Camellia sinensis: History
View Latest Version
Please note this is an old version of this entry, which may differ significantly from the current revision.
Subjects: Biology
Contributor:
Mohamed Ashour

Tea, Camellia sinensis, which belongs to the family Theaceae, is a shrub or evergreen tree up to 16 m in height. Green tea is very popular because of its marked health benefits comprising its anticancer, anti-oxidant, and antimicrobial activities, as well as its effectiveness in reducing body weight. Additionally, it was recognized by Chinese people as an effective traditional drink required for the prophylaxis against many health ailments. This is due to the complex chemical composition of green tea, which comprises different classes of chemical compounds, such as polyphenols, alkaloids, proteins, minerals, vitamins, amino acids, and others. The beneficial health effects of green tea ultimately led to its great consumption and increase its liability to be adulterated by either low-quality or non-green tea products with concomitant decrease in activity.

  • biological activity
  • Camellia sinensis
  • phytochemistry
  • quality control

1. Introduction

Natural products were widely employed for many centuries in home remedies, as well as in over-the-counter drug products and as raw materials for the manufacturing of various pharmaceuticals, cosmeceuticals, and nutraceuticals, both in developed as well as developing countries [1][2]. They provide a cost-effective natural solution for many ailments and possess nearly the same effectiveness as synthetic pharmaceuticals. They act via a multi-systemic effect but with relatively lower hazardous adverse effects in comparison to synthetic ones [3][4].
However, natural products are facing many challenges concerning their usage, exemplified by the difficulties related to the acquisition of sufficient pure amounts, particularly for those plants that grow in small quantities or at distant locations. Besides, a lot of problems are sparked regarding the standardization, as well as the determination, of a specific dose in a manner appropriate to the intended use. It is worthy to highlight that although natural remedies are relatively safe [5][6], the majority of lethal events reported in relation to herbal products’ consumption are mainly attributable to their poor quality that eventually hindered their usage as raw materials in many pharmaceutical industries [7].
Establishing internationally recognized guidelines for assessing the quality of natural products appeared to be mandatory. Sensory, macroscopic, and microscopic examinations are the first essential steps for establishing the identity and the degree of purity of herbal materials in regard to authentic/genuine samples of the material in question. Many analytical tools are employed in quality control, including both spectroscopic and chromatographic methods [8].
Tea, Camellia sinensis (L.) Kuntze or Thea sinensis F. Theaceae, is a shrub or evergreen tree up to 16 m tall [9]. Its leaves are alternate, exstipulate, lanceolate to obovate, up to 30 cm long, 2–5 cm broad, pubescent, sometimes becoming glabrous, serrate, acute or acuminate. Fresh leaves are often picked from late March and early April to July every year [10]. Green tea represents about 20% of the dried tea which is manufactured annually and is mainly consumed in Asian countries, such as Japan, owing to its relative safety and cheaper price in comparison to other beverages [11]. This was concomitantly reflected by the annual increase in its production, which is estimated to be 6.4 percent. It is noteworthy to mention that China, India, and Sri Lanka are the biggest tea-producing countries, respectively, as reported by the 22nd Tea session held by FAO-Intergovernmental Group. Kenya and Sri Lanka constitute the two major tea-exporting countries, respectively.

2. Health Benefits and Biological Activities of Green Tea (C. sinensis)

Green tea is well-known for its marked health benefits, and, additionally, it was recognized by Chinese people as an effective traditional drink required for the prophylaxis against many health ailments [12]. Most of its crucial health benefits and biological activities are discussed below and summarized in the supplementary data Table S1.

2.1. Antioxidant and Hepatoprotective Activity

In traditional medicines, green tea is considered a reference drug for many plant species with respect to its anti-oxidant potency [13]. This activity is mainly attributed to its polyphenols that are represented by its flavanols, which can be readily oxidized to the corresponding o-quinones, and thus function as hydrogen acceptors, as well as hydrogen donors [14]. The interaction with reactive oxygen species could be accomplished by the polyphenolic compounds existing in green tea via possessing different degrees of free radical scavenging properties, particularly toward oxygen-free radicals [15] and to some extent toward nitrogen (NO) species’ production inhibition [16]. The linkage of flavan-3-ol to gallic acid (GA) and the O-trihydroxy structure in the B ring are important criteria for the O2− and NO scavenging activity of tea polyphenol [17]. Besides, green tea polyphenols possessing ortho-dihydroxyl functional groups, exemplified by epi-catechin and epi-catechin gallate, are good antioxidants that act in synergism with endogenous α-tocopherol [18].
The mechanistic potency for the anti-oxidant activity of green tea polyphenols (GTPs) was shown in different studies. GTPs act in different ways to suppress the active oxygen species generated from phenolic metabolites of benzene [19] and protect some treated oils from oxidation [20]. Other examples include increasing the excretion of carcinogenic products formed endogenously [21] and causing a marked enhancement in the salivary antioxidants in smokers, in both the short- and long term [22].
Green tea can effectively inhibit induced dose-dependent oxidative DNA damage and cell proliferation in the liver, as well as hepatotoxicity [23]. It induces the activity of some hepatic phase II enzymes, such as hepatic glutathione S-transferase (GST) [24], correcting the imbalances of the anti-oxidative system [25][26] and counteracting the induced lowered glutathione [27] in the liver. Epi-gallo catechin gallate (EGCG) and (−)-epigallocatechin-3-(3”-Omethyl) gallate are potent hepatoprotective agents, as they suppress cytotoxin-induced cell death, such as suppression of induced morphological change and induced cell death in a dose-dependent manner [28][29].
Additionally, high amounts of total phenolic compounds and caffeine prevents fat storage in the liver in high-fat diet cases [30]. Green tea is a source of highly important hexogen antioxidants that cannot be synthesized by our body and counterattack free radicals produced during metabolism of xenobiotics in the liver [31].
Moreover, green tea leaves can cause a significant reduction in elevated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatic protein carbonyls, and ROS, and thus prevent the induced liver damage [32]. Dietary green tea extract treatment reduces liver injury during nonalcoholic steatohepatitis by decreasing the pro-inflammatory signaling [33]. In addition, the extract has a substantial therapeutic effect against alcohol-induced hepatic mitochondrial DNA damage [34].

2.2. Anticancer and Anti-Mutagenic Activity

Green tea polyphenolics GTPs are considered to be dietary chemopreventive compounds due to their potent effect on apoptosis and cell cycle progression inhibition [35]. It acts through different mechanisms to promote the function of P-glycoprotein-mediated efflux, reducing the cellular exposure to xenobiotics [36], and through the induction of the microsomal detoxification enzyme [37]. Green tea behaves as a potent anticancer, owing to its polyphenolics, which are effective against various chemically induced carcinogens, in addition to their pronounced effect on tumor suppression [38].
Many studies showed that green tea catechins inhibit matrix metalloproteinases (MMPs), which play an important role in tumor invasion and metastasis [39]. Epi-gallo catechin gallate (EGCG) is effective against cancer [40] via the prohibition of cell cycle progression [41]. It inhibits fatty-acid synthase (FAS) [42], modulates protease activity during endothelial morphogenesis [43], and inhibits the vascular endothelial growth factor (VEGF) family [44], so it prohibits angiogenesis, which is a crucial step in the growth and metastasis of cancers [45]. Additionally, the cytotoxic activity of EGCG is also due to its auto-oxidation products, which also possess equivalent cytotoxic activities to EGCG [46]. Moreover, methylxanthines and polysaccharide inhibit tumor metastasis [47].
Green tea exerts a significant anticarcinogenic effect against many different types of cancer. Oral or topical application of green tea polyphenols possesses a considerable potential to antagonize the tumorigenic effects of some polycyclic aromatic hydrocarbons on skin [48]. Regarding photo-carcinogenesis, oral administration of green tea inhibits the formation of skin lesions produced by UVB light in a dose-dependent manner and prolongs the time of tumor appearance and decreases their number [49]. However, topical application of GTPs or EGCG protects against UVB-induced local and systemic immune suppression and skin cancer induction [50]. Also, it was found that green tea consumption reduces UVB-induced skin redness and causes significantly fewer UVA+B light-induced skin papillomas and tumors, and thus diminishes the incidence of skin cancer [51]. Moreover, many studies reported that green tea can be used in the treatment of malignant melanoma [52]. Green tea treatment was also found to decrease the induced fore-stomach, duodenal, large intestine, and colon tumors, and it can protect against the metastatic process in gastric cancer cells and strongly inhibit the growth of hepatocellular carcinoma cells [53][54][55]. Furthermore, green tea exerted an antagonistic effect on induced micronuclei and apoptosis in colonic crypt cells [56]. Moreover, it inhibits the hyperoxidation of membrane phospholipids, which reflect the degree of DNA damage and carcinogenic alteration [57], and it causes less metachronous colorectal adenomas incidences in patients who have undergone the complete removal of colorectal adenomas [58].
Regarding lung cancer, green tea infusion revealed a notable efficacy in the alleviation of lung cancer via EGCG, which reduces the mean number of lung tumors, causes a decline in the multiplicity of lung adenomas, and counteracts metastasis with concomitant inhibition of induced lung tumorigenesis, acting synergistically with other cancer preventive agents [59][60]. Furthermore, EGCG also inhibits lung cancer stem cells [61] and stimulates apoptotic induction in human lung cancer cells [62].
Concerning leukemia, crude catechins exemplified by (+)-gallocatechin, EGC, EC, EGCG, and ECG have a suppressive effect on erythroblastic leukemia cells in a dose-dependent manner [63]. EGCG inhibits the growth of human leukemic cell lines without causing side effects and in a specific way [64]. Furthermore, EGCG exhibits antileukemic activity by inducing the differentiation of the leukemia cells, suppressing their proliferation [65] and inducing apoptosis of B-cell and T-cell chronic lymphocytic leukemia in a dose-dependent manner, without affecting healthy B-and T-cells [66]. In addition, green tea intake has a small protective effect against acute myeloid leukemia [67]. Moreover, breast cancer could be ameliorated via the daily consumption of green tea catechins. It could effectively reduce mortality triggered from induced mammary carcinogenesis, in addition to reducing the average sizes of tumors [68]. Polyphenon E, which contains about 58.4% EGCG, was noticed to exert a mild inhibitory effect on the early promotion stage [69]; however, catechins may act in the post-initiation stage, but not in a dose-dependent manner, in addition to reducing recurrences [70][71]. Recently, it was found that green tea drinkers have no excess risk for epithelial ovarian cancer [72]. Furthermore, green tea has proved to have antiproliferative effects against human prostate cancer cells [73] and can lead to cell growth inhibition in some prostate cancer cells [74] showing potent inhibition of 5α-reductase enzyme, which may be involved in the development of benign prostatic hyperplasia, hirsutism, and prostate cancer [75][76]. GTPs also strongly inhibit the growth of renal cell carcinoma cell lines in a concentration-dependent manner [77]. It is worthy to highlight that green tea catechins possessing the gallate group act as anticancer agents on glioblastoma cells and can prevent the inflammatory processes associated with aggressive glioma tumor growth [78][79]. Nowadays, green tea serves as a diet-derived immune-modulatory chemopreventive agent; as many of its contained flavonoids stimulate natural killer (NK) cell activity, so it may be used in the treatment and prevention of malignant diseases [80].
Meanwhile, aqueous extract of green tea has a marked antimutagenic activity against different major classes of dietary and occupational carcinogens [81]. This activity may be attributed to different mechanisms, such as improving the fidelity of DNA replication [82], affecting carcinogen metabolism [83], direct interaction between the reactive genotoxic species of the various promutagens, and nucleophilic tea components. In addition, it causes a potent inhibition of the cytochrome P450-dependent bioactivation of the promutagens [84], acting intracellularly as a blocking or suppressive agent [85], and potent dose-dependent antigenotoxic activity [86]. Besides the antimutagenic activity of green tea, it has anticlastogenic effects [87].

