Antidiabetic Activity of Ficusonolide, a Triterpene Lactone from Ficus foveolata (Wall. ex Miq.): In Vitro, in Vivo, and in Silico Approaches

Abstract

Diabetes is a chronic condition which is locally managed through the stem of Ficus foveolata. To find the exact chemical constituent responsible for this activity, a triterpene lactone (ficusonolide) isolated from F. foveolata was studied for antidiabetic potential through the in vitro antidiabetic paradigm employing L-6 cells and an in vivo antidiabetic assay against non-insulin-dependent rats. The results on glucose uptake in the L-6 cell line indicated that ficusonolide has enhanced the uptake of glucose by 53.27% over control at a dose of 100 μg/mL, while at doses of 50 and 25 μg/mL, the glucose uptake was enhanced by 22.42 and 14.34%, respectively. The extract of F. foveolata (100 mg/kg) and ficusonolide (50 mg/kg) demonstrated a significant (p < 0.001) decline in streptozotocin-induced hyperglycemia of diabetic rats. Ficusonolide displayed conspicuous inhibitory activity against the molecular docking studies with proteins such as dipeptidyl peptidase-IV (DPP-IV), protein tyrosine phosphatase 1B (PTP-1B), α-glucosidase, and α-amylase subjected to molecular targets. Detailed computational and structural insights affirmed promising interactions between target proteins and ficusonolide. In conclusion, the plant and its isolated compound have significant antidiabetic activity with a possible mechanism of interaction with DPP-IV, PTP-1B, α-glucosidase, and α-amylase.