Liver disease is a reduced function in toxin elimination of liver as a result of damage or injure, causing by medication, viral infection,....
Green tea, a precious drink processes numbers of health benefit known to almost everyone in Asia and Western world.
However, as yin in nature herbal medicine ,or food, long term injection of large amounts may obstruct the balance of yin-yang, induced "yin excessive syndrome" or "yang vacuity syndrome" including weaken immunity and painful case of GERD,... according to traditional Chinese medicine's Yin-Yang theory.
According to the joint study lead by the Zhujiang Hospital of Southern Medical University Guangzhou, in the review of the data base of PubMed, CNKI, Wanfang and Weipu databases, regular green tea drinking is associated to a significant reduction in the risk of liver disease(1), including hepatocellular carcinoma, liver steatosis, hepatitis, liver cirrhosis and chronic liver disease.
Green tea demonstrated a reduced risk of liver disease regardless of races and geographies(1) of the patients resided such as Asian, American and European subgroups.
According to the joint study lead by the Zhujiang Hospital of Southern Medical University Guangzhou, in the review of the data base of PubMed, CNKI, Wanfang and Weipu databases, regular green tea drinking is associated to a significant reduction in the risk of liver disease(1), including hepatocellular carcinoma, liver steatosis, hepatitis, liver cirrhosis and chronic liver disease.
Green tea demonstrated a reduced risk of liver disease regardless of races and geographies(1) of the patients resided such as Asian, American and European subgroups.
1. Liver Cancer
2. Non-alcoholic Fatty Liver Disease
Non-alcoholic Fatty Liver Disease is a condition caused by over accumulated of fat in the liver.
According to the University of Connecticut, Storrs, the efficacy of green tea for treatment of obese patients with nonalcoholic fatty liver disease is associated to polyphenolic catechins in induction of hypolipidemic, thermogenic, antioxidant, and anti-inflammatory activities(7).
These chemical compound have also found to mitigate the occurrence and progression of NAFLD.
Dr. Masterjohn C(7), the lead author said, "(The phytochemical compounds are) demonstrating the hepatoprotective properties of green tea and its catechins and the proposed mechanisms by which these targeted dietary agents protect against NAFLD".
In mice fed on a high-fat diet for 24 weeks, then injected with EGCG (10, 20 and 40 mg·kg(-1)·d(-1), ip), for 4 weeks, researchers found that treated mice showed a significant improvement of high-fat diet in induced the body weight, grade 2 or 3 liver fatty degeneration (steatosis, lobular inflammation and ballooning), severe hyperlipidemia, hyperglycemia, hyperinsulinemia and insulin resistance(8)..
The phytocheimcal EGCG, in dose-dependent also enhanced insulin clearance and upregulated IDE protein expression and enzyme activity(8) in regulated levels of glucose in the liver of treated mice.
In fact EGCG not only promoted weigh loss but also attenuated symptoms of mice with nonalcoholic fatty liver disease.
Administration of green tea polyphenols (GTP) on non-alcoholic fatty liver disease (NAFLD) in Zucker fatty (ZF) rats, not only decreased weight gain and significantly lowered visceral fat but also reduced fasting serum insulin, glucose and lipids levels(9), through ameliorated expression of hepatic TG accumulation and cytoplasmic lipid droplet(9) as well as diminished hepatic lipogenesis and triglycerides out flux from liver(9).
3. Liver Cirrhosis
Liver cirrhosis is a condition of abnormal function of liver due to damage liver tissue replaced by scar tissue.
According to statistic, risk of liver cirrhosis is 1.6% in adult population.
Green tea polyphenols in reduced risk and treatment of patients with liver cirrhosis was found to associate to numbers of implication, involving various mechanisms.
In male SD rats model induced liver cirrhosis through carbon tetrachloride(CCL4), randomly assigned to 3 groups, including normal group, green tea extract (GTE) group and cirrhosis group, with GTE group and the cirrhosis group were injected subcutanuously 2 times/wk over 9 weeks with 40% Carbon tetrachloride (CCl4), researcher found that green tea treatment groups displayed a significant reduction of concentration of hydroxyproline(11), an amino acid produced during the hydrolysis of collagen initiate scar accumulation in the liver damage tissue caused by CCl4)(11) in compared to cirrhosis group.
Green tea application also exhibited antioxidant activities in decreased expression of malondialdehyde (MDA)(11), a highly toxic reactive species in precipitated liver damage induced by application of carbon tetrachloride(CCL4).
Green tea extract ameliorated the liver damage cell in formation of cirrhosis through attenuating the expression of transforming growth factor beta 1 or TGF-β1(11) in initiated cell growth, cell proliferation.
In differentiation of 11 patients with hepatitis C and detectable viremia of 4 Child-Pugh (CP) class A cirrhosis, 4 Child-Pugh class B cirrhosis, and 3 noncirrhotic, researchers at the Thomas Jefferson University indicated that injection of a single oral dose of green tea extract 400 mg containing 94% pure EGCG demonstrated a strong effect in reduced cirrhosis over expression in induction of liver tumor growth(12) by inhibiting the virus hepatitis in facilitated production of ROS species through chronic liver inflammation(12), according to the blood sample withdrawn from the patients without inducing liver toxicity.
Dr. Halegoua-De Marzio D(11), after taking into account of other con founders said, "A single 400-mg oral dose of EGCG was safe and well tolerated by all of the patients in the study" and disposition of EGCG was not significantly altered in these patients with cirrhosis".
In the concern of abnormal angiogenesis in patients with liver cirrhosis in induction of severe complications such as variceal haemorrhage and encephalopathy, Dr. Hsu SJ and colleges conducted a study to investigate the effect of green tea extract in Spraqtue-Dawley rats liver induced in by common BDL (bile duct ligation) in compared to control given distill water for 28 days and found that group treated with green tea extract expressed a strong implication in ameliorated the severity of portosystemic shunting(10), a rare malformation of the vessels supplying blood to the liver caused by excessive shunting of blood from the liver portal vein to the lower and middle body into the right atrium of the heart due to liver cirrhosis(10) in induction portal hypertension, one of complication of variceal haemorrhage in patient with chronic liver cirrhosis and mesenteric angiogenesis(10) in development of new blood vessels to supply oxygen and nutrients to initiate liver cancer.
