Objective:

2

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

Methods:

2

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 expression

s 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:

2

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:

2

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.