Frontiers in Pharmacology (Dec 2024)

Macranthoidin B restrains the epithelial-mesenchymal transition through COX-2/PGE2 pathway in endometriosis

  • Yi Ding,
  • Yi Ding,
  • Xiaoqian Yang,
  • Qinghua Wei,
  • Xuanming Bi,
  • Yuxin Zhang,
  • Yuxia Ma,
  • Meisen Yang,
  • Xiaoyu Xu,
  • Cong Li,
  • Qin Wang,
  • Yi Chen

DOI
https://doi.org/10.3389/fphar.2024.1492098
Journal volume & issue
Vol. 15

Abstract

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IntroductionMacranthoidin B is one of the primary and unique triterpenoid saponin metabolites from Lonicera macranthoides Hand. –Mazz, which is used to treat endometriosis (EMS) in traditional Chinese medicine. However, the effect of macranthoidin B remains unknown in EMS. This study aimed to elucidate the effect and mechanism of macranthoidin B in EMS.MethodsUsing rat autograft EMS model, the volume of ectopic endothelium, the histopathology, serum E2 and PROG were evaluated after macranthoidin B’s treatment. In primary endometriotic stromal and HEC1-B cells, the invasion and metastasis were assessed by scratch wound and Transwell tests. The epithelial-mesenchymal transition and COX-2/PGE2 pathway were examined in vivo and in vitro. Macranthoidin B were combined with LPS or celecoxib.ResultsIn a rat autograft EMS model, macranthoidin B suppressed ectopic lesion volume, improved histopathological morphology, and regulated serum estradiol (E2) and progesterone (PROG) levels. Additionally, macranthoidin B inhibited invasion and metastasis of primary endometriotic stromal cells and HEC1-B cells. Mechanistically, macranthoidin B suppressed COX-2/PGE2 pathway and epithelial-mesenchymal transition both in vivo and in vitro. LPS, the COX-2/PGE2 pathway activator, showed the promotion of epithelial-mesenchymal transition, invasion and metastasis. Macranthoidin B exhibited the antagonistic effects against LPS. Celecoxib, the COX-2/PGE2 pathway inhibitor, restrained the epithelial-mesenchymal transition, invasion and metastasis. This effect of celecoxib was enhanced by macranthoidin B.Discussion Macranthoidin B prevents epithelial-mesenchymal transition through COX-2/PGE2 pathway in EMS. It will facilitate the macranthoidin B’s development and broaden its potential application.

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