Patients
with chronic hepatitis often use alternative and complementary therapies they
hope will improve liver health, but most such products have not been studied in
controlled trials.
According to the researchers, green tea polyphenols exhibit
both antioxidant and anti-inflammatory properties. These polyphenols consist of
several components, including (-)-epigallocatechins gallate (EGCG), (-)-epigallocatechin,
(-)-epicatechin gallate, and (-)-epicatechin. EGCG, the strongest antioxidant,
modulates a number of events in the progression of liver injury, such as oxidative
stress and inflammation.
Study
1
The first study investigated the effect of EGCG on artificially
induced (by CCI4) inflammatory response and oxidative stress in liver fibrosis
in mice. Male ICR mice were injected with CCl4 with or without EGCG for a period
of 8 weeks. EGCG (85% pure, 50 mg/kg) was injected 3 times weekly.
Liver
tissue and blood samples were collected for ALT testing, collagen analysis, PCR,
and Western blot analysis. Frozen samples were analyzed for tumor necrosis factor
alpha (TNF-alpha), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS),
and nitrotyrosine. Nuclear factor kappa B (NF-kB) activity was assessed by electrophoretic
mobility shift assay (EMSA).
Results
An extensive amount of induced liver injury in CCl4-treated mice was detected,
as shown by a high level of serum ALT, greater areas of collagen, increased oxidative
stress as indicated by high levels of nitrotyrosine formation, and increased DNA-binding
activity of NF-kB.
Expression levels of NF-kB regulated genes TNF-alpha, COX-2, and iNOS were markedly
up-regulated after CCl4 administration.
Pretreatment with EGCG effectively reduced CCl4-induced liver injury as shown
by the lower level of serum ALT (P < 0.01) and collagen accumulation (P <
0.001).
Treatment with EGCG was also associated with significant reduction in the expression
of COX-2, iNOS, TNF-alpha, nitrotyrosine, and NF-kB (P < 0.01).
"Our
results suggest that EGCG attenuates CCl4-induced fibrosis, probably through the
inhibition of proinflammatory mediators and the reduction in the level of oxidative
stress," the researchers concluded. "The decreased expression of proinflammatory
mediators is mediated by decreased activity of NF-kB, which leads to a decrease
in levels of proinflammatory mediators."
Study
2
In the second study, the same research team examined the effect
of an 85% pure EGCG extract on the development of pathological and biochemical
changes in a recently described dietary model of non-alcoholic fatty liver disease
(NAFLD).
In this
study, female Sprague-Dawley rats were fed a diet containing fish oil as a source
of fat (35% of calories), to simulate NAFLD. Control rats were fed commercial
rat chow. To test the effect of EGCG on NAFLD, the rats in the NAFLD group were
injected with EGCG (50 mg/kg) 3 times weekly, while the control group received
a placebo without EGCG. Blood was collected for measurement of ALT, and liver
tissue was obtained for histology and biochemical analysis, including fat accumulation
(graded 0-4), necrosis, inflammation, collagen formation, levels of TNF-alpha,
COX-2, iNOS, and nitrotyrosine, and NF-kB activity.
Results
The NAFLD rats showed significant fatty changes, necrosis, and inflammation.
The presence of fatty liver and necroinflammation was accompanied by a significant
increase in NF-kB activity and upregulation of TNF-alpha, COX-2, iNOS, and nitrotyrosine
compared with the controls (P < 0.01).
Fibrosis was also greater in the NAFLD group.
Treatment with EGCG significantly attenuated the pathological changes, including
fibrosis, and down-regulated expression of TNF-alpha, COX-2, iNOS, and nitrotyrosine
(P < 0.01).
Treatment with EGCG also significantly decreased NF-kB activity (P < 0.01). "EGCG
reduced the severity of liver injury in an experimental model of NAFLD,"
the researchers stated. "The improved pathology occurred in association with
lower concentrations of lipid peroxides and pro-inflammatory mediators."
Based
on the results of both studies, the researchers suggested that green tea polyphenols
may be a useful therapeutic agent for treatment of hepatic fibrosis and a useful
supplement in the treatment of NAFLD.
University of Hong Kong, Hong
Kong SAR, China; Nagasaki University Graduate School of Biomedical Sciences, Hong
Kong SAR, China; Hong Kong Polytechnic University, Hong Kong SAR, China; Dalhousie
University School of Medicine, Halifax, NS, Canada.
11/14/06
References
G
L Tipoe, T Leung, E C Liong, and others. Antioxidant and Antiinflammatory Effects
of Green Tea Polyphenols in Carbon Tetrachloride Induced Liver Fibrosis in Mice.
57th AASLD. Boston, MA. October 27-31, 2006. Abstract 1062.
G
L Tipoe, C Ho, E G Liong, and others. Green Tea Polyphenols Ameliorate Pathological
Changes, Oxidative Stress and Pro-inflammatiory Markers in an Animal Model of
Non-Alcoholic Fatty Liver Disease [NAFLD]. 57th AASLD. Boston, MA. October 27-31,
2006. Abstract 1063.
An extensive amount of induced liver injury in CCl4-treated mice was detected,
as shown by a high level of serum ALT, greater areas of collagen, increased oxidative
stress as indicated by high levels of nitrotyrosine formation, and increased DNA-binding
activity of NF-kB. 
