Phytochemical profiling and evaluation of the antidiabetic potential of Ichnocarpus frutescens (Krishna Sariva): kinetic study, molecular modelling, and free energy approach

This research explored novel antidiabetic drugs from natural sources using the Ayurvedic Rasayana herb Ichnocarpus frutescens through invitro enzyme assay, kinetics study, and computational approaches. Invitro enzyme inhibition assay demonstrated the promising inhibitory activity of root extract against alpha-amylase (alpha-A) and alpha-glucosidase (alpha-G) enzyme with IC50 value 7.34 +/- 0.22 mg/ml and 4.40 +/- 0.25 mg/ml respectively. Enzyme kinetic study revealed the competitive inhibition of both proteins by Ichnocarpus frutescens extract. High-Resolution Liquid Chromatography Mass Spectrometer and Docking study revealed the better binding energy of phytoconstituents 23-Acetoxysoladulcidine, Atrovirinone, Bismurrayaquinone A, Lamprolobine, Zygadenine, and Gambiriin A3 than standard drug acarbose. Molecular modelling showed stable protein-ligands binding interaction during the 100 ns simulation. It revealed comparable Root Mean Square Deviation, Radius of Gyration, and Solvent Accessible Surface Area of these compounds with acarbose. The active site residues of both proteins remained stable and showed significantly less Root Mean Square Fluctuation. Molecular Mechanics with Generalised Bonn Surface Area analysis has illustrated the similar inhibitory activity of Zygadenine for alpha-A, 23-Acetoxysoladulcidine, and Gambiriin A3 for alpha-G protein, compared to the FDA-approved drug acarbose. Thus, the study suggested that the root of Ichnocarpus frutescens can be used as alpha-A and alpha-G inhibitors and be considered a compelling lead for the medication of type 2 diabetes. [Graphical Abstract]]