血必净抗炎作用药效物质基础和多靶点作用效应

Effects of the Multi-Target Capability of Xuebijing and Its Inflammatory Pharmacodynamic Material Basis

研究了血必净抗炎作用的药效物质基础,并在分子层面上对复方多靶点作用进行阐释.借助于计算机辅助药物设计技术,构建血必净化学成分数据库,综合应用同源模建、分子对接、药效团模型、数据库搜索等方法,探讨其与炎症靶点5-脂氧合酶(5-LOX)、环氧合酶-2(COX-2)、IKK-2受体的相互作用关系.血必净化学成分中与靶点5-LOX、COX-2、IKK-2结合效应较好的分别有30、36、8个分子;有16个分子与2个或3个靶点存在作用,其中15个分子对靶点5-LOX和COX-2有抑制作用,迷迭香酸对3个靶点均有作用.从分子层次上阐释了复方血必净抗炎作用的药效物质基础和多靶点作用效应,为血必净复方的临床应用提供了科学依据;同时,也为寻找新型抗炎药物提供一定的参考和借鉴.

The inflammatory effects, pharmacodynamical basis, and multi-targeting properties of Xuebijing, a traditional Chinese medicine （TCM） prescription, were investigated on molecular level. Using computer aided drug design （CADD） consisting of homology modeling, molecular docking, pharmacophore construction, and virtual screening was carried out to search for the molecules included in Xuebijing that inhibit the three inflammatory related targets： 5-1ipoxygenase （5-LOX）, cyclooxygenase-2 （COX-2）, and IKK-2. An aggregate analysis was then performed to evaluate the chemical compositions of Xuebijing molecules. There were 30, 36, and 8 molecules that showed good interaction with the inflammatory targets： 5-LOX, COX-2, and IKK-2, respectively. There were 16 molecules that inhibited two or three targets among which 15 molecules inhibited both 5-LOX and COX-2, rosmarinic acid inhibits all targets. This investigation shows that there are many multi-targeting molecules in Xuebijing. Our research gives a molecular description of the multi-target effect and a pharmacodynamical material basis of the inflammatory effect. On the other hand, as multi-target could be a new trend in the field of drug design, our research points the way to discovering new anti-inflammation entities.