Screening of Bioactive Phytochemicals from Gentiana kurroo for Diabetes Management: An Integrated Molecular Docking and In vitro Enzyme Inhibition Study

Background

Diabetes mellitus is a multifactorial metabolic disorder requiring multi-target therapeutic strategies. Medicinal plants rich in bioactive phytochemicals represent promising alternatives to conventional antidiabetic drugs. Gentiana kurroo, an endangered Himalayan herb, is traditionally used for metabolic and inflammatory disorders and contains compounds with potential glucose-lowering activity.

Objectives

This study aimed to evaluate phytochemicals from G. kurroo for antidiabetic potential using molecular docking against key diabetic targets followed by in vitro enzyme inhibition assays.

Materials and Methods

Five phytoconstituents (amarogentin, gentiopicroside, gentianine, gentianidine, and isogentisin) were docked against PPAR-γ (3DZY), glucokinase (4IXC), SIRT6 (3K35), GSK-3 (3F7Z), and tyrosine kinase (1IR3) using AutoDock Tools 1.5.6, with acarbose as reference. Drug-likeness and ADME profiles were predicted using SwissADME and pkCSM. Based on docking performance, gentiopicroside and isogentisin were further evaluated in vitro for α-amylase and α-glucosidase inhibition.

Results

Gentiopicroside and isogentisin showed strong binding affinities (-7.2 to -9.0 kcal/mol) across multiple targets with stable hydrogen-bond and hydrophobic interactions. Both compounds complied with Lipinski’s rule of five and exhibited favorable ADME profiles. In vitro assays demonstrated significant, concentration-dependent inhibition of α-amylase and α-glucosidase, comparable to acarbose (p<0.05).

Conclusion

The combined in silico and in vitro findings suggest that gentiopicroside and isogentisin from G. kurroo are promising multi-target antidiabetic candidates. Further in vivo and clinical studies are required to validate their therapeutic potential.