2.3. Antimicrobial and Antiviral Activity

Many studies reported the antimicrobial activity of green tea. Green tea is effective against Staphylococcus epidermidis, Staphylococcus aureus, and Vibrio cholerae O1, owing to the bactericidal catechins that primarily cause defection in the bacterial membranes [88]. Green tea is also effective against various bacteria that cause dental caries, such as Escherichia coli, Streptococcus salivarius, and Streptococcus mutans [89]. EGCG and gallocatechin gallate (GCG) markedly inhibit the secretion of extracellular Vero toxins from enterohemorrhagic Escherichia coli cells into the culture supernatant fluid [90]. Raw extract of green tea, especially gallocatechin gallate (GCG), is able to suppress 1-deoxy-d-xylulose 5-phosphate reductoisomerase activity, which is an antimicrobial target [91]. Furthermore, it can also reduce the lethality of ricin toxin [92], but it has a poor activity against Babesia divergens that infect cattle [93].
EGCG can inhibit the activity of Salmonella typhimurium type III, and thus reduce the bacterial invasion into host cells [94]. Green tea extract is bactericidal against Gram positive bacteria and bacteriostatic against Gram negative ones, with less antifungal activity against Aspergillus niger and Penicillium chrysogenum [95].
In addition, tea polyphenols have the ability to inhibit the development and growth of bacterial spores, as in case of Bacillus stearothermophilus and Clostridium thermoaceticum, due to their ability to decrease the heat resistance of these bacterial spores when added at high temperature [96]. However, chlorogenic acid induces the apoptotic markers through excessive potassium efflux and an apoptotic volume reduction, which induces cytosolic calcium uptake and cell cycle arrest in Candida albicans, in addition to its ability to induce caspase activation and DNA fragmentation [97].
Tea exhibits antiviral activity against human viruses and serves as a diet-derived immune-modulatory chemopreventive agent, as many of its contained flavonoids stimulate NK cell activity, so it may be used in the treatment and prevention of viral diseases [80]. Recently, it was found that EGCG is capable of inhibiting the Brazilian strain of Zika virus entry [98]. Additionally, topical application of EGCG can be used to prevent the sexual transmission of HIV, as it disaggregates existing amyloid fibrils termed semen-derived enhancers of viral infection fibers and inhibits the formation of new ones [99].

2.4. Anti-Schisosomiasis and Antiparasitic Activity

Green tea could be able to protect liver cells in mice after being infected with Schistosoma mansoni, and thus decreases cellular necrosis and regenerates total protein and glycogen levels partially. This could be achieved through suppression of the oxidative stress, owing to its scavenging properties toward free radicles [100]. Moreover, green tea has an antiparasitic activity as it noncompetitively inhibits the activity of Toxocara canis [101].

2.5. Cardioprotective Activity

Green tea could improve the risk factors for heart disease [102], as it significantly reduces total cholesterol, low density lipoprotein (LDL) cholesterol, and blood pressure [103]. It also improves microvascular function and skin oxygen tension in both older and younger populations [104]. Nonfermented Chinese green tea is considered to be an ideal beverage to prevent the incidence of coronary heart disease. Its consumption, together with its catechin-rich fractions, lowers the risk of coronary heart diseases through delaying atherogenesis by significantly preventing endothelial cell induced LDL oxidation and foam cell formation [105]. The inhibition of advanced glycation end products formation in collagen represents another important mechanism for the protective effects of green tea catechins against cardiovascular diseases [106].
The consumption of green tea decreases the risk of myocardial infarction (MI) in a dose-dependent manner up to ≥4 cups/day [107], as it reduces cardiac hypertrophy, improves systolic and diastolic dysfunction, restores the antioxidant enzyme activity, and stimulates the glucose pathway and mitochondrial function with reduced apoptosis after MI [108]. High dietary intake of green tea may be useful in the reduction and prevention of cardiac injury following ischemia [109].
The flavonoids that exist in green tea perform its cardio-protective effect by improving the reserve in coronary flow velocity [110]. EGCG is able to reduce both arsenic- and doxorubicin-induced cardiotoxicity [111]. It reduces the inflammation and preserves the cardiac function, with lowered mortality rate [112]. Concerning EC, it may be involved in treating cardiac arrhythmia [113]. Meanwhile, EC supplementation has a cardioprotective effect without changing blood pressure, arterial stiffness, or the blood lipid profile [114].
Additionally, green tea can be used as anti-hypercholesterolemic agent by acting in several ways, such as enhancing hepatic excretion of cholesterol or inhibiting absorption of cholesterol in the alimentary tract [115]. This is accompanied by increasing fecal bile acids and cholesterol excretion, resulting in the lowering of the plasma cholesterol [116] and the lowering of LDL oxidation by increasing cellular antioxidant status or inhibiting oxidizing enzyme activities in the arterial wall [117]. Other possible mechanisms include diminishing the levels of α-ketoglutarate and pyruvate dehydrogenases enzymes, which are vital in the cholesterol biosynthesis [118] or inhibition of the rate limiting enzyme of cholesterol biogenesis, squalene epoxidase (SE) [119]. Green tea also causes a prolongation in LDL oxidation lag time by flavonoids [120], inhibition of serum triglyceride elevation [121], and prevention of fat storage in the liver, lowering blood lipids and increasing fecal excretion of triglycerides [30].
Fresh green tea fermented under nitrogen gas produces γ-aminobutyric acid (GABA)-rich tea, which was proved to prevent the occurrence of hypertension [122]. Theanine exerted a significant decline in blood pressure following a dose-dependent manner [123]. EGCG and EGC were found to inhibit dopa decarboxylase enzymes in a concentration- and time-dependent manner, which is a known target for drugs used in hypertension [124]. EGCG that was chronically infused in the hypothalamic paraventricular nucleus (PVN) attenuates hypertension by chronic inhibition of ROS, in addition to regulating the balance of neurotransmitters, as well as cytokines, in the PVN [125]. Green tea extract was found to prevent high angiotensin II dose-induced hypertension and the accompanied organ damage by preventing or scavenging superoxide anion generation [126]. Decaffeinated green tea extract also reduces the metabolic syndrome through reduction of the formation of ROS, which results in lowered blood pressure [127].
Regarding green tea anti-thrombotic activity, it was found that unprocessed tea extracts can significantly reduce the levels of thromboxane-B2 and then eliminate the aggregation of platelets to produce microthrombi, while processed ones are unable to form any inhibition, significantly owing to the presence of a heat-labile compound [118]. Possibly, green tea has a fibrinolytic effect [102]. In addition, the catechins inhibit induced platelet aggregation in vitro in a dose-dependent manner, without changing the coagulation parameters [128]. The tea can also be used to prevent red blood cell hemolysis [129]. Different green tea extracts have different degrees of inhibition of dehydration of stored sickle cells, and this inhibitory activity increases by increasing the number of hydroxyl groups [130].

2.6. Antidiabetic and Anti-Obesity Activity

Green tea is used for the amelioration of diabetes and its complications, acting as a renoprotective in diabetes mellitus, in addition to the ability of EGCG to inhibit angiogenesis that is involved in many diseases, such as diabetic retinopathy [45][131]. Furthermore, EGCG can help in controlling hyperglycemia and alleviating diabetes complications via reducing plasma glucose, insulin level, and liver and kidney weight [132]. Recently, it was found that EGCG is useful for resensitizing insulin-resistant muscle [133].
The administration of GTPs significantly increases glucose tolerance and reduces induced elevated serum glucose levels [134]. Floratheasaponins A, B, and C in the flower buds of green tea exhibit potent inhibitory effects against sucrose-induced serum glucose elevation [135]. Green tea water-soluble polysaccharide fraction has an inhibitory effect against α-amylase, which leads to decreased blood glucose levels [136], along with galloyl moiety in catechin, which increases the inhibition of pancreatic α-amylase, due to enhanced association with the enzyme active site [137].
Regarding obesity, green tea extract is a well-tolerated natural product for the management of obesity by reducing fat digestion through marked inhibition of digestive lipases, such as gastric and pancreatic lipases, especially by saponins, which lead to altered lipid emulsification in gastric or duodenal media [138]. In addition, it stimulates thermogenesis/energy expenditure and fat oxidation mainly by EGCG and caffeine [139], without significant differences in either plasma cholesterol or blood pressure [140]. Furthermore, chronic usage of short-time decoction of green tea decreases perirenal and epididymal adipose tissues and weight gains in high-fat diet cases [30].
Recent studies confirm that a mixture of green tea catechins and caffeine has a beneficial effect on body-weight management through sustained energy expenditure, fat oxidation, and preservation of fat-free body mass [141]. Polyphenols such as EGCG can increase lipolysis, in addition to possessing anti-adipogenic effects through being a fatty-acid synthase (FAS), which is a possible therapeutic target for appetite and weight control [142][143]. Polyphenols have “exercise mimetic” properties through exercise-inducible pathways [139].

2.7. Gastrointestinal Tract Problems Relieving Activity

The purified green tea EC can cause both endothelium-dependent and -independent mesenteric arteries relaxation [144]. However, EGCG preserves the aortic thickness and regenerates elastin content, due to its anti-inflammatory effect, so could prevent abdominal aortic aneurysm [145]. Furthermore, high green tea consumption is associated with a reduction in the risk of precancerous chronic atrophic gastritis [146].
In addition, floratheasaponins A, B, and C in flower buds exhibit potent inhibitory effects against ethanol- and indomethacin-induced gastric mucosal lesions, so green tea seems to have a gastro-protective effect [135]. However, daily intake of green tea is able to alter the growth and composition of the intestinal flora and modulate the genesis of potentially harmful agents like Clostridium difficile and Clostridium perfringens, due to the effect of its components, such as vitamin C and polyphenols [147]. Green tea has recently proved to modulate the fecal microbiome and thus endogenous metabolites [148].

2.8. Neuroprotective Activity

Green tea extract has a protective effect on the ischemia/reperfusion-induced brain injury and behavior deficit. It also reduces the number of ischemia/reperfusion-induced apoptotic neuronal cells [149]. GTPs, EGCG, ECG, EGC, and EC are able to protect synaptosomes from induced lipid peroxidation damage [150]. EGCG alone has a protective effect against stress-induced neural injuries [151]. EGCG was shown to be easily absorbed from the digestive tract and penetrate the brain, reaching levels similar to those found in lung, liver, kidney, and others [152]. It has a neuroprotective effect against neuronal damage following transient global ischemia in the gerbils acting by different mechanisms as angiogenesis in the early stage of ischemic stroke promoting [153][154]. Regarding neurotoxicity, l-theanine has a protective effect against cadmium-induced neurotoxicity by reducing brain cadmium levels and oxidative damage, which lead to neurodegenerative diseases [155].
In addition, GTPs can be considered therapeutic agents to alter brain aging processes by serving as neuroprotective agents in major neurodegenerative disorders, such as Parkinson’s disease and Alzheimer’s disease [156][157]. In addition, green tea catechin intake may be useful in the improvement of the morphologic and functional changes that occur naturally in the accelerated senile brains [158]. EGCG and EGC were found to be inhibitors of dopa decarboxylase enzyme in a concentration- and time-dependent manner [124]. Green tea containing high levels of EGCG prevents the loss of tyrosine hydroxylase (TH)-positive cells in the substantia nigra [159]. Both tea and EGCG, when used alone or with Parkinson’s disease’s inducers, can decrease the neuronal nitric oxide synthase (nNOS) expressions in the substantia nigra, which provides a neuroprotective effect [160].
Regarding Alzheimer’s disease, EGCG may be beneficial for its prevention, as it has protective effects against amyloid ß-induced hippocampal neuronal apoptosis [161] in which neuronal loss is accompanied by the deposition of amyloid ß protein in senile plaques [162]. EGCG regulates the growth and survival of astrocytes without being cytotoxic. Green tea catechins possess an inhibitory effect against β-secretase, which is known as one of the most important amyloid precursor protein cleaving enzymes in Alzheimer’s disease [163]. EC reduces amyloid-β-induced β-secretase-1 expression and thus inhibits the most toxic amyloid-β aggregates [164].
The theanine existing in green tea enhances the memory and learning ability, owing to its significant effect on the release or reduction of memory- and learning-linked neurotransmitters, such as dopamine and serotonin [123][165]. Polyphenols also have a potential role in the prevention/treatment of dementia [166]. It was proved that combined ingestion of EGC and GA increases the learning ability in a better way than EGCG, which reaches the brain parenchyma at a very low concentration [167]. Additionally, theanine may affect emotions by interacting with neurotransmitters in the brain, due to a modulation of synaptic transmission [38]. Moreover, drinking theanine-rich and low-caffeine green tea has anti-stress effects, as theanine, EGC, and arginine together can counteract the effect of caffeine and EGCG on psychosocial stress-induced adrenal hypertrophy [168]. Theanine also produces a marked relaxation effect due to its rapid absorption and transportation to the brain in 30 min, without suffering any metabolic degradation [123].

2.9. Anti-Inflammatory, Analgesic, Antipyretic, and Anti-Allergic Activity

Green tea is considered to be a potent anti-inflammatory and antipyretic agent [169][170]. EGCG reduces nitric oxide production via its gallate structure [171]. It inhibits the endothelial cell growth which leads to the inhibition of angiogenesis that is involved in many diseases, such as chronic inflammation [45]. The non-polyphenolic fraction of green tea represented by Pheophytin a and b exerts suppressive activities against the activation of human polymorphonuclear neutrophils (PMNs) associated with inflammatory reactions in a dose-dependent manner [172]. Moreover, green tea extract/tablets showed a high efficacy in controlling pain, particularly in patients suffering from osteoarthritis as well as [173].
Regarding the anti-allergic activity of green tea, polyphenols are considered to be the major inhibitory components of hot-water-soluble extracts of green tea against histamine release from mast cells [174]. In addition, green tea has an anti-allergic effect due to leaf saponins [175] and floratheasaponins from flower buds that possess anti-allergic activities, as well [176]. It was reported that methylated EGCG blocks the production of two compounds in the body mainly involved in producing an allergic response, histamine and immunoglobulin E (IgE), and works by triggering and sustaining allergic reactions. It is worthy to mention that green tea can activate heat-generating mechanisms in the body such that a fall in core body temperature can be lowered upon cold exposure [177].

2.10. Skeletomuscular System Relieving Activity

EGCG has direct vasodilator action in skeletal muscle and increasing muscle microvascular blood flow [178]. It can induce myogenic differentiation [179] and increase the recovery of muscle mass and function [180]. Moreover, EGCG induces apoptotic cell death of osteoclasts in a dose-dependent manner with no effect on osteoblasts [181]. Appropriate concentrations of EGCG have an anti-inflammatory effect in the treatment of collagen membranes and thus can be used in bone regeneration [182]. It was also found that green tea has a protective effect against induced bone and hyaline cartilage alteration [183]. Furthermore, EGCG enhances osteoprotegerin synthesis, which is secreted from osteoblasts, and suppresses osteoclastic bone resorption, especially in the elderly [184]. Meanwhile, EGCG has the potential to inhibit the development of arthritis, as pretreatment with EGCG inhibits the release of induced lactate dehydrogenase in human chondrocytes of osteoarthritis cartilage [185]. Green tea extract can also be used as an adjunctive treatment, because it can control the pain and improve the knee-joint physical function in adults with osteoarthritis [186].
Green tea can be useful as a medicament for treatment of infected root canals, as Japanese green tea extracts have antibacterial and bactericidal effects against some facultative anaerobes and obligative anaerobes [187]. It also has a high amount of fluoride, which may help strengthen teeth and bones and reduce tooth decay [188]. Besides fluoride, green tea has a high concentration of polysaccharides, such as pectin, which enhances the inhibition activity against Streptococcus mutans, thus preventing dental caries [189]. Green tea is also effective against other various bacteria that cause dental caries, such as Escherichia coli and Streptococcus salivarius [89]. The combination of green tea and miswak (Salvadora persica L.) extracts exhibits synergistic antiplaque properties [190]. Additionally, green tea can be used to prevent periodontal diseases, due to its matrix metalloproteinases (MMPs) inhibitory activity in a dose-dependent manner [191], with particular reduction in their secretion in gingival fibroblasts [192].

2.11. Miscellaneous Activity

Moreover, green tea experienced a lot of pronounced activities in relieving skin damage and promoting wound healing. Oral or topical treatment of GTPs prevents damages such as ultraviolet (UV)-induced sunburn response, immuno-suppression, and photo-aging [193], such as dermal extracellular damage [194] and DNA damage [195]. Treating the skin with green tea extracts inhibits induced erythema response in a dose-dependent manner, especially when treated with EGCG and ECG [196], due to the ability of EGCG to inhibit UVB-induced oxidative stress [197]. In addition, green tea ethanol extract is effective in the healing process of surgical wounds, as it decreases the healing duration [198]. Recently, it was found that tannase-converted green tea extract can be used in cosmetics as a skin anti-wrinkling or depigmenting agent [199], as tannase-derived bioconversion, which occurs on catechins compositions in green tea, was found to be useful in improving the antioxidant and radicals scavenging activities [200].
It is notable that anti-amyloidogenic activity has been attributed to oxidized EGCG comparable to the intact molecule, as it has a disruptive effect on preformed fibrils more than the native form [201]. Green tea revealed a high potency in the prohibition of proMMP-9 and MMP-9 activities, which play an important role in the development of pulmonary hypertension [202]; meanwhile, l-theanine proved efficacy in the alleviation of oxidative stress-induced airway inflammation in asthma [203]. Recent studies showed that dietary supplementation enriched with green tea promotes the antioxidant defense system in plasma and thus provides protection against oxidative damage induced by both short-term muscular endurance test and long-term strength training [204]. Additionally, the tea extract can prolong the time to exhaustion [205] and improve vascular function and physical performance in healthy individuals [206].
Green tea extract has a protective effect against induced reproductive toxicities and reduced testicular androgen receptors [207]. In addition, green tea improves induced damage of the reproductive system; this is probably due to its high catechins content [208], as catechins have a quenching effect on the reactive oxygen species that lead to oxidative stress in male and female reproduction systems and cause infertility [209]. EGCG increases the total efficiency of fertilization through improving the in vitro penetration rate of the sperms [210]. Meanwhile, oral administration of polyphenone-60 (P-60), green tea extract catechins, can stimulate goiter and reduce weights of the body, testis, and prostate gland, along with elevation in plasma thyroid stimulating hormone (TSH), luteinizing hormone (LH), and testosterone levels and reduction in tri-iodothyronine (T3) and thyroxine (T4). P-60, as a whole, and some of its constituents, can inhibit human placental aromatase activity which then can be used as preventive agents against benign prostatic hypertrophy (BPH) [211].
Regarding the effect of green tea extract on eyes, it has potential cataracto-static ability and can delay the progression of lens opacity, as it decreases smoking-induced frequencies of micronuclei in peripheral-blood lymphocytes [212]. It also counteracts the oxidative insult caused by cigarette smoke that causes oxidative damage to the constituent molecules and consequent lenticular opacity [213]. GTPs can bind to the cleft between the domains of human γB-crystallin protein, which is then protected from UV induced-oxidative stress [214].
Green tea may have selective protective effects within the body, especially on the kidney [215]. Green tea tannins, especially EGCG and ECG, cause a dose-dependent decrease in the progression of renal failure [216]. Recently, it was found that green tea extract can prevent the induced lipid peroxidation and antioxidant depletion in the kidney [217].

This entry is adapted from the peer-reviewed paper 10.3390/antiox8100455

References

  1. Fathy, S.; Emam, M.; Agwa, S.A.; Zahra, F.A.; Youssef, F.; Sami, R. The antiproliferative effect of Origanum majorana on human hepatocarcinoma cell line: Suppression of NF-kB. Cell. Mol. Biol. 2016, 62, 80–84.
  2. Ashour, M.L.; Youssef, F.S.; Gad, H.A.; El-Readi, M.Z.; Bouzabata, A.; Abuzeid, R.M.; Sobeh, M.; Wink, M. Evidence for the anti-inflammatory activity of Bupleurum marginatum (Apiaceae) extracts using in vitro and in vivo experiments supported by virtual screening. J. Pharm. Pharmacol. 2018, 70, 952–963.
  3. Janibekov, A.A.; Youssef, F.S.; Ashour, M.L.; Mamadalieva, N.Z. New flavonoid glycosides from two Astragalus species (Fabaceae) and validation of their antihyperglycaemic activity using molecular modelling and in vitro studies. Ind. Crop. Prod. 2018, 118, 142–148.
  4. Thabet, A.A.; Youssef, F.S.; El-Shazly, M.; El-Beshbishy, H.A.; Singab, A.N.B. Validation of the antihyperglycaemic and hepatoprotective activity of the flavonoid rich fraction of Brachychiton rupestris using in vivo experimental models and molecular modelling. Food Chem. Toxicol. 2018, 114, 302–310.
  5. Youssef, F.S.; Labib, R.M.; Eldahshan, O.A.; Singab, A.N. Synergistic hepatoprotective and antioxidant effect of Artichoke, Fig, Mulberry Herbal mixture on HepG2 Cells and their metabolic profiling Using NMR coupled with chemometrics. Chem. Biodivers. 2017, 14, e1700206.
  6. Talaat, A.N.; Ebada, S.S.; Labib, R.M.; Esmat, A.; Youssef, F.S.; Singab, A.N.B. Verification of the anti-inflammatory activity of the polyphenolic-rich fraction of Araucaria bidwillii Hook. using phytohaemagglutinin-stimulated human peripheral blood mononuclear cells and virtual screening. J. Ethnopharmacol. 2018, 226, 44–47.
  7. Couturier, F.J.; Colemont, L.J.; Fierens, H.; Verhoeven, V.M. Toxic hepatitis due to a food supplement: “Natural” is no synonym for “harmless”. Clin. Res. Hepatol. Gastroenterol. 2016, 40, e38–e43.
  8. Aboulwafa, M.M.; Youssef, F.S.; Gad, H.A.; Sarker, S.D.; Nahar, L.; Al-Azizi, M.M.; Ashour, M.L. Authentication and discrimination of green tea samples using UV-Visible, FTIR and HPLC techniques coupled with chemometrics analysis. J. Pharm. Biomed. Anal. 2018, 164, 653–658.
  9. Ferrara, L.; Montesano, D.; Senatore, A. The distribution of minerals and flavonoids in the tea plant (Camellia sinensis). Il Farmaco 2001, 56, 397–401.
  10. Chen, Q.; Guo, Z.; Zhao, J. Identification of green tea’s (Camellia sinensis L.) quality level according to measurement of main catechins and caffeine contents by HPLC and support vector classification pattern recognition. J. Pharm. Biomed. Anal. 2008, 48, 1321–1325.
  11. Graham, H.N. Green tea composition, consumption, and polyphenol chemistry. Prev. Med. 1992, 21, 334–350.
  12. Samali, A.; Rukaiyatu, A.; Mustapha, K. Qualitative and quantitative evaluation of some herbal teas commonly consumed in Nigeria. Afr. J. Pharm. Pharmacol. 2012, 6, 384–388.
  13. McCune, L.M.; Johns, T. Antioxidant activity in medicinal plants associated with the symptoms of diabetes mellitus used by the Indigenous Peoples of the North American boreal forest. J. Ethnopharmacol. 2002, 82, 197–205.
  14. Barroso, M.F.; Ramalhosa, M.J.; Alves, R.C.; Dias, A.; Soares, C.M.D.; Oliva-Teles, M.T.; Delerue-Matos, C. Total antioxidant capacity of plant infusions: Assessment using electrochemical DNA-based biosensor and spectrophotometric methods. Food Cont. 2016, 68, 153–161.
  15. Zhao, B.; Guo, Q.; Xin, W. Free radical scavenging by green tea polyphenols. Methods Enzymol. 2001, 335, 217.
  16. Sarkar, A.; Bhaduri, A. Black tea is a powerful chemopreventor of reactive oxygen and nitrogen species: Comparison with its individual catechin constituents and green tea. Biochem. Biophys. Res. Commun. 2001, 284, 173–178.
  17. Nakagawa, T.; Yokozawa, T. Direct scavenging of nitric oxide and superoxide by green tea. Food Chem. Toxicol. 2002, 40, 1745–1750.
  18. Cai, Y.-J.; Ma, L.-P.; Hou, L.-F.; Zhou, B.; Yang, L.; Liu, Z.-L. Antioxidant effects of green tea polyphenols on free radical initiated peroxidation of rat liver microsomes. Chem. Phys. Lipids 2002, 120, 109–117.
  19. Khan, S.G.; Katiyar, S.K.; Agarwal, R.; Mukhtar, H. Enhancement of antioxidant and phase II enzymes by oral feeding of green tea polyphenols in drinking water to SKH-1 hairless mice: Possible role in cancer chemoprevention. Cancer Res. 1992, 52, 4050–4052.
  20. Wanasundara, U.N.; Shahidi, F. Antioxidant and pro-oxidant activity of green tea extracts in marine oils. Food Chem. 1998, 63, 335–342.
  21. Rashidinejad, A.; Birch, E.J.; Hindmarsh, J.; Everett, D.W. Molecular interactions between green tea catechins and cheese fat studied by solid-state nuclear magnetic resonance spectroscopy. Food Chem. 2017, 215, 228–234.
  22. Azimi, S.; Mansouri, Z.; Bakhtiari, S.; Tennant, M.; Kruger, E.; Rajabibazl, M.; Daraei, A. Does green tea consumption improve the salivary antioxidant status of smokers? Arch. Oral Biol. 2017, 78, 1–5.
  23. Hasegawa, R.; Chujo, T.; Sai-Kato, K.; Umemura, T.; Tanimura, A.; Kurokawa, Y. Preventive effects of green tea against liver oxidative DNA damage and hepatotoxicity in rats treated with 2-nitropropane. Food Chem. Toxicol. 1995, 33, 961–970.
  24. Bu-Abbas, A.; Clifford, M.; Walker, R.; Ioannides, C. Contribution of caffeine and flavanols in the induction of hepatic phase II activities by green tea. Food Chem. Toxicol. 1998, 36, 617–621.
  25. Lee, S.F.; Liang, Y.C.; Lin, J.K. Inhibition of 1, 2, 4-benzenetriol-generated active oxygen species and induction of phase II enzymes by green tea polyphenols. Chem. Biol. Int. 1995, 98, 283–301.
  26. Kim, E.; Lee, M.; Kim, S.S.; Kim, J.H.; Jeon, Y.K.; Kim, B.H.; Kim, I.J.; Kim, Y.K. Green tea but not coffee consumption is inversely associated with metabolic syndrome; An epidemiological study in Korean adults. Diabetes Res. Clin. Practice 2016, 120, S85.
  27. Chen, J.; Wang, P.; Xia, Y.; Xu, M.; Pei, S. Genetic diversity and differentiation of Camellia sinensis L. (cultivated tea) and its wild relatives in Yunnan province of China, revealed by morphology, biochemistry and allozyme studies. Genet. Resour. Crop Evol. 2005, 52, 41–52.
  28. Sobeh, M.; Mahmoud, M.F.; Petruk, G.; Rezq, S.; Ashour, M.L.; Youssef, F.S.; El-Shazly, A.M.; Monti, D.M.; Abdel-Naim, A.B.; Wink, M. Syzygium aqueum: A polyphenol-rich leaf extract exhibits antioxidant, hepatoprotective, pain-killing and anti-inflammatory activities in animal models. Front. Pharmacol. 2018, 9, 556.
  29. Sobeh, M.; Youssef, F.S.; Esmat, A.; Petruk, G.; El-Khatib, A.H.; Monti, D.M.; Ashour, M.L.; Wink, M. High resolution UPLC-MS/MS profiling of polyphenolics in the methanol extract of Syzygium samarangense leaves and its hepatoprotective activity in rats with CCl4-induced hepatic damage. Food Chem. Toxicol. 2018, 113, 145–153.
  30. Hamdaoui, M.H.; Snoussi, C.; Dhaouadi, K.; Fattouch, S.; Ducroc, R.; Le Gall, M.; Bado, A. Tea decoctions prevent body weight gain in rats fed high-fat diet; black tea being more efficient than green tea. J. Nutr. Intermed. Metab. 2016, 6, 33–40.
  31. Casas-Grajales, S.; Muriel, P. Chapter 43—The Liver, Oxidative Stress, and Antioxidants. In Liver Pathophysiology; Academic Press: Boston, MA, USA, 2017; pp. 583–604.
  32. Jayashree, G.V.; Krupashree, K.; Rachitha, P.; Khanum, F. Patulin induced oxidative stress mediated apoptotic damage in mice, and its modulation by Green tea leaves (GTL). J. Clin. Exp. Hepatol. 2017, 7, 127–134.
  33. Li, J.; Sapper, T.N.; Mah, E.; Moller, M.V.; Kim, J.B.; Chitchumroonchokchai, C.; McDonald, J.D.; Bruno, R.S. Green tea extract treatment reduces NFκB activation in mice with diet-induced nonalcoholic steatohepatitis by lowering TNFR1 and TLR4 expression and ligand availability. J. Nutr. Biochem. 2017, 41, 34–41.
  34. Reddyvari, H.; Govatati, S.; Matha, S.K.; Korla, S.V.; Malempati, S.; Pasupuleti, S.R.; Bhanoori, M.; Nallanchakravarthula, V. Therapeutic effect of green tea extract on alcohol induced hepatic mitochondrial DNA damage in albino wistar rats. J. Adv. Res. 2017, 8, 289–295.
  35. Ahmad, N.; Cheng, P.; Mukhtar, H. Cell cycle dysregulation by green tea polyphenol epigallocatechin-3-gallate. Biochem. Biophys. Res. Commun. 2000, 275, 328–334.
  36. Wang, E.-J.; Barecki-Roach, M.; Johnson, W.W. Elevation of P-glycoprotein function by a catechin in green tea. Biochem. Biophys. Res. Commun. 2002, 297, 412–418.
  37. Embola, C.; Sohn, O.; Fiala, E.; Weisburger, J. Induction of UDP-glucuronosyltransferase 1 (UDP-GT1) gene complex by green tea in male F344 rats. Food Chem. Toxicol. 2002, 40, 841–844.
  38. Pan, C.-Y.; Kao, Y.-H.; Fox, A.P. Enhancement of inward Ca 2+ currents in bovine chromaffin cells by green tea polyphenol extracts. Neurochem. Int. 2002, 40, 131–137.
  39. Jha, S.; Kanaujia, S.P.; Limaye, A.M. Direct inhibition of matrix metalloproteinase-2 (MMP-2) by (−)-epigallocatechin-3-gallate: A possible role for the fibronectin type II repeats. Gene 2016, 593, 126–130.
  40. Chen, Z.P.; Schell, J.B.; Ho, C.-T.; Chen, K.Y. Green tea epigallocatechin gallate shows a pronounced growth inhibitory effect on cancerous cells but not on their normal counterparts. Cancer Lett. 1998, 129, 173–179.
  41. Ahmad, N.; Adhami, V.M.; Gupta, S.; Cheng, P.; Mukhtar, H. Role of the retinoblastoma (PRB)–E2F/DP pathway in cancer chemopreventive effects of green tea polyphenol epigallocatechin-3-gallate. Arch. Biochem. Biophys. 2002, 398, 125–131.
  42. Wang, X.; Tian, W. Green tea epigallocatechin gallate: A natural inhibitor of fatty-acid synthase. Biochem. Biophys. Res. Commun. 2001, 288, 1200–1206.
  43. Morbidelli, L. Polyphenol-based nutraceuticals for the control of angiogenesis: Analysis of the critical issues for human use. Pharmacol. Res. 2016, 111, 384–393.
  44. Rashidi, B.; Malekzadeh, M.; Goodarzi, M.; Masoudifar, A.; Mirzaei, H. Green tea and its anti-angiogenesis effects. Biomed. Pharmacother. 2017, 89, 949–956.
  45. Cao, Y.; Cao, R.; Bråkenhielm, E. Antiangiogenic mechanisms of diet-derived polyphenols. J. Nutr. Biochem. 2002, 13, 380–390.
