Inhibition of the Jagged-1/Notch1/Hes1 Signaling Pathway by Evodiamine Attenuates Epithelial-Mesenchymal Transition in Mice with Adenomyosis

Abstract

Background: Evodiamine has been documented to suppress epithelial-mesenchymal transition (EMT), but its effects on adenomyosis are poorly understood. This study investigates evodiamines potential effects and mechanisms in treating adenomyosis. Methods: The cohort comprised 90 women (34 healthy controls and 56 adenomyosis patients). The Jagged-1/Notch1/hairy expression levels and hairy and enhancer of split 1 (Hes1) signaling pathway in human endometrial tissues were assessed using western blot analysis. An adenomyosis mouse model was created using 1 mg/kg tamoxifen, followed by treatment with evodiamine and dual antiplatelet therapy (DAPT). Expression levels of alpha-smooth muscle actin (α-SMA), collagen I, neural cadherin (N-cadherin), epithelial cadherin (E-cadherin), Snail, and Vimentin were evaluated using western blot analysis. Immunohistochemistry was used to assess Jagged-1, Notch1, and Hes1 levels. Hematoxylin and eosin (H&E) staining evaluated the depth of endometrial infiltration into the myometrium, and Masson trichrome staining quantified collagen content. Results: The Jagged-1/Notch1/(hairy and enhancer of split 1) Hes1 pathway was found to be activated in the endometrial tissues of adenomyosis patients. In adenomyosis mice, evodiamine treatment led to the inhibition of the Jagged-1/Notch1/Hes1 pathway, along with observable morphological changes, such as reduced adenomyosis nodules with congestion. This improvement was significant compared to the control group (p < 0.05). Furthermore, evodiamine and DAPT treatments reduced endometrial infiltration into the myometrium and collagen deposition while suppressing the expression of α-SMA, collagen I, N-cadherin, Snail, and Vimentin, and upregulating E-cadherin expression. The inhibitory effect was significantly greater than that in the control group (p < 0.05). Conclusion: Evodiamine mitigated adenomyosis by regulating EMT through the inactivation of the Jagged-1/Notch1/Hes1 pathway. This finding suggests that evodiamine could be a potential treatment option for adenomyosis.