Dong Dong, Zhou Nan-Nan, Liu Rui-Xuan, Xiong Jia-Wei, Pan Hui, Sun Si-Qi, Ma Lei, Wang Rui
Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
Acta Pharmacol Sin. 2017 May;38(5):699-709. doi: 10.1038/aps.2016.180. Epub 2017 Feb 27.
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 PGE, 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·d, ig) or a positive control antifani (10 mg·kg·d, 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.
知母皂苷元-AA13（AA13）是从中药知母中提取的一种新型知母皂苷元合成衍生物。在本研究中，我们研究了AA13对脂多糖（LPS）诱导的巨噬细胞炎症因子产生的影响以及AA13在二甲苯诱导的耳水肿炎症模型中的抗炎活性。巨噬细胞（RAW264.7细胞和小鼠腹腔巨噬细胞）暴露于LPS（1μg/mL）；用AA13（5-20μmol/L）预处理剂量依赖性地抑制LPS诱导的NO、TNF-α和PGE的产生以及LPS刺激的COX-2和iNOS的表达水平。此外，用AA13预处理剂量依赖性地抑制LPS刺激的RAW264.7细胞中p38和JNK的磷酸化，但对ERK没有影响。此外，用AA13预处理可抑制LPS诱导的RAW264.7细胞中核因子（NF）-κB的激活。AA13的体内抗炎活性在小鼠炎症模型中得到证实：用AA13（20mg·kg·d，ig）或阳性对照药抗炎灵（10mg·kg·d，ig）预处理3天可显著减轻二甲苯诱导的耳水肿。我们的结果表明，AA13在体外有效抑制LPS诱导的巨噬细胞炎症反应，并在体内减轻二甲苯诱导的耳水肿。
