Amygdalin inhibits 17β-estradiol-induced mesenchymal transition through TGF- β/Smad signaling in normal and endometriotic endometrial epithelial cells.

Endometriosis is a common gynecological disorder characterized by chronic pelvic pain, infertility, and systemic symptoms, with currently limited treatment options. Amygdalin, a cyanogenic glycoside derived from bitter apricot kernels, has shown potential in endometriosis management, though its molecular mechanism remains unclear. In this study, we investigated the effects of amygdalin on epithelial‑mesenchymal transition (EMT) in both normal and endometriotic endometrial epithelial cells and explored the underlying signaling pathways involved. We found that amygdalin inhibited the proliferation of endometriotic eutopic epithelial cells (EECs) and suppressed 17β‑estradiol‑induced proliferation, invasion, migration, angiogenesis, inflammatory cytokine secretion, and expression of EMT‑related markers in normal epithelial cells (NECs). Mechanistically, amygdalin blocked 17β‑estradiol‑induced EMT in NECs by inhibiting the TGF‑β pathway, as confirmed by TGF‑β knockdown and pharmacological inhibition. Notably, these findings were further validated in primary endometrial epithelial cells isolated from patients with endometriosis, where amygdalin significantly suppressed cell proliferation and downregulated key proteins within the TGF‑β signaling pathway. Taken together, our results demonstrate that amygdalin attenuates 17β‑estradiol‑driven migration, invasion, and EMT in endometrial epithelial cells by modulating TGF‑β signaling. Its efficacy in patient‑derived cells further supports its potential as a therapeutic agent for endometriosis.