Sarsasapogenin-AA13 inhibits LPS-induced inflammatory responses in macrophage cells in vitro and relieves dimethylbenzene-induced ear edema in mice

摘要

Sarsasapogenin-AA13 (AA13) is a novel synthetic derivative of sarsasapogenin extracted from the Chinese herb Rhizoma Anemarrhenae.In this study we investigated the effects of AA13 on lipopolysaccharide (LPS)-induced production of inflammatory factors in macrophage cells and the anti-inflammatory activity of AA13 in an inflammatory model of dimethylbenzene-induced ear edema.Macrophage cells (RAW264.7 cells and mouse peritoneal macrophages) were exposed to LPS (1 μg/mL);pretreatment with AA13 (5-20 μmol/L) dose-dependently inhibited LPS-induced production of NO,TNF-α and PGE2,and LPS-stimulated expression levels of COX-2 and iNOS.Furthermore,pretreatment with AA13 dose-dependently suppressed LPS-stimulated phosphorylation of p38 and JNK,but had no effect on ERK in RAW264.7 cells.Moreover,pretreatment with AA13 inhibited LPS-induced activation of the nuclear factor (NF)-κB in RAW264.7 cells.The in vivo anti-inflammatory activity of AA13 was demonstrated in a mouse inflammatory model:pre-treatment with either AA13 (20 mg·kg-1·d-1,ig) or a positive control antifani (10 mg·kg-1·d-1,ig) for 3 d significantly relieved dimethylbenzene-induced ear edema.Our results demonstrate that AA13 effectively inhibit LPS-induced inflammatory responses in macrophage cells in vitro and relieve dimethylbenzene-induced ear edema in vivo.