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

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

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.

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).

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. Similar content being viewed by others Availability of Data and Materials Data may be made available from the corresponding author upon reasonable request.

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Additional information Supported by Zhejiang Province Medical and Health Technology Plan Project (Nos. 2021KY504, 2023KY054 and 2025KY553), Zhejiang Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women’s Hospital, Zhejiang University School of Medicine (No. ZDFY2022-CD-8) Electronic Supplementary Material Rights and permissions About this article Cite this article Yang, Qm., Chen, Y., Xia, Lh. et al. Curcumin Inhibits Fibroblast Differentiation and Epithelial-Mesenchymal Transition to Alleviate Adenomyosis through TGF-β1/Smad3 Pathway. Chin. J. Integr. Med. 32, 407–414 (2026). https://doi.org/10.1007/s11655-025-4215-0 Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s11655-025-4215-0