枸杞多酚拮抗二苯甲酮-3生殖毒性的机制研究

doi:10.3969/j.issn.1004-616x.2025.06.003

癌变·畸变·突变 ›› 2025, Vol. 37 ›› Issue (6): 438-444.doi: 10.3969/j.issn.1004-616x.2025.06.003

• 论著 • 上一篇

枸杞多酚拮抗二苯甲酮-3生殖毒性的机制研究

金泽^1,2, 孙嘉禾^1,2, 李舒慧^1,2, 德小明³, 郭军⁴, 徐海明³, 李红梅¹

1. 宁夏医科大学生育力保持重点实验室, 宁夏银川 750004;
2. 宁夏医科大学第三临床医学院, 宁夏银川 750004;
3. 宁夏医科大学公共卫生学院, 宁夏银川 750004;
4. 宁夏中医研究院, 宁夏银川 750021

收稿日期:2025-08-07 修回日期:2025-11-12 发布日期:2025-12-06
通讯作者: 徐海明，E-mail：xuhaiming5689467@163.com;李红梅，E-mail：lihongmei@nxmu.edu.cn
作者简介:金泽，E-mail：19995328314@163.com。
基金资助:
2024年宁夏回族自治区重点研发计划重点项目(2024ZDYF0607)

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

JIN Ze^1,2, SUN Jiahe^1,2, LI Shuhui^1,2, DE Xiaoming³, GUO Jun⁴, XU Haiming³, LI Hongmei¹

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

摘要/Abstract

摘要： 目的：探讨枸杞多酚是否通过调控双硫死亡过程拮抗二苯甲酮-3(BP-3)的生殖毒性。方法：利用PubMed、中国知网、CTD、ChemicalBook、PubChem等数据库，分别获取双硫死亡核心调控蛋白、BP-3致雄性泌尿生殖毒性靶点及枸杞多酚主要活性成分的潜在靶点；使用Venny 2.1.0获取上述靶点集的交集；将获得的共同靶点导入STRING数据库构建蛋白相互作用网络；利用DAVID数据库进行GO/KEGG功能富集分析；采用Cytoscape 3.10.1构建“枸杞多酚的主要活性成分-共同靶点-通路”网络；使用AutoDock Vina将BP-3及枸杞多酚的主要活性成分与共同靶点进行对接，评估结合能。结果：筛选获得BP-3致雄性泌尿生殖毒性靶点75个、枸杞多酚的主要活性成分潜在靶点160个、双硫死亡的核心调控蛋白4 383个，共同靶点共9个；药代动力学分析显示桑色素、异鼠李素、阿魏酸、对香豆酸和肉桂酸具有较好的肠道吸收性和类药性；GO/KEGG富集分析提示BP-3与枸杞多酚的主要活性成分可作用于雄性泌尿生殖系统；网络分析提示若干关键靶点可能在枸杞多酚的主要活性成分缓解BP-3损伤中发挥重要作用；分子对接证实BP-3及枸杞多酚的主要活性成分能以氢键等形式结合于PTGS2、ESR1、ESR2、CYP1A1的活性位点附近氨基酸，且结合能较强。结论：枸杞多酚的主要活性成分可在一定程度上缓解BP-3诱导的雄性泌尿生殖损伤，其拮抗效应可能由关键靶点PTGS2、ESR1、ESR2、CYP1A1介导。

关键词: 二苯甲酮-3, 双硫死亡, 雄性泌尿生殖毒性, 枸杞多酚, 网络药理学, 分子对接

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

中图分类号:

R994.6

金泽, 孙嘉禾, 李舒慧, 德小明, 郭军, 徐海明, 李红梅. 枸杞多酚拮抗二苯甲酮-3生殖毒性的机制研究[J]. 癌变·畸变·突变, 2025, 37(6): 438-444.

JIN Ze, SUN Jiahe, LI Shuhui, DE Xiaoming, GUO Jun, XU Haiming, LI Hongmei. Antagonistic mechanism of Lycium barbarum polyphenols on reproductive toxicity of benzophenone-3[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2025, 37(6): 438-444.

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枸杞多酚拮抗二苯甲酮-3生殖毒性的机制研究

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

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