基于数据挖掘和网络药理学的中药治疗弱精子症用药规律及潜在机制研究

Study on the Fundamental Patterns and Potential Mechanism of Traditional Chinese Medicine for Treating Weak Spermatogenesis Based on Data Mining and Network Pharmacology

目的基于数据挖掘和网络药理学方法,深入研究中药治疗弱精子症的用药规律及潜在作用机制,并结合分子对接进行验证。方法在中英文数据库中检索并筛选出中药治疗弱精子症的文献,构建弱精子症中药处方数据库,运用R语言对其进行性味归经频次统计、关联规则分析、系统聚类分析,筛选得到核心药物组合。运用网络药理学方法预测核心药物的潜在活性成分、作用靶点,进而构建PPI网络,筛选出核心药物组合治疗弱精子症的关键靶点,随后进行GO、KEGG富集分析,利用上述数据构建成分-交集靶点-信号通路网络图,筛选主要成分。选取关键靶点及主要成分进行分子对接,验证成分-靶点之间的结合活性。结果纳入文献103篇,筛选出治疗弱精子症的中药复方或中成药109个,涉及中药189味。结合关联规则、系统聚类分析,得到核心药物组合“覆盆子-车前子-枸杞子-菟丝子-五味子”。进而筛选出潜在活性成分67种,获得231个成分作用靶点以及699个疾病相关靶点,得到交集靶点46个,进而构建PPI网络,筛选出关键靶点。富集分析发现,交集靶点涉及TNF、MAPK、IL17、HIF-1、mTOR、PI3K-Akt、NF-κB、p53等多条信号通路,包含细胞凋亡、炎症反应、氧化应激、细胞分化、促性腺激素分泌、细胞周期、血管生成等。分子对接结果显示,关键靶点与主要成分之间结合活性较好,其中β-谷甾醇与CASP3靶点结合能最低。结论中药治疗弱精子症组方用药多以补肾益精、健脾益气为主,辅以活血化瘀、利湿泄浊等,注重调畅气机;核心药物组合治疗弱精子症的关键靶点和信号通路主要参与炎症反应、氧化应激、细胞凋亡等,为后续中医药干预弱精子症的临床与实验研究提供思路和参考。

Objective Based on data mining and network pharmacology methods,in-depth study on the dosing pattern and potential mechanism of action of traditional Chinese medicine for treating weak spermatozoa,combined with molecular docking for validation.Methods We searched and screened the literature of traditional Chinese medicines for treating weak spermatids in Chinese and English databases,constructed a prescription database of traditional Chinese medicines for weak spermatids,and screened the core drug combinations by applying the R language to carry out the frequency statistics of sex and flavor attribution,association rule analysis,and systematic clustering analysis.The network pharmacology method was used to predict the potential active ingredients and targets of the core drugs,and then the PPI network was constructed to screen out the key targets of the core drug combinations for the treatment of weak spermatogenesis,followed by GO and KEGG enrichment analysis,and the above data were used to construct the component-intersecting target-signaling pathway network diagram to screen out the main components.The key targets and main components were selected for molecular docking to verify the binding activity between components-targets.Results 103 papers were included in the literature,and 109 Chinese herbal compounds or proprietary Chinese medicines were screened for the treatment of weak spermatogenesis,involving 189 flavors of Chinese medicines.Combined with association rules and systematic clustering analysis,the core drug combination of"raspberry-psyllium-wolfberry-cuscuta-schizandra"was obtained.Then 67 potential active ingredients were screened out,and 231 component targets and 699 disease-related targets were obtained.46 intersecting targets were obtained,and then a PPI network was constructed to screen out the key targets.Enrichment analysis revealed that the intersected targets involved TNF,MAPK,IL17,HIF-1,mTOR,PI3K-Akt,NF-κB,p53 and other signaling pathways,including apoptosis,inflammation,oxidative stress,cell differentiation,gonadotropin secretion,cell cycle,angiogenesis and so on.The molecular docking results showed that the binding activity between the key targets and the main components was good,among whichβ-sitosterol had the lowest binding energy to the CASP3 target.Results 103 articles were included,leading to the selection of 109 TCM formulas,involving 189 different medicinal ingredients.By applying association rules and systematic cluster analysis,the core drug combination was identified.Furthermore,67 potential active ingredients were screened,resulting in 231 component-target interactions and 699 disease-related targets.The intersection yielded 46 key targets,then used to construct the PPI network.Enrichment analysis revealed the involvement of multiple signaling pathways,such as TNF,MAPK,IL17,HIF-1,mTOR,PI3K-Akt,NF-κB,p53,encompassing processes like apoptosis,inflammatory response,oxidative stress,cell differentiation,gonadotropin secretion,cell cycle,and angiogenesis.Molecular docking results indicated favorable binding activities between key targets and significant components,withβ-sitosterol showing the lowest binding affinity to the CASP3 target.Conclusion TCM prescriptions for asthenozoospermia primarily focus on reinforcing the kidney,replenishing vital essence,invigorating the spleen,promoting blood circulation,and removing dampness and turbidity while emphasizing the smooth flow of vital energy.The key targets and signaling pathways identified in the core drug combination for treating asthenozoospermia are mainly associated with inflammatory responses,oxidative stress,and apoptosis,providing valuable insights and references for future clinical and experimental research on TCM interventions for asthenozoospermia.