Evaluation of antidiabetic potential of Plumbago indica Roots: insights from in vitro, in vivo and in silico studies

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by elevated blood glucose levels due to insufficient insulin production or decreased insulin sensitivity. Despite advances in antidiabetic pharmacotherapy, the limitations and adverse effects of current treatments highlight the need for natural products as alternative therapies. The present investigation was carried out to evaluate the anti-diabetic activity of the methanol extract (PIME) and ethyl acetate fraction (PIEAF) of roots of Plumbago indica using in vitro , in vivo and in silico models. The in vitro study was done by α-glucosidase and α- amylase inhibition assays. The effect of PIME and PIEAF on serum parameters and histopathological changes was assessed in streptozotocin/nicotinamide-induced type 2 diabetes mellitus in rats. The in vitro studies showed that PIEAF and PIME inhibited α-glucosidase and α- amylase enzymes in a dose dependent manner. In vivo studies indicated that administration of PIME and PIEAF led to the reduction in serum glucose, cholesterol, triglycerides, hepatic enzyme levels and significantly improved renal function and oxidative stress markers. Taking Plumbagin as the marker compound in P. indica , the HPLC analysis of PIME was carried out and it showed that the plumbagin content was 0.26%. In silico studies revealed that plumbagin inhibited α-glucosidase activity through optimal orientation and strong molecular affinity. P. indica roots showed strong promising potential as a treatment for diabetes, probably due to its antioxidant properties and higher content of plumbagin than other species of Plumbago .