Computation and Experimental Approaches to Uncover the Antidiabetic Potential of Leaf Insulin (Tithonia diversifolia) Extract Based on Flavonoid Constituents

Abstract

Insulin leaves (Tithonia diversifolia) are traditionally used by the community to lower blood sugar, although this has not been scientifically proven. Insulin leaves are known to contain flavonoids, which are responsible for the antidiabetic activity of these leaves. Therefore, this research was conducted to investigate the antidiabetic effects of insulin leaves, specifically through their flavonoid content. The insulin leaves were extracted with 90% methanol as a solvent and then identified for flavonoