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

  • Front Pharmacol. 2024 Dec 12:15:1492098. doi: 10.3389/fphar.2024.1492098.
Yi Ding  #  1  2 ,  Xiaoqian Yang  #  2 ,  Qinghua Wei  #  2 ,  Xuanming Bi  2 ,  Yuxin Zhang  2 ,  Yuxia Ma  2 ,  Meisen Yang  3 ,  Xiaoyu Xu  2 ,  Cong Li  4 ,  Qin Wang  5 ,  Yi Chen  1
Affiliations
  • 1. School of Chinese Materia Medica, Chongqing University of Chinese Medicine, Chongqing, China.
  • 2. College of Pharmaceutical Sciences and Chinese Medicine, Southwest University, Chongqing, China.
  • 3. Traditional Chinese Medicine Industry Center of Xiushan Tujia & Miao Autonomous County, Agriculture and Rural Affairs Committee of Xiushan Tujia & Miao Autonomous County, Chongqing, China.
  • 4. Department of Obstetrics and Gynecology, First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • 5. Department of Pharmacy, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, China.
  • # Contributed equally.
PMID: 39726776 DOI: 10.3389/fphar.2024.1492098
Abstract

Introduction: Macranthoidin 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.

Methods: Using 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.

Results: In 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.

Keywords
COX-2/PGE2 pathway; endometriosis; epithelial-mesenchymal transition; invasion and metastasis; macranthoidin B.
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