as a drink, which can have many systemic health effects or an “extract” can be made from the leaves for medicine. Green tea contains thousands of bioactive ingredients, which are almost contributed by polyphenols, which play a key role in preventing and treating many diseases. This literature review aimed to illustrate the phytoconstituent and marketed products of the plant “Green tea”.

Keywords: Camellia sinensis, Green Tea, Theaceae, Medicinal properties

INTRODUCTION: In past times, plants have been a good source of medicine. Ayurveda and other Indian literature mention the use of plants in the treatment of various human diseases. India has about 45,000 plant species, and several have been claimed to possess medicinal effects ¹. Population rise, inadequate supply of drugs, high cost of treatment, and drug resistance encountered in synthetic drugs have led to an elevated emphasis on using plants to treat human diseases. India is one of the ancient civilizations known for its rich repository of medicinal plants ². The Ancient Chinese Proverb ‘Better to be deprived of food for three days than tea for one’ shows the importance of tea in the day-to-day life of the Chinese. The Chinese have known about the medicinal benefits of green tea since ancient times, using it to treat everything from headaches to depression ³. Tea is one of the most commonly consumed drinks on the earth, next to water and well ahead of coffee, beer, wine, and carbonated soft drinks. Camellia sinensis is a species of plant whose leaves and leaf buds are used to make Chinese tea. It is of the genus Camellia, a genus of flowering plants in the family Theaceae. Common names include tea plant, tea tree, and tea shrub ^{3, 4}. The cultivation of tea plants is economically important in many countries, and the tea plant Camellia sinensis is grown in as many as 30 countries, as shown in Fig. 1 and 2.

Four types of tea are produced from this same plant, depending on how the tea leaves are processed ^{4, 5}. These are white, green, oolong, and black tea. White tea is produced from very young leaves and buds that have not yet turned green, and the only processing is drying. Oolong tea is made from partially fermented mature leaves, and black tea is from fully fermented mature leaves. Green tea is produced from mature leaves with minimal processing (only drying) ⁶.

Green tea, which makes up around 20% of tea production worldwide, is consumed mainly in China, Korea, and Japan. Black tea contains up to three times the amount of caffeine as green tea. Black, green, and oolong tea are all excellent sources of vitamin C ⁷.

FIG. 1: CAMELLIA SINENSIS                         

FIG. 2: FLOWER OF CAMELLIA SINENSIS

The chemical composition of green tea varies with climate, season, horticultural practices, and position of the leaf on the harvested shoot ⁸. The most relevant components of green tea medicinally are the polyphenols, with the flavonoids being the most important. The most pertinent flavonoids are the catechins, which comprise 80% -90% of the flavonoids and approximately 40% of the water-soluble solids in green tea ^{9, 10, 11}.

The health benefits of green tea depend on its bioavailability after consumption. The catechins and their metabolites may be detected in blood plasma, urine, and tissues. The four major catechins in green tea are (-) – epicatechin, (-) – epicatechin -3-gallate, (-) – epigallocatechin and (-) – epigallocatechin-3- gallate (EGCG). EGCG is the primary component, accounting for 40% of the polyphenolic mixture ¹². One cup of green tea usually contains about 300-400mg of polyphenols, which are considered non-toxic. Polyphenols are quickly oxidized after harvesting due to the enzyme polyphenol oxidase, and tea leaves are steamed at high temperatures to evaluate this enzyme ¹³. Other compounds are alkaloids (caffeine, theophylline, and theobromine), amino acids, carbohydrates, proteins, chlorophyll, volatile organic compounds, fluoride, aluminum, minerals, and trace elements ¹⁴.

Health Benefits of Green Tea: The importance of green tea lies in the fact that it is rich in catechin, polyphenols, and especially EGCG ¹. The EGCG is an important antioxidant: besides slowing the growth of cancer cells, it kills cancer cells without injuring healthy tissue. It has also successfully lowered LDL and cholesterol levels, inhibiting the unusual formation of blood clots, depletion of platelet aggregation, lipid regulation, and inhibition of proliferation and passage of smooth muscle cells ^{5, 6}. Inhibition of rare blood clot formation is important when considering that thrombosis (formation of abnormal blood clots) is the leading cause of heart attacks and stroke ¹⁵. Green tea’s chemical composition is highly complex due to the abundance of different classes of chemical compounds, which are illustrated below ^16-20.

