中药复方治疗原发性骨质疏松用药规律及作用机制分析

Regularity and mechanism of traditional Chinese medicine compound prescriptions in the treatment of primary osteoporosis

背景:中药复方治疗原发性骨质疏松有着较久的历史,并且疗效确切,但其用药规律及作用机制尚不明确。目的:利用数据挖掘与网络药理学的方法学,探究现代中医家治疗原发性骨质疏松的用药规律、分子层面的作用机制并一定程度的加以验证。方法:将中国知网、万方、维普、PubMed等数据库收录的相关文献作为数据来源,使用Microsoft EXCEL 2019、IBM SPSS 25.0等软件统计和提取相关资料。将数据统计得到的高频药物进行关联规则分析和聚类分析,综合两者结果得到中药复方治疗原发性骨质疏松的核心药物组合,利用网络药理学阐释此组合发挥治疗作用的机制并借助分子对接加以验证。结果与结论:最终纳入151篇文献,筛选出方剂207首,涉及中药285味。①通过上述两种分析综合得到重要药物组合10组,其中置信度和提升度最高的核心药物组合为“骨碎补-杜仲-当归”,其组合治疗原发性骨质疏松的关键成分为槲皮素、山奈酚、柚皮素等,核心靶点为SRC原癌基因(SRC proto-oncogene)、磷脂酰肌醇-3-激酶调节亚单位1(PIK3R1)、RELA原癌基因(RELA)等,主要通路为癌症信号通路、JAK-STAT信号通路、VEGF信号通路、核因子κB信号通路等。②将关键活性成分与核心靶点进行分子对接,两者展示出较好的结合性。③中药复方治疗原发性骨质疏松核心药物组合可利用其多种活性成分,通过多条信号通路、作用于多个靶点发挥疗效,可为后续治疗原发性骨质疏松新药的研发提供理论基础。

BACKGROUND:Traditional Chinese medicine compound prescription has a long history in the treatment of primary osteoporosis,and the curative effect is definite,but the medication rule and mechanism are not clear.OBJECTIVE:Using the methodology of data mining and network pharmacology,to explore and verify the law of drug use and molecular mechanism of modern traditional Chinese medicine in the treatment of primary osteoporosis.METHODS:The relevant documents included in CNKI,WanFang,VIP and PubMed were used as data sources,and the relevant data were statistically counted and extracted by Microsoft EXCEL2019,IBMSPSS25.0 and other software.The high-frequency drugs obtained from the data statistics were analyzed by association rules analysis and cluster analysis,and the core drug combination of traditional Chinese medicine compound prescription in the treatment of primary osteoporosis was obtained by combining the two results.The therapeutic mechanism of this combination was explained by network pharmacology and verified by molecular docking.RESULTS AND CONCLUSION:Finally,151 articles were included and 207 prescriptions were selected,involving 285 flavors of Chinese herbs.(1)Ten groups of important drug combinations were obtained through the above two analyses,among which the core drug combination with the highest confidence and improvement was“Drynaria-Eucommia-Angelica.”The key components of the combination in the treatment of primary osteoporosis were quercetin,kaempferol,naringenin and so on.The core targets were SRC proto-oncogene,phosphoinositide-3-Kinase regulatory subunit 1 and RELA proto-oncogene.The main pathways were cancer signaling pathway,JAK-STAT signaling pathway,VEGF signaling pathway,and NF-κB signaling pathway.(2)The key active components were docked with the core targets,and the two showed a good combination.To conclude,Chinese herbal compound therapy in the treatment of primary osteoporosis can use a variety of active components to exert its efficacy through multiple signal pathways and acting on multiple targets,which can provide a theoretical basis for the research and development of new drugs for the follow-up treatment of primary osteoporosis.