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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- 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
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
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Yuanqi Liang
1