title: Geniposide Inhibits Alpha-Naphthylisothiocyanate-Induced Intrahepatic Cholestasis: The Downregulation of STAT3 and NF[Formula: see text]B Signaling Plays an Important Role.
abstract: Traditional medicinal formulation of Yin-zhi-huang (YZH) is widely used in the clinic for the treatment of jaundice and chronic liver diseases in East Asian countries. However, the pharmacologically active components of YZH and the underlying mechanism are still unknown. Geniposide (GEN) was recently identified as one of the most abundant circulating components in YZH. In this study, we investigated the protective effect of GEN against liver injuries induced by alpha-naphthylisothiocyanate (ANIT). 50[Formula: see text]mg/kg of GEN was administered to ICR mice once daily for 5 days, and challenge of ANIT 75[Formula: see text]mg/kg was performed on the 4th day. Blood and liver tissues were collected on day 6 and subjected to biochemical, histopathological and pathway analyses. The biochemical and pathological findings showed that GEN almost totally attenuated ANIT-induced cholestasis and liver injury compared with the vehicle/ANIT group. The altered gene transcription related to bile acid metabolism and transport was normalized by co-treatment with GEN. The expressions of tumor necrosis factor-[Formula: see text] and the suppressor of cytokine signaling 3 were significantly decreased in the GEN/ANIT group. Western blot revealed that GEN inhibited the activation and expression of STAT3 and NF[Formula: see text]B. These data suggest GEN inhibits ANIT-induced hepatotoxicity. The protective effect is associated with the downregulation of STAT3 and NF[Formula: see text]B signaling.
authors.affiliation: * Key Laboratory of Phytochemical R&D of Hunan Province, Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research, (Ministry of Education of China), Hunan Normal University, Changsha 410081, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Tan
authors.affiliation: † Medical School of Ningbo University, Ningbo 315211, China.
authors.forename: Aiming
authors.initials: A
authors.lastname: Liu
authors.affiliation: † Medical School of Ningbo University, Ningbo 315211, China.
authors.forename: Min
authors.initials: M
authors.lastname: Luo
authors.affiliation: † Medical School of Ningbo University, Ningbo 315211, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Yin
authors.affiliation: † Medical School of Ningbo University, Ningbo 315211, China.
authors.forename: Danjun
authors.initials: D
authors.lastname: Song
authors.affiliation: † Medical School of Ningbo University, Ningbo 315211, China.
authors.forename: Manyun
authors.initials: M
authors.lastname: Dai
authors.affiliation: † Medical School of Ningbo University, Ningbo 315211, China.
authors.forename: Pengxu
authors.initials: P
authors.lastname: Li
authors.affiliation: † Medical School of Ningbo University, Ningbo 315211, China.
authors.forename: Zanbo
authors.initials: Z
authors.lastname: Chu
authors.affiliation: † Medical School of Ningbo University, Ningbo 315211, China.
authors.forename: Zuquan
authors.initials: Z
authors.lastname: Zou
authors.affiliation: * Key Laboratory of Phytochemical R&D of Hunan Province, Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research, (Ministry of Education of China), Hunan Normal University, Changsha 410081, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Ma
authors.affiliation: * Key Laboratory of Phytochemical R&D of Hunan Province, Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research, (Ministry of Education of China), Hunan Normal University, Changsha 410081, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Guo
authors.affiliation: * Key Laboratory of Phytochemical R&D of Hunan Province, Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research, (Ministry of Education of China), Hunan Normal University, Changsha 410081, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Chen
mesh_terms: D015058:1-Naphthylisothiocyanate / Q000009:adverse effects; D000818:Animals; D002780:Cholestasis, Intrahepatic / Q000139:chemically induced / Q000188:drug therapy*; D015536:Down-Regulation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D006801:Humans; D039823:Iridoids / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha
chemical_list: D004365:Drugs, Chinese Herbal; D039823:Iridoids; D016328:NF-kappa B; D050796:STAT3 Transcription Factor; D014409:Tumor Necrosis Factor-alpha; C007835:geniposide; D015058:1-Naphthylisothiocyanate
keywords: -Naphthylisothiocyanate; Geniposide; Hepatotoxicity; NFB; STAT3