Endocrine Abstracts

Endometriosis is one of the commonly occurring disorders of reproductive women, which represents attachment of functional endometrial cells and tissue outside the uterine cavity, culminates into infertility. This invasive disorder is still under quest for novel treatment strategies. Naringenin is a plant-derived flavonoid having anti-proliferative, anti-inflammatory, and anti-angiogenic properties in chronic and metabolic diseases. The study was planned with an objective to demonstrate the therapeutic prevention of endometriosis by naringenin in rats and to examine its impact on various cellular aspects with a view to define the mechanism involved. Endometriosis was induced in rats by autologous transplantation of uterine tissue in the mesenteric arteries. Endometriotic rats were given naringenin (50 mg/kg/bwt daily) and dienogest (0.3 mg/kg/bwt daily) for 21 days. The endometrial implant volumes, weight, nitric oxide release, TNF-α level in serum and the histopathologic scores were significantly reduced in the naringenin treated group as compared to the endometriotic control group. Cell proliferation, migration and invasion were inhibited by naringenin (at dose of 1 μM and 5 μM) in endometriotic cells in-vitro. Naringenin caused dose-dependent loss of mitochondrial membrane potential and induced apoptosis. Naringenin ameliorated the expression of various proteins (TAK1, PAK1, VEGF and PCNA) involved in development and progression of endometriotic cells. A significant modulation in level of antioxidant transcription factors, their downstream and repressor molecules was found in endometriotic lesion developed in naringenin treated rats as compared to that of control endometriotic rats. Naringenin prevented the invasion of endometrial cells by inhibiting the expression of MMP-2 and MMP-9. We conclude that naringenin may have a therapeutic potential in the treatment of endometriosis due to ROS mediated apoptosis and its anti-invasive effects.