The effect of green tea GTP extract in reduced progression of liver cirrhosis was attributed to the suppression of hypoxia-inducible factor 1-alpha (HIF-1α)(10) in expression of liver disease of diverse etiologies, including chronic liver diseases caused by viral infection, excessive alcohol consumption and activation of protein kinase B (Akt)(10) in regulated infectious liver cell survival, cell-cycle progression,... and levels of VEGF(10) in reflection of increased portal hypertension or decreased hepatic regenerative activity or the combination of both.
Dr.Hsu SJ(10), the lead author said after the conclusion, "GTP appears to be an appropriate agent in controlling portal hypertension-related complications via anti-angiogenesis.
4. Liver Fibrosis
Liver fibrosis is a liver disease with excessive accumulation of scar tissue as a result of inflammation and liver cell death
According to Fibro Test, approximately, the prevalence of advanced fibrosis was 2.8% in a general population aged 40 years or older.
Application of a novel bio-nano particle named 'Chitosan nano-encapsulated green tea extract' at the ultrastructural level on 25 adult rats induced liver toxicity by injection of carbon-tetrachloride and ethanol doses for 3 weeks, expressed a significant reduction of nearly 25% of the sub-cellular area infected with hepatic fibrosis(13).
The efficacy of Chitosan nano-encapsulated green tea extract in decreased liver fibroids was attributed to the antioxidant activity in inhibited the expression of the injected chemicals in induction over production of reactive oxygen species (ROS)(13) in chain reaction to elevated oxidative stress in initiation of liver cell apoptosis.
Observed by scanning electron microscopy, oral administration of novel bio-nano particle also exerted a strong free radical scavengers effect in protected against changes of cell surface structure and surrounding area between the hepatocytes(14), thus ameliorated risk of collagen deposit to cause liver fibroids.
In carbon tetrachloride CCL4 induced fibrotic liver tissues in rat models, treatment of green tea extract (GTE) encapsulated into Chitosan Nanoparties (CS-NPs) revealed that collagen fibers of 250 to 300 nm widths found in the fibrotic liver samples of control group with no treatment in compared to no collagen fibers in green tea treatment group(11).
The effectiveness of GTE is reduced expression of collagen fibers in the liver a was found to correlate to the antioxidant expression in reduced CCL4(11) in induction of over production of free radicals in precipitated liver tissue damage.
In the evaluation of the protective effect of green tea extract (GT) on hepatic fibrosis in vitro and in vivo in dimethylnitrosamine (DMN)-induced rats, researchers at the Korea University, indicated that application of GT inhibited activated HSC-T6(15), a rat hepatic stellate cell line which is considered as the major cell type involved in liver fibrosis.
The application also attenuated the collagen deposition which are elevated and acted as a biomaker for progression of liver fibrosis, particularly, in expression of collagen type 1 formation of scar tissue in response to liver damage(15), found in the early event in the development of hepatic fibrosis, confirmed both by liver histology and by quantitative measurement of hepatic hydroxyproline content.
Dr. Kim HK(15), the lead author said, "green tea administration can effectively improve liver fibrosis caused by DMN, and may be used as a therapeutic option and preventive measure against hepatic fibrosis".
5. Autoimmune Hepatitis
Autoimmune hepatitis is a medical condition characterized by immune system attacking the liver cells in induction of liver cirrhosis as a result of long term liver cellular inflammation and necrosis.
The study of concanavalin A (ConA) (25 mg/kg) induced autoimmune hepatitis in mice, pretreatment of green tea exerted a strong inhibition of inflammatory cytokines through increased Bcl-2 expression(16) with function of blocking the apoptotic death of some cells and deceased activity of protein Bax in activated p53, a tumor suppressor to induce cell death and caspase-3, and Caspase-9 proteins(16) in signaling molecules in responsible for executing cell death in compared to ConA-treated group within 8 hours of applications, according to observation of TUNEL assay by detecting apoptotic cells that undergo extensive DNA degradation.
In other words, green tea EGCG administration reduced expression of ConA in induction of decreased numbers of infectious cells being attacked by the immune system, thus ameliorating risk of liver cell damage.
Application of green tea bioactive polyphenols Epigallocatechin-3-gallate (10 or 30 mg/kg) orally twice daily for 10 days before ConA injection also demonstrated a significant activity in reduced activation of BNIP3(16), a member of the apoptotic Bcl-2 protein family in mediated infectious cell apoptosis through autophagy(16) in induced destruction of damaged or redundant cellular components in compared to lectin ConA.
The result of green tea EGCG efficacy in induction of BNIP3 to decrease expression of concanavalin A (ConA) in reduction of numbers infectious cell proliferation was attributed to the IL-6/JAK/STAT3(16) signaling pathway which plays an important role in the mechanisms in exhibited green tea EGCG antioxidant activity in blocking infectious cells migration and invasion in exhibited hepatoprotective effect.
In other words, said, Dr. Li S(16), the lead scientist "EGCG attenuated liver injury in ConA-induced hepatitis by down-regulating IL-6/JAKs/STAT3/BNIP3-mediated apoptosis and autophagy".
Further differentiation also found that green tea EGCG administration inhibited the immune over reaction and pathological damage by decreased expression of inflammatory cytokines induced by Tumor necrosis factor (TNF)(16), tumor necrosis factor alpha, a cell signaling protein (cytokine) in activated systemic inflammation in the acute phase infection.
Green tea also modulated the inflammatory factors, interleukin 6 (IL-6)(16), the pro inflammatory cytokines and anti inflammatory mytokins promptly and transiently produced in response to infections and tissue injuries and interferon-gamma (IFN-γ)(16), a cytokine that plays an important role in inducing and modulating immune responses to the infectious tissue, as well as cytokine interleukin-1β (IL-1β)(16), a key mediator of the inflammatory response in protected body against pathological invasion.
6. Hepatitis B
Hepatitis B is a viral infection of acute and chronic liver disease, caused by a double stranded DNA virus HBV transmitted through infected blood, semen, or other body fluid.
According to the statistic, positive carriers among Canadian is estimated to be 0.5% to 1.0%., depending to ethnicity.
According to the evaluation of the effect of green tea bioactive polyphenos epigallocatechin-3 gallate (EGCG) and risk of hepatitis B, application of the phytochemical inhibited HBV replication in the testing Hep3B2.1-7 hepatocellular carcinoma cell line(17), through a significant effect in reduced prevalence of liver damage caused by hepatitis B virus.
