基于网络药理学考察八正散加减方治疗慢性前列腺炎的作用及可能机制

Study on the action mechanism of Ba-Zheng-San in the treatment of chronic prostatitis based on network pharmacology

目的通过网络药理学探讨八正散加减方治疗慢性前列腺炎可能作用机制。方法使用TCMSP在线数据库收集八正散加减方方剂中药味成分和靶点、通过GeneCards及OMIM在线数据库获取慢性前列腺炎异常表达基因列表。通过Venn数据库获取交集基因,通过STRING、Cytoscape 3.2.1构建蛋白相互作用网络。使用DAVID在线数据库对交集基因进行基因本体论(GO)和KEGG富集分析。结果通过网络药理学分析认为,八正散加减方对慢性前列腺炎有潜在的治疗作用,其作用机制可能是通过影响核受体、类固醇激素受体、蛋白质异二聚体、单加氧酶、醇脱氢酶及氧化还原酶活性等。另一方面,调控近端启动子序列特异性DNA结合、谷胱甘肽结合、RNA聚合酶Ⅱ近端启动子序列特异性DNA结合、雌激素受体结合、泛素样蛋白连接酶结合、类固醇激素受体结合、RNA聚合酶Ⅱ基础转录因子结合过程也可能是八正散加减方发挥作用的方式。涉及的通路可能有:(1)AGE-RAGE信号通路;(2)IL-17信号通路;(3)Th17信号通路。分析结果提示八正散加减方可能对前列腺癌信号通路具有调节作用。结论八正散加减方治疗慢性前列腺炎具有多靶点、多通路的特点。通过网络药理学分析可以为进一步开发八正散加减方提供理论依据。

Objective Predicting the possible mechanism of modified Ba-Zheng-San for Chronic prostatitis through network pharmacology.Methods The TCMSP online database was used to collect the modified Ba-Zheng-San compounds and targets,the OMIM online database and the GeneCards online database were used to predict the chronic prostatitis targets,and the above targets were converted into gene names through the Uniprot online database.Enter the drug and disease gene names in the Venn online database to obtain intersection genes,construct a drug-disease intersection target gene protein interaction network through the STRING online database,and use Cytoscape 3.2.1 software to visualize the results.Combine DAVID online database to perform gene ontology(GO)and KEGG enrichment analysis of intersection genes.Results According to network pharmacological analysis,modified Ba-Zheng-San may treat chronic prostatitis by affecting nuclear receptors activity,steroid hormone receptors activity,protein heterodimerization activity,monooxygenase activity,alcohol dehydrogenase(NADP^+)activity and oxidoreductase activity.Regulation of proximal promoter sequence-specific DNA binding,glutathione binding,RNA polymeraseⅡproximal promoter sequence-specific DNA binding,estrogen receptor binding,ubiquitin-like protein ligase binding,steroid hormone receptor binding and RNA polymeraseⅡbasal transcription factor binding may also be a way for Ba-Zheng-San to play a role.The pathways involved may be:(1)AGE-RAGE signaling pathway;(2)IL-17 signaling pathway;(3)Th17 signaling pathway.The analysis results also suggest that modified Ba-Zheng-San subtraction may have a regulatory effect on prostate cancer signaling pathway.Conclusion Modified Ba-Zheng-San has the characteristics of multiple targets and multiple pathways in the treatment of Chronicprostatitis.