title: Protective effect of Acanthopanax gracilistylus-extracted Acankoreanogenin A on mice with fulminant hepatitis.
abstract: The release of pro-inflammatory cytokines in both acute (IL-1β and TNF-α) and chronic [high mobility group box 1 protein (HMGB1)] phases, is thought to play important roles in the development of fulminant hepatitis (FH). Triterpenoid Acankoreanogenin A (AA) which is extracted from the leaves of the Acanthopanax gracilistylus W.W. Smith (AGS) has shown its inhibiting effect on TNF-α, IL-1β and HMGB1 release in vitro in our preliminary experiments. In present study, we investigated the effect of AA on mice with fulminant hepatitis in vivo. Fulminant hepatitis mice model was established by intraperitoneally injecting galactosamine (GalN) and lipopolysaccharide (LPS). The levels of serum of TNF-α, IL-1β, ALT, AST and HMGB1 from AA-treated mice were measured at different time points. Our results demonstrated that pre-treatment of mice with AA markedly reduced the serum levels of TNF-α, IL-1β, HMGB1, ALT and AST with the improvement in histological features. And the survival rate from AA-treated fulminant hepatitis mice was increased. Furthermore, delayed administration of AA after peak occurrence of the early pro-inflammatory cytokines still endowed significant protection against GalN/LPS-induced lethality. The post-treatment of AA could significantly attenuate the release of HMGB1, but not the TNF-α and IL-1β. These results indicate that AA inhibits the systemic release of pro-inflammatory cytokine HMGB1, and dose-dependently rescue the mice from lethal GalN/LPS-induced fulminant hepatitis, which suggests this component as a candidate therapy for fulminant hepatitis.
authors.affiliation: Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, People's Republic of China. zhangbx73@126.com
authors.forename: Bao-Xin
authors.initials: BX
authors.lastname: Zhang
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.forename: Zu-Ping
authors.initials: ZP
authors.lastname: Zhang
authors.forename: Hong-Bo
authors.initials: HB
authors.lastname: Liu
authors.forename: Rong-Rong
authors.initials: RR
authors.lastname: Zhou
authors.forename: Bai-Yun
authors.initials: BY
authors.lastname: Zhong
authors.forename: Ming-Xiang
authors.initials: MX
authors.lastname: Zou
authors.forename: Xia-Hong
authors.initials: XH
authors.lastname: Dai
authors.forename: Mei-Fang
authors.initials: MF
authors.lastname: Xiao
authors.forename: Xiang-Qian
authors.initials: XQ
authors.lastname: Liu
authors.forename: Xue-Gong
authors.initials: XG
authors.lastname: Fan
mesh_terms: D000410:Alanine Transaminase / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D028001:Eleutherococcus; D005260:Female; D005688:Galactosamine / Q000494:pharmacology; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism
chemical_list: D004365:Drugs, Chinese Herbal; D024243:HMGB1 Protein; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D005688:Galactosamine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C400150:Acanthopanax gracilistylus, extract