Injection of EGCG at the dose of less than 100 μM in the observed liver cancer cell line showed no effect in induced cell apoptosis and decreased proliferation but exhibited a strong effect in ameliorated expression of surface antigen of the hepatitis B virus (HBsAg)(18) and antigen of hepatitis B virus(18) circulated in infected blood (HBeAg) levels found by the ELISA method and the polymerase chain reaction (PCR)assay.
Differentiation in different HepG2 2.2.15 cells to compare the effective of green tea with standard antiretroviral medication lamivudine (3TC), researchers indicated that administration of EGCG shows a significant inhibition of viral proliferation through attenuated expression of levels of HBsAg and HBeAg in the supernatant and extracellular HBV DNA(18) in a dose- and time-dependent manner.
At doses of 50-200 μg/ml EGCG displayed strong effects in compared to lamivudine (3TC) at dose of 200 μg/ml(18).
Application of EGCG also suppressed the extracellular HBV DNA(18), a nutrient source for viral cell proliferation and survival through attachment, aggregation, and stabilization of microcolonies.
The results of the experiments pointed out that green tea EGCG comprises a potential anti-HBV activity with low toxicity.
In the investigation of green tea EGCG effect in the early stages of infection caused by four different Hepatitis B virus genotypes A and D researchers also found that at dose of more than 80%, the phyochemical inhibited both DMSO-differentiated HuS-E/2 cells and HA-NTCP-expressing Huh7 cells(19) involved cancer cell process in early stage of proliferation through induced protein degradation and ameliorated serum of tansferrin(19).(the iron-binding blood plasma glycoproteins that control the level of free iron in biological fluids)which is considered as a liver fibrosis biomarker in patients with chronic hepatitis B.
However, treatment of cells with EGCG had no effect on HBV genome replication or virion secretion(19) and the characteristic of HBV virion and the expression of known HBV entry factors were unaltered(19) out side of the host before attacking the liver tissue.
7. Hepatitis C
Hepatitis C is medical condition induced by contaminated food intake containing hepatitis C virus (HCV). Hepatitis C has been found to associate with sever liver damage.
According to statistic, approximately 130–150 million people around the world are living with chronic HCV.
In Huh7.5.1 cells, a HCV cell culture (HCVcc) system using a JFH1-GFP chimeric virus, application of green tea EGCG with 50 % effective concentration (EC(50)) of 17.9 μM demonstrated a strong effect in interrupted HCV progression through monitoring HCV RNA and protein levels in Huh7.5.1 cells infected with the JFH1 virus(21) by preventing the mRNA in transferring infectious cell transcription in facilitated cell proliferation and division.
Injection of green tea at dose of 50 and 25 μM EGCG, expressed a significant inhibition of the presence of HCV after 2 and 5 passages in HCV cell culture (HCVcc) experiment(21), using an American Type Culture Collection (ATCC) reference strain, with little affect to the viral internal ribosome entry site (IRES) in initiated substitution of RNA sequences for viral protein synthesis(21) in shutting off classic host translation to evade host immune response.
Notably, in comparison of effect of green tea with potent anti-HCV medicine, cyclosporin A and tamoxifen, researchers indicated that application of green tea showed a strong anti HCV viral activity, similarly to those of anti hepatitis medicine through its antioxidant expression of flavonoids epigallocatechin gallate (EGCG) and 7,8-benzoflavone (α-naphthoflavone)(21), observed in HCV cell culture (HCVcc) by blocking the entry point of the virus in initiated infection to host cells(21) and stimulating the viral cell cycle arrest at the late stage of HCV life cycle(21), respectively
Some researchers in the evaluation of green tea polyphenols (-)-epigallocatechin-3-gallate (EGCG) in hepatitis C infection suggested that EGCG processed anti viral expression through interrupting the cross link between HCV life cycle involving steps of entry, replication(22).
Injection of a concentration of 50 μM of EGCG was found to inhibit HCV infectivity by more than 90% at an early step of the viral life cycle(20).
The interrupted property in blocking the HCV entry cycle to induce infection to the host cell was confirmed with HCV pseudoparticles(20), a experiment model system in expression of cellular attachment which is the essential component of the HCV entry process.
Green tea EGCG also prevented attachment of of the virus to the cell surface in ameliorated HCV infection to the host cell without effecting viral replication and virion secretion outside of the host(20).
Summary
Green tea with abundant bioactive polyphenols may be considered as function foods for reduced risk and treatment of various types of liver diseases. However, intake of green supplement should be taken with extreme care as toxicity was reported in numbers of medical literature, such as
The single ingredients extract has also been found to induce hepotoxocity(2)(4) and acute liver dysfunction(4) in many occasions due to overdoses and long term usages.
Additionally, according to the Baylor College of Medicine and Dalhousie University, Halifax reported, "(There is) a case of acute impending liver failure in an adolescent male using a weight-loss product containing green tea extract" and "acute liver toxicity observed in individuals consuming supplements containing green tea extract"(3).
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Author biography: Kyle J. Norton
Health article writer and researcher; Over 10.000 articles and research papers have been written and published on line, including world wide health, ezine articles, article base, healthblogs, selfgrowth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bio science, ISSN 0975-6299.
