title: Antioxidation, anti-inflammation and anti-apoptosis by paeonol in LPS/d-GalN-induced acute liver failure in mice.
abstract: To evaluate the hepatoprotective effects and potential mechanisms of paeonol (Pae) against acute liver failure (ALF) induced by lipopolysaccharide (LPS)/d-galactosamine (d-GalN) in mice, we examined anti-oxidative, anti-inflammatory and anti-apoptotic activities of Pae. We found that Pae pretreatment markedly reduced the activities of alanine transaminase and aspartate transaminase as well as the histopathological changes induced by LPS/d-GalN. Catalase, glutathione and superoxide dismutase activities increased and reactive oxygen species activity decreased after Pae treatment compared with LPS/d-GalN treatment. Pretreatment with Pae also significantly inhibited the expression levels of iNOS, nitric oxide (NO), COX-2 and prostaglandin E2(PGE2). In addition, Pae administration prevented the phosphorylated expression of IκB kinase, inhibitor kappa B in the nuclear factor-kappa B (NF-κB) signaling pathway, and suppressed the phosphorylated expression of extracellular signal-regulated kinase (ERK), c-jun-N-terminal kinase and p38 in the MAPK signaling pathway. Pretreatment with Pae also inhibited hepatocyte apoptosis by reducing the expression of caspases 3, 8, 9, and Bax, and increasing Bcl-2. In total, protective effects of Pae against LPS/d-GalN-induced ALF in mice are attributed to its antioxidative effect, inflammatory suppression in NF-κB and MARK signaling pathways, and inhibition of hepatocyte apoptosis inhibition. Therefore, Pae can be a potential therapeutic agent in attenuating LPS/d-GalN-induced ALF in the future.
authors.affiliation: College of Pharmaceutical Sciences, Southwest University, Chongqing 400716, PR China.
authors.forename: Xiaobao
authors.initials: X
authors.lastname: Gong
authors.affiliation: College of Animal Science and Technology, Southwest University, Chongqing 400716, PR China.
authors.forename: You
authors.initials: Y
authors.lastname: Yang
authors.affiliation: College of Pharmaceutical Sciences, Southwest University, Chongqing 400716, PR China.
authors.forename: Ligua
authors.initials: L
authors.lastname: Huang
authors.affiliation: The Ninth People's Hospital of Chongqing, Chongqing 400700, PR China.
authors.forename: Qingyan
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: The Ninth People's Hospital of Chongqing, Chongqing 400700, PR China.
authors.forename: Rong-Zhen
authors.initials: RZ
authors.lastname: Wan
authors.affiliation: The Ninth People's Hospital of Chongqing, Chongqing 400700, PR China. Electronic address: zhp1004@126.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: College of Pharmaceutical Sciences, Southwest University, Chongqing 400716, PR China. Electronic address: zbs360@swu.edu.cn.
authors.forename: Baoshun
authors.initials: B
authors.lastname: Zhang
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D001219:Aspartate Aminotransferases / Q000097:blood; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D005688:Galactosamine / Q000276:immunology; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017114:Liver Failure, Acute / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D004365:Drugs, Chinese Herbal; D008070:Lipopolysaccharides; D016328:NF-kappa B; C524375:paeonal; D005688:Galactosamine; D052247:Nitric Oxide Synthase Type II; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D020169:Caspases
keywords: Acute liver failure; Antiapoptotic; Antiinflammatory; Antioxidation; Paeonol