苦蘵中睡茄交酯类成分的抗炎靶标预测

Prediction of anti-inflammatory targets of withanolides from Physalis angulata L

目的应用分子对接技术预测苦蘵中睡茄交酯类成分的抗炎活性靶标,并利用LPS诱导细胞炎症模型验证化合物的体外抗炎活性。方法以计算机辅助药物设计(CADD)中的分子对接技术为研究方法,以前期从苦蘵分离鉴定的9个睡茄交酯类成分组成配体数据库,选择环氧合酶-2(COX-2)、诱导型一氧化氮合酶(iNOS)、细胞外调节激酶(ERK)、p38、应激活化蛋白激酶(JNK)、核转录因子(NF-κB)等6个与抗炎活性密切相关的靶点组成受体数据库,对睡茄交酯类化合物的作用靶点及抗炎机制进行预测,进一步利用细胞炎症模型验证化合物对LPS诱导巨噬细胞释放炎症介质一氧化氮(NO)的抑制活性。结果对比分析了9个睡茄交酯化合物作用于各靶点的主要活性位点,化合物1-4均对LPS诱导细胞释放NO表现出抑制活性。结论苦蘵中睡茄交酯类活性成分可能是通过阻断ERK信号转导途径来发挥抗炎作用。

Objective To predict the anti-inflammatory effect of withanolide constituents from Physalis angulata L.and their target proteins with molecular docking technology and to evaluate the potential anti-inflammatory activities of these compounds in vitro by lipopolysaccharide(LPS)-induced RAW 264.7 macrophage cells.Methods A small molecule database based on 9 withanolide constituents isolated from Physalis angulata L.was established,and molecular docking technology in computer-aided drug design(CADD)was used to dock the small molecules with target proteins(COX-2,iNOS,ERK,p38,JNK,NF-κB)to predict the target and the anti-inflammatory mechanism of withanolide constituents.Furthermore,the inhibitory activities on the overproduction of inflammatory mediator NO were measured by Griess method.Results The main active sites of 9 withanolide compounds acting on each target were compared and analyzed,compounds 1,2,3,4 inhibited the overproduction of NO induced by LPS.Conclusion With anolides from Physalis angulata L.may exert anti-inflammatory founction through blocking the ERK transduction pathway.