摘要
目的:采用网络药理学研究方法,基于网络药理学和玄府理论探讨三化汤治疗缺血性脑卒中(ischemic stroke,IS)的机制。方法:将玄府与现代医学的血脑屏障联系起来,分析三化汤通过调气开通玄府法治疗IS。利用中药相关数据库搜索出三化汤(大黄、厚朴、羌活、枳实)的有效化学成分,这些成分按照口服生物利用度(oral bioavailability,OB)、类药性(drug-likeness,DL)及血脑屏障(blood-brain barrier,BBB)透过性差异分类,并找到对应靶点。将疾病靶点与药物靶点进行交集,筛选得到疾病-药物成分共同靶蛋白。应用STRING平台构建蛋白-蛋白相互作用(PPI)(protein-protein interactions)网络模型。采用Cytoscape的Metascape分析三化汤治疗IS相关靶点的基因功能及代谢通路。结果:根据OB≥30%、DL≥0.18及血脑屏障(blood brain barrier,BBB)≥0.3或BBB<0.3筛选标准,经数据库分析共筛选出三化汤的42种主要成分及与IS相关的靶点1230个,同时筛选出相关信号通路21个;分子对接结果提示三化汤各核心成分大部分能够与核心靶点产生稳定结合,其中大黄、羌胡的β-谷固醇、枳实的柚皮素核心靶点产生强烈结合活性,提示其可能是三化汤治疗IS的核心组分。结论:发现三化汤可能通过CASP3、PTGS2、JUN、TNF、IL6和VEGFA等多核心靶点,改善血脑屏障通透性、抗炎、抗氧化、促进血管生成、抑制细胞凋亡多途径发挥对IS治疗作用,KEGG富集结果显示主要通过与钙离子相关通路、cAMP信号通路、VEGF信号通路、胆碱能突触通路、5-羟色胺通路、IL-17信号通路、动脉粥样硬化、PI3K-Akt信号通路、PPAR信号通路等治疗IS。
Objective:To investigate the mechanism of Sanhua Decoction in the treatment of ischemic stroke(is)based on network pharmacology and the theory of Xuanfu by using network pharmacology.Methods:to relate the blood-brain barrier of Scrophularia to modern medicine,and analyze the therapeutic effect of Sanyao Decoction on is by regulating Qi to open Scrophularia.The relevant databases of traditional Chinese medicine(TCM)were used to search out the effective chemical constituents of Sanyuan Decoction(Dahuang,Houpu,Qiang,and citrus aurantium),which were classified according to oral bioavailability(OB),drug resistance(DL),and blood-brain barrier(BBB)permeability differences,and to find the corresponding targets.The disease targets were intersected with the drug targets,and the screening resulted in the disease drug ingredient common target proteins.String platform was applied to construct a protein-protein interaction(PPI)(protein protein interactions)network model.The gene functions and metabolic pathways of is related targets treated with Sanhua Decoction were analyzed by metscape of Cytoscape.Results:according to the screening criteria of ob≥30%,DL≥0.18 and blood-brain barrier(BBB)≥0.3 or BBB<0.3,a total of 42 principal components of sanyui Decoction and 1230 targets related to is were screened out by database analysis,while 21 related signaling pathways were screened out;Molecular docking results suggested that most of the core components of Sanyui decoction could produce stable binding with core targets,among which rhubarb and Qiang Huβ-naringenin from sitosterol,citrus aurantium,yielded strong binding activity,suggesting that it may be a core component of Sanyao Decoction for is treatment.Conclusions:it was found that Sanyao Decoction might exert its effects on is treatment by improving BBB permeability,anti inflammation,antioxidation,promoting angiogenesis and inhibiting apoptosis through multi-core targets including CASP3,PTGS2,Jun,TNF,IL6 and VEGFA,and the KEGG enrichment results showed that it was mainly through calcium ion related pathway,cAMP signaling pathway,VEGF signaling pathway,cholinergic synaptic pathway,serotonin pathway,IL-17 signaling pathway Atherosclerosis,PI3K Akt signaling pathway,PPAR signaling pathway,and other treatments for is.
作者
王娟
王廷华
白雪
WANG Juan;WANG Tinghua;BAI Xue(Affiliated Hospital of Traditional Chinese Medicine of Southwest Medical University,Sichuan Luzhou 646000,China;West China Hospital of Sichuan University,Sichuan Chengdu 610041,China)
出处
《中医药临床杂志》
2022年第10期1871-1882,共12页
Clinical Journal of Traditional Chinese Medicine
关键词
玄府理论
血脑屏障
网络药理学
缺血性脑卒中
三化汤
分子对接
Xuanfu theory
Blood-brain Barrier
Network pharmacology
Ischemic stroke
Sanhua Decoction
Molecular docking
