Title:Mechanism of Shizi Sanhua Decoction on Male Oligospermia Revealed by
Herbs-Ingredients and Disease Co-Target Genes Sub-Network
Volume: 17
Issue: 10
Author(s): Haibin Li, Hongwen Cao, Dan Wang, Yigeng Feng*, Lei Chen*Renjie Gao*
Affiliation:
- Surgical Department I (Urology Department), LONGHUA Hospital Shanghai University of Traditional Chinese Medicine,
Shanghai 200032, China
- Surgical Department I (Urology Department), LONGHUA Hospital Shanghai University of Traditional Chinese Medicine,
Shanghai 200032, China
- Surgical Department I (Urology Department), LONGHUA Hospital Shanghai University of Traditional Chinese Medicine,
Shanghai 200032, China
Keywords:
Shizi sanhua decoction, oligospermia, traditional chinese medicine, systems pharmacology database and analysis platform, protein-protein interaction, KEGG.
Abstract:
Background: Shizi Sanhua Decoction, a traditional Chinese medicine (TCM) prescription,
shows a 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, intersecting
with oligospermia-related 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. Herbs, ingredients
and KEGG enrichment information were projected onto the identified highly condensed subnetwork
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 cotarget
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 was
demonstrated in the sub-network of herbs-ingredients and disease co-target genes. 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 carcinogenesisreactive
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.