TABLE 1: CHEMICAL COMPOSITION OF GREEN TEA LEAVES

Polyphenols: These represent the most crucial group of green tea leaf constituents, and thus they are considered the approved dietary source of polyphenols that account for 50–70% of tea aqueous extract. Mostly, these polyphenols are flavonoids that are biosynthetically constructed in considerable quantities ranging from 0.5% to 1.5%, with more than 4000varieties ²¹. The most abundant flavonoids in green tea contain catechins (flavan-3-ols), which constitute about 30–40% of its dry weight ²².

Tannins are the second most significant polyphenols present in tea products. In inclusion, phenolic acids comprising caffein acid (5), chlorogenic acid (6), coumaric acid (7), gallic acid (GA) (8), and quinic acid ester (9), as well as flavanols represented mostly by kaempferol (10), myricetin (11), and quercetin (12), are also found ^{23, 24, 25}. Nagma Khan et al. researched (2018) on the anticarcinogenic effects of tea polyphenols ²⁶. She proved in in-vitro studies that (ECG) epicatechin-3-gallate, a natural polyphenolic component of green tea, inhibited the invasion of (NSCLC) non-small cell lung cancer cells by suppressing the levels of matrix metalloproteinase (MMP)-2 and urokinase-type plasminogen activator (uPA) ²⁷.

Mukhtar and Ahmad, 2000; Khan et al., 2006 researched green tea’s anticarcinogenic properties. Some epidemiological studies also support tea’s protective role against cancer development. Studies conducted in Asia, where green tea is consumed frequently and in large amounts, tend to show a beneficial effect on cancer prevention ³⁸.

Nagma Khan researched (2018) on the antidiabetic effects of tea polyphenols. Diabetes is one of the major health problems worldwide. Type-1 diabetes is not preventable and is treated by insulin supplementation. However, type-2 diabetes can be prevented or reversed by altering diet and managing lifestyle factors. EGCG has been reported to inhibit starch hydrolysis and acted as an inhibitor by binding to the active site of α-amylase and α-glucosidase. The antidiabetic action of EGCG was explored in a high-fat diet and streptozotocin (STZ)-induced type-2 diabetes. Treatment with EGCG enhanced glucose homeostasis and repressed the process of gluconeogenesis and lipogenesis in the liver. It also activated PXR/CAR, accompanied by upgrading PXR/CAR-mediated phase II drug metabolism enzyme expression in the small intestine and liver, relating SULT1A1, UGT1A1, and SULT2B1b ²⁹. The antihyperglycemic effect of polyphenols was reported by Gomes et al. ⁹³. EGCG inhibited intestinal glucose uptake by the sodium-dependent glucose transporter SGLT1, indicating its increase in controlling blood sugar ⁹⁴.

Logesh Rajan researched green tea polyphenols’ activity for cardiometabolic health in 2022. Cardiovascular disease (CVD) is a chronic severe multifactorial disease that adversely affects an individual’s health, well-being, and lifestyle. The world health organization (WHO) projected cardiovascular diseases as the primary cause of death ²⁸.

Christy Tangney researched green tea polyphenols’ activity on cardiovascular and inflammation in 2015. Atherosclerosis, the pathological condition often underlying cardiovascular disease (CVD), is a chronic inflammatory condition involved in initiating and perpetuating atherosclerotic lesions, which may erode or rupture, leading to clinical events such as angina, myocardial infarction or cerebrovascular attack. Because a poor quality diet, smoking, and physical inactivity account for much of the modifiable CVD risk, the role of diets rich in bioactive compounds in maintaining or improving cardiovascular health is of utmost interest. As this underlying chronic inflammation plays a crucial role in the development and progression of CVD, bioactive compounds with anti-inflammatory properties, such as polyphenols.

Sabu M. C. researched the antidiabetic activity of green tea polyphenols in November 2002. In his in vitro studies, he found that an aqueous solution of green tea polyphenols (GTP) would inhibit lipid peroxidation and scavenge hydroxyl superoxide radicals ²⁹.

Badriyah Shadid Alotaibi researched green tea polyphenols’ activity for cardiovascular diseases in 2021. Polyphenols have long been recognized as health-promoting entities, including beneficial effects on cardiovascular disease. Still, their reputation has been boosted recently following several encouraging clinical studies in multiple chronic pathologies that seem to validate efficacy. The health benefits of polyphenols have been linked to their well-established potent antioxidant activity.

Peter W. Taylor carried out a study on green tea polyphenols’ activity for antimicrobial properties in 2009. Studies conducted over the last 20 years have shown that the green tea polyphenolic catechins, in particular (−)-epigallocatechingallate (EGCg) and (−)-epicatechingallate (ECg), can inhibit the growth of a wide range of Gram-positive and Gram-negative bacterial species with moderate potency. Evidence suggests these molecules may help control common oral infections, such as dental caries and periodontal disease. Sub-inhibitory concentrations of EGCG and ECG can suppress the expression of bacterial virulence factors and can reverse the resistance of the opportunistic pathogen Staphylococcus aureus to β-lactam antibiotics.

