Nimbolide as a bioactive compound in food science: inhibition of proliferation and glycolysis in endometriosis cells

Endometriosis is a common gynecological disorder characterized by the ectopic growth of endometrial-like tissue, often leading to chronic pain and infertility. Despite its high prevalence, the underlying mechanisms are still poorly understood. Nimbolide, a bioactive compound derived from Azadirachta indica (neem), has been shown to possess various biological activities, including anti-malarial, anti-inflammatory, and anti-cancer properties. However, its effects on endometriosis have largely remained unexplored. Human endometriosis cell lines (End1/E6E7) were cultured and treated with varying concentrations of nimbolide for 48 hours. Cell proliferation was assessed using the MTT assay, and apoptosis was analyzed by flow cytometry with annexin V/PI staining. Cellular motility was evaluated using wound healing assays, glycolysis was examined by measuring lactate production, and Western blotting was performed to determine the expression levels of key proteins involved in the Phosphoinositide 3-Kinase/Protein Kinase B (PI3K/AKT) signaling pathway. Our findings reveal that nimbolide inhibited the proliferation of human endometriosis cells by inducing apoptosis and suppressing cellular motility. Furthermore, it disrupted abnormal glycolysis. Mechanistic analysis showed that nimbolide exerted its effects by inhibiting the PI3K/AKT signaling pathway, a key regulator of cell growth and metabolism in endometriosis. These findings suggest that nimbolide may serve as a potential therapeutic agent for managing endometriosis by targeting cell proliferation, motility, and glycolytic metabolism through the inhibition of the PI3K/AKT pathway.