An in vitro and in silico antidiabetic approach of GC–MS detected friedelin of Bridelia retusa

Abstract

Bridelia retusa is a medicinal plant widely used to treat diabetes by ethnic populations worldwide, has been subjected to GC–MS-based profiling for the bark and fruit and identified 96 phytochemicals using ethyl acetate and methanol solvents. The DPPH antioxidant assay recorded that methanolic fruit extract had a maximum antioxidant activity of 83.01 % (IC_50-103.03 µg/ml). The α-amylase inhibition activity was found maximum in ethyl acetate bark extract with 76.34 % (127.37 µg/ml), while methanolic fruit extract exhibited the highest α-glucosidase inhibition activity with 86.18 % (106.15 µg/ml). Subsequently, we have compared the antidiabetic potential for 3 pharmacologically significant bioactive constituents friedelin, imidazole & sylvestrene through docking and drug likeliness study and found friedelin has a maximum binding affinity with different protein targets followed by sylvestrene and is most suitable candidate for drug development for hyperglycemia. Molecular dynamics simulations revealed friedelin as the most stable binder to anti-diabetic target proteins, with notable structural insights provided by RMSD, RMSF, SASA, and PCA analyses. MM-PBSA calculations emphasized the significance of various energies with the α-amylase-Friedelin complex exhibiting the highest binding energy.