Jing Luo performed a study on green tea polyphenols’ activity for anti-aging properties in 2021. Polyphenols are the largest, most studied group of naturally occurring antioxidants, which can be structurally categorized into phenolic acids, flavonoids, stilbenes, lignans, and other polyphenols with a hydroxyl group(s) attached to the carbon atom on the aromatic ring ¹⁰. It was reported that the dietary consumption of polyphenols is much higher than the daily intake of several essential micronutrients, such as vitamins C, E, and carotenoids ¹¹. Over the past two decades, polyphenolic compounds have attracted considerable research interest because of their wide distribution in different foods and their potent antioxidant properties ¹¹. In addition, polyphenols were reported to modulate energy metabolism in a manner favorable for well-being and longevity and reduce the risk of aging-related chronic diseases ¹².

Xanthine Bases/Purine Alkaloids: They are usually represented by caffeine, the second principal constituent of the dry leaf; its metabolites, theophylline, and theobromine, are also in minor amounts ³⁶. Xanthine alkaloids are a combination of an imidazole ring and pyrimidine rings. The class of xanthine alkaloids mostly contains caffeine, theobromine, and theophylline ³⁷. The caffeine content in coffee is about 0.4-2.4% dry weight. The content of caffeine in young leaves of camellia sinensis, camellia assamica, and camellia aliens is 2%-3% dry weight. Still, it presents less than 0.02% in camellia kissi, while caffeine content in tea (infusion) is between 1.0% and 3.5% of the composition ^{38, 39}.

The interesting fact is that methylxanthines produce significant biological results. Caffeine is used as an analgesic, and it is used along with some other analgesics such as paracetamol, ibuprofen, or acetylsalicylic acid ⁴⁰. Methylxanthines also possess psychostimulatory activity. The procedure of adenosine receptor (A1 and A2A receptor) antagonism was suggested behind the neuroprotective effects of caffeine ⁴¹. However, the useful effects justified the protection against blood-brain barrier dysfunction. It is clear from the more recent animal and epidemiologic studies that there is a link between midlife caffeine consumption and lower disease incidence. Methylxanthines have also been used for respiratory diseases ^{42, 43, 44}.

Gangchen et al. (2015) researched green tea polyphenols showing that it decreases uric acid level through xanthin oxidase. Green tea is in Chinese material media, mainly inducing urination and quenching thirst ⁴⁵.

Shu-Hua Ouyang (2021) studiedthe antidepressant purine effect on alkaloids from green tea. He investigated the antidepressant-like effects and mechanism of theacrine in chronic unpredictable mild stress ⁴⁶.

Triterpenoid Saponins: They are constituted by floratheasaponin A, B, C, D, E, and F (21–26), which exist at high concentrations in seeds and flowers ⁴⁷.

Tea plants have a collection of more than 70 different saponins with tissue-specific and maturation-specific distribution (Guo et al., 2018) ⁴⁸. A recent study showed evidence of 50 putative saponins in tea extracts that could be detected with ultrahigh-performance liquid chromatography coupled tandem mass spectrometer (UPLC–MS/MS) (Wu et al. 2019). The researchers used LC–MS/MS to understand which tea saponin molecules are present in tea tissues and infusions that are taken up by beverage drinkers. They identified saponin molecules according to MS spectra of relative peaks and retention times (Wu et al. 2019) from two different types of green teas (YR and LGP) ^49-55. Since, there are reports on the anticancer effect of tea saponins from Camellia species and their bioactive mechanism (Murakami et al. 2000; Ghosh et al. 2006; Morikawa et al. 2007; Zhao et al. 2015; Matsuda et al. 2016; Jia et al. 2017; Cui et al. 2018), we then tested the anticancer activity of tea whole saponin extracts by measuring their cytotoxicity ⁵⁶. Some tea saponins were reported to have a potent result in inhibiting cancer cell proliferation and inducing apoptosis in cancer cells (Ghosh et al. 2006; Zhao et al. 2015; Cui et al. 2018) ⁵⁷. Saponins were used in a serial concentration study to treat human TSCC cell lines (TCA8113) and hepatocellular carcinoma cell lines (HepG2) and to examine their cytotoxicity activity ⁵⁸. They notice clear inhibitory effects of total tea saponins on the proliferation of both human cell lines, although at different sensitivities. When TCA8113 cells were treated with 0.025mg/mL solution made of tea total saponin extract powder, about 75% of the cells survived ⁵⁹. When the concentration reached 0.05mg/mL, only 20% of the cells survived. The calculated IC₅₀ against TCA8113 cells was about 29.20lg/ml ₆₀. When HepG2 cells were treated with 0.01mg/mL total saponin extract solution, about 70% of cancer cells remained alive. When the concentration reached 0.05mg/mL, only 18% of the cells survived. When 0.05mg/mL was applied to HepG2 cells, the cell survival rate decreased rapidly to less than 12%. The IC50 for TCA8113 cells was much higher than that against HepG2 cells, which was 17.54lg/ml ^61-66.