Sources
(1) The effect of green tea intake on risk of liver disease: a meta analysis by Yin X1, Yang J2, Li T3, Song L4, Han T5, Yang M1, Liao H1, He J1, Zhong X1.(PubMed)
(2) Green tea extract: a potential cause of acute liver failure by Patel SS1, Beer S, Kearney DL, Phillips G, Carter BA.(PubMed)
(3) Green tea extract: a potential cause of acute liver failure by Patel SS1, Beer S, Kearney DL, Phillips G, Carter BA.(PubMed)
(4) Acute liver failure induced by green tea extracts: case report and review of the literature by Molinari M1, Watt KD, Kruszyna T, Nelson R, Walsh M, Huang WY, Nashan B, Peltekian K.(PubMed)
(5) Tea polyphenols EGCG and TF restrict tongue and liver carcinogenesis simultaneously induced by N-nitrosodiethylamine in mice by Sur S1, Pal D2, Roy R2, Barua A2, Roy A3, Saha P2, Panda CK4.(PubMed)
(6) Tea polyphenols epigallocatechin gallete and theaflavin restrict mouse liver carcinogenesis through modulation of self-renewal Wnt and hedgehog pathways by Sur S1, Pal D2, Mandal S3, Roy A4, Panda CK5.(PubMed)
(7) Therapeutic potential of green tea in nonalcoholic fatty liver disease by Masterjohn C1, Bruno RS.(PubMed)
(8) Green tea polyphenol epigallocatechin-3-gallate ameliorates insulin resistance in non-alcoholic fatty liver disease mice by Gan L1, Meng ZJ1, Xiong RB2, Guo JQ1, Lu XC1, Zheng ZW1, Deng YP1, Luo BD1, Zou F3, Li H1.(PubMed)
(9) Green tea polyphenols ameliorate non-alcoholic fatty liver disease through upregulating AMPK activation in high fat fed Zucker fatty rats by Tan Y1, Kim J1, Cheng J1, Ong M1, Lao WG1, Jin XL1, Lin YG1, Xiao L1, Zhu XQ1, Qu XQ1.(PubMed)
(10) Green tea polyphenol decreases the severity of portosystemic collaterals and mesenteric angiogenesis in rats with liver cirrhosis by Hsu SJ, Wang SS, Hsin IF, Lee FY, Huang HC, Huo TI, Lee WS, Lin HC, Lee SD.(PubMed)
(11) [Green tea extracts protected against carbon tetrachloride-induced chronic liver damage and cirrhosis].[Article in Chinese] by Xiao J1, Lu R, Shen X, Wu M.(PubMed)
(12) Limited sampling estimates of epigallocatechin gallate exposures in cirrhotic and noncirrhotic patients with hepatitis C after single oral doses of green tea extract by Halegoua-De Marzio D1, Kraft WK, Daskalakis C, Ying X, Hawke RL, Navarro VJ.(PubMed)
(13) Effect of Green Tea Extract Encapsulated Into Chitosan Nanoparticles on Hepatic FibrosisCollagen Fibers Assessed by Atomic Force Microscopy in Rat Hepatic Fibrosis Model by Safer AM, Hanafy NA, Bharali DJ, Cui H, Mousa SA.(PubMed)
(14) Quantification of the Healing Effect in Hepatic Fibrosis Induced by Chitosan Nano-Encapsulated Green Tea in Rat Model by Safer AM, Sen A, Hanafy NA, Mousa SA.(PubMed)
(15) Antifibrotic effects of green tea on in vitro and in vivo models of liver fibrosis by Kim HK1, Yang TH, Cho HY.(PubMed)
(16) Epigallocatechin-3-gallate attenuates apoptosis and autophagy in concanavalin A-induced hepatitis by inhibiting BNIP3. by Li S1, Xia Y1, Chen K1, Li J1, Liu T1, Wang F1, Lu J1, Zhou Y1, Guo C1.(PMC)
(17) (-)-Epigallocatechin-3-gallate inhibits entry of hepatitis B virus into hepatocytes by Huang HC1, Tao MH2, Hung TM3, Chen JC4, Lin ZJ5, Huang C6.(PubMed)
(18) Preventive effects of a major component of green tea, epigallocathechin-3-gallate, on hepatitis-B virus DNA replication by Karamese M1, Aydogdu S, Karamese SA, Altoparlak U, Gundogdu C.(PubMed)
(19) Green tea polyphenol, epigallocatechin-3-gallate, possesses the antiviral activity necessary to fight against the hepatitis B virus replication in vitro by Pang JY1, Zhao KJ, Wang JB, Ma ZJ, Xiao XH.(PubMed)
(20) (-)-Epigallocatechin-3-gallate is a new inhibitor of hepatitis C virus entry by Calland N1, Albecka A, Belouzard S, Wychowski C, Duverlie G, Descamps V, Hober D, Dubuisson J, Rouillé Y, Séron K.(PubMed)
(21) (-)-Epigallocatechin-3-gallate inhibits the replication cycle of hepatitis C virus by Chen C1, Qiu H, Gong J, Liu Q, Xiao H, Chen XW, Sun BL, Yang RG.(PubMed)
(22) A cell-based, microplate colorimetric screen identifies 7,8-benzoflavone and green tea gallate catechins as inhibitors of the hepatitis C virus by Fukazawa H1, Suzuki T, Wakita T, Murakami Y.(PubMed)
Liver cancer is a medical condition caused by cell growth disorderly and uncontrollably in the liver tissue. At the later stage, the cancerous cells may travel a distance away to infect other healthy organs and tissues.
In the review of medical literature published online, green tea bioactive phytochemicals such as Epigallocatechin gallate (EGCG) and Theaflavin (TF), in prevention and treatment of liver cancer have been postulated by several mechanisms.
In liver cancer, animal model induced by chronic exposure of N-nitrosodiethylamine (NDEA), a carcinogenic and mutagenic organic compound, application of green tea bioactive compounds Epigallocatechin gallate (EGCG) and Theaflavin (TF) demonstrated a strong effect in reduced initiation of cancer formation and potential chemopreventive effect in pre and post treatment of the injected animal(5).
Further observation showed that EGCG/TF action in restrain the over expression of liver cancer also modulate similarly to those of CD44-specific cell membrane binding combined with near-infrared irradiation in induction of cellular apoptosis(5).
High CD44-positive expression is found to associate to acute cancer cells killing.
The restriction processes of EGCG/TF in modification of onset of liver cancer development, was also found to modify multiple biogenesis involved maintaining a relatively stable equilibrium in organs tissues(self-renewal Wnt/β-catenin, Hh/Gli1 pathways) in gene with implication of cell cycle progression, apoptosis and cellular transformation and cell differentiation and proliferation(Cyclin D1, cMyc and EGFR) and tumor suppressor (E-cadherin)(5) during the carcinogenesis processes.
The therapeutic efficacy of tea polyphenols epigallocatechin gallete (EGCG) and theaflavin (TF) also regulated the proteins expression of cell differentiation, polarity and proliferation(the self-renewal Wnt and Hedgehog (Hh) pathways)(6).during CCl4/N-nitosodiethylamine-induced mouse liver carcinogenesis.
Application of green tea bioactive tea polyphenols epigallocatechin gallete (EGCG) and theaflavin (TF) induced chemo preventive potential in maintain cell integrity at the 30 weeks of CCl4/N-nitosodiethylamine application(6).
Continuous administration of EGCG/TF also exerted a strong impact in reduced proliferation and increased apoptosis, as well as decreased function of hepatic progenitor cells (HPCs) in participated restoration of the cancerous liver tissue and population with cancer stem cell-like characteristics in liver carcinoma(6) observed by AFP and CD44 expression.in CCl4/N-nitosodiethylamine-induced mouse liver carcinogenesis.
