Deciphering the Therapeutic Mechanisms of Wuzi Ershen Decoction in Treating Oligoasthenozoospermia through the Network Pharmacology Approach.
Deciphering the Therapeutic Mechanisms of Wuzi Ershen Decoction in Treating Oligoasthenozoospermia through the Network Pharmacology Approach.
复制标题
网络药理学解析五子二参汤治疗少精症的作用机制
DOI：
10.1155/2021/5591844
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Luo J
中科院分区：
文献类型：
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作者：
Hu M;Zhong Y;Xiao W;Wang Y;Tang T;Wang S;Cui H;Li T;Luo J
全球约15%的夫妇受到不孕不育的影响，其中男性因素占40-50%。少精子症是男性不育的最常见原因。不幸的是，除了辅助生殖技术（ART）外，仍然缺乏有效的药物治疗。此前研究人员发现，五子二神汤（WZESD）可以增加精子数量，增强精子活力，提高精液质量。然而，其药理机制仍不清楚。 本研究基于TCMSP和BATMAN-TCM数据库并结合PubMed数据库中的文献检索，筛选化合物并预测WZESD的靶点。我们通过GeneCards获得了与少弱精子症相关的蛋白质，并将其提交给STRING以获得蛋白质-蛋白质相互作用（PPI）网络。将WZESD的潜在目标映射到网络，并通过拓扑筛选枢纽目标。我们使用在线平台 Metascape 和 Enrichr 进行 GO 和 KEGG 富集分析。 AutoDock Vina 用于进一步验证化合物与目标之间的结合模式。 总共获得了 276 种生物活性化合物，并针对 681 个蛋白质。获得了446个少弱精子症疾病特异性蛋白，进一步生物信息学分析发现它们主要参与配子形成、减数分裂和精子分化。蛋白质相互作用网络分析表明，WZESD 的靶蛋白与少弱精子症疾病特异性蛋白相关。 WZESD锚定的79个疾病特异性蛋白靶点主要参与细胞对有机环状化合物的反应、细胞凋亡过程的调节、一氧化氮生物合成和代谢过程、氧化应激和蛋白质磷酸化调节，这些都是少弱精子症的原因。分子对接模拟进一步验证了源自WZESD的生物活性化合物与目标蛋白表现出高结合效率。 该研究从网络药理学的角度揭示了WZESD治疗少弱精子症的治疗机制，可为进一步的实验研究和临床应用提供有价值的参考。
Infertility affects approximately 15% of couples around the world, and male factors are accounted for 40–50%. Oligoasthenozoospermia is the most common reason for male infertility. Unfortunately, effective drug therapy is still lacking except for assisted reproductive technology (ART). Previous researchers found that Wuzi Ershen decoction (WZESD) can increase sperm count, enhance sperm vitality, and improve semen quality. However, the pharmacological mechanisms remain unclear. In this study, we screened compounds and predicted the targets of WZESD based on the TCMSP and BATMAN-TCM database combined with literature searching in the PubMed database. We obtained proteins related to oligoasthenozoospermia through GeneCards and submitted them to STRING to obtain the protein-protein interaction (PPI) network. Potential targets of WZESD were mapped to the network, and the hub targets were screened by topology. We used online platform Metascape and Enrichr for GO and KEGG enrichment analyses. AutoDock Vina was utilized for further verification of the binding mode between compounds and targets. Totally, 276 bioactive compounds were obtained and targeted 681 proteins. 446 oligoasthenozoospermia disease-specific proteins were acquired, and further bioinformatics analysis found that they were mainly involved in the formation of gametes, meiosis, and sperm differentiation. Protein interaction network analysis revealed that target proteins of WZESD were associated with oligoasthenozoospermia disease-specific proteins. The 79 targets of disease-specific proteins, which were anchored by WZESD, mainly participate in the cellular response to the organic cyclic compound, regulation of the apoptotic process, nitricoxide biosynthetic and metabolic process, oxidative stress, and protein phosphorylation regulation, which are the causes for oligoasthenozoospermia. Molecular docking simulation further validated that bioactive compounds originated from WZESD with targeted proteins showed high binding efficiency. This study uncovers the therapeutic mechanisms of WZESD for oligoasthenozoospermia treatment from the perspective of network pharmacology and may provide a valuable reference for further experimental research studies and clinical applications.