Amino Acids: Amino acids constitute about 1–4% of dry weight and are represented by arginine, aspartic acid, glutamic acid, glutamine, and serine, as well as theanineor 5-Nethylglutamine, which account for more than 90% of the whole amino acids present in the leaves of C. sinensis ⁶⁷. It is worth mentioning that theanine is the major amino acid that exists in the largest amounts, comprising about 1–2% of the dry weight of the green tea leaf, and thus it is considered the third major constituent of dry leaf. Furthermore, it is recognized to be the only amino acid that slowly exists in tea plants to which green tea’s flavor and exotic taste are attributed ^{68, 69}. Tryptophan, glycine, tyrosine, valine, leucine, threonine, and lysineare also found ⁷⁰.

L-THE was first isolated and identified in 1949 as a water-soluble non-proteinogenic amino acid predominantly found in the tea plant (Camellia sinensis) and responsible for a unique taste similar to the savory taste sensation that monosodium glutamate produces known as ‘umami’ ⁷¹. According to the universal nomenclature of the International Union of Pure and Applied Chemistry, L-THE is ‘2-amino-4-(ethylcarbamoyl) butyric acid.’ It is referred to by many different names, including ‘gammaglutamylethylamide’ and ‘gamma-glutamyl-L-ethyl amide’ reflecting the presence of glutamine, a conditionally essential amino acid found as a core unit in its structure ^{72, 73}. Theanine may occur as a racemic mix of its L- and D- enantiomers that compete for absorption and urinary excretion. D- enantiomer is reported to be metabolized faster, while L- is preferentially metabolized by kidneys ⁷⁴.

The potential health benefits associated with the consumption of L-THE include improvements in emotional status, quality of sleep, suppression of hypertension, and improvements in mood and cognition ⁷⁵. Additionally, consuming L-THE in combination with caffeine promotes antioxidant and anti-inflammatory activity in the brain, possibly reducing the risk of cognitive impairment ^{75, 76}. The current evidence on the consumption of L-THE in humans and its effects on stress and anxiety is equivocal. To date, the majority of evidence is based on animal research, which has commonly used pure L-THE, and in combination with other bioactive such as caffeine and catechins that can potentially have synergistic and, in some cases, potentially antagonistic effects ^77-80. Essential amino acids are mainly responsible for stimulating muscle protein anabolism in the aged (Volpi et al., 2003). It is considered that 15 g of essential amino acids taken as a bolus is required for maximum stimulation of muscle protein synthesis (Wolfe, 2002). This indicates that the quality of protein is critical in the diet of older people ^{80, 81, 101}.

Studies on Beneficial Effects of Green Tea Extracts: Studies using animal models have shown that green tea catechins may offer some protection against degenerative diseases ²⁹. Several studies have shown that green tea has anti-hepatotoxicity ²⁹, protective ²⁹ hepatoma anti-inflammatory properties after cancer onset and hypolipidemic activity in mice treated with liver disease. Green tea catechins may also act as immunomodulators for immunosuppression therapy with antineoplastic agents ³⁰ and tumor modification or carcinogen therapy ²⁹. Additionally, green tea, extracts, and isolates effectively prevent oxidative stress ³¹ and neurological problems ³².

Green tea consumption has also been associated with preventing many types of cancer, including lung, colon, esophagus, mouth, stomach, small intestine, kidney, pancreas, and mammary glands ³³. Several epidemiological studies and clinical trials have shown that green tea (and, to a lesser extent, black tea and oolong tea) can reduce the risk of many chronic diseases ³⁴. This beneficial effect was attributed to many polyphenols, which are powerful antioxidants. In particular, green tea can lower blood pressure, reducing the risk of stroke and coronary heart disease. Some animal studies have suggested that green tea may protect against the development of coronary heart disease by reducing blood glucose levels and body weight ³⁵. However, all these data are based on middle-aged animal populations, not older populations, whose nutritional status tends to be more adversely affected by age-related biological and socioeconomic factors ³⁶.