Also, during the restriction processes of EGCG/TF, the bioactive compounds also modulated the expression of tumor progression to a more invasive phenotype(phospho-β-catenin-Y-654), tumor suppressor(β-catenin), the proliferation, migration and invasion of liver cancer gene(sFRP1 ) and gene in control tumor suppressor(β-catenin)(6).
In other words, green tea EGCG/TF inhibited the contaminated cells inflicted by injection of CCl4/N-nitosodiethylamine to prevent the initiation of liver cancer through modulation of certain gene expressions involved in liver cancer progression.
In short, the inhibition of liver carcinogenesis by EGCG/TF was attributed to reduction in hepatocyte progenitor cell and stem cell population in restored liver cancerous cells damage through various mechanisms indicated above.
In the review of medical literature published online, green tea bioactive phytochemicals such as Epigallocatechin gallate (EGCG) and Theaflavin (TF), in prevention and treatment of liver cancer have been postulated by several mechanisms.
In liver cancer, animal model induced by chronic exposure of N-nitrosodiethylamine (NDEA), a carcinogenic and mutagenic organic compound, application of green tea bioactive compounds Epigallocatechin gallate (EGCG) and Theaflavin (TF) demonstrated a strong effect in reduced initiation of cancer formation and potential chemopreventive effect in pre and post treatment of the injected animal(5).
Further observation showed that EGCG/TF action in restrain the over expression of liver cancer also modulate similarly to those of CD44-specific cell membrane binding combined with near-infrared irradiation in induction of cellular apoptosis(5).
High CD44-positive expression is found to associate to acute cancer cells killing.
The restriction processes of EGCG/TF in modification of onset of liver cancer development, was also found to modify multiple biogenesis involved maintaining a relatively stable equilibrium in organs tissues(self-renewal Wnt/β-catenin, Hh/Gli1 pathways) in gene with implication of cell cycle progression, apoptosis and cellular transformation and cell differentiation and proliferation(Cyclin D1, cMyc and EGFR) and tumor suppressor (E-cadherin)(5) during the carcinogenesis processes.
The therapeutic efficacy of tea polyphenols epigallocatechin gallete (EGCG) and theaflavin (TF) also regulated the proteins expression of cell differentiation, polarity and proliferation(the self-renewal Wnt and Hedgehog (Hh) pathways)(6).during CCl4/N-nitosodiethylamine-induced mouse liver carcinogenesis.
Application of green tea bioactive tea polyphenols epigallocatechin gallete (EGCG) and theaflavin (TF) induced chemo preventive potential in maintain cell integrity at the 30 weeks of CCl4/N-nitosodiethylamine application(6).
Continuous administration of EGCG/TF also exerted a strong impact in reduced proliferation and increased apoptosis, as well as decreased function of hepatic progenitor cells (HPCs) in participated restoration of the cancerous liver tissue and population with cancer stem cell-like characteristics in liver carcinoma(6) observed by AFP and CD44 expression.in CCl4/N-nitosodiethylamine-induced mouse liver carcinogenesis.
Also, during the restriction processes of EGCG/TF, the bioactive compounds also modulated the expression of tumor progression to a more invasive phenotype(phospho-β-catenin-Y-654), tumor suppressor(β-catenin), the proliferation, migration and invasion of liver cancer gene(sFRP1 ) and gene in control tumor suppressor(β-catenin)(6).
In other words, green tea EGCG/TF inhibited the contaminated cells inflicted by injection of CCl4/N-nitosodiethylamine to prevent the initiation of liver cancer through modulation of certain gene expressions involved in liver cancer progression.
In short, the inhibition of liver carcinogenesis by EGCG/TF was attributed to reduction in hepatocyte progenitor cell and stem cell population in restored liver cancerous cells damage through various mechanisms indicated above.
Non-alcoholic Fatty Liver Disease is a condition caused by over accumulated of fat in the liver.
According to the University of Connecticut, Storrs, the efficacy of green tea for treatment of obese patients with nonalcoholic fatty liver disease is associated to polyphenolic catechins in induction of hypolipidemic, thermogenic, antioxidant, and anti-inflammatory activities(7).
These chemical compound have also found to mitigate the occurrence and progression of NAFLD.
Dr. Masterjohn C(7), the lead author said, "(The phytochemical compounds are) demonstrating the hepatoprotective properties of green tea and its catechins and the proposed mechanisms by which these targeted dietary agents protect against NAFLD".
In mice fed on a high-fat diet for 24 weeks, then injected with EGCG (10, 20 and 40 mg·kg(-1)·d(-1), ip), for 4 weeks, researchers found that treated mice showed a significant improvement of high-fat diet in induced the body weight, grade 2 or 3 liver fatty degeneration (steatosis, lobular inflammation and ballooning), severe hyperlipidemia, hyperglycemia, hyperinsulinemia and insulin resistance(8)..
The phytocheimcal EGCG, in dose-dependent also enhanced insulin clearance and upregulated IDE protein expression and enzyme activity(8) in regulated levels of glucose in the liver of treated mice.
In fact EGCG not only promoted weigh loss but also attenuated symptoms of mice with nonalcoholic fatty liver disease.
Administration of green tea polyphenols (GTP) on non-alcoholic fatty liver disease (NAFLD) in Zucker fatty (ZF) rats, not only decreased weight gain and significantly lowered visceral fat but also reduced fasting serum insulin, glucose and lipids levels(9), through ameliorated expression of hepatic TG accumulation and cytoplasmic lipid droplet(9) as well as diminished hepatic lipogenesis and triglycerides out flux from liver(9).
3. Liver Cirrhosis
Liver cirrhosis is a condition of abnormal function of liver due to damage liver tissue replaced by scar tissue.
According to statistic, risk of liver cirrhosis is 1.6% in adult population.
Green tea polyphenols in reduced risk and treatment of patients with liver cirrhosis was found to associate to numbers of implication, involving various mechanisms.
In male SD rats model induced liver cirrhosis through carbon tetrachloride(CCL4), randomly assigned to 3 groups, including normal group, green tea extract (GTE) group and cirrhosis group, with GTE group and the cirrhosis group were injected subcutanuously 2 times/wk over 9 weeks with 40% Carbon tetrachloride (CCl4), researcher found that green tea treatment groups displayed a significant reduction of concentration of hydroxyproline(11), an amino acid produced during the hydrolysis of collagen initiate scar accumulation in the liver damage tissue caused by CCl4)(11) in compared to cirrhosis group.
