Curcumin Inhibits Fibroblast Differentiation and Epithelial-Mesenchymal Transition to Alleviate Adenomyosis through TGF-β1/Smad3 Pathway

Qing-Mei Yang; Yang Chen; Li-Hua Xia; Han Xu; Xiao-Fen Jin; Qing Wu

doi:10.1007/s11655-025-4215-0

Curcumin Inhibits Fibroblast Differentiation and Epithelial-Mesenchymal Transition to Alleviate Adenomyosis through TGF-β1/Smad3 Pathway

Chin J Integr Med. 2026 Jan 15. doi: 10.1007/s11655-025-4215-0. Online ahead of print.

Authors

Qing-Mei Yang^{1

2}, Yang Chen¹, Li-Hua Xia¹, Han Xu¹, Xiao-Fen Jin³, Qing Wu⁴

Affiliations

¹ Center for Reproductive Medicine, Department of Gynecology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, 310014, China.
² Department of Gynecology, Yibin First People's Hospital, Yibin, Sichuan Province, 644000, China.
³ Zhejiang Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, 310001, China.
⁴ Center for Reproductive Medicine, Department of Gynecology, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, 310014, China. okwq31@163.com.

PMID: 41540162
DOI: 10.1007/s11655-025-4215-0

Abstract

Objective: To investigate the therapeutic effects and mechanisms of curcumin (Cur) in adenomyosis (AM).

Methods: A mouse uterine AM model was established by exposing ICR neonatal mice to tamoxifen (TAM). Female neonatal mice (day 1, n=24) were numbered and randomly divided into control, model (TAM 1 mg/kg per day, day 2 to 5), low- and high-doses Cur groups (TAM 1 mg/kg per day, day 2 to 5; Cur 50 and 200 mg/kg per day, respectively, week 13 to 15), by a random number table, with 6 mice in each group. The effect of Cur was assessed by a hot-plate test on mice and uterine sections for hematoxylin and eosin (HE), Masson staining, and immunohistochemistry staining of E-cadherin, N-cadherin, matrix metalloproteinases (MMP) 9 and MMP 11. Ishikawa (IK) cell phenotypic transformation was induced by transforming growth factor beta 1 (TGF-β1), and the mRNA and protein expressions of E-cadherin, N-cadherin, MMP 9, MMP 11 and p-Smad3/Smad3 were detected by quantitative real-time PCR and Western blot after Cur treatment.

Results: In vivo study results showed that Cur significantly improved pain tolerance (P<0.01). The degrees of lesion fibrosis and invasion of ectopic glands in model mice were significantly higher than those in control mice, and the degrees were significantly reduced after high-dose Cur treatment (P<0.01). High-dose Cur reversed the decrease of E-cadherin and the increase of the levels of N-cadherin, MMP 9 and MMP11 by inhibiting the production of TGF-β1 in the uterine tissue (P<0.01). In vitro study, Cur increased the protein expression of E-cadherin and reduced the protein expressions of N-cadherin, MMP 9 and MMP 11 (P<0.01). Cur effectively inhibited the phosphorylation of p-Smad3/Smad3 in IK cells induced by TGF-β1 (P<0.01).

Conclusion: Cur effectively alleviates AM and inhibits fibroblast differentiation and epithelial-mesenchymal transition by TGF-β1/Smad3 pathway, which provides a new approach for treating AM by non-hormonal drugs.

Keywords: adenomyosis; curcumin; epithelial-mesenchymal transition; transforming growth factor-β1.