Clin Exp Reprod Med.  2020 Jun;47(2):108-113. 10.5653/cerm.2019.03475.

Eupatilin treatment inhibits transforming growth factor beta-induced endometrial fibrosis in vitro

• Lee CJ
• Hong SH
• Yoon MJ
• Lee KA
• Choi DH
• Kwon H
• Ko JJ
• Koo HS
• Kang YJ

• KMID: 2502744
• DOI: http://doi.org/10.5653/cerm.2019.03475

Abstract

Objective
Endometrial fibrosis, the primary pathological feature of intrauterine adhesion, may lead to disruption of endometrial tissue structure, menstrual abnormalities, infertility, and recurrent pregnancy loss. At present, no ideal therapeutic strategy exists for this fibrotic disease. Eupatilin, a major pharmacologically active flavone from Artemisia, has been previously reported to act as a potent inducer of dedifferentiation of fibrotic tissue in the liver and lung. However, the effects of eupatilin on endometrial fibrosis have not yet been investigated. In this study, we present the first report on the impact of eupatilin treatment on transforming growth factor beta (TGF-β)-induced endometrial fibrosis.
Methods
The efficacy of eupatilin on TGF-β–induced endometrial fibrosis was assessed by examining changes in morphology and the expression levels of fibrosis markers using immunofluorescence staining and quantitative real-time reverse-transcription polymerase chain reaction.
Results
Eupatilin treatment significantly reduced the fibrotic activity of TGF-β–induced endometrial fibrosis in Ishikawa cells, which displayed more circular shapes and formed more colonies. Additionally, the effects of eupatilin on fibrotic markers including alpha-smooth muscle actin, hypoxia-inducible factor 1 alpha, collagen type I alpha 1 chain, and matrix metalloproteinase-2, were evaluated in TGF-β–induced endometrial fibrosis. The expression of these markers was highly upregulated by TGF-β pretreatment and recovered to the levels of control cells in response to eupatilin treatment.
Conclusion
Our findings suggest that suppression of TGF-β–induced signaling by eupatilin might be an effective therapeutic strategy for the treatment of endometrial fibrosis.

Keyword

Endometrial fibrosis; Eupatilin; Transforming growth factor beta