title: Protective Effect of Gallotannin-Enriched Extract Isolated from Galla Rhois against CCl₄-Induced Hepatotoxicity in ICR Mice.
abstract: 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.
authors.affiliation: Department of Biomaterials Science, College of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang 627-706, Korea. ydrener@gmail.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Go
authors.affiliation: Department of Biomaterials Science, College of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang 627-706, Korea. prettyjiunx@naver.com.
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Kim
authors.affiliation: Department of Biomaterials Science, College of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang 627-706, Korea. haha414@naver.com.
authors.forename: Eun Kyoung
authors.initials: EK
authors.lastname: Koh
authors.affiliation: Department of Biomaterials Science, College of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang 627-706, Korea. rabit357@naver.com.
authors.forename: Sung Hwa
authors.initials: SH
authors.lastname: Song
authors.affiliation: Department of Biomaterials Science, College of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang 627-706, Korea. cnzkcnzk16@hanmail.net.
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Sung
authors.affiliation: Department of Biomaterials Science, College of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang 627-706, Korea. donc99@hanmail.net.
authors.forename: Hyun Ah
authors.initials: HA
authors.lastname: Lee
authors.affiliation: Department of Organic Material Science and Engineering, Pusan National University, Busan 609-735, Korea. youngheelee@pusan.ac.kr.
authors.forename: Young Hee
authors.initials: YH
authors.lastname: Lee
authors.affiliation: Department of Clinical Laboratory Science, College of Nursing and Healthcare Science, Dong-Eui University, Busan 614-714, Korea. yonglim@deu.ac.kr.
authors.forename: Yong
authors.initials: Y
authors.lastname: Lim
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju 361-763, Korea. jinthong@chungbuk.ac.kr.
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
authors.affiliation: Department of Biomaterials Science, College of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang 627-706, Korea. dyhwang@pusan.ac.kr.
authors.forename: Dae Youn
authors.initials: DY
authors.lastname: Hwang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D001042:Aphids / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001688:Biological Products / Q000378:metabolism / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D019610:Cytoprotection; D005786:Gene Expression Regulation; D047348:Hydrolyzable Tannins / Q000378:metabolism / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000097:blood / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008813:Mice, Inbred ICR; D009336:Necrosis; D018384:Oxidative Stress / Q000187:drug effects; D029045:Rhus / Q000469:parasitology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D001688:Biological Products; D015415:Biomarkers; D016207:Cytokines; C000612600:Galla Rhois; D047348:Hydrolyzable Tannins; D018836:Inflammation Mediators; D002251:Carbon Tetrachloride
keywords: Galla Rhois; hepatic fibrosis; hepatotoxicity; inflammation; oxidative stress