Antidiabetic activity of bioactive fractions from Momordica cymbalaria Fenzl ex Naudin leaves: In vitro, in silico and in vivo evaluation

This study evaluated the antidiabetic activity of Momordica cymbalaria Fenzl ex Naudin (MC) leaf fractions, a traditionally used remedy in southern India, through comprehensive in vitro , in silico , and in vivo investigations to run scientific validation for its therapeutic potential. MC leaves were extracted by cold maceration with 60% methanol and fractionated based on polarity into five fractions (MF1-MF5). Fractions underwent phytochemical screening, total phenolic and flavonoid measurement, and in vitro antidiabetic tests ( α -amylase & α -glucosidase inhibition, glucose diffusion). In rats that were driven to diabetes by streptozotocin and nicotinamide, the most active fraction (MF3, 200 and 400 mg/kg) was tested orally for 21 days. GC-MS spectrometry was used to track down the bioactive chemicals, and molecular docking studies assessed their interactions with 21 diabetes-related protein targets. MF3 exhibited the highest phenolic (427.33 mg/g GAE) and flavonoid (394.35 mg/g QE) content with potent α -amylase (IC 50 = 63.07 μg/mL) and α -glucosidase (IC 50 = 118.65 μg/mL) inhibition, comparable to acarbose. In diabetic rats, MF3 (400 mg/kg) expressively diminished blood glucose quantity (from 311.33 ± 43.59 to 99 ± 12.85 mg/dL, P < 0.001), improved body weight, normalized lipid profiles, and restored hepatic antioxidant enzymes. GC-MS identified 22 compounds, with 3-Buten-2-one derivative showing excellent binding affinity (≤ −10.0 kcal/mol) to key diabetes-related targets including maltase-glucoamylase and dipeptidyl peptidase-4. The results of this research provide credence to the long-standing belief that MC leaf fractions, and MF3 in particular, possess substantial antidiabetic properties, lending credence to the plant's traditional usage. These promising discoveries necessitate further clinical trials to verify their validity and establish the plant's medicinal effectiveness.