Abstract
Introduction: Melia dubia seeds are traditionally used against diabetes mellitus and cancer. Molecular docking studies were performed to evaluate the binding affinity of major compounds against α-glucosidase and the mechanistic target of rapamycin (mTOR), a key regulator of cell growth and proliferation.
Methods: Phytoconstituents of the alcoholic seed extract were analyzed using network pharmacology to identify key molecular targets along with signaling pathways involved in diabetes and cancer. Molecular docking studies were performed to identify the binding affinity for major compounds against α-glucosidase and mTOR, which regulates cell division and proliferation. In vitro antidiabetic activity was assessed using an α-glucosidase inhibition assay, while anticancer activity was evaluated through a cytotoxicity assay using the MTT method.
Results: Network pharmacology analysis revealed that the phytoconstituents modulate critical pathways, consisting of phosphoinositide 3-kinase–Akt, adenosine monophosphate-activated protein kinase, nuclear factor kappa-B, vascular endothelial growth factor, and insulin signaling pathways. Molecular docking demonstrated strong binding affinities of compounds such as 2-phenylanthraquinone, 2,2-dimethylpropyl, and quebrachamine with α-glucosidase and the mTOR. The extract exhibited significant α-glucosidase inhibition with an IC₅₀ value of 33.59 µg/mL, against 28.11 µg/mL for Acarbose. A cytotoxicity assay showed dose-dependent cancer cell inhibition with an IC₅₀ of 31.82 µg/mL, compared to 20.41 µg/mL for cisplatin.
Conclusion: The findings may support the dual antidiabetic and anticancer potential of the alcoholic extract of M. dubia seeds. The integrated in silico and in vitro results suggest a promising natural therapeutic candidate requiring further validation.