Abstract
Background 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. Methods 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. Results 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. Conclusions 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.
Highlights
Infertility, defined as the inability to achieve a clinical pregnancy within 12 months of regular unprotected intercourse, is estimated to affect 15% of all couples globally [1]
Candidate bioactive ingredients of 12 herbs in Wuzi Ershen decoction (WZESD) were screened from the Traditional Chinese Medicine Systems Pharmacology database (TCMSP, http://lsp.nwu.edu.cn/tcmsp.php) [25], the BATMAN-traditional Chinese medicine (TCM) [26, 27] database, and literature searching in the PubMed database
TCMSP database is a unique systems pharmacology platform designed for herbal medicines. e newly developed TCMSP provides up-to-date, quantitative, and system information about TCM ingredients, ADME-related properties, targets, and diseases [28]. e newest version of TCMSP comprises 510 effective herbal entries registered in the Chinese Pharmacopoeia with more than 31,000 ingredients, which spread over 18 different drug classes [29]
Summary
Infertility affects approximately 15% of couples around the world, and male factors are accounted for 40–50%. 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. E 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. Is 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 Conclusions. is 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
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