蛭蛇通络胶囊抗炎及舒张血管的有效组分辨识

Identification of Effective Components in Zhishe Tongluo Capsules for Anti-inflammation and Vasodilation

目的:研究蛭蛇通络胶囊及其拆方组分肠吸收液对炎症和血管舒张的影响,并通过网络药理学方法探究拆方的有效性。方法:通过脂多糖(LPS)刺激小鼠巨噬细胞株RAW264.7产生炎症因子观察抗炎作用,离体血管活性实验观察舒张作用。通过数据库检索蛭蛇通络胶囊的化学成分及成分靶点,并将蛭蛇通络胶囊和水蛭、乌梢蛇、红花组分分别与炎症和血管舒张相交集,构建蛋白相互作用网络并富集分析。结果:按照蛭蛇通络胶囊的制备工艺路线进行拆方,制备各组分和全方的肠吸收液。均以含水蛭、乌梢蛇和红花组分效果最佳,能有效抑制炎症因子的表达及调节血管舒张的活性。获得蛭蛇通络胶囊抑制炎症共778个靶点,舒张血管共181个靶点,水蛭、乌梢蛇和红花组分抑制炎症共312个靶点,舒张血管共82个靶点。蛭蛇通络胶囊和水蛭、乌梢蛇、红花组分抑制炎症的基因本体(GO)生物学过程分析主要与调节激素水平和有机羟基化合物代谢过程有关,舒张血管主要涉及血液循环和分泌调节;抑制炎症与舒张血管的京都基因与基因组百科全书(KEGG)通路富集分析都涉及环磷酸腺苷(cAMP)信号通路。结论:蛭蛇通络胶囊可通过抗炎和舒张血管发挥治疗脑卒中的作用,其中水蛭、乌梢蛇和红花是抗炎和舒张血管的主要有效药味组分。

Objective:To investigate the effects of the intestinal absorption solutions containing Zhishe Tongluo Capsules and modified prescriptions on inflammation and vasodilation and explore the efficacy of the modified prescriptions through network pharmacology.Methods:The anti-inflammatory effect was observed based on inflammatory factors produced by lipopolysaccharide(LPS)-stimulated RAW264.7 cells.The vasodilation effect was examined by the in vitro vasoactivity assay.The chemical components and targets of Zhishe Tongluo Capsules were obtained through database retrieval.Zhishe Tongluo Capsules,Hirudo,Zaocys,and Carthami Flos extracts were intersected with targets of inflammation and vasodilation to construct a protein-protein interaction(PPI)network,followed by enrichment analysis.Results:The prescription of Zhishe Tongluo Capsules was disassembled into several modified prescriptions according to the production process,and the intestinal absorption solutions of Zhishe Tongluo Capsules and modified prescriptions were obtained.The optimal inhibitory effect against the expression of inflammatory factors and promoting effect on vasodilation were observed in the groups containing Hirudo,Zaocys,and Carthami Flos extracts.A total of 778 targets of Zhishe Tongluo Capsules for inhibiting inflammation and 181 targets for vasodilation were obtained,and 312 targets of Hirudo,Zaocys,and Carthami Flos extracts for inhibiting inflammation and 82 targets for vasodilation were screened out.As revealed by Gene Ontology(GO)enrichment analysis,the biological processes of Zhishe Tongluo Capsules,Hirudo,Zaocys,and Carthami Flos extracts were mainly related to the regulation of hormone levels and metabolic process of organic hydroxy compounds in inhibiting inflammation,and blood circulation and secretion regulation in treating vasodilation.The Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis showed that the pathways involved cyclic adenosine monophosphate(cAMP)signaling pathway.Conclusion:Zhishe Tongluo Capsules can play a role in the treatment of stroke by inflammation resistance and vasodilation,where Hirudo,Zaocys,and Carthami Flos are the main effective combination.