  46. Wei, Y.; Chen, P.; Ling, T.; Wang, Y.; Dong, R.; Zhang, C.; Zhang, L.; Han, M.; Wang, D.; Wan, X.; et al. Certain (−)-epigallocatechin-3-gallate (EGCG) auto-oxidation products (EAOPs) retain the cytotoxic activities of EGCG. Food Chem. 2016, 204, 218–226.
  47. Park, H.-R.; Hwang, D.; Suh, H.-J.; Yu, K.-W.; Kim, T.Y.; Shin, K.-S. Antitumor and antimetastatic activities of rhamnogalacturonan-II-type polysaccharide isolated from mature leaves of green tea via activation of macrophages and natural killer cells. Int. J. Biol. Macromol. 2017, 99, 179–186.
  48. Khan, W.; Wang, Z.; Athar, M.; Bickers, D.; Mukhtar, H. Inhibition of the skin tumorigenicity of (k)-7P, 8wdihydroxy-90, IOa-epoxy-7, 8, 9, 10-tetrahydrobenzo [a] pyrene by tannic acid, green tea polyphenols and quercetin in Sencar mice. Cancer Lett. 1988, 42, 7–12.
  49. Conney, A.H.; Wang, Z.-Y.; Huang, M.-T.; Ho, C.-T.; Yang, C.S. Inhibitory effect of green tea on tumorigenesis by chemicals and ultraviolet light. Prev. Med. 1992, 21, 361–369.
  50. Katiyar, S.K.; Perez, A.; Mukhtar, H. Green tea polyphenol treatment to human skin prevents formation of ultraviolet light B-induced pyrimidine dimers in DNA. Clin. Cancer Res. 2000, 6, 3864–3869.
  51. Record, I.R.; Dreosti, I.E. Protection by black tea and green tea against UVB and UVA+ B induced skin cancer in hairless mice. Mut. Res. Fundam. Mol. Mech. Mutagenes. 1998, 422, 191–199.
  52. Liao, B.; Ying, H.; Yu, C.; Fan, Z.; Zhang, W.; Shi, J.; Ying, H.; Ravichandran, N.; Xu, Y.; Yin, J.; et al. (−)-Epigallocatechin gallate (EGCG)-nanoethosomes as a transdermal delivery system for docetaxel to treat implanted human melanoma cell tumors in mice. Int. J. Pharm. 2016, 512, 22–31.
  53. Uesato, S.; Kitagawa, Y.; Kamishimoto, M.; Kumagai, A.; Hori, H.; Nagasawa, H. Inhibition of green tea catechins against the growth of cancerous human colon and hepatic epithelial cells. Cancer Lett. 2001, 170, 41–44.
  54. Yang, F.; Oz, H.S.; Barve, S.; De Villiers, W.J.; McClain, C.J.; Varilek, G.W. The green tea polyphenol (−)-epigallocatechin-3-gallate blocks nuclear factor-κB activation by inhibiting IκB kinase activity in the intestinal epithelial cell line IEC-6. Mol. Pharmacol. 2001, 60, 528–533.
  55. Arcone, R.; Palma, M.; Pagliara, V.; Graziani, G.; Masullo, M.; Nardone, G. Green tea polyphenols affect invasiveness of human gastric MKN-28 cells by inhibition of LPS or TNF-α induced Matrix Metalloproteinase-9/2. Biochim. Open 2016, 3, 56–63.
  56. Zao, J.; Zhu, Q.; Cheng, S. The antagonistic action effects of green tea on micronuclei and apoptosis induced by 1, 2-dimethylhydrazine (1, 2 DMH) in colonic crypt cells of mice. Acta Nutr. Sin. 1992, 14, 251–259.
  57. Matsumoto, H.; Yamane, T.; Inagake, M.; Nakatani, H.; Iwata, Y.; Takahashi, T.; Nishimura, H.; Nishino, H.; Nakagawa, K.; Miyazawa, T. Inhibition of mucosal lipid hyperoxidation by green tea extract in 1, 2-dimethylhydrazine-induced rat colonic carcinogenesis. Cancer Lett. 1996, 104, 205–209.
  58. Shin, C.M.; Lee, D.H.; Seo, A.Y.; Lee, H.J.; Kim, S.B.; Son, W.-C.; Kim, Y.K.; Lee, S.J.; Park, S.-H.; Kim, N.; et al. Green tea extracts for the prevention of metachronous colorectal polyps among patients who underwent endoscopic removal of colorectal adenomas: A randomized clinical trial. Clin. Nutr. 2017, 37, 452–458.
  59. Xu, Y.; Ho, C.-T.; Amin, S.G.; Han, C.; Chung, F.-L. Inhibition of tobacco-specific nitrosamine-induced lung tumorigenesis in A/J mice by green tea and its major polyphenol as antioxidants. Cancer Res. 1992, 52, 3875–3879.
  60. Cao, J.; Xu, Y.; Chen, J.; Klaunig, J.E. Chemopreventive effects of green and black tea on pulmonary and hepatic carcinogenesis. Toxicol. Sci. 1996, 29, 244–250.
  61. Zhu, J.; Jiang, Y.; Yang, X.; Wang, S.; Xie, C.; Li, X.; Li, Y.; Chen, Y.; Wang, X.; Meng, Y.; et al. Wnt/β-catenin pathway mediates (−)-Epigallocatechin-3-gallate (EGCG) inhibition of lung cancer stem cells. Biochem. Biophys. Res. Commun. 2017, 482, 15–21.
  62. Oya, Y.; Mondal, A.; Rawangkan, A.; Umsumarng, S.; Iida, K.; Watanabe, T.; Kanno, M.; Suzuki, K.; Li, Z.; Kagechika, H.; et al. Down-regulation of histone deacetylase 4, −5 and −6 as a mechanism of synergistic enhancement of apoptosis in human lung cancer cells treated with the combination of a synthetic retinoid, Am80 and green tea catechin. J. Nutr. Biochem. 2017, 42, 7–16.
  63. Fujie, K.; Aoki, T.; Ito, Y.; Maeda, S. Sister-chromatid exchanges induced by trihalomethanes in rat erythroblastic cells and their suppression by crude catechin extracted from green tea. Mut. Res. Genet. Toxicol. 1993, 300, 241–246.
  64. Otsuka, T.; Ogo, T.; Eto, T.; Asano, Y.; Suganuma, M.; Niho, Y. Growth inhibition of leukemic cells by (−)-epigallocatechin gallate, the main constituent of green tea. Life Sci. 1998, 63, 1397–1403.
  65. Lung, H.L.; Ip, W.K.; Wong, C.K.; Mak, N.K.; Chen, Z.Y.; Leung, K.N. Anti-proliferative and differentiation-inducing activities of the green tea catechin epigallocatechin-3-gallate (EGCG) on the human eosinophilic leukemia EoL-1 cell line. Life Sci. 2002, 72, 257–268.
  66. Cornwall, S.; Cull, G.; Joske, D.; Ghassemifar, R. Green tea polyphenol “epigallocatechin-3-gallate”, differentially induces apoptosis in CLL B-and T-Cells but not in healthy B-and T-Cells in a dose dependant manner. Leuk. Res. 2016, 51, 56–61.
  67. Parodi, S.; Merlo, D.F.; Stagnaro, E. Coffee and tea consumption and risk of leukaemia in an adult population: A reanalysis of the Italian multicentre case-control study. Cancer Epidemiol. 2017, 47, 81–87.
  68. Hirose, M.; Hoshiya, T.; Akagi, K.; Futakuchi, M.; Ito, N. Inhibition of mammary gland carcinogenesis by green tea catechins and other naturally occurring antioxidants in female Sprague-Dawley rats pretreated with 7, 12-dimethylbenz [a] anthracene. Cancer Lett. 1994, 83, 149–156.
  69. Hirose, M.; Mizoguchi, Y.; Yaono, M.; Tanaka, H.; Yamaguchi, T.; Shirai, T. Effects of green tea catechins on the progression or late promotion stage of mammary gland carcinogenesis in female Sprague-Dawley rats pretreated with 7, 12-dimethylbenz (a) anthracene. Cancer Lett. 1997, 112, 141–147.
  70. Tanaka, H.; Hirose, M.; Kawabe, M.; Sano, M.; Takesada, Y.; Hagiwara, A.; Shirai, T. Post-initiation inhibitory effects of green tea catechins on 7, 12-dimethylbenz [a] anthracene-induced mammary gland carcinogenesis in female Sprague–Dawley rats. Cancer Lett. 1997, 116, 47–52.
  71. Li, W.; He, N.; Tian, L.; Shi, X.; Yang, X. Inhibitory effects of polyphenol-enriched extract from Ziyang tea against human breast cancer MCF-7 cells through reactive oxygen species-dependent mitochondria molecular mechanism. J. Food Drug Anal. 2016, 24, 527–538.
  72. Leung, A.C.Y.; Cook, L.S.; Swenerton, K.; Gilks, B.; Gallagher, R.P.; Magliocco, A.; Steed, H.; Köbel, M.; Nation, J.; Brooks-Wilson, A.; et al. Tea, coffee, and caffeinated beverage consumption and risk of epithelial ovarian cancers. Cancer Epidemiol. 2016, 45, 119–125.
  73. Gupta, S.; Ahmad, N.; Nieminen, A.-L.; Mukhtar, H. Growth inhibition, cell-cycle dysregulation, and induction of apoptosis by green tea constituent (−)-epigallocatechin-3-gallate in androgen-sensitive and androgen-insensitive human prostate carcinoma cells. Toxicol. Appl. Pharmacol. 2000, 164, 82–90.
  74. Wang, S.I.; Mukhtar, H. Gene expression profile in human prostate LNCaP cancer cells by (−) epigallocatechin-3-gallate. Cancer Lett. 2002, 182, 43–51.
  75. Hiipakka, R.A.; Zhang, H.-Z.; Dai, W.; Dai, Q.; Liao, S. Structure–activity relationships for inhibition of human 5α-reductases by polyphenols. Biochem. Pharmacol. 2002, 63, 1165–1176.
  76. Sawada, N. Risk and preventive factors for prostate cancer in Japan: The Japan public health center-based prospective (JPHC) study. J. Epidemiol. 2017, 27, 2–7.
  77. Carvalho, M.; Jerónimo, C.; Valentão, P.; Andrade, P.B.; Silva, B.M. Green tea: A promising anticancer agent for renal cell carcinoma. Food Chem. 2010, 122, 49–54.
  78. Annabi, B.; Lachambre, M.-P.; Bousquet-Gagnon, N.; Pagé, M.; Gingras, D.; Béliveau, R. Green tea polyphenol (−)-epigallocatechin 3-gallate inhibits MMP-2 secretion and MT1-MMP-driven migration in glioblastoma cells. Biochim. Biophys. Acta (BBA) Mol. Cell Res. 2002, 1542, 209–220.
  79. Mazzio, E.A.; Bauer, D.; Mendonca, P.; Taka, E.; Soliman, K.F.A. Natural product HTP screening for attenuation of cytokine-induced neutrophil chemo attractants (CINCs) and NO2—in LPS/IFNγ activated glioma cells. J. Neuroimmunol. 2017, 302, 10–19.
  80. Burkard, M.; Leischner, C.; Lauer, U.M.; Busch, C.; Venturelli, S.; Frank, J. Dietary flavonoids and modulation of natural killer cells: Implications in malignant and viral diseases. J. Nutr. Biochem. 2017, 46, 1–12.
  81. Edenharder, R.; Sager, J.W.; Glatt, H.; Muckel, E.; Platt, K.L. Protection by beverages, fruits, vegetables, herbs, and flavonoids against genotoxicity of 2-acetylaminofluorene and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in metabolically competent V79 cells. Mut. Res. Genet. Toxicol. Environ. Mut. 2002, 521, 57–72.
  82. Kada, T.; Kaneko, K.; Matsuzaki, S.; Matsuzaki, T.; Hora, Y. Detection and chemical identification of natural bio-antimutagens: A case of the green tea factor. Mut. Res. Fundam. Mol. Mech. Mutagenes. 1985, 150, 127–132.
  83. Wang, Z.Y.; Cheng, S.J.; Zhou, Z.C.; Athar, M.; Khan, W.A.; Bickers, D.R.; Mukhtar, H. Antimutagenic activity of green tea polyphenols. Mut. Res. Genet. Toxicol. 1989, 223, 273–285.
  84. Bu-Abbas, A.; Clifford, M.; Walker, R.; Ioannides, C. Marked antimutagenic potential of aqueous green tea extracts: Mechanism of action. Mutagenesis 1994, 9, 325–331.
  85. Kuroda, Y. Bio-antimutagenic activity of green tea catechins in cultured Chinese hamster V79 cells. Mut. Res. Environ. Mut. Relat. Subj. 1996, 361, 179–186.
  86. Okai, Y.; Higashi-Okai, K. Potent suppressing activity of the non-polyphenolic fraction of green tea (Camellia sinensis) against genotoxin-induced umu C gene expression in Salmonella typhimurium (TA 1535/pSK 1002)–association with pheophytins a and b. Cancer Lett. 1997, 120, 117–123.
  87. Gupta, S.; Saha, B.; Giri, A.K. Comparative antimutagenic and anticlastogenic effects of green tea and black tea: A review. Mut. Res. Rev. Mut. Res. 2002, 512, 37–65.
