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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1457467

Mangiferin Ameliorates Polycystic Ovary Syndrome in Rats by Modulating Insulin Resistance, Gut Microbiota, and Ovarian Cell Apoptosis

Provisionally accepted
Yong Zhang Yong Zhang 1Chen Mimi Chen Mimi 1Yingjie Li Yingjie Li 1,2Yichen Guo Yichen Guo 3Yansu Yu Yansu Yu 1*Zhi Zhou Zhi Zhou 3*Hui Lu Hui Lu 3*Si Yao Si Yao 1,4*Chongming Wu Chongming Wu 5*Xiaopo Zhang Xiaopo Zhang 4*Ning Ma Ning Ma 3*Weiying Lu Weiying Lu 3*
  • 1 School of Basic Medicine and Life Sciences, Hainan Medical University, Haikou, Hainan Province, China
  • 2 School of Pharmacy, Harbin University of Commerce, Harbin, Heilongjiang Province, China
  • 3 Hainan Women and Children's Medical Center, Haikou, Hainan Province, China
  • 4 School of Life and Pharmaceutical Sciences, Hainan Medical University, Haikou, China
  • 5 School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, China

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

    Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder characterized by hyperandrogenism, prolonged anovulation and polycystic ovaries. However, there are no effective interventions to treat this disorder. As previously shown, mangiferin modulated the AMPK and NLRP3 signal pathways to alleviate nonalcoholic fatty liver disease (NAFLD). In recent years, mangiferin has emerged as a promising drug candidate for treating metabolic diseases. In this study, we aim to investigate the effects and mechanisms of mangiferin in PCOS rats induced by letrozole (LET) combined with a high-fat diet (HFD). The efficacy of mangiferin in PCOS rats was evaluated through estrous cycle detection, serum/tissue biochemical analysis, and hematoxylin and eosin (HE) staining of ovarian tissue. The mechanisms of mangiferin's effects on PCOS rats were analyzed using 16S rRNA sequencing, RNA-seq, western blotting (WB), and immunohistochemical (IHC) staining. Our results displayed that mangiferin showed a promising effect in PCOS rats. It improved lipid metabolism, glucose tolerance, insulin resistance, hormonal imbalance, ovarian dysfunction, and adipocyte abnormalities. RNA-seq analysis indicated that mangiferin may be involved in several signal pathways, including apoptosis, necrosis, and inflammation. Furthermore, western blot and immunohistochemical staining demonstrated that mangiferin regulates Caspase-3 and Cytc, exhibiting anti-apoptotic activity in the ovaries. Additionally, mangiferin significantly altered the gut microbiota community of PCOS rats, changing the abundance of firmicutes, bacteroidota, proteobacteria, and actinobacteria at the phylum level and the abundance of Blautia, Coprococcus, Roseburia, and Pseudomonas at the genus level. In conclusion, mangiferin is a promising and novel therapeutic agent for PCOS as it ameliorates insulin resistance, gut microbiota and ovarian cell apoptosis.

    Keywords: Mangiferin, pcos, Hormonal imbalance, Insulin Resistance, Gut Microbiota, Ovarian cell apoptosis, female rats

    Received: 30 Jun 2024; Accepted: 29 Aug 2024.

    Copyright: © 2024 Zhang, Mimi, Li, Guo, Yu, Zhou, Lu, Yao, Wu, 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:
    Yansu Yu, School of Basic Medicine and Life Sciences, Hainan Medical University, Haikou, Hainan Province, China
    Zhi Zhou, Hainan Women and Children's Medical Center, Haikou, Hainan Province, China
    Hui Lu, Hainan Women and Children's Medical Center, Haikou, Hainan Province, China
    Si Yao, School of Basic Medicine and Life Sciences, Hainan Medical University, Haikou, Hainan Province, China
    Chongming Wu, School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China
    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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