基于网络药理学和分子对接探讨龟鹿二仙胶治疗少、弱精子症作用机制＊

目的 基于网络药理学和分子对接探讨龟鹿二仙胶治疗少、弱精子症（AS）的物质基础及作用机制。方法 运用TCMSP数据库筛选龟鹿二仙胶中枸杞子、人参的活性成分及靶标,检索文献及BATMAN-TCM、DrugBank、ETCM、化学专业数据库获取鹿角胶、龟板胶活性成分及靶标;运用GeneCards、OMIM、DrugBank、TTD、DisGeNET数据库筛选AS靶标;运用R语言软件映射得到龟鹿二仙胶治疗AS靶标,运用Cytoscape平台构建龟鹿二仙胶-药物活性成分-靶标及龟鹿二仙胶-药物活性成分-靶标-AS间的互作网络图;运用STRING平台构建治疗靶标间互作网络图;运用ClueGo插件对治疗靶标行GO生物功能分析,R语言软件行KEGG通路富集分析;并运用ZINC、RCSB PDB数据库,AutoDock、PyMOL软件对药物有效活性成分与关键靶标作分子对接。结果 从龟鹿二仙胶中共获得83个有效活性成分,得到53个龟鹿二仙胶治疗AS的潜在靶标,这些靶标主要涉及氧化应激、脂质沉积负调节等生物学过程,并主要富集在PI3K/Akt,HIF-1等信号通路上;分子对接验证显示对接得分 < -5 kcal·mol^-1占82.5%,即大部分靶标与成分的结合活性较好。结论 通过网络药理学及分子对接证实了龟鹿二仙胶多成分、多靶标、多途径的作用特点,预测了龟鹿二仙胶可能通过PI3K/Akt,HIF-1等途径,从而调控氧化应激、脂质代谢等生物学过程治疗AS的可能作用机制,为进一步研究其活性成分和作用机制提供理论依据。

Mechanism of Guilu-Erxian-Glue in Treating Oligozoospermia and Asthenospermia (AS) Based on Network Pharmacology and Molecular Docking

Objective To explore the material basis and mechanism of Guilu-Erxian-Glue (GLEXG) in treating oligozoospermia and asthenospermia (AS) based on network pharmacology and molecular docking.Methods TCMSP database was used to screen the active components and targets of Fructus Lycii and Radix Ginseng, and the literatures, BATMAN-TCM, DrugBank, ETCM and Chemical Professional database were used to screen the components and targets of Antler Gum and Tortoise Shell Gum; GeneCards, OMIM, DrugBank, TTD, DisGeNET database were used to screen AS targets. The therapeutic target of GLEXG was mapped by R language, and Cytoscape platform was used to construct the interaction network of GLEXG-component-target and GLEXG-component-AS-target. The interaction network diagram of therapeutic target was constructed by STRING; the function of GO biology was analyzed by ClueGo platform; KEGG pathway was enriched by R language; ZINC and RCSB PDB database, AutoDock and PyMOL software were used for molecular docking between potential components and key targets.Results 83 active components and 53 potential targets of GLEXG were obtained in treating AS. These targets were mainly involved in biological processes such as oxidative stress and negative regulation of lipid storage, and mainly concentrated in PI3K/Akt, HIF-1 signal pathways; Molecular docking verification showed that the docking score was < -5 kcal·mol^-1 accounted for 82.5%, which means that most of the targets had high docking activity with the components.Conclusion The characteristics of multi-component, multi-target and multi-pathway of GLEXG were confirmed by network pharmacology and molecular docking, and the potential mechanism of GLEXG in treating AS is predicted via PI3K/Akt, HIF-1 pathway to regulate oxidation stress and lipid metabolism, which can provide theoretical basis for further study of its components and mechanism.