Carcinogenesis, Teratogenesis & Mutagenesis ›› 2025, Vol. 37 ›› Issue (6): 438-444.doi: 10.3969/j.issn.1004-616x.2025.06.003

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Antagonistic mechanism of Lycium barbarum polyphenols on reproductive toxicity of benzophenone-3

JIN Ze1,2, SUN Jiahe1,2, LI Shuhui1,2, DE Xiaoming3, GUO Jun4, XU Haiming3, LI Hongmei1   

  1. 1. Key Laboratory of Fertility Preservation and Maintenance of Ningxia Medical University, Yinchuan 750004;
    2. Third Clinical Medical College of Ningxia Medical University, Yinchuan 750004;
    3. School of Public Health, Ningxia Medical University, Yinchuan 750004;
    4. Ningxia Research Institute of Traditional Chinese Medicine, Yinchuan 750021, Ningxia, China
  • Received:2025-08-07 Revised:2025-11-12 Published:2025-12-06

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Abstract: OBJECTIVE：To investigate whether Lycium barbarum polyphenols antagonize reproductive toxicity of benzophenone-3 (BP-3) by regulating the disulfide death process. METHODS：Databases including PubMed，CNKI，CTD，ChemicalBook，and PubChem were reviewed to retrieve core regulatory proteins of disulfidptosis，targets associated with BP-3-induced male genitourinary toxicity，and potential targets of major active components of Lycium barbarum polyphenols. Intersections of these target sets were identified using Venny 2.1.0. Common targets were imported into the STRING database to construct a protein-protein interaction (PPI) network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were performed via the DAVID database. A "major active components of Lycium barbarum polyphenols—common targets—pathways" network was built using Cytoscape 3.10.1. Molecular docking of BP-3 and major active components of Lycium barbarum polyphenols with common targets was conducted using AutoDock Vina to evaluate binding energies. RESULTS：A total of 75 targets related to BP-3-induced male genitourinary toxicity，160 potential targets of Lycium barbarum polyphenols' major active components，and 4 383 core disulfidptosis regulatory proteins were screened，yielding 9 common targets. Pharmacokinetic analysis indicated that morin，isorhamnetin，ferulic acid，p-coumaric acid，and cinnamic acid exhibited favorable intestinal absorption and drug-likeness. GO/KEGG enrichment analyses suggested that both BP-3 and Lycium barbarum polyphenols' major active components targeted the male genitourinary system. Network analysis revealed that key targets may play crucial roles in mitigating BP-3-induced damage by Lycium barbarum polyphenols' major active components. Molecular docking confirmed that BP-3 and these active components could bind near the active sites of PTGS2，ESR1，ESR2，and CYP1A1 via hydrogen bonds and other interactions，with strong binding energies. CONCLUSION：Major active components of Lycium barbarum polyphenols may alleviate BP-3-induced male genitourinary injury to a certain extent，and this antagonistic effect is likely mediated by key targets including PTGS2，ESR1，ESR2，and CYP1A1.

Key words: benzophenone-3, disulfideptosis, male genitourinary toxicity, Lycium barbarum polyphenols, network pharmacology, molecular docking

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