基于网络药理学探讨聚精助育汤健脾益肾活血核心药对治疗少弱精子症的作用机制

Discussion on the mechanism of the core drug pair of invigorating the spleen,tonifying the kidney,and activating blood circulation in Jujing Zhuyu Decoction in the treatment of oligoasthenozoospermia based on network pharmacology

目的应用网络药理学方法研究聚精助育汤健脾益肾活血核心药对治疗少弱精子症的物质基础和潜在作用机制。方法检索核心药对的活性成分、作用靶点及疾病相关靶点,两者进行映射后得到核心药对治疗少弱精子症的潜在靶点,随后进行蛋白质互作(PPI)网络、成分-靶点网络的构建及富集分析,筛选出核心药对治疗少弱精子症的关键靶点及主要活性成分,并进行分子对接,验证成分-靶点之间的结合活性。结果共获得143种潜在活性成分及77个潜在作用靶点,其中细胞肿瘤抗原p53(TP-53)、白介素-6(IL-6)、雌激素受体1(ESR1)等为关键靶点,槲皮素、木犀草素、β-谷甾醇等为主要活性成分。富集分析发现,靶点涉及的信号通路有细胞凋亡、缺氧诱导因子-1(HIF-1)信号通路、MAPK信号通路、p53信号通路等。分子对接显示,关键靶点与主要活性成分之间结合活性较好。结论核心药对可能通过调控细胞增殖分化、炎症反应、细胞凋亡、氧化应激、自噬等途径发挥治疗少弱精子症的作用,初步揭示了健脾、益肾、活血理论的科学内涵,为临床采用健脾、益肾、活血法治疗少弱精子症奠定了基础。

Objective To investigate the material basis and potential mechanism of the core drug pair of invigorating the spleen,tonifying the kidney,and activating blood circulation in Jujing Zhuyu Decoction in treating oligoasthenozoospermia by applying network pharmacology method.Methods The active ingredients,functional targets and disease-related targets of core drug pair were searched.After mapping both sets,potential targets for treating oligoasthenozoospermia by the core drug pairs were identified.Subsequently,protein-protein interactions(PPI)networks and component-target networks were constructed,and enrichment analysis were performed to screen out the key targets and major active ingredients for treating oligoasthenozoospermia by the core drug pairs.Molecular docking was conducted to validate the binding activity between the ingredients and targets.Results A total of 143 potential active ingredients and 77 potential functional targets were obtained,with cell tumor antigen p53(TP-53),interleukin-6(IL-6),and estrogen receptor 1(ESR1)as the key targets,and quercetin,luteolin,andβ-sitosterol as the major active ingredients.The enrichment analysis revealed targets were involved in signaling pathways such as cell apoptosis,hypoxia-inducible factor-1(HIF-1)signaling pathway,mitogen-activated protein kinases(MAPK)signaling pathway,and p53 signaling pathway,etc.The molecular docking demonstrated good binding activity between the key targets and major active ingredients.Conclusions The core drug pairs may exert their effects in treating oligoasthenozoospermia by regulating pathways such as cell proliferation and differentiation,inflammatory response,cell apoptosis,oxidative stress,and autophagy,etc.It initially reveals the scientific connotation of invigorating the spleen,tonifying the kidney,and activating blood circulation theories,laying the foundation for the clinical application of invigorating the spleen,tonifying the kidney,and activating blood circulation methods in the treatment of oligoasthenozoospermia.