[Anti-inflammatory mechanism of Xixian Tongshuan Preparation based on molecular simulation methods]

Inflammatory response is caused by exogenous and endogenous stimuli,resulting in a non-specific resistance reaction.After acute ischemic cerebral infarction,inflammatory factors gather and adhere in the ischemic area of leukocyte infiltration,and the released inflammatory factors causes the injury cascade,aggravate the brain tissue damage and the symptoms of neurological deficits,and hinder the repair of brain neurons and the recovery of nerve function. In this paper,the key targets in the arachidonic acid metabolic pathway were studied. The Hiphop pharmacophore model of s PLA2-ⅡA and COX-2 inhibitors was built. According tothe two previously constructed 5-LOX and LTA4 H target inhibitors,the pharmacophore model was used to initially screen out the composition database of all of 13 traditional Chinese medicines in Xixian Tongshuan Preparation. The molecular matching study was carried out by selecting the matching value greater than 0. 6,and the component with the CDOCKER score greater than 80% of the original ligand score was used as the potential active inhibitor of the target. Considering the pharmacophore matching value,the molecular docking score and the interaction between the components and the target,one Chuanxiong component and one safflower component were selected as potential inhibitors of s PLA2-ⅡA; two Chuanxiong components,two Panax notoginseng,one safflower component,one angelica component,one valerian component were taken as a potential inhibitor of COX-2; two Gentiana components,one safflower component,one valerian component,one P. notoginseng component and one Angelica component were taken as potential inhibitors of 5-LOX; and two Gentiana components,two Chuanxiong components,and two safflower components were taken as potential inhibitors of LTA4 H. This study screened out the potential inhibitors of the four targets in a high-efficiency and low-cost manner,and explained that Xixian Tongshuan Preparation showed an effect in the treatment of inflammatory responses caused by ischemic stroke by acting both LOX pathway and COX pathway in the metabolic pathway.