title: Antipyretic and anti-inflammatory effects of asiaticoside in lipopolysaccharide-treated rat through up-regulation of heme oxygenase-1.
abstract: Asiaticoside (AS), a triterpenoid isolated from Centella asiatica, has been found to exhibit antioxidant and anti-inflammatory activities in several experimental animal models. However, the underlying mechanisms remain elusive. In this study, we provide experimental evidences that AS dose-dependently inhibited lipopolysaccharide (LPS)-induced fever and inflammatory response, including serum tumor necrosis factor (TNF)-α and interleukin (IL)-6 production, liver myeloperoxidase (MPO) activity, brain cyclooxygenase-2 (COX-2) protein expression and prostaglandin E2 (PGE2 ) production. Interestingly, AS increased serum IL-10 level, liver heme oxygenase-1 (HO-1) protein expression and activity. Furthermore, we found that the suppressive effects of AS on LPS-induced fever and inflammation were reversed by pretreatment with ZnPPIX, a HO-1 activity inhibitor. In summary, our results suggest that AS has the antipyretic and anti-inflammatory effects in LPS-treated rat. These effects could be associated with the inhibition of pro-inflammatory mediators, including TNF-α and IL-6 levels, COX-2 expression and PGE2 production, as well as MPO activity, which might be mediated by the up-regulation of HO-1.
authors.affiliation: Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing, China.
authors.forename: JingYuan
authors.initials: J
authors.lastname: Wan
authors.forename: Xia
authors.initials: X
authors.lastname: Gong
authors.forename: Rong
authors.initials: R
authors.lastname: Jiang
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D058633:Antipyretics / Q000494:pharmacology*; D028041:Centella / Q000737:chemistry; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism*; D007249:Inflammation / Q000188:drug therapy; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides; D008099:Liver / Q000201:enzymology; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014315:Triterpenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D058633:Antipyretics; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009195:Peroxidase; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D015232:Dinoprostone; C004446:asiaticoside