Metabolomic study on immunological stress-mediated hepatotoxicity of Polygonum multiflorum and its processed products of nine times steaming and nine times sunning / 药学学报

ABSTRACT

It is investigated that the hepatotoxicity of Polygonum multiflorum (PM)was attenuated by its processed products of nine times steaming and nine times sunning(RPM)based on immunological stress-mediated animal model by using metabolomics method. Sprague-Dawley(SD)rats were intragastrically administered with(5.4 g crude drug per kg body weight)of 50% alcohol extracts of PM and its processed products of nine times steaming and nine times sunning respectively or co-treated with non-toxic dose of lipopolysaccharide(LPS, 2.8 mg·kg-1)via tail vein injection. The plasma alanine aminotransferase(ALT)and aspartate aminotransferase(AST)activities were assayed and the isolated livers were evaluated for histopathological changes. Global metabolomics profiling, multivariate analysis and data base searching were performed to discover common differential metabolites for idiosyncratic liver injury. The results showed that co-treatment with non-toxic dose of LPS and PM could result in significant liver injury, indicated by the elevation of plasma ALT and AST activities, as well as obvious liver histologic damage; whereas RPM failed to induce detectable liver injury. Furthermore, 10 potential metabolomics biomarkers that differentially expressed in LPS/PM group compared with LPS/RPM without liver injury were identified by untargeted metabolomics, mainly involved ten pathways sphingolipid metabolism, linoleic acid metabolism, taurine and hypotaurine metabolism, steroid hormone biosynthesis, galactose metabolism, steroid biosynthesis, metabolism of xenobiotics by cytochrome P450, pyrimidine metabolism, biosynthesis of unsaturated fatty acids, primary bile acid biosynthesis. This work illustrated the idiosyncratic hepatotoxicity of heshouwu and provided a metabolomic insight into diosyncratic liver injury of PM and RPM.