Icariin rescues Reproductive damage caused by Manganese: Network pharmacology and Experimental validation
Year: 2025
Type: preprint
Abstract: The global escalation of male infertility, a critical reproductive health crisis affecting approximately 15% of couples worldwide, is increasingly attributed to environmental exposures to toxic heavy metals, with manganese (Mn) emerging as a significant occupational and environmental contaminant. Despite its association with impaired spermatogenesis and testicular dysfunction, no effective clinical interventions exist to counteract heavy metal-induced reproductive toxicity. This study investigates the therapeutic potential of icariin (ICA) in mitigating Mn-exposure male reproductive damage through a multi-omics strategy combining network pharmacology, molecular docking, and in vitro validation. Disease-drug-target network analysis prioritized sphingolipid metabolism and NF-κB signaling as key pathways modulated by ICA, with molecular docking confirming high-affinity interactions between ICA and core targets. Experimental validation using Mn-exposure mouse spermatogonial GC-1 cells demonstrated that ICA significantly rescued cytotoxicity (MTT assay) and reversed dysregulated gene expression patterns. Specifically, the qPCR revealed significant upregulation the expression of TRIAP1, HSP90AA1 and NF-κB in the Mn-exposure group compared to the control group. Compared with the Mn-exposure group, the ICA intervention group exhibited significant downregulation the expression these genes, thereby highlighting dual regulatory effects on apoptotic resistance and inflammatory homeostasis. These findings establish ICA as a promising candidate for addressing heavy metal-associated male reproductive disorders, offering mechanistic insights into its cytoprotective and anti-inflammatory actions.
Authors: Jiaqi He, Tongci Li, Yan Liang, Ying Tian, Xiang Lu, Jidong Zhang, Jun Tan
Institution: Zunyi Medical University
Language: English
Subfield: Pharmacology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4412100742