Antipyretic and Anti-inflammatory Effects of Asiaticoside in Lipopolysaccharide-treated Rat through Up-regulation of Heme Oxygenase-1

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)- and interleukin (IL)-6 production, liver myeloperoxidase (MPO) activity, brain cyclooxygenase-2 (COX-2) protein expression and prostaglandin E-2 (PGE(2)) 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- and IL-6 levels, COX-2 expression and PGE(2) production, as well as MPO activity, which might be mediated by the up-regulation of HO-1. Copyright (c) 2012 John Wiley & Sons, Ltd.