Integrated Phytochemical, In-Vitro Enzyme Inhibitory, Molecular Docking and ADME Evaluation of Combretum Ovalifolium Roxb. Leaf Extracts as a Potential Source of Antidiabetic Agents

Abstract

Background: Diabetes mellitus remains a major metabolic disorder for which identification of complementary and novel therapeutic agents is an active area of research. Medicinal plants contain chemically diverse constituents that may modulate carbohydrate-digesting enzymes and other antidiabetic targets.
Objective: The present study evaluated the phytochemical profile and in vitro carbohydrate-hydrolysing enzyme inhibitory activity of petroleum ether, chloroform and ethanolic leaf extracts of Combretum ovalifolium Roxb., supported by HPTLC fingerprinting, molecular docking against human dipeptidyl peptidase-IV (DPP-IV) and in silico drug-likeness/ADME assessment.
Methods: Leaf extracts were prepared by Soxhlet extraction and subjected to preliminary phytochemical screening. The ethanolic extract was fingerprinted by HPTLC using silica gel 60 F254 plates and toluene:ethyl acetate:formic acid (5:4:1, v/v/v). α-Amylase, α-glucosidase and β-galactosidase inhibition were assessed at 10–500 µg/mL. Twenty phytoconstituents reported from the genus Combretum were docked against DPP-IV (PDB ID: 2ONC) using AutoDock Vina/PyRx. SwissADME was used to assess physicochemical and drug-likeness parameters.
Results: The ethanolic extract showed a broad phytochemical profile and produced three major HPTLC peaks at Rf 0.096, 0.153 and 0.920 at 366 nm. For α-amylase, IC50 values were 61.35, 138.00 and 86.23 µg/mL for petroleum ether, chloroform and ethanol extracts, respectively. For α-glucosidase, the corresponding IC50 values were 139.20, 74.44 and 58.00 µg/mL, while β-galactosidase IC50 values were 70.74, 78.93 and 64.97 µg/mL. In docking, arjunic acid (-15.7 kcal/mol) and betulinic acid (-14.5 kcal/mol) showed the most favourable predicted binding affinities, compared with metformin (-8.6 kcal/mol). Quercetin, luteolin, kaempferol, apigenin, genkwanin and several other compounds complied with Lipinski criteria, whereas larger compounds such as punicalagin showed multiple violations.
Conclusion: C. ovalifolium leaf extracts demonstrated measurable in vitro inhibition of three carbohydrate-related enzymes, while selected Combretum-derived phytoconstituents showed favourable predicted DPP-IV binding and variable drug-likeness. The findings support further chemical identification, target-based validation and in vivo investigation, but do not by themselves establish clinical antidiabetic efficacy.