title: Hyperin attenuates inflammation by activating PPAR-γ in mice with acute liver injury (ALI) and LPS-induced RAW264.7 cells.
abstract: Hyperin (HP) is a flavonoid compound found in various plants like Ericaceae, Guttifera and Celastraceae. The present study has revealed that HP has a variety of pharmacological effects including anti-oxidant, anticancer, and anti-coagulant, especially anti-inflammatory. However, the potential molecular mechanism of anti-inflammatory is still unrevealed. In this study, HP not only significantly attenuated inflammation in C57BL/6J mice with acute liver injury (ALI), but also reduced the expression of TNF-α and IL-6 in lipopolysaccharide (LPS)-induced RAW264.7 cells. Furthermore, our findings showed that HP remarkably induced the expression of PPAR-γ in vivo and in vitro. Interestingly, compared with the HP treatment group, a specific blocking agent of PPAR-γ T0070907 and PPAR-γ small interfering (si)-RNA-mediated silencing in RAW264.7 cells were used to evaluate the involvement of HP in alleviating LPS-induced inflammation. More importantly, over-expression of PPAR-γ had an opposite effect on the expression of TNF-α and IL-6 in LPS-induced RAW264.7 cells after treatment with HP. In addition, HP remarkably inhibited the expression of P-ERK1/2 and P-P38 MAPK. Taken together, all the above results indicate that HP may serve as an effective modulator of PPAR-γ, further down-regulating ERK1/2 and p38 MAPK during the pathogenesis of inflammation.
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: 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: 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: Xiao-Qin
authors.initials: XQ
authors.lastname: Wu
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: 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: 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.
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. Electronic address: beb0202@126.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000819:agonists* / Q000037:antagonists & inhibitors; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology; D000067996:RAW 264.7 Cells; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D000093242:Interleukin-6 Inhibitors; D015850:Interleukin-6
chemical_list: D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D047495:PPAR gamma; D011794:Quercetin; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; D000093242:Interleukin-6 Inhibitors; C577686:interleukin-6, mouse; D015850:Interleukin-6; C021304:hyperoside
keywords: Acute liver injury (ALI); ERK1/2; Hyperin; P38 MAPK; PPAR-γ