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ORIGINAL RESEARCH article

Front. Endocrinol.

Sec. Reproduction

Volume 16 - 2025 | doi: 10.3389/fendo.2025.1517934

Laurolitsine Ameliorates Insulin Resistance, Ovarian Dysfunction and Gut Microbiota Dysbiosis in DHEA plus HFD-induced PCOS Mice

Provisionally accepted
Yong  ZhangYong Zhang1Mimi  ChenMimi Chen2Zhi  ZhouZhi Zhou3Yichen  GuoYichen Guo3Linlin  ZhengLinlin Zheng2Yansu  YuYansu Yu2Jialu  LiuJialu Liu1Yuanyuan  ZhouYuanyuan Zhou1Hui  LuHui Lu2Si  YaoSi Yao2Xiaopo  ZhangXiaopo Zhang1*Ning  MaNing Ma3*Weiying  LuWeiying Lu3*
  • 1School of Life and Pharmaceutical Sciences, Hainan Medical University, Haikou, China
  • 2School of Basic Medicine and Life Sciences, Hainan Medical University, Haikou, Hainan Province, China
  • 3Hainan Women and Children's Medical Center, Haikou, Hainan Province, China

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

Background: Polycystic ovary syndrome (PCOS) is a complex endocrine reproductive disorder that affects 10%-13% of women worldwide, characterized by hyperandrogenemia, ovulatory dysfunction, and polycystic ovary formation. Currently, there are no effective specific treatments for PCOS. Therefore, identifying safe and effective therapeutic drugs for PCOS is clinically important.In this study, a PCOS mouse model was induced using dehydroepiandrosterone (DHEA) plus high-fat diet (HFD) to investigate the therapeutic effects of laurolitsine (LL). The efficacy of LL was evaluated by estrous cycle, glucose tolerance test (OGTT), insulin tolerance test (ITT), and serum biochemical markers. Histopathological analysis of ovarian, gonadal fat, and liver tissues was performed using hematoxylin and eosin (H&E) staining. Furthermore, RNA-seq analysis and 16S rRNA sequencing were performed to explore the potential mechanisms underlying LL's effects on PCOS mice.Results: LL exhibited therapeutic effects in PCOS mice. LL improved lipid metabolism, glucose tolerance, insulin resistance, hormonal imbalance, and ovarian dysfunction in PCOS mice. RNA-seq analysis revealed that LL may improve PCOS by modulating key metabolic processes, including hormone response, fatty acid metabolism, and lipid metabolism in the ovaries. Additionally, LL significantly modulated the gut microbiota composition in PCOS mice, particularly reducing the abundance of Proteobacteria and Lactobacillus johnsonii, while increasing the abundance of Akkermansia muciniphila.LL is a promising and novel therapeutic agent for PCOS, as it ameliorates insulin resistance, ovarian dysfunction, and gut microbiota.

Keywords: Laurolitsine, pcos, Insulin Resistance, Hormonal imbalance, Ovarian dysfunction, Gut Microbiota

Received: 27 Oct 2024; Accepted: 28 Jul 2025.

Copyright: © 2025 Zhang, Chen, Zhou, Guo, Zheng, Yu, Liu, Zhou, Lu, Yao, Zhang, Ma and Lu. 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:
Xiaopo Zhang, School of Life and Pharmaceutical Sciences, Hainan Medical University, Haikou, China
Ning Ma, Hainan Women and Children's Medical Center, Haikou, Hainan Province, China
Weiying Lu, Hainan Women and Children's Medical Center, Haikou, Hainan Province, China

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