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ORIGINAL RESEARCH article

Front. Endocrinol.

Sec. Reproduction

Volume 16 - 2025 | doi: 10.3389/fendo.2025.1642197

Exploration of the Active Components and Mechanisms of Epimedium for the Treatment of Undescended Testis

Provisionally accepted
Zhonglei  DengZhonglei Deng1Sirui  ZhangSirui Zhang1Haiyang  ZhaoHaiyang Zhao2Shijia  XuShijia Xu1Miao  QiMiao Qi1Tianle  PuTianle Pu1Hui  WangHui Wang1*
  • 1Nanjing Medical University, Nanjing, China
  • 2Shanghai University of Traditional Chinese Medicine, Shanghai, China

The final, formatted version of the article will be published soon.

Background: Undescended Testis, the most common congenital male reproductive disorder in children, demonstrates complex pathogenesis with genetic predisposition.While early surgical intervention (before 18 months) remains standard care, pharmacological options are limited.Purpose: Explore the therapeutic potential of Traditional Chinese medicine for Undescended Testis. Study design: This study employs multiple bioinformatics approaches to search for potential Traditional Chinese Medicines for Undescended Testis treatment and investigate their therapeutic mechanisms. Methods: This study integrated medication regularity analysis, network pharmacology, Mendelian randomization, and molecular docking, with exploration conducted through cellular and animal models. Results: Our analysis identified 27 bioactive Epimedium compounds, with quercetin, kaempferol, and Icariin showing particular promise. Protein interaction networks revealed AKT1, PARP1, and PGR as key targets. Functional enrichment analysis primarily focused on biological processes including response to stress-induced damage (such as reactive oxygen species, chemical toxins, and other stressors), steroid signaling and receptor activation, transmembrane signal transduction, as well as cellular proliferation and apoptosis regulation. Molecular docking demonstrated Yinyanghuo B's strong binding affinity with PARP1 (-7.2 kcal/mol). Mendelian randomization confirmed PARP1 reduction's causal relationship with lower Undescended Testis risk. We constructed animal and cellular heat stress models to simulate Undescended Testis, and subsequent experiments observed significant DNA damage. Thermally stressed TM4 cells showed significant PARP1 upregulation, suggesting its critical role in testicular heat stress response by accelerating DNA damage repair. Conclusion: These findings potentially provide mechanistic evidence supporting Epimedium's traditional use while advancing Traditional Chinese Medicine modernization through contemporary pharmacological validation.

Keywords: undescended testis, Epimedium, Network Pharmacology, Mendelian randomization, Traditional Chinese Medicine

Received: 06 Jun 2025; Accepted: 05 Aug 2025.

Copyright: © 2025 Deng, Zhang, Zhao, Xu, Qi, Pu and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Hui Wang, Nanjing Medical University, Nanjing, China

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