  88. Ikigai, H.; Nakae, T.; Hara, Y.; Shimamura, T. Bactericidal catechins damage the lipid bilayer. Biochim. Biophys. Acta (BBA) Biomembr. 1993, 1147, 132–136.
  89. Rasheed, A.; Haider, M. Antibacterial activity of Camellia sinensis extracts against dental caries. Arch. Pharm. Res. 1998, 21, 348–352.
  90. Sugita-Konishi, Y.; Hara-Kudo, Y.; Amano, F.; Okubo, T.; Aoi, N.; Iwaki, M.; Kumagai, S. Epigallocatechin gallate and gallocatechin gallate in green tea catechins inhibit extracellular release of Vero toxin from enterohemorrhagic Escherichia coli O157: H7. Biochim. Biophys. Acta (BBA) Gen. Subj. 1999, 1472, 42–50.
  91. Hui, X.; Liu, H.; Tian, F.-L.; Li, F.-F.; Li, H.; Gao, W.-Y. Inhibition of green tea and the catechins against 1-deoxy-d-xylulose 5-phosphate reductoisomerase, the key enzyme of the MEP terpenoid biosynthetic pathway. Fitoterapia 2016, 113, 80–84.
  92. Dyer, P.D.R.; Kotha, A.K.; Gollings, A.S.; Shorter, S.A.; Shepherd, T.R.; Pettit, M.W.; Alexander, B.D.; Getti, G.T.M.; El-Daher, S.; Baillie, L.; et al. An in vitro evaluation of epigallocatechin gallate (eGCG) as a biocompatible inhibitor of ricin toxin. Biochim. Biophys. Acta (BBA) Gen. Subj. 2016, 1860, 1541–1550.
  93. Rizk, M.A.; El-Sayed, S.A.E.-S.; AbouLaila, M.; Tuvshintulga, B.; Yokoyama, N.; Igarashi, I. Large-scale drug screening against Babesia divergens parasite using a fluorescence-based high-throughput screening assay. Vet. Parasitol. 2016, 227, 93–97.
  94. Tsou, L.K.; Yount, J.S.; Hang, H.C. Epigallocatechin-3-gallate inhibits bacterial virulence and invasion of host cells. Bioorg. Med. Chem. 2017, 25, 2883–2887.
  95. Piva, G.; Fracassetti, D.; Tirelli, A.; Mascheroni, E.; Musatti, A.; Inglese, P.; Piergiovanni, L.; Rollini, M. Evaluation of the antioxidant/antimicrobial performance of Posidonia oceanica in comparison with three commercial natural extracts and as a treatment on fresh-cut peaches (Prunus persica Batsch). Postharvest Biol. Technol. 2017, 124, 54–61.
  96. Sakanaka, S.; Juneja, L.R.; Taniguchi, M. Antimicrobial effects of green tea polyphenols on thermophilic spore-forming bacteria. J. Biosci. Bioeng. 2000, 90, 81–85.
  97. Yun, J.; Lee, D.G. Role of potassium channels in chlorogenic acid-induced apoptotic volume decrease and cell cycle arrest in Candida albicans. Biochim. Biophys. Acta (BBA) Gen. Subj. 2017, 1861, 585–592.
  98. Carneiro, B.M.; Batista, M.N.; Braga, A.C.S.; Nogueira, M.L.; Rahal, P. The green tea molecule EGCG inhibits Zika virus entry. Virology 2016, 496, 215–218.
  99. Hartjen, P.; Frerk, S.; Hauber, I.; Matzat, V.; Thomssen, A.; Holstermann, B.; Hohenberg, H.; Schulze, W.; zur Wiesch, J.S.; van Lunzen, J. Assessment of the range of the HIV-1 infectivity enhancing effect of individual human semen specimen and the range of inhibition by EGCG. AIDS Res. Ther. 2012, 9, 2.
  100. Bin Dajem, S.M.; Shati, A.A.; Adly, M.A.; Ahmed, O.M.; Ibrahim, E.H.; Mostafa, O.M.S. Green tea (Camellia sinesis) ameliorates female Schistosoma mansoni-induced changes in the liver of Balb/C mice. Saudi J. Biol. Sci. 2011, 18, 361–368.
  101. Wickramasinghe, S.; Yatawara, L.; Nagataki, M.; Agatsuma, T. Arginine kinase in Toxocara canis: Exon–intron organization, functional analysis of site-directed mutants and evaluation of putative enzyme inhibitors. Asian Pac. J. Trop. Med. 2016, 9, 995–1001.
  102. Vinson, J.A.; Dabbagh, Y.A. Effect of green and black tea supplementation on lipids, lipid oxidation and fibrinogen in the hamster: Mechanisms for the epidemiological benefits of tea drinking. FEBS Lett. 1998, 433, 44–46.
  103. Hartley, L.; Flowers, N.; Holmes, J.; Clarke, A.; Stranges, S.; Hooper, L.; Rees, K. Green and Black Tea for the Primary Prevention of Cardiovascular Disease; The Cochrane Library: Bethesda, MD, USA, 2013.
  104. Wasilewski, R.; Ubara, E.O.; Klonizakis, M. Assessing the effects of a short-term green tea intervention in skin microvascular function and oxygen tension in older and younger adults. Microvasc. Res. 2016, 107, 65–71.
  105. Yang, T.; Koo, M. Inhibitory effect of Chinese green tea on endothelial cell-induced LDL oxidation. Atherosclerosis 2000, 148, 67–73.
  106. Song, D.U.; Do Jung, Y.; Chay, K.O.; Chung, M.A.; Lee, K.H.; Yang, S.Y.; Shin, B.A.; Ahn, B.W. Effect of drinking green tea on age-associated accumulation of Maillard-type fluorescence and carbonyl groups in rat aortic and skin collagen. Arch. Biochem. Biophys. 2002, 397, 424–429.
  107. Pang, J.; Zhang, Z.; Zheng, T.-z.; Bassig, B.A.; Mao, C.; Liu, X.; Zhu, Y.; Shi, K.; Ge, J.; Yang, Y.-j. Green tea consumption and risk of cardiovascular and ischemic related diseases: A meta-analysis. Int. J. Cardiol. 2016, 202, 967–974.
  108. Lustosa, B.B.; Polegato, B.; Minicucci, M.; Rafacho, B.; Santos, P.P.; Fernandes, A.A.; Okoshi, K.; Batista, D.; Modesto, P.; Gonçalves, A.; et al. Green tea (Cammellia sinensis) attenuates ventricular remodeling after experimental myocardial infarction. Int. J. Cardiol. 2016, 225, 147–153.
  109. Bordoni, A.; Hrelia, S.; Angeloni, C.; Giordano, E.; Guarnieri, C.; Caldarera, C.M.; Biagi, P.L. Green tea protection of hypoxia/reoxygenation injury in cultured cardiac cells. J. Nutr. Biochem. 2002, 13, 103–111.
  110. Cheng, T.O. All teas are not created equal: The Chinese green tea and cardiovascular health. Int. J. Cardiol. 2006, 108, 301–308.
  111. Sun, T.-L.; Liu, Z.; Qi, Z.-J.; Huang, Y.-P.; Gao, X.-Q.; Zhang, Y.-Y. (−)-Epigallocatechin-3-gallate (EGCG) attenuates arsenic-induced cardiotoxicity in rats. Food Chem. Toxicol. 2016, 93, 102–110.
  112. Oyama, J.; Shiraki, A.; Nishikido, T.; Maeda, T.; Komoda, H.; Shimizu, T.; Makino, N.; Node, K. EGCG, a green tea catechin, attenuates the progression of heart failure induced by the heart/muscle-specific deletion of MnSOD in mice. Int. J. Cardiol. 2017, 69, 417–427.
  113. Ale-Agha, N.; Stahl, W.; Sies, H. (−)-Epicatechin effects in rat liver epithelial cells: Stimulation of gap junctional communication and counteraction of its loss due to the tumor promoter 12-O-tetradecanoylphorbol-13-acetate. Biochem. Pharmacol. 2002, 63, 2145–2149.
  114. Dower, J.I.; Geleijnse, J.M.; Gijsbers, L.; Zock, P.L.; Kromhout, D.; Hollman, P.C. Effects of the pure flavonoids epicatechin and quercetin on vascular function and cardiometabolic health: A randomized, double-blind, placebo-controlled, crossover trial. Am. J. Clin. Nutr. 2015, 101, 914–921.
  115. Keiichiro, M.; Mayumi, F.; Hara, Y. Effect of green tea catechins on plasma cholesterol level in cholesterol-fed rats. J. Nutr. Sci. Vitaminol. 1986, 32, 613–622.
  116. Yang, T.T.; Koo, M.W. Chinese green tea lowers cholesterol level through an increase in fecal lipid excretion. Life Sci. 1999, 66, 411–423.
  117. Afzalpour, M.E.; Ghasemi, E.; Zarban, A. Effects of 10 weeks of high intensity interval training and green tea supplementation on serum levels of Sirtuin-1 and peroxisome proliferator-activated receptor gamma co-activator 1-alpha in overweight women. Sci. Sports 2017, 32, 82–90.
  118. Ali, M.; Afzal, M.; Gubler, C.; Burka, J.F. A potent thromboxane formation inhibitor in green tea leaves. Prostaglandins Leukot. Essent. Fat. Acids 1990, 40, 281–283.
  119. Abe, I.; Seki, T.; Umehara, K.; Miyase, T.; Noguchi, H.; Sakakibara, J.; Ono, T. Green tea polyphenols: Novel and potent inhibitors of squalene epoxidase. Biochem. Biophys. Res. Commun. 2000, 268, 767–771.
  120. Kasaoka, S.; Hase, K.; Morita, T.; Kiriyama, S. Green tea flavonoids inhibit the LDL oxidation in osteogenic disordered rats fed a marginal ascorbic acid in diet. J. Nutr. Biochem. 2002, 13, 96–102.
  121. Yoshikawa, M.; Morikawa, T.; Yamamoto, K.; Kato, Y.; Nagatomo, A.; Matsuda, H. Floratheasaponins A−C, acylated oleanane-type triterpene oligoglycosides with anti-hyperlipidemic activities from flowers of the Tea plant (Camellia sinensis). J. Nat. Prod. 2005, 68, 1360–1365.
  122. Abe, Y.; Umemura, S.; Sugimoto, K.-I.; Hirawa, N.; Kato, Y.; Yokoyama, N.; Yokoyama, T.; Iwai, J.; Ishii, M. Effect of green tea rich in γ-aminobutyric acid on blood pressure of Dahl salt-sensitive rats. Am. J. Hypertens. 1995, 8, 74–79.
  123. Juneja, L.R.; Chu, D.-C.; Okubo, T.; Nagato, Y.; Yokogoshi, H. L-theanine—A unique amino acid of green tea and its relaxation effect in humans. Trends Food Sci. Technol. 1999, 10, 199–204.
  124. Bertoldi, M.; Gonsalvi, M.; Voltattorni, C.B. Green tea polyphenols: Novel irreversible inhibitors of dopa decarboxylase. Biochem. Biophys. Res. Commun. 2001, 284, 90–93.
  125. Yi, Q.-Y.; Li, H.-B.; Qi, J.; Yu, X.-J.; Huo, C.-J.; Li, X.; Bai, J.; Gao, H.-L.; Kou, B.; Liu, K.-L.; et al. Chronic infusion of epigallocatechin-3-O-gallate into the hypothalamic paraventricular nucleus attenuates hypertension and sympathoexcitation by restoring neurotransmitters and cytokines. Toxicol. Lett. 2016, 262, 105–113.
  126. Antonello, M.; Montemurro, D.; Bolognesi, M.; Di Pascoli, M.; Piva, A.; Grego, F.; Sticchi, D.; Giuliani, L.; Garbisa, S.; Rossi, G.P. Prevention of hypertension, cardiovascular damage and endothelial dysfunction with green tea extracts. Am. J. Hypertens. 2007, 20, 1321–1328.
  127. Ihm, S.-H.; Jang, S.-W.; Kim, O.-R.; Chang, K.; Oak, M.-H.; Lee, J.-O.; Lim, D.-Y.; Kim, J.-H. Decaffeinated green tea extract improves hypertension and insulin resistance in a rat model of metabolic syndrome. Atherosclerosis 2012, 224, 377–383.
  128. Kang, W.-S.; Lim, I.-H.; Yuk, D.-Y.; Chung, K.-H.; Park, J.-B.; Yoo, H.-S.; Yun, Y.-P. Antithrombotic activities of green tea catechins and (−)-epigallocatechin gallate. Thromb. Res. 1999, 96, 229–237.
  129. Lau, K.-M.; He, Z.-D.; Dong, H.; Fung, K.-P.; But, P.P.-H. Anti-oxidative, anti-inflammatory and hepato-protective effects of Ligustrum robustum. J. Ethnopharmacol. 2002, 83, 63–71.
  130. Ohnishi, S.T.; Ohnishi, T.; Ogunmola, G.B. Green tea extract and aged garlic extract inhibit anion transport and sickle cell dehydration in vitro. Blood Cells Mol. Dis. 2001, 27, 148–157.
