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

作　　者：Dong DONG Nan-nan ZHOU Rui-xuan LIU Jia-wei XIONG Hui PAN Si-qi SUN Lei MA Rui WANG 

机构地区：[1]Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai200237, China

出　　处：《Acta Pharmacologica Sinica》2017年第5期699-709,共11页中国药理学报（英文版）

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 ceils and mouse peritoneal macrophages） were exposed to LPS （1 pg/mL）; pretreatment with AA13 （5-20 pmol/L） dose-dependently inhibited LPS-induced production of NO, TNF-a 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）-KB 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-k-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.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 ceils and mouse peritoneal macrophages） were exposed to LPS （1 pg/mL）; pretreatment with AA13 （5-20 pmol/L） dose-dependently inhibited LPS-induced production of NO, TNF-a 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）-KB 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-k-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.

关 键 词：SARSASAPOGENIN AA13 antifani ANTI-INFLAMMATION inflammatory factor nuclear factor-KB mitogen-activated proteinkinases ear edema 

分 类 号：R[医药卫生]