摘要
目的 利用网络药理学方法及分子对接技术探讨中医“药物金三角”的代表用药人参、丹参、葶苈子治疗慢性心力衰竭的潜在作用机制。方法 从公开数据库获取中医“药物金三角”的代表用药人参、丹参、葶苈子的活性成分并进行靶点预测,将其与心力衰竭致病基因相映射以获取作用靶点。随后对药物作用于心力衰竭的靶点进行富集分析,并对关键信号通路中的靶点与成分进行分子对接验证。结果 共获得药物潜在活性成分187个,对应靶点455个,作用于心力衰竭的靶点共97个,其中肿瘤坏死因子(TNF)、血管内皮生长因子A(VEGFA)、信号转导和转录激活因子3(STAT3)、丝裂原激活的蛋白激酶8(MAPK8)、清蛋白(ALB)为关键靶点。经过富集分析,发现中医“药物金三角”治疗心力衰竭涉及对药物的反应、炎症应答、对外部刺激的反应等生物过程,可作用于环磷酸腺苷(cAMP)信号通路、环磷酸鸟苷(cGMP)-蛋白激酶G(PKG)信号通路、心肌收缩、心肌细胞中的肾上腺素能信号、醛固酮的合成和分泌等重要通路。分子对接结果显示,关键信号通路中的靶点与成分平均结合能为-29.246 kJ/mol,说明靶点与成分之间具有良好的对接关系。结论 中医“药物金三角”的代表用药人参、丹参、葶苈子可通过复杂网络形式调控心肌收缩、心脏负荷、心室重构等生理病理过程,从而发挥治疗心力衰竭的作用。
Objective To explore the potential mechanism of Panax Ginseng, Radix Salviae, and Lepidii Semen Descurainiae Semen, the representative herbs of "Golden Triangle of Traditional Chinese Medicine(GTTCM)",in treating chronic heart failure by the combination of network pharmacology and molecular docking.Methods The active components of Panax Ginseng, Radix Salviae, and Lepidii Semen Descurainiae Semen were retrieved and obtained from the public database, for by predicting the targets, and mapping them with the pathogenic genes of heart failure to obtain the common targets.Then, enrichment analysis was carried out on the common targets, and molecular docking was used to verify the interactions among targets and components in the key signaling pathways.Results A total of 187 potential active components were obtained, corresponding to 455 targets.And there were 97 common targets, among which tumor necrosis factor(TNF),vascular endothelial growth factor A(VEGFA),signal transducers and activators of transcription 3(STAT3),mitogen-activated protein kinase(MAPK) 8,and albumin(ALB) were considered to be crucial.After enrichment analysis, it was found that the biological processed of GTTCM in treating heart failure involves drug response, inflammatory response, and response to external stimuli, and the key pathways includes cyclic adenosine monophosphate(cAMP) signaling pathway, cyclic guanosine monophosphate(cGMP)-protein kinase G(PKG) signaling pathway, cardiac muscle contraction, adrenergic signaling in cardiomyocytes, aldosterone synthesis and secretion.The results of molecular docking showed that the average binding energy of targets and components in the key signaling pathways was-29.246 kJ/mol, which indicated that there were good docking relationships between targets and components.Conclusion The GTTCM could regulate physiological and pathological processes such as myocardial contraction, cardiac load, and ventricular remodeling through complex network, so as to play a role in treating heart failure.
作者
黎燚华
陈琦
康亮
张志敏
赵新军
李荣
LI Yihua;CHEN Qi;KANG Liang;ZHANG Zhimin;ZHAO Xinjun;LI Rong(Guangzhou University of Chinese Medicine,Guangzhou 510405,Guangdong,China)
出处
《中西医结合心脑血管病杂志》
2022年第21期3855-3863,共9页
Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease
基金
广州中医药大学“双一流”与高水平大学学科协同创新团队项目(No.2021xk52)
广州市科技局2022“市校(院)联合资助项目”。
关键词
心力衰竭
人参
丹参
葶苈子
网络药理学
分子对接
heart failure
Panax Ginseng
Radix Salviae
Lepidii Semen Descurainiae Semen
network pharmacology
molecular docking