  131. Peixoto, E.B.; Papadimitriou, A.; Teixeira, D.A.T.; Montemurro, C.; Duarte, D.A.; Silva, K.C.; Joazeiro, P.P.; Lopes de Faria, J.M.; Lopes de Faria, J.B. Reduced LRP6 expression and increase in the interaction of GSK3β with p53 contribute to podocyte apoptosis in diabetes mellitus and are prevented by green tea. J. Nutr. Biochem. 2015, 26, 416–430.
  132. Sampath, C.; Rashid, M.R.; Sang, S.; Ahmedna, M. Green tea epigallocatechin 3-gallate alleviates hyperglycemia and reduces advanced glycation end products via nrf2 pathway in mice with high fat diet-induced obesity. Biomed. Pharmacother. 2017, 87, 73–81.
  133. Pournourmohammadi, S.; Grimaldi, M.; Stridh, M.H.; Lavallard, V.; Waagepetersen, H.S.; Wollheim, C.B.; Maechler, P. Epigallocatechin-3-gallate (EGCG) activates AMPK through the inhibition of glutamate dehydrogenase in muscle and pancreatic ß-cells: A potential beneficial effect in the pre-diabetic state? Int. J. Biochem. Cell Biol. 2017, 88, 220–225.
  134. Sabu, M.; Smitha, K.; Kuttan, R. Anti-diabetic activity of green tea polyphenols and their role in reducing oxidative stress in experimental diabetes. J. Ethnopharmacol. 2002, 83, 109–116.
  135. Yoshikawa, M.; Wang, T.; Sugimoto, S.; Nakamura, S.; Nagatomo, A.; Matsuda, H.; Harima, S. Functional saponins in tea flower (flower buds of Camellia sinensis): Gastroprotective and hypoglycemic effects of floratheasaponins and qualitative and quantitative analysis using HPLC. J. Pharm. Soc. Jpn. 2008, 128, 141–151.
  136. Han, Q.; Yu, Q.-Y.; Shi, J.; Xiong, C.-Y.; Ling, Z.-J.; He, P.-M. Molecular characterization and hypoglycemic activity of a novel water-soluble polysaccharide from tea (Camellia sinensis) flower. Carbohydr. Polym. 2011, 86, 797–805.
  137. Sun, L.; Warren, F.J.; Netzel, G.; Gidley, M.J. 3 or 3′-Galloyl substitution plays an important role in association of catechins and theaflavins with porcine pancreatic α-amylase: The kinetics of inhibition of α-amylase by tea polyphenols. J. Funct. Foods. 2016, 26, 144–156.
  138. Juhel, C.; Armand, M.; Pafumi, Y.; Rosier, C.; Vandermander, J.; Lairon, D. Green tea extract (AR25®) inhibits lipolysis of triglycerides in gastric and duodenal medium in vitro. J. Nutr. Biochem. 2000, 11, 45–51.
  139. Levy, Y.; Narotzki, B.; Reznick, A.Z. Green tea, weight loss and physical activity. Clin. Nutr. 2017, 36, 315.
  140. Diepvens, K.; Kovacs, E.; Vogels, N.; Westerterp-Plantenga, M. Metabolic effects of green tea and of phases of weight loss. Physiol. Behav. 2006, 87, 185–191.
  141. Janssens, P.L.H.R.; Hursel, R.; Westerterp-Plantenga, M.S. Nutraceuticals for body-weight management: The role of green tea catechins. Physiol. Behav. 2016, 162, 83–87.
  142. Loftus, T.M.; Jaworsky, D.E.; Frehywot, G.L.; Townsend, C.A.; Ronnett, G.V.; Lane, M.D.; Kuhajda, F.P. Reduced food intake and body weight in mice treated with fatty acid synthase inhibitors. Science 2000, 288, 2379–2381.
  143. Wu, M.; Liu, D.; Zeng, R.; Xian, T.; Lu, Y.; Zeng, G.; Sun, Z.; Huang, B.; Huang, Q. Epigallocatechin-3-gallate inhibits adipogenesis through down-regulation of PPARγ and FAS expression mediated by PI3K-AKT signaling in 3T3-L1 cells. Eur. J. Pharmacol. 2017, 795, 134–142.
  144. Huang, Y.; Chan, N.W.K.; Lau, C.W.; Yao, X.Q.; Chan, F.L.; Chen, Z.Y. Involvement of endothelium/nitric oxide in vasorelaxation induced by purified green tea (−) epicatechin. Biochim. Biophys Acta (BBA) Gen. Subj. 1999, 1427, 322–328.
  145. Setozaki, S.; Minakata, K.; Masumoto, H.; Hirao, S.; Yamazaki, K.; Kuwahara, K.; Ikeda, T.; Sakata, R. Prevention of abdominal aortic aneurysm progression by oral administration of green tea polyphenol in a rat model. J. Vasc. Surg. 2016, 65, 1803–1812.
  146. Shibata, K.; Moriyama, M.; Fukushima, T.; Kaetsu, A.; Miyazaki, M.; Une, H. Green tea consumption and chronic atrophic gastritis: A cross-sectional study in a green tea production village. J. Epidemiol. 2000, 10, 310–316.
  147. Ahn, Y.-J.; Kawamura, T.; Kim, M.; Yamamoto, T.; Mitsuoka, T. Tea polyphenols: Selective growth inhibitors of Clostridium spp. Agric. Biol. Chem. 1991, 55, 1425–1426.
  148. Jung, E.S.; Park, H.M.; Hyun, S.M.; Shon, J.-C.; Liu, K.-H.; Hwang, J.S.; Lee, C.H. Modulation of gut microbiome by green tea diet and its correlation with metabolic changes. Drug Metab. Pharmacokinet. 2017, 32, S62.
  149. Hong, J.T.; Ryu, S.R.; Kim, H.J.; Lee, J.K.; Lee, S.H.; Kim, D.B.; Yun, Y.P.; Ryu, J.H.; Lee, B.M.; Kim, P.Y. Neuroprotective effect of green tea extract in experimental ischemia-reperfusion brain injury. Brain Res. Bull. 2000, 53, 743–749.
  150. Guo, Q.; Zhao, B.; Li, M.; Shen, S.; Xin, W. Studies on protective mechanisms of four components of green tea polyphenols against lipid peroxidation in synaptosomes. Biochim. Biophys. Acta (BBA) Lipid Lipid Metab. 1996, 1304, 210–222.
  151. Zhao, X.; Liu, F.; Jin, H.; Li, R.; Wang, Y.; Zhang, W.; Wang, H.; Chen, W. Involvement of PKCα and ERK1/2 signaling pathways in EGCG’s protection against stress-induced neural injuries in Wistar rats. Neuroscience 2017, 346, 226–237.
  152. Suganuma, M.; Okabe, S.; Oniyama, M.; Tada, Y.; Ito, H.; Fujiki, H. Wide distribution of [3H](-)-epigallocatechin gallate, a cancer preventive tea polyphenol, in mouse tissue. Carcinogenesis 1998, 19, 1771–1776.
  153. Nagai, K.; Jiang, M.H.; Hada, J.; Nagata, T.; Yajima, Y.; Yamamoto, S.; Nishizaki, T. (−)-Epigallocatechin gallate protects against NO stress-induced neuronal damage after ischemia by acting as an anti-oxidant. Brain Res. 2002, 956, 319–322.
  154. Bai, Q.; Lyu, Z.; Yang, X.; Pan, Z.; Lou, J.; Dong, T. Epigallocatechin-3-gallate promotes angiogenesis via up-regulation of Nfr2 signaling pathway in a mouse model of ischemic stroke. Behav. Brain Res. 2017, 321, 79–86.
  155. Ben, P.; Zhang, Z.; Zhu, Y.; Xiong, A.; Gao, Y.; Mu, J.; Yin, Z.; Luo, L. l-Theanine attenuates cadmium-induced neurotoxicity through the inhibition of oxidative damage and tau hyperphosphorylation. Neurotoxicology 2016, 57, 95–103.
  156. Levites, Y.; Youdim, M.B.H.; Maor, G.; Mandel, S. Attenuation of 6-hydroxydopamine (6-OHDA)-induced nuclear factor-kappaB (NF-κB) activation and cell death by tea extracts in neuronal cultures1. Biochem. Pharmacol. 2002, 63, 21–29.
  157. Weinreb, O.; Mandel, S.; Amit, T.; Youdim, M.B. Neurological mechanisms of green tea polyphenols in Alzheimer’s and Parkinson’s diseases. J. Nutr. Biochem. 2004, 15, 506–516.
  158. Unno, K.; Takabayashi, F.; Kishido, T.; Oku, N. Suppressive effect of green tea catechins on morphologic and functional regression of the brain in aged mice with accelerated senescence (SAMP10). Exp. Gerontol. 2004, 39, 1027–1034.
  159. McConnell, J.S.; McConnell, R.; Hossner, L. Ultraviolet spectra of acetic acid, glycine, and glyphosate. Proc. Ark. Acad. Sci. 1993, 47, 73–76.
  160. Choi, J.-Y.; Park, C.-S.; Kim, D.-J.; Cho, M.-H.; Jin, B.-K.; Pie, J.-E.; Chung, W.-G. Prevention of nitric oxide-mediated 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-induced Parkinson’s disease in mice by tea phenolic epigallocatechin 3-gallate. Neurotoxicology 2002, 23, 367–374.
  161. Choi, Y.-T.; Jung, C.-H.; Lee, S.-R.; Bae, J.-H.; Baek, W.-K.; Suh, M.-H.; Park, J.; Park, C.-W.; Suh, S.-I. The green tea polyphenol (−)-epigallocatechin gallate attenuates β-amyloid-induced neurotoxicity in cultured hippocampal neurons. Life Sci. 2001, 70, 603–614.
  162. Selkoe, D.J. Deciphering Alzheimer’s disease: The amyloid precursor protein yields new clues. Science 1990, 248, 1058–1060.
  163. Jeon, S.-Y.; Bae, K.; Seong, Y.-H.; Song, K.-S. Green tea catechins as a BACE1 (β-Secretase) inhibitor. Bioorg. Med. Chem. Lett. 2003, 13, 3905–3908.
  164. Geiser, R.J.; Chastain, S.E.; Moss, M.A. Regulation of Bace1 Mrna Expression in Alzheimer’S Disease by Green Tea Catechins and Black Tea Theaflavins. Biophys. J. 2017, 112, 362a.
  165. Kaur, T.; Pathak, C.M.; Pandhi, P.; Khanduja, K.L. Effects of green tea extract on learning, memory, behavior and acetylcholinesterase activity in young and old male rats. Brain Cogn. 2008, 67, 25–30.
  166. Molino, S.; Dossena, M.; Buonocore, D.; Ferrari, F.; Venturini, L.; Ricevuti, G.; Verri, M. Polyphenols in dementia: From molecular basis to clinical trials. Life Sci. 2016, 161, 69–77.
  167. Pervin, M.; Unno, K.; Nakagawa, A.; Takahashi, Y.; Iguchi, K.; Yamamoto, H.; Hoshino, M.; Hara, A.; Takagaki, A.; Nanjo, F.; et al. Blood brain barrier permeability of (−)-epigallocatechin gallate, its proliferation-enhancing activity of human neuroblastoma SH-SY5Y cells, and its preventive effect on age-related cognitive dysfunction in mice. Biochem. Biophys. Rep. 2017, 9, 180–186.
  168. Unno, K.; Hara, A.; Nakagawa, A.; Iguchi, K.; Ohshio, M.; Morita, A.; Nakamura, Y. Anti-stress effects of drinking green tea with lowered caffeine and enriched theanine, epigallocatechin and arginine on psychosocial stress induced adrenal hypertrophy in mice. Phytomedicine 2016, 23, 1365–1374.
  169. Wang, Z.Y.; Khan, W.A.; Bickers, D.R.; Mukhtar, H. Protection against polycyclic aromatic hydrocarbon-induced skin tumor initiation in mice by green tea polyphenols. Carcinogenesis 1989, 10, 411–415.
  170. Yang, F.; De Villiers, W.J.; McClain, C.J.; Varilek, G.W. Green tea polyphenols block endotoxin-induced tumor necrosis factor-production and lethality in a murine model. J. Nutr. 1998, 128, 2334–2340.
  171. Chan, M.M.-Y.; Fong, D.; Ho, C.-T.; Huang, H.-I. Inhibition of inducible nitric oxide synthase gene expression and enzyme activity by epigallocatechin gallate, a natural product from green tea. Biochem. Pharmacol. 1997, 54, 1281–1286.
  172. Higashi-Okai, K.; Otani, S.; Okai, Y. Potent suppressive activity of pheophytin a and b from the non-polyphenolic fraction of green tea (Camellia sinensis) against tumor promotion in mouse skin. Cancer Lett. 1998, 129, 223–228.
  173. Ashraf, A.; Sadrneshin, S.; Mosavat, S.H.; Hashempur, M.H. Efficacy of the green tea (Camellia sinensis) tablet in knee osteoarthritis. Eur. J. Integr. Med. 2016, 8, 10–11.
  174. Maeda, Y. Inhibitory effects of tea extracts on histamine release from mast cells. J. Jpn. Food Hyg. 1980, 30, 295–299.
  175. Akagi, M.; Fukuishi, N.; Tomoko, K.; SAGESAKA, Y.M.; Akagi, R. Anti-allergic effect of tea-leaf saponin (TLS) from tea leaves (Camellia sinensis var. sinensis). Biol. Pharm. Bull. 1997, 20, 565–567.