Tea components have antioxidant, antimutagenic, and anticarcinogenic effects and could protect humans from the risk of cancer caused by environmental agents ³⁷. Sano et al. ³⁸ reported the inhibitory effects of green tea leaves against tert-butyl hydroperoxide-induced lipid peroxidation, and a similar antioxidant effect on the kidney was observed after the oral administration of the major tea polyphenol EGCG. The active oxygen method tested the antioxidant efficiency of raw catechin powder and individual catechins. Crude catechins reduced peroxide formation much more effectively than dl-α-tocopherol ³⁹. Shim et al. ⁴⁰ studied the chemopreventive effect of green tea among cigarette smokers and found that it could block the cigarette-induced increase in sister chromatid exchange frequency.

In humans, Hirasawa and Takada ⁴⁹ studied the antifungal activity of green tea catechins against Candida albicans and the benefit of combined treatment with catechins and lower doses of antifungals, which may help avoid antifungal side effects. Green tea consumption is also associated with increased bone mineral density. It has been identified as an independent protective factor against hip fracture risk, independent of smoking, hormone replacement therapy, drinking coffee, and adding milk to tea ⁵⁰. Park et al. ⁵¹ observed the positive effects of green tea extracts and GTP on bone cell proliferation and activity. The proliferation of hepatic stellate cells is closely related to the progression of liver fibrosis in chronic liver diseases, and EGCG has a potential inhibitory effect on the proliferation of these cells ^{52, 53}.

Tea has been shown to have anticarcinogenic effects against breast cancer in experimental studies ⁶². However, there has been conflicting epidemiological evidence that tea protects against breast cancer ⁶². A case-control study was conducted in Southeast China between 2004 and 2005 ⁶³. Incident cases included 1009 patients aged 20-87 years with histologically confirmed breast cancer and 1009 age-matched controls of healthy women randomly selected from breast clinics.

Hsu et al. ⁶⁴ demonstrated the effects of decaffeinated green tea extract (catechin) supplementation on hemodialysis-induced reactive oxygen species, atherosclerotic disease risk factors, and pro-inflammatory cytokines. The Pharma-cokinetics of a single oral dose of catechins were compared between healthy subjects and hemodialysis patients. The authors compared the antioxidant effects of three doses (0, 455, and 910 mg) of oral catechins with oral vitamin C (500 mg) during hemodialysis.In a study by Sabu et al. ⁸⁵, the administration of GTP (500 mg/kg) to normal rats significantly increased glucose tolerance at 60 min. GTPs were also found to significantly reduce serum glucose levels in alloxan diabetic rats at a dose of 100 mg/kg. Continued daily administration (15 days) of the extract at a dose of 50 or 100 mg/kg resulted in a 29% and 44% reduction of the elevated serum glucose level caused by alloxan administration.

A study by Waltner-Law et al. ⁹¹ provided convincing in vitro evidence that EGCG reduces glucose production in H4IIE rat hepatoma cells. Researchers have shown that EGCG mimics insulin increases tyrosine phosphorylation on the insulin receptor and insulin receptor substrate, and decreases gene expression of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase. Recently, green tea and green tea extracts have been shown to beneficially modify glucose metabolism in experimental models of type II diabetes mellitus ^{35, 100}. Lambert et al. ¹⁰² demonstrated that intragastric administration of EGCG at a dose of 75 mg/kg resulted in a Cmax of 128 mg/L of total plasma EGCG and a terminal half-life of 83 min. Moreover, in humans, oral EGCG intake at a dose of 50 mg (0.7 mg/kg) resulted in a Cmax of 130 mg/L of total plasma EGCG and a terminal half-life of 112 min ¹⁰⁰.

TABLE 2: EFFECTS OF GREEN TEA COMPONENTS

TABLE 3: MARKETED PRODUCTS OF GREEN TEA EXTRACT

CONCLUSION: Green tea catechins have proved to be most versatile in providing health benefits. This means that there are potential health benefits for everyone in the consumption of green tea. Even moderate consumption (drinking 1–2 cups of tea per day) may have benefits. Fortunately, a wide variety of research has been performed using green tea catechins. This article shows that green tea has its place in both the conventional and alternative medical communities and in the modern world believing in the adage and preservative measures.

ACKNOWLEDGEMENT: Nil

CONFLICTS OF INTEREST: Nil  

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     Thakur A, Aggarwal S and Kumar A: Evidence-based health benefits of multifaceted plant green Tea: A REVIEW. Int J Pharm Sci & Res 2024; 15(5): 1304-14. doi: 10.13040/IJPSR.0975-8232.15(5).1304-14.

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