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Protective Effect of Gallotannin-Enriched Extract Isolated from Galla Rhois against CCl4-Induced Hepatotoxicity in ICR Mice

Department of Biomaterials Science, College of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang 627-706, Korea
Department of Organic Material Science and Engineering, Pusan National University, Busan 609-735, Korea
Department of Clinical Laboratory Science, College of Nursing and Healthcare Science, Dong-Eui University, Busan 614-714, Korea
College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju 361-763, Korea
Author to whom correspondence should be addressed.
Nutrients 2016, 8(3), 107;
Received: 27 December 2015 / Revised: 31 January 2016 / Accepted: 14 February 2016 / Published: 23 February 2016
To investigate the toxicity, protective effects, and action mechanism of gallotannin-enriched extracts isolated from Galla Rhois (GEGR) against carbon tetrachloride (CCl4)-induced hepatotoxicity in Institute for Cancer Research (ICR) mice, alterations in serum biochemical indicators, histopathological structure, antioxidative status, hepatic apoptosis-related proteins, and liver fibrosis regulating factors were measured in mice pretreated with GEGR for five days before CCl4 injection. The GEGR/CCl4 treated group showed decreased levels of three serum marker enzymes (ALP, AST, and ALT) representing liver toxicity, although LDH levels remained constant. Necrotic area indicating hepatic cell death significantly inhibited, while malondialdehyde (MDA) concentration and superoxide dismutase (SOD) expression were dramatically recovered in the GEGR preadministrated group. In mechanism analyses of GEGR, the formation of active caspase-3 and enhancement of Bax/Bcl-2 expression was effectively inhibited in the GEGR/CCl4 treated group. The level of pro-inflammatory cytokines, TNF-α and IL-6, as well as the phosphorylation of p38 and JNK in the TNF-α downstream signaling pathway was rapidly recovered in the GEGR/CCl4 treated group, while anti-inflammatory cytokine (IL-10) increased slightly in the same group. Furthermore, the GEGR/CCl4 treated group showed a significant decrease in collagen accumulation results from alleviation of MMP-2 expression, TGF-β1 secretion and the phosphorylation of Smad2/3. Taken together, these results suggest that GEGR may induce remarkable protective effects against hepatic injury induced by CCl4 treatment through upregulation of the anti-inflammatory and antioxidant system. View Full-Text
Keywords: hepatotoxicity; hepatic fibrosis; Galla Rhois; inflammation; oxidative stress hepatotoxicity; hepatic fibrosis; Galla Rhois; inflammation; oxidative stress
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Go, J.; Kim, J.E.; Koh, E.K.; Song, S.H.; Sung, J.E.; Lee, H.A.; Lee, Y.H.; Lim, Y.; Hong, J.T.; Hwang, D.Y. Protective Effect of Gallotannin-Enriched Extract Isolated from Galla Rhois against CCl4-Induced Hepatotoxicity in ICR Mice. Nutrients 2016, 8, 107.

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