丹参从瘀论治抑郁症的潜在靶点及作用机制研究

Study on Potential Targets and Mechanisms of Salvia miltiorrhiza in the Treatment of Depression Through Promoting Blood Circulation and Removing Stasis

目的探讨丹参从瘀论治抑郁症的潜在靶点及作用机制。方法基于已建立的丹参活性成分库,利用Swiss Target Prediction在线工具获得治疗抑郁症的作用靶标;采用Cytoscape 3.7.1软件构建丹参活性成分-抑郁症作用靶标网络,进一步通过STRING数据库进行疾病靶蛋白相互作用分析并构建PPI网络;运用数据库Metascape进行GO生物学过程和KEGG通路富集分析;利用DiscoveryStudio软件进行关键成分及靶点的分子对接能计算。结果成分-靶点网络涉及54个丹参活性成分和36个与抑郁症相关的靶点,其中MAOA、ESR1、SLC6A4、HTR2、PTGS2等靶点与丹参多个活性成分具有较强的结合能力。经GO和KEGG通路富集分析,发现丹参活性成分可能通过参与5-羟色胺能神经系统、色氨酸代谢过程以及雌激素受体信号传导等通路,综合调节神经递质水平,影响离子迁移、细胞分泌、激素水平、细胞内信号传导等生物过程而发挥抗抑郁作用。这3条通路与丹参活血化瘀机制具有密切相关性,并且炎症反应在活血化瘀机制中具有重要意义。结论丹参中丹酚酸G、丹酚酸J、木犀草素、丹参环庚三烯酚酮、丹参二醇B、原紫草酸、异隐丹参酮等,可能通过PTGS2、MAOA、SLC6A4、HTR2A、ESR1等多个靶点,通过影响5-羟色胺能神经系统、色氨酸代谢过程以及雌激素受体信号传导等发挥治疗抑郁症的作用,体现了中药多成分-多靶点-多途径的作用特点。本文为丹参从瘀论治抑郁症的进一步研究提供参考依据,同时也为其他活血化瘀类中药的研究与应用提供新的思路。

Objective To discover the potential targets and mechanisms of Salvia miltiorrhiza in treating depression through promoting blood circulation and removing stasis.Methods According to the Salvia miltiorrhiza components database and target proteins in treating depression obtained from Swiss target prediction online tool,we constructed the network of“chemical components of Salvia miltiorrhiza-target proteins of depression”using Cytoscape 3.7.1 software.The interaction of disease target protein was analyzed through the STRING database.The GO biological process and the KEGG pathway enrichment analysis were performed by Metascape to predict mechanisms of Salvia miltiorrhiza in treating depression.Discovery Studio was utilized to predict the binding ability between candidate targets and components.Results The component-target network consisted of 54 active components of Salvia miltiorrhiza and 36 potential targets protein in treating depression.MAOA,ESR1,SLC6A4,HTR2 and PTGS2 have been found to have strong binding ability with active components in Salvia miltiorrhiza.GO enrichment and KEGG pathway analysis showed that the process of Salvia miltiorrhiza treated in depression may be involved in serotonergic nerves system,tryptophan metabolism process,estrogen receptor signaling pathways.These pathways are related to comprehensive regulation of neurotransmitter level,ion migration,cell secretion,hormone level,intracellular signal transduction and other biological processes.The three signaling pathways play a role in the treatment of depression through promoting blood circulation and removing stasis,which is related to inflammatory reaction closely.Conclusion Main efficacy components of Salvia miltiorrhiza,such as salvianolic acid G,salvianolic acid J,luteolin,miltipolone,tanshindiol B,prolithospermic acid,isocryptotanshi-none may play the role in the treatment of depression by targeting PTGS2,MAOA,SLC6A4,HTR2A,ESR1 and influencing erotonergic nerves system,tryptophan metabolism process and estrogen receptor signaling pathways,which indicates multiple ingredients-multi targets-multi pathways characteristics of traditional Chinese medicines.The study provides a reference for further study of Salvia miltiorrhiza in the treatment of depression through promoting blood circulation and removing stasis.Moreover,it gives new idea for research and application of other traditional Chinese medicine for promoting blood circulation and removing stasis.