Green tea application also exhibited antioxidant activities in decreased expression of malondialdehyde (MDA)(11), a highly toxic reactive species in precipitated liver damage induced by application of carbon tetrachloride(CCL4).
Green tea extract ameliorated the liver damage cell in formation of cirrhosis through attenuating the expression of transforming growth factor beta 1 or TGF-β1(11) in initiated cell growth, cell proliferation.
In differentiation of 11 patients with hepatitis C and detectable viremia of 4 Child-Pugh (CP) class A cirrhosis, 4 Child-Pugh class B cirrhosis, and 3 noncirrhotic, researchers at the Thomas Jefferson University indicated that injection of a single oral dose of green tea extract 400 mg containing 94% pure EGCG demonstrated a strong effect in reduced cirrhosis over expression in induction of liver tumor growth(12) by inhibiting the virus hepatitis in facilitated production of ROS species through chronic liver inflammation(12), according to the blood sample withdrawn from the patients without inducing liver toxicity.
Dr. Halegoua-De Marzio D(11), after taking into account of other con founders said, "A single 400-mg oral dose of EGCG was safe and well tolerated by all of the patients in the study" and disposition of EGCG was not significantly altered in these patients with cirrhosis".
In the concern of abnormal angiogenesis in patients with liver cirrhosis in induction of severe complications such as variceal haemorrhage and encephalopathy, Dr. Hsu SJ and colleges conducted a study to investigate the effect of green tea extract in Spraqtue-Dawley rats liver induced in by common BDL (bile duct ligation) in compared to control given distill water for 28 days and found that group treated with green tea extract expressed a strong implication in ameliorated the severity of portosystemic shunting(10), a rare malformation of the vessels supplying blood to the liver caused by excessive shunting of blood from the liver portal vein to the lower and middle body into the right atrium of the heart due to liver cirrhosis(10) in induction portal hypertension, one of complication of variceal haemorrhage in patient with chronic liver cirrhosis and mesenteric angiogenesis(10) in development of new blood vessels to supply oxygen and nutrients to initiate liver cancer.
The effect of green tea GTP extract in reduced progression of liver cirrhosis was attributed to the suppression of hypoxia-inducible factor 1-alpha (HIF-1α)(10) in expression of liver disease of diverse etiologies, including chronic liver diseases caused by viral infection, excessive alcohol consumption and activation of protein kinase B (Akt)(10) in regulated infectious liver cell survival, cell-cycle progression,... and levels of VEGF(10) in reflection of increased portal hypertension or decreased hepatic regenerative activity or the combination of both.
Dr.Hsu SJ(10), the lead author said after the conclusion, "GTP appears to be an appropriate agent in controlling portal hypertension-related complications via anti-angiogenesis.
4. Liver Fibrosis
Liver fibrosis is a liver disease with excessive accumulation of scar tissue as a result of inflammation and liver cell death
According to Fibro Test, approximately, the prevalence of advanced fibrosis was 2.8% in a general population aged 40 years or older.
Application of a novel bio-nano particle named 'Chitosan nano-encapsulated green tea extract' at the ultrastructural level on 25 adult rats induced liver toxicity by injection of carbon-tetrachloride and ethanol doses for 3 weeks, expressed a significant reduction of nearly 25% of the sub-cellular area infected with hepatic fibrosis(13).
The efficacy of Chitosan nano-encapsulated green tea extract in decreased liver fibroids was attributed to the antioxidant activity in inhibited the expression of the injected chemicals in induction over production of reactive oxygen species (ROS)(13) in chain reaction to elevated oxidative stress in initiation of liver cell apoptosis.
Observed by scanning electron microscopy, oral administration of novel bio-nano particle also exerted a strong free radical scavengers effect in protected against changes of cell surface structure and surrounding area between the hepatocytes(14), thus ameliorated risk of collagen deposit to cause liver fibroids.
In carbon tetrachloride CCL4 induced fibrotic liver tissues in rat models, treatment of green tea extract (GTE) encapsulated into Chitosan Nanoparties (CS-NPs) revealed that collagen fibers of 250 to 300 nm widths found in the fibrotic liver samples of control group with no treatment in compared to no collagen fibers in green tea treatment group(11).
The effectiveness of GTE is reduced expression of collagen fibers in the liver a was found to correlate to the antioxidant expression in reduced CCL4(11) in induction of over production of free radicals in precipitated liver tissue damage.
In the evaluation of the protective effect of green tea extract (GT) on hepatic fibrosis in vitro and in vivo in dimethylnitrosamine (DMN)-induced rats, researchers at the Korea University, indicated that application of GT inhibited activated HSC-T6(15), a rat hepatic stellate cell line which is considered as the major cell type involved in liver fibrosis.
The application also attenuated the collagen deposition which are elevated and acted as a biomaker for progression of liver fibrosis, particularly, in expression of collagen type 1 formation of scar tissue in response to liver damage(15), found in the early event in the development of hepatic fibrosis, confirmed both by liver histology and by quantitative measurement of hepatic hydroxyproline content.
Dr. Kim HK(15), the lead author said, "green tea administration can effectively improve liver fibrosis caused by DMN, and may be used as a therapeutic option and preventive measure against hepatic fibrosis".
5. Autoimmune Hepatitis
Autoimmune hepatitis is a medical condition characterized by immune system attacking the liver cells in induction of liver cirrhosis as a result of long term liver cellular inflammation and necrosis.
The study of concanavalin A (ConA) (25 mg/kg) induced autoimmune hepatitis in mice, pretreatment of green tea exerted a strong inhibition of inflammatory cytokines through increased Bcl-2 expression(16) with function of blocking the apoptotic death of some cells and deceased activity of protein Bax in activated p53, a tumor suppressor to induce cell death and caspase-3, and Caspase-9 proteins(16) in signaling molecules in responsible for executing cell death in compared to ConA-treated group within 8 hours of applications, according to observation of TUNEL assay by detecting apoptotic cells that undergo extensive DNA degradation.
In other words, green tea EGCG administration reduced expression of ConA in induction of decreased numbers of infectious cells being attacked by the immune system, thus ameliorating risk of liver cell damage.
Application of green tea bioactive polyphenols Epigallocatechin-3-gallate (10 or 30 mg/kg) orally twice daily for 10 days before ConA injection also demonstrated a significant activity in reduced activation of BNIP3(16), a member of the apoptotic Bcl-2 protein family in mediated infectious cell apoptosis through autophagy(16) in induced destruction of damaged or redundant cellular components in compared to lectin ConA.
