柴胡龙骨牡蛎汤治疗原发性高血压作用网络与机制预测

Efficacy network and mechanism prediction of Chaihu Longgu Muli Decoction in treatment of essential hypertension

目的运用网络药理学研究方法,分析柴胡龙骨牡蛎汤治疗原发性高血压作用网络与潜在机制。方法借助TCMSP、TCMID、Stitch等数据库获取柴胡龙骨牡蛎汤的化学成分及对应靶点,PubMed、CTD、TTD、OMIM、DrugBank等数据库检索原发性高血压的疾病靶点;对药物与疾病靶点相映射得柴胡龙骨牡蛎汤治疗原发性高血压的作用靶点,运用Cytoscape和STRING软件构建"化合物-靶点"作用网络与蛋白相互作用(PPI)网络,筛选发挥治疗作用的关键成分与关键靶点,对关键靶点进行GO和pathway富集分析获知其潜在作用机制。结果预测得到柴胡龙骨牡蛎汤作用于原发性高血压的有效成分137个,靶点168个,关键成分有槲皮素、β-谷甾醇、山柰酚、豆甾醇4个,关键靶点有IL6、AKT1、MAPK8等12个,GO和pathway分析结果显示,柴胡龙骨牡蛎汤治疗高血压与AP-1家族转录因子的激活、白细胞介素-10信号、白细胞介素-4信号和白细胞介素-13信号、细胞凋亡的内在途径、MAPK靶向/由MAP激酶介导的核事件等通路有关。结论柴胡龙骨牡蛎汤治疗原发性高血压是通过上述潜在的"多成分-多靶点-多途径"来发挥作用的,该研究为柴胡龙骨牡蛎汤治疗原发性高血压物质基础及作用机制的进一步研究奠定基础。

Objective To study the efficacy network and potential mechanisms of effects of Chaihu Longgu Muli Decoction in the treatment of essential hypertension by using network pharmacology methods.Methods TCMSP,TCMID,and Stitch were used to obtain the components and their corresponding targets.PubMed,CTD,TTD,OMIM,and DrugBank were used to search disease targets of essential hypertension.The common targets between components and disease targets were screened and builded the"compound–target"efficacy network and the protein-protein interaction network by STRING and Cytoscape.The key components and core targets of Chaihu Longgu Muli Decoction in the treatment of hypertension were screened in these networks.Finally,relevant software was applied to GO analysis and pathway analysis of core targets to predict potential mechanisms.Results A total of 137 components of Chaihu Longgu Muli Decoction and 168 targets of essential hypertension were screened.According to the analysis,quercetin,β-sitosterol,kaempferol,and stigmasterol were found as the four key components and 12 core targets such as IL-6,AKT1,and MAPK8 were found involving the Chaihu Longgu Muli Decoction-induced treatment of essential hypertension.The result of GO analysis and KEGG pathway analysis showed that the mechanisms of Chaihu Longgu Muli Decoction for treating essential hypertension were related to pathways such as activation of AP-1 family transcription factors,interleukin-10 signaling,interleukin-4 signaling,interleukin-13 signaling,the intrinsic pathway of apoptosis,and MAPK targeting/by MAP kinase-mediated nuclear events.Conclusion The mechanisms of the effect of Chaihu Longgu Muli Decoction in the treatment of essential hypertension were through the above-mentioned"multi-components-multi-targets-multi-pathways".This study provides a foundation for further investigation of the effective compound and specific mechanisms of Chaihu Longgu Muli Decoction in the treatment of essential hypertension.