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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1426660
This article is part of the Research Topic Advances in the Pharmacotherapy of Chronic Pelvic Pain Conditions View all articles

Evodiamine Suppresses Endometriosis Development Induced by Early EBV Exposure through Inhibition of ERβ

Provisionally accepted
Junling Wang Junling Wang 1Yuanqi Liang Yuanqi Liang 1Xiaoru Liang Xiaoru Liang 1Huijuan Peng Huijuan Peng 1Yongxia Wang Yongxia Wang 1Mingtao Xu Mingtao Xu 1Xuefang Liang Xuefang Liang 1Helen Yao Helen Yao 2Xiaohan Liu Xiaohan Liu 3Liqin Zeng Liqin Zeng 3Dongfang Xiang Dongfang Xiang 1PAUL YAO PAUL YAO 1*
  • 1 Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China
  • 2 University of California, Riverside, Riverside, California, United States
  • 3 Sun Yat-sen University, Guangzhou, Guangdong Province, China

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

    Endometriosis (EMS) is characterized as a prevalent gynecological inflammatory disorder marked by the existence of endometrial tissues situated beyond the uterus. This condition leads to chronic pelvic pain and may contribute to infertility. In this investigation, we explored the potential mechanism underlying the development of endometriosis (EMS) triggered by transient exposure to either latent membrane protein 1 (LMP1) or Epstein-Barr virus (EBV) in a mouse model. Additionally, we examined the potential inhibitory effect of evodiamine (EDM) on EMS. We found that transient exposure to either EBV or LMP1 triggers persistent estrogen receptor β (ERβ) expression through epigenetic modifications in both endometrial stromal and epithelial cells, subsequently modulating EMS-related cell metabolism, encompassing gene expression, oxidative stress, mitochondrial function, cell proliferation and the release of pro-inflammatory cytokines. Furthermore, 4.0 µM of EDM can efficiently reverse this effect in in vitro cell culture studies. Additionally, 20 mg/kg body weight of EDM treatment can partly suppress EMS development in the in vivo EMS mouse model. In conclusion, transient EBV/LMP1 exposure triggers permanent ERβ expression, favoring later EMS development, EDM inhibits EMS development through ERβ suppression. This presents a novel mechanism for the development of EMS in adulthood stemming from early EBV exposure during childhood. Moreover, evodiamine stands out as a prospective candidate for treating EMS.

    Keywords: Endometriosis, Epstein-Barr virus, estrogen receptor β, Evodiamine, Latent membrane protein 1

    Received: 01 May 2024; Accepted: 17 Jul 2024.

    Copyright: © 2024 Wang, Liang, Liang, Peng, Wang, Xu, Liang, Yao, Liu, Zeng, Xiang and YAO. 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: PAUL YAO, Guangzhou University of Chinese Medicine, Guangzhou, 510006, Guangdong Province, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.