The result of green tea EGCG efficacy in induction of BNIP3 to decrease expression of concanavalin A (ConA) in reduction of numbers infectious cell proliferation was attributed to the IL-6/JAK/STAT3(16) signaling pathway which plays an important role in the mechanisms in exhibited green tea EGCG antioxidant activity in blocking infectious cells migration and invasion in exhibited hepatoprotective effect.
In other words, said, Dr. Li S(16), the lead scientist "EGCG attenuated liver injury in ConA-induced hepatitis by down-regulating IL-6/JAKs/STAT3/BNIP3-mediated apoptosis and autophagy".
Further differentiation also found that green tea EGCG administration inhibited the immune over reaction and pathological damage by decreased expression of inflammatory cytokines induced by Tumor necrosis factor (TNF)(16), tumor necrosis factor alpha, a cell signaling protein (cytokine) in activated systemic inflammation in the acute phase infection.
Green tea also modulated the inflammatory factors, interleukin 6 (IL-6)(16), the pro inflammatory cytokines and anti inflammatory mytokins promptly and transiently produced in response to infections and tissue injuries and interferon-gamma (IFN-γ)(16), a cytokine that plays an important role in inducing and modulating immune responses to the infectious tissue, as well as cytokine interleukin-1β (IL-1β)(16), a key mediator of the inflammatory response in protected body against pathological invasion.
6. Hepatitis B
Hepatitis B is a viral infection of acute and chronic liver disease, caused by a double stranded DNA virus HBV transmitted through infected blood, semen, or other body fluid.
According to the statistic, positive carriers among Canadian is estimated to be 0.5% to 1.0%., depending to ethnicity.
According to the evaluation of the effect of green tea bioactive polyphenos epigallocatechin-3 gallate (EGCG) and risk of hepatitis B, application of the phytochemical inhibited HBV replication in the testing Hep3B2.1-7 hepatocellular carcinoma cell line(17), through a significant effect in reduced prevalence of liver damage caused by hepatitis B virus.
Injection of EGCG at the dose of less than 100 μM in the observed liver cancer cell line showed no effect in induced cell apoptosis and decreased proliferation but exhibited a strong effect in ameliorated expression of surface antigen of the hepatitis B virus (HBsAg)(18) and antigen of hepatitis B virus(18) circulated in infected blood (HBeAg) levels found by the ELISA method and the polymerase chain reaction (PCR)assay.
Differentiation in different HepG2 2.2.15 cells to compare the effective of green tea with standard antiretroviral medication lamivudine (3TC), researchers indicated that administration of EGCG shows a significant inhibition of viral proliferation through attenuated expression of levels of HBsAg and HBeAg in the supernatant and extracellular HBV DNA(18) in a dose- and time-dependent manner.
At doses of 50-200 μg/ml EGCG displayed strong effects in compared to lamivudine (3TC) at dose of 200 μg/ml(18).
Application of EGCG also suppressed the extracellular HBV DNA(18), a nutrient source for viral cell proliferation and survival through attachment, aggregation, and stabilization of microcolonies.
The results of the experiments pointed out that green tea EGCG comprises a potential anti-HBV activity with low toxicity.
In the investigation of green tea EGCG effect in the early stages of infection caused by four different Hepatitis B virus genotypes A and D researchers also found that at dose of more than 80%, the phyochemical inhibited both DMSO-differentiated HuS-E/2 cells and HA-NTCP-expressing Huh7 cells(19) involved cancer cell process in early stage of proliferation through induced protein degradation and ameliorated serum of tansferrin(19).(the iron-binding blood plasma glycoproteins that control the level of free iron in biological fluids)which is considered as a liver fibrosis biomarker in patients with chronic hepatitis B.
However, treatment of cells with EGCG had no effect on HBV genome replication or virion secretion(19) and the characteristic of HBV virion and the expression of known HBV entry factors were unaltered(19) out side of the host before attacking the liver tissue.
7. Hepatitis C
Hepatitis C is medical condition induced by contaminated food intake containing hepatitis C virus (HCV). Hepatitis C has been found to associate with sever liver damage.
According to statistic, approximately 130–150 million people around the world are living with chronic HCV.
In Huh7.5.1 cells, a HCV cell culture (HCVcc) system using a JFH1-GFP chimeric virus, application of green tea EGCG with 50 % effective concentration (EC(50)) of 17.9 μM demonstrated a strong effect in interrupted HCV progression through monitoring HCV RNA and protein levels in Huh7.5.1 cells infected with the JFH1 virus(21) by preventing the mRNA in transferring infectious cell transcription in facilitated cell proliferation and division.
Injection of green tea at dose of 50 and 25 μM EGCG, expressed a significant inhibition of the presence of HCV after 2 and 5 passages in HCV cell culture (HCVcc) experiment(21), using an American Type Culture Collection (ATCC) reference strain, with little affect to the viral internal ribosome entry site (IRES) in initiated substitution of RNA sequences for viral protein synthesis(21) in shutting off classic host translation to evade host immune response.
Notably, in comparison of effect of green tea with potent anti-HCV medicine, cyclosporin A and tamoxifen, researchers indicated that application of green tea showed a strong anti HCV viral activity, similarly to those of anti hepatitis medicine through its antioxidant expression of flavonoids epigallocatechin gallate (EGCG) and 7,8-benzoflavone (α-naphthoflavone)(21), observed in HCV cell culture (HCVcc) by blocking the entry point of the virus in initiated infection to host cells(21) and stimulating the viral cell cycle arrest at the late stage of HCV life cycle(21), respectively
Some researchers in the evaluation of green tea polyphenols (-)-epigallocatechin-3-gallate (EGCG) in hepatitis C infection suggested that EGCG processed anti viral expression through interrupting the cross link between HCV life cycle involving steps of entry, replication(22).
Injection of a concentration of 50 μM of EGCG was found to inhibit HCV infectivity by more than 90% at an early step of the viral life cycle(20).
The interrupted property in blocking the HCV entry cycle to induce infection to the host cell was confirmed with HCV pseudoparticles(20), a experiment model system in expression of cellular attachment which is the essential component of the HCV entry process.
Green tea EGCG also prevented attachment of of the virus to the cell surface in ameliorated HCV infection to the host cell without effecting viral replication and virion secretion outside of the host(20).
