目的:利用网络药理学和分子对接技术探索龟龄集胶囊治疗少弱精子症的作用机制.方法:通过中药系统药理学数据库与分析平台(TCMSP)、中药靶点数据库(BATMAN-TCM)和网络药理学研究数据库(STITCH)收集龟龄集胶囊的活性成分并预测其作用靶点,同时从基因综合数据库(GeneCards)、疾病相关基因数据库(DisGENET)、遗传药理学与药物基因组学数据库(PharmGkb)中获取少弱精子症的基因靶点,将药物成分靶点与疾病靶点进行映射,找出交集基因,并建立"药物-成分-作用靶点"网络.运用蛋白质相互作用数据库(STRING)筛选出共同靶点,制作蛋白质-蛋白质相互作用网络,使用作图软件Cytoscape绘制药物-有效成分-靶点-疾病网络图,然后将药物-疾病交集基因上传至生物数据在线分析软件DAVID,对龟龄集胶囊治疗少弱精子症的靶蛋白在生物过程、细胞组分和分子功能中的角色进行注释,并进行京都基因与基因组百科全书(KEGG)通路富集分析.选择基因本体论(GO)功能中的生物过程、细胞组分、分子功能的前10项,以及与少弱精子症相关的20条KEGG通路(P＜0.01),作为龟龄集胶囊治疗少弱精子症的主要信号通路,并探讨其可能的作用机制.结果:通过筛选,发现龟龄集胶囊治疗少弱精子症的潜在靶点有134个,主要涉及的通路包括脂质与动脉粥样硬化、缺氧诱导因子(Hypoxia Inducible Factor,HIF)-1信号通路、叉头框蛋白O(Forkhead Box Protein O,FoxO)信号通路等.分子对接结果显示,药物核心成分与核心蛋白结合良好.结论:龟龄集胶囊治疗少弱精子症体现了中成药治疗疾病的整体性,具有多通路、多成分、多靶点的特点,其有效成分包括槲皮素、山柰酚和β-谷甾醇,通过作用于肿瘤蛋白p53(Tumor Protein p53,TP53)、白细胞介素(Interleukin,IL)-6、表皮生长因子受体(Epidermal Growth Factor Receptor,EGFR)等蛋白调控磷脂酰肌醇3激酶(Phosphatidylinositol 3-kinase,PI3K)-蛋白激酶B(Akt)、HIF-1、FoxO等信号通路,从而改善精液质量,达到治疗少弱精子症的目的.
A study on the mechanism of the Guilingji capsules in the treatment of oligoasthenozoospermia based on network pharmacology and molecular docking
Objective:To explore the molecular mechanism of treatment of oligoasthenozoospermia with the Guilingji capsules(龟龄集胶囊)by network pharmacology and molecular docking techniques.Methods:The active ingredients of the Guilingji capsules were collected and their targets were predicted through TCMSP,BATMANT-TCM,and STITCH.At the same time,gene targets of oligoasthenozoospermia were obtained from GeneCards,DisGENET,PharmGkb.Drug component targets were mapped to disease targets to identify intersection genes,and establish a drug-component-action target network.The protein interaction network database STRING was used to screen out common targets to make protein-protein interaction network.The mapping software Cytoscape was used to draw the drug-active ingredient-target-disease network graph.Then,the drug-disease intersection gene was uploaded to the biological data online analysis software DAVID,and the roles of target proteins in biological processes(BP),cell components(CC)and molecular functions(MF)in the treatment of oligoasthenozoospermia with the Guilingji capsules were annotated,and KEGG pathway enrichment analysis was performed.The top 10 items of BP,CC,MF in GO function and 20 KEGG pathways associated with oligoasthenozoospermia(P＜0.01)were selected as the main signaling pathways in the treatment of oligoasthenozoospermia with the Guilingji capsules,and the possible mechanism of action was discussed.Results:There were 134 potential targets of the Guilingji capsules for the treatment of oligoasthenozoospermia.The main pathways involved lipid and arteriosclerosis,hypoxia-inducing-factor-1(HIF-1)signaling pathway,FoxO signaling pathway,etc.The results of molecular docking showed that the core components of the drug were well bound to the core proteins.Conclusion:The treatment of oligoasthenozoospermia with the Guilingji capsules reflects the integrality of Chinese patent medicine in the treatment of diseases,and has the characteristics of multi-pathway,multi-component and multi-target.Its active components include quercetin,kaempferol and β-sitosterol.By acting on tumor protein p53(TP53),interleukin-6(IL-6),epidermal growth factor receptor 1(EGFR)and other proteins,it regulates PI3K-Akt,HIF-1,FoxO and other signaling pathways to improve semen quality and achieve the purpose of the treatment of olgoasthenozoospermia.
The Guilingji capsulesOligoasthenozoospermiaNetwork pharmacologyMolecular docking
万方数据
维普
