title: Asiatic acid from Potentilla chinensis attenuate ethanol-induced hepatic injury via suppression of oxidative stress and Kupffer cell activation.
abstract: This study examined the effect of Asiatic acid from Potentilla chinensis (AAPC) on chronic ethanol-induced hepatic injury. Rats underwent intragastric administration of ethanol (5.0–9.0 g/kg) once a day for 12 weeks. A subset of rats were also intragastrically treated with AAPC (2, 4 or 8 mg/kg) once a day. In the end, AAPC treatment significantly protected against ethanol-induced liver injury, as evidenced by the decrease in serum alanine and aspartate aminotransferases levels and the attenuation of histopathological changes in rats. Additionally, AAPC significantly decreased blood alcohol and acetaldehyde concentrations by enhancing alcohol dehydrogenase and aldehyde dehydrogenase activities. Mechanistically, studies showed that AAPC remarkably alleviated the formations of malondialdehyde and myeloperoxidase, restored impaired antioxidants, including superoxide dismutase, glutathione peroxidase, glutathione reductase and catalase, and inhibited cytochrome P450 (CYP)2E1 activity. Moreover, the over-expression of cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), the elevated plasma endotoxin level and the up-regulated Toll-like receptor 4 (TLR4), CD14 and myeloid differentiation factor 88 (MyD88) as well as nuclear factor-κB were also suppressed by AAPC in ethanol-intoxicated rats. In conclusion, the protective effect of AAPC on ethanol-induced hepatotoxicity was mainly due to its ability to attenuate oxidative stress and inhibit Kupffer cell activation by decreasing the level of plasma endotoxin and the expression of TLR4, CD14 and MyD88.
authors.forename: Jinbin
authors.initials: J
authors.lastname: Wei
authors.forename: Quanfang
authors.initials: Q
authors.lastname: Huang
authors.forename: Renbin
authors.initials: R
authors.lastname: Huang
authors.forename: Yongxing
authors.initials: Y
authors.lastname: Chen
authors.forename: Shujuan
authors.initials: S
authors.lastname: Lv
authors.forename: Ling
authors.initials: L
authors.lastname: Wei
authors.forename: Chunhong
authors.initials: C
authors.lastname: Liang
authors.forename: Shuang
authors.initials: S
authors.lastname: Liang
authors.forename: Lang
authors.initials: L
authors.lastname: Zhuo
authors.forename: Xing
authors.initials: X
authors.lastname: Lin
mesh_terms: D000079:Acetaldehyde / Q000097:blood; D000818:Animals; D002374:Catalase / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D004731:Endotoxins / Q000097:blood; D000431:Ethanol / Q000097:blood / Q000633:toxicity; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D053978:Pentacyclic Triterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D009195:Peroxidase / Q000378:metabolism; D008517:Phytotherapy; D031987:Potentilla; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D004731:Endotoxins; D053583:Interleukin-1beta; D018950:Lipopolysaccharide Receptors; C507781:Myd88 protein, rat; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D053978:Pentacyclic Triterpenes; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol; C017032:asiatic acid; D002374:Catalase; D009195:Peroxidase; D005979:Glutathione Peroxidase; D019392:Cytochrome P-450 CYP2E1; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D000079:Acetaldehyde