Hyperin attenuates inflammation by activating PPAR-γ in mice with acute liver injury (ALI) and LPS-induced RAW264.7 cells

Hyperin (HP) is a flavonoid compound found in various plants like Ericaceae, Guttifera and Celastraceae. The present study has revealed that HP has a variety of pharmacological effects including anti-oxidant, anticancer, and anti-coagulant, especially anti-inflammatory. However, the potential molecular mechanism of anti-inflammatory is still unrevealed. In this study, HP not only significantly attenuated inflammation in C57BL/61 mice with acute liver injury (ALI), but also reduced the expression of TNF-alpha and IL-6 in lipopolysaccharide (LPS)-induced RAW264.7 cells. Furthermore, our findings showed that HP remarkably induced the expression of PPAR-gamma in vivo and in vitro. Interestingly, compared with the HP treatment group, a specific blocking agent of PPAR-gamma T0070907 and PPAR-gamma small interfering (si)-RNA-mediated silencing in RAW264.7 cells were used to evaluate the involvement of HP in alleviating LPS-induced inflammation. More importantly, over-expression of PPAR-gamma had an opposite effect on the expression of TNF-alpha and IL-6 in LPS-induced RAW264.7 cells after treatment with HP. In addition, HP remarkably inhibited the expression of P-ERK1/2 and P-P38 MAPK. Taken together, all the above results indicate that HP may serve as an effective modulator of PPAR-gamma, further down-regulating ERK1/2 and p38 MAPK during the pathogenesis of inflammation. (C) 2015 Elsevier B.V. All rights reserved.