Mechanism of Shizi Sanhua Decoction on male oligospermia revealed by herbs-ingredients and disease co-target genes sub-network

Background: Shizi Sanhua Decoction, a traditional Chinese medicine (TCM) prescription, shows treatment advantage on male oligospermia. While due to the complexity of the compatibility (multiple herbs composition), the underlying mechanism remains to be deciphered. Methods: Herbs-ingredients-target genes were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and SWISSADME database, which were then intersected with oligospermia-related genes derived from DisGeNET to obtain co-target genes. The protein-protein interaction (PPI) network of co-target genes was constructed based on the STRING database, and highly condensed sub-networks and top 10 Hub genes were identified with the CytoHubba plug-in. The information of herbs, ingredients, and KEGG enrichment were projected onto the identified highly condensed sub-network to build Herbs-ingredients and disease co-target genes sub-network. Results: After integration of herbs-ingredients-target genes (n=453) with disease genes (n=329), 29 co-target genes were obtained. Among them, PARP1, AR, CYP17A1, ESR1, ABCB1, STS, CFTR, SOAT1, NR5A1, and HIF1A were related to male infertility (WP4673-WikiPathways). Sub-network analysis further revealed the top 10 Hub genes, and the relation with the herbs and ingredients were demonstrated in herbs-ingredients and disease co-target genes sub-network. As expected, reproductive-related biological processes (mammary gland epithelium development, GO:0061180; Oocyte meiosis, hsa04114; Progesterone-mediated oocyte maturation, hsa04914) were enriched. Thyroid hormone signaling pathway (hsa04919), Serotonergic synapse (hsa04726), Chemical carcinogenesis-reactive oxygen species (hsa05208), and Endocrine resistance (hsa01522) may contribute to the development of male oligospermia. Conclusion: Constructed herbs-ingredients and disease co-target genes sub-network discloses specific bioprocesses and molecular targets of Shizi Sanhua Decoction in oligospermia treatment.