Summary
Green tea with abundant bioactive polyphenols may be considered as function foods for reduced risk and treatment of various types of liver diseases. However, intake of green supplement should be taken with extreme care as toxicity was reported in numbers of medical literature, such as
The single ingredients extract has also been found to induce hepotoxocity(2)(4) and acute liver dysfunction(4) in many occasions due to overdoses and long term usages.
Additionally, according to the Baylor College of Medicine and Dalhousie University, Halifax reported, "(There is) a case of acute impending liver failure in an adolescent male using a weight-loss product containing green tea extract" and "acute liver toxicity observed in individuals consuming supplements containing green tea extract"(3).
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Author biography: Kyle J. Norton
Health article writer and researcher; Over 10.000 articles and research papers have been written and published on line, including world wide health, ezine articles, article base, healthblogs, selfgrowth, best before it's news, the karate GB daily, etc.,.
Named TOP 50 MEDICAL ESSAYS FOR ARTISTS & AUTHORS TO READ by Disilgold.com Named 50 of the best health Tweeters Canada - Huffington Post
Nominated for shorty award over last 4 years
Some articles have been used as references in medical research, such as international journal Pharma and Bio science, ISSN 0975-6299.
Sources
(1) The effect of green tea intake on risk of liver disease: a meta analysis by Yin X1, Yang J2, Li T3, Song L4, Han T5, Yang M1, Liao H1, He J1, Zhong X1.(PubMed)
(2) Green tea extract: a potential cause of acute liver failure by Patel SS1, Beer S, Kearney DL, Phillips G, Carter BA.(PubMed)
(3) Green tea extract: a potential cause of acute liver failure by Patel SS1, Beer S, Kearney DL, Phillips G, Carter BA.(PubMed)
(4) Acute liver failure induced by green tea extracts: case report and review of the literature by Molinari M1, Watt KD, Kruszyna T, Nelson R, Walsh M, Huang WY, Nashan B, Peltekian K.(PubMed)
(5) Tea polyphenols EGCG and TF restrict tongue and liver carcinogenesis simultaneously induced by N-nitrosodiethylamine in mice by Sur S1, Pal D2, Roy R2, Barua A2, Roy A3, Saha P2, Panda CK4.(PubMed)
(6) Tea polyphenols epigallocatechin gallete and theaflavin restrict mouse liver carcinogenesis through modulation of self-renewal Wnt and hedgehog pathways by Sur S1, Pal D2, Mandal S3, Roy A4, Panda CK5.(PubMed)
(7) Therapeutic potential of green tea in nonalcoholic fatty liver disease by Masterjohn C1, Bruno RS.(PubMed)
(8) Green tea polyphenol epigallocatechin-3-gallate ameliorates insulin resistance in non-alcoholic fatty liver disease mice by Gan L1, Meng ZJ1, Xiong RB2, Guo JQ1, Lu XC1, Zheng ZW1, Deng YP1, Luo BD1, Zou F3, Li H1.(PubMed)
(9) Green tea polyphenols ameliorate non-alcoholic fatty liver disease through upregulating AMPK activation in high fat fed Zucker fatty rats by Tan Y1, Kim J1, Cheng J1, Ong M1, Lao WG1, Jin XL1, Lin YG1, Xiao L1, Zhu XQ1, Qu XQ1.(PubMed)
(10) Green tea polyphenol decreases the severity of portosystemic collaterals and mesenteric angiogenesis in rats with liver cirrhosis by Hsu SJ, Wang SS, Hsin IF, Lee FY, Huang HC, Huo TI, Lee WS, Lin HC, Lee SD.(PubMed)
(11) [Green tea extracts protected against carbon tetrachloride-induced chronic liver damage and cirrhosis].[Article in Chinese] by Xiao J1, Lu R, Shen X, Wu M.(PubMed)
(12) Limited sampling estimates of epigallocatechin gallate exposures in cirrhotic and noncirrhotic patients with hepatitis C after single oral doses of green tea extract by Halegoua-De Marzio D1, Kraft WK, Daskalakis C, Ying X, Hawke RL, Navarro VJ.(PubMed)
(13) Effect of Green Tea Extract Encapsulated Into Chitosan Nanoparticles on Hepatic FibrosisCollagen Fibers Assessed by Atomic Force Microscopy in Rat Hepatic Fibrosis Model by Safer AM, Hanafy NA, Bharali DJ, Cui H, Mousa SA.(PubMed)
(14) Quantification of the Healing Effect in Hepatic Fibrosis Induced by Chitosan Nano-Encapsulated Green Tea in Rat Model by Safer AM, Sen A, Hanafy NA, Mousa SA.(PubMed)
(15) Antifibrotic effects of green tea on in vitro and in vivo models of liver fibrosis by Kim HK1, Yang TH, Cho HY.(PubMed)
(16) Epigallocatechin-3-gallate attenuates apoptosis and autophagy in concanavalin A-induced hepatitis by inhibiting BNIP3. by Li S1, Xia Y1, Chen K1, Li J1, Liu T1, Wang F1, Lu J1, Zhou Y1, Guo C1.(PMC)
(17) (-)-Epigallocatechin-3-gallate inhibits entry of hepatitis B virus into hepatocytes by Huang HC1, Tao MH2, Hung TM3, Chen JC4, Lin ZJ5, Huang C6.(PubMed)
(18) Preventive effects of a major component of green tea, epigallocathechin-3-gallate, on hepatitis-B virus DNA replication by Karamese M1, Aydogdu S, Karamese SA, Altoparlak U, Gundogdu C.(PubMed)
(19) Green tea polyphenol, epigallocatechin-3-gallate, possesses the antiviral activity necessary to fight against the hepatitis B virus replication in vitro by Pang JY1, Zhao KJ, Wang JB, Ma ZJ, Xiao XH.(PubMed)
(20) (-)-Epigallocatechin-3-gallate is a new inhibitor of hepatitis C virus entry by Calland N1, Albecka A, Belouzard S, Wychowski C, Duverlie G, Descamps V, Hober D, Dubuisson J, Rouillé Y, Séron K.(PubMed)
(21) (-)-Epigallocatechin-3-gallate inhibits the replication cycle of hepatitis C virus by Chen C1, Qiu H, Gong J, Liu Q, Xiao H, Chen XW, Sun BL, Yang RG.(PubMed)
(22) A cell-based, microplate colorimetric screen identifies 7,8-benzoflavone and green tea gallate catechins as inhibitors of the hepatitis C virus by Fukazawa H1, Suzuki T, Wakita T, Murakami Y.(PubMed)
