title: Geniposide alleviates inflammation by suppressing MeCP2 in mice with carbon tetrachloride-induced acute liver injury and LPS-treated THP-1 cells.
abstract: Geniposide (GP), an iridoid glucoside extracted from Gardenia jasminoides Ellis fruits, has been used as a herbal medicine to treat liver and gall bladder disorders for many years. However the mechanism of anti-inflammatory is largely unknown. In this study, GP significantly attenuated inflammation in acute liver injury (ALI) mice model and in lipopolysaccharide (LPS)-induced THP-1 cells. It was demonstrated that GP obviously decreased the expression of Methyl-CpG binding protein 2 (MeCP2) in vivo and in vitro. Knockdown of MeCP2 with siRNA suppressed the expressions of IL-6 and TNF-α, while over-expression of MeCP2 had a proinflammatory effect on the expression of IL-6 and TNF-α in LPS-induced THP-1 cells. Mechanistically, it was indicated that GP had anti-inflammatory effects at least in part, through suppressing MeCP2. Interestingly, GP could attenuate expressions of Sonic hedgehog (Shh) and GLIS family zinc finger 1 (GLIS1) but increase Ptched1 (PTCH1) expression. Similar findings were also demonstrated at the protein level by siRNA MeCP2. Furthermore, over-expression of MeCP2 obviously increased Shh and GLIS1 expressions but reduced PTCH1 expression. Taken together, GP may serve as an effective modulator of MeCP2-hedgehog pathway (Hh)-axis during the pathogenesis of inflammation. Our findings shed light on the potential therapeutic feature of GP in recovering inflammatory diseases.
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Hefei 230032, China; Anhui Institute of Innovative Drugs, Hefei 230032, China.
authors.forename: Tao-Tao
authors.initials: TT
authors.lastname: Ma
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Hefei 230032, China; Anhui Institute of Innovative Drugs, Hefei 230032, China.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Li
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Hefei 230032, China; Anhui Institute of Innovative Drugs, Hefei 230032, China.
authors.forename: Wan-Xia
authors.initials: WX
authors.lastname: Li
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Hefei 230032, China; Anhui Institute of Innovative Drugs, Hefei 230032, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Hefei 230032, China; Anhui Institute of Innovative Drugs, Hefei 230032, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Huang
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Hefei 230032, China; Anhui Institute of Innovative Drugs, Hefei 230032, China.
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Meng
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Hefei 230032, China; Anhui Institute of Innovative Drugs, Hefei 230032, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University (AMU), Anhui Medical University, Hefei 230032, China; Anhui Institute of Innovative Drugs, Hefei 230032, China. Electronic address: lj@ahmu.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D002252:Carbon Tetrachloride Poisoning / Q000188:drug therapy* / Q000473:pathology; D002460:Cell Line; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects; D055785:Gene Knockdown Techniques; D053823:Hedgehog Proteins / Q000096:biosynthesis / Q000235:genetics; D007249:Inflammation / Q000188:drug therapy*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D039823:Iridoids / Q000494:pharmacology* / Q000627:therapeutic use; D008099:Liver / Q000473:pathology; D051783:Methyl-CpG-Binding Protein 2 / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D053823:Hedgehog Proteins; D015850:Interleukin-6; D039823:Iridoids; C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2; D034741:RNA, Small Interfering; C465570:Shh protein, mouse; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse; C007835:geniposide
keywords: Acute liver injury (ALI); Geniposide (GP); Hedgehog pathway (Hh); Inflammation; MeCP2