  176. Yoshikawa, M.; Nakamura, S.; Kato, Y.; Matsuhira, K.; Matsuda, H. Medicinal Flowers. XIV. 1) New acylated oleanane-type triterpene oligoglycosides with antiallergic activity from flower buds of chinese tea plant (Camellia sinensis). Chem. Pharm. Bull. 2007, 55, 598–605.
  177. Pandit, C.; Anilakumar, K.R. Cold adaptive thermogenesis following consumption of certain pungent spice principles: A validation study. J. Therm. Biol. 2017, 64, 35–40.
  178. Ng, H.L.H.; Premilovac, D.; Rattigan, S.; Richards, S.M.; Muniyappa, R.; Quon, M.J.; Keske, M.A. Acute vascular and metabolic actions of the green tea polyphenol epigallocatechin 3-gallate in rat skeletal muscle. J. Nutr. Biochem. 2017, 40, 23–31.
  179. Kim, A.R.; Kim, K.M.; Byun, M.R.; Hwang, J.-H.; Park, J.I.; Oh, H.T.; Jeong, M.G.; Hwang, E.S.; Hong, J.-H. (−)-Epigallocatechin-3-gallate stimulates myogenic differentiation through TAZ activation. Biochem. Biophys. Res. Commun. 2017, 29, 378–384.
  180. Takahashi, H.; Suzuki, Y.; Mohamed, J.S.; Gotoh, T.; Pereira, S.L.; Alway, S.E. Epigallocatechin-3-gallate increases autophagy signaling in resting and unloaded plantaris muscles but selectively suppresses autophagy protein abundance in reloaded muscles of aged rats. Exp. Gerontol. 2017, 92, 55–56.
  181. Nakagawa, H.; Wachi, M.; Woo, J.-T.; Kato, M.; Kasai, S.; Takahashi, F.; Lee, I.-S.; Nagai, K. Fenton reaction is primarily involved in a mechanism of (−)-epigallocatechin-3-gallate to induce osteoclastic cell death. Biochem. Biophys. Res. Commun. 2002, 292, 94–101.
  182. Chu, C.; Deng, J.; Xiang, L.; Wu, Y.; Wei, X.; Qu, Y.; Man, Y. Evaluation of epigallocatechin-3-gallate (EGCG) cross-linked collagen membranes and concerns on osteoblasts. Mater. Sci. Eng. C 2016, 67, 386–394.
  183. Tomaszewska, E.; Dobrowolski, P.; Winiarska-Mieczan, A.; Kwiecień, M.; Tomczyk, A.; Muszyński, S.; Radzki, R. Alteration in bone geometric and mechanical properties, histomorphometrical parameters of trabecular bone, articular cartilage, and growth plate in adolescent rats after chronic co-exposure to cadmium and lead in the case of supplementation with green, black, red and white tea. Environ. Toxicol. Pharmacol. 2016, 46, 36–44.
  184. Kuroyanagi, G.; Tokuda, H.; Yamamoto, N.; Kainuma, S.; Fujita, K.; Ohguchi, R.; Kawabata, T.; Sakai, G.; Matsushima-Nishiwaki, R.; Harada, A.; et al. (−)-Epigallocatechin gallate synergistically potentiates prostaglandin E2-stimulated osteoprotegerin synthesis in osteoblasts. Prostaglandins Lipid Med. 2017, 128–129, 27–33.
  185. Ahmed, S.; Rahman, A.; Hasnain, A.; Lalonde, M.; Goldberg, V.M.; Haqqi, T.M. Green tea polyphenol epigallocatechin-3-gallate inhibits the IL-1β-induced activity and expression of cyclooxygenase-2 and nitric oxide synthase-2 in human chondrocytes. Free Radic. Biol. Med. 2002, 33, 1097–1105.
  186. Hashempur, M.H.; Sadrneshin, S.; Mosavat, S.H.; Ashraf, A. Green tea (Camellia sinensis) for patients with knee osteoarthritis: A randomized open-label active-controlled clinical trial. Clin. Nutr. 2016, 37, 85–90.
  187. Horiba, N.; Maekawa, Y.; Ito, M.; Matsumoto, T.; Nakamura, H. A pilot study of Japanese green tea as a medicament: Antibacterial and bactericidal effects. J. Endod. 1991, 17, 122–124.
  188. You, S. Study on feasibility of Chinese green tea polyphenols (CTP) for preventing dental caries. Chin. J. Stomatol. 1993, 28, 197–199.
  189. Kawarai, T.; Narisawa, N.; Yoneda, S.; Tsutsumi, Y.; Ishikawa, J.; Hoshino, Y.; Senpuku, H. Inhibition of Streptococcus mutans biofilm formation using extracts from Assam tea compared to green tea. Arch. Oral Biol. 2016, 68, 73–82.
  190. Abdulbaqi, H.R.; Himratul-Aznita, W.H.; Baharuddin, N.A. Anti-plaque effect of a synergistic combination of green tea and Salvadora persica L. against primary colonizers of dental plaque. Arch. Oral Biol. 2016, 70, 117–124.
  191. Kim-Park, W.K.; Allam, E.S.; Palasuk, J.; Kowolik, M.; Park, K.K.; Windsor, L.J. Green tea catechin inhibits the activity and neutrophil release of Matrix Metalloproteinase-9. J. Tradit. Complement. Med. 2016, 6, 343–346.
  192. Morin, M.-P.; Grenier, D. Regulation of matrix metalloproteinase secretion by green tea catechins in a three-dimensional co-culture model of macrophages and gingival fibroblasts. Arch. Oral Biol. 2017, 75, 89–99.
  193. Hu, S.; Zhang, X.; Chen, F.; Wang, M. Dietary polyphenols as photoprotective agents against UV radiation. J. Funct. Foods 2017, 30, 108–118.
  194. Jongil, K.; Jaesung, H.; Younki, C.; Yongku, H.; Youngjin, J.; Yang, K.-H. Protective effects of green tea polyphenols on the ultraviolet-induced dermal extracellular damage. J. Dermatol. Sci. 1998, 16, 127.
  195. Katiyar, S.K.; Bergamo, B.M.; Vyalil, P.K.; Elmets, C.A. Green tea polyphenols: DNA photodamage and photoimmunology. J. Photochem. Photobiol. B Biol. 2001, 65, 109–114.
  196. Elmets, C.A.; Singh, D.; Tubesing, K.; Matsui, M.; Katiyar, S.; Mukhtar, H. Cutaneous photoprotection from ultraviolet injury by green tea polyphenols. J. Am. Acad. Dermatol. 2001, 44, 425–432.
  197. Katiyar, S.K.; Afaq, F.; Azizuddin, K.; Mukhtar, H. Inhibition of UVB-induced oxidative stress-mediated phosphorylation of mitogen-activated protein kinase signaling pathways in cultured human epidermal keratinocytes by green tea polyphenol (−)-epigallocatechin-3-gallate. Toxicol. Appl. Pharmacol. 2001, 176, 110–117.
  198. Asadi, S.Y.; Parsaei, P.; Karimi, M.; Ezzati, S.; Zamiri, A.; Mohammadizadeh, F.; Rafieian-kopaei, M. Effect of green tea (Camellia sinensis) extract on healing process of surgical wounds in rat. Int. J. Surg. 2013, 11, 332–337.
  199. Hong, Y.-H.; Jung, E.Y.; Noh, D.O.; Suh, H.J. Physiological effects of formulation containing tannase-converted green tea extract on skin care: Physical stability, collagenase, elastase, and tyrosinase activities. Int. Med. Res. 2014, 3, 25–33.
  200. Lu, M.-J.; Chen, C. Enzymatic tannase treatment of green tea increases in vitro inhibitory activity against N-nitrosation of dimethylamine. Process Biochem. 2007, 42, 1285–1290.
  201. An, T.-T.; Feng, S.; Zeng, C.-M. Oxidized epigallocatechin gallate inhibited lysozyme fibrillation more strongly than the native form. Redox Biol. 2017, 11, 315–321.
  202. Sarkar, J.; Nandy, S.K.; Chowdhury, A.; Chakraborti, T.; Chakraborti, S. Inhibition of MMP-9 by green tea catechins and prediction of their interaction by molecular docking analysis. Biomed. Pharmacother. 2016, 84, 340–347.
  203. Hwang, Y.P.; Jin, S.W.; Choi, J.H.; Choi, C.Y.; Kim, H.G.; Kim, S.J.; Kim, Y.; Lee, K.J.; Chung, Y.C.; Jeong, H.G. Inhibitory effects of l-theanine on airway inflammation in ovalbumin-induced allergic asthma. Food Chem. Toxicol. 2017, 99, 162–169.
  204. Jówko, E.; Sacharuk, J.; Balasińska, B.; Ostaszewski, P.; Charmas, M.; Charmas, R. Green tea extract supplementation gives protection against exercise-induced oxidative damage in healthy men. Nutr. Res. 2011, 31, 813–821.
  205. Mohamad Shalan, N.A.A.; Mustapha, N.M.; Mohamed, S. Morinda citrifolia leaf enhanced performance by improving angiogenesis, mitochondrial biogenesis, antioxidant, anti-inflammatory & stress responses. Food Chem. 2016, 212, 443–452.
  206. Sanguigni, V.; Manco, M.; Sorge, R.; Gnessi, L.; Francomano, D. Natural antioxidant ice cream acutely reduces oxidative stress and improves vascular function and physical performance in healthy individuals. Nutrition 2017, 33, 225–233.
  207. Abdelrazek, H.M.A.; Helmy, S.A.; Elsayed, D.H.; Ebaid, H.M.; Mohamed, R.M. Ameliorating effects of green tea extract on cadmium induced reproductive injury in male Wistar rats with respect to androgen receptors and caspase-3. Reprod. Biol. 2016, 16, 300–308.
  208. Zanchi, M.M.; Manfredini, V.; dos Santos Brum, D.; Vargas, L.M.; Spiazzi, C.C.; Soares, M.B.; Izaguirry, A.P.; Santos, F.W. Green tea infusion improves cyclophosphamide-induced damage on male mice reproductive system. Toxicol. Rep. 2015, 2, 252–260.
  209. Roychoudhury, S.; Agarwal, A.; Virk, G.; Cho, C.-L. Potential role of green tea catechins in the management of oxidative stress-associated infertility. Reprod. BioMed. 2017, 34, 487–498.
  210. Gadani, B.; Bucci, D.; Spinaci, M.; Tamanini, C.; Galeati, G. Resveratrol and Epigallocatechin-3-gallate addition to thawed boar sperm improves in vitro fertilization. Theriogenology 2017, 90, 88–93.
  211. Satoh, K.; Sakamoto, Y.; Ogata, A.; Nagai, F.; Mikuriya, H.; Numazawa, M.; Yamada, K.; Aoki, N. Inhibition of aromatase activity by green tea extract catechins and their endocrinological effects of oral administration in rats. Food Chem. Toxicol. 2002, 40, 925–933.
  212. Xue, K.X.; Wang, S.; Ma, G.J.; Zhou, P.; Wu, P.Q.; Zhang, R.F.; Xu, Z.; Chen, W.S.; Wang, Y.Q. Micronucleus formation in peripheral-blood lymphocytes from smokers and the influence of alcohol-and tea-drinking habits. Int. J. Cancer 1992, 50, 702–705.
  213. Shalini, V.K.; Luthra, M.; Srinivas, L.; Rao, S.H.; Basti, S.; Reddy, M.; Balasubramanian, D. Oxidative damage to the eye lens caused by cigarette smoke and fuel smoke condensates. Ind. J. Biochem. Biophys. 1994, 31, 261–266.
  214. Chaudhury, S.; Roy, P.; Dasgupta, S. Green tea flavanols protect human γB-crystallin from oxidative photodamage. Biochimie 2017, 137, 46–55.
  215. Alessio, H.M.; Hagerman, A.E.; Romanello, M.; Carando, S.; Threlkeld, M.S.; Rogers, J.; Dimitrova, Y.; Muhammed, S.; Wiley, R.L. Consumption of green tea protects rats from exercise-induced oxidative stress in kidney and liver. Nutr. Res. 2002, 22, 1177–1188.
  216. Yokozawa, T.; Dong, E.; Oura, H. Proof that green tea tannin suppresses the increase in the blood methylguanidine level associated with renal failure. Exp. Toxicol. Pathol. 1997, 49, 117–122.
  217. Delwing-Dal Magro, D.; Roecker, R.; Junges, G.M.; Rodrigues, A.F.; Delwing-de Lima, D.; da Cruz, J.G.P.; Wyse, A.T.S.; Pitz, H.S.; Zeni, A.L.B. Protective effect of green tea extract against proline-induced oxidative damage in the rat kidney. Biomed. Pharmacother. 2016, 83, 1422–1427.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
This entry is offline, you can click here to edit this entry!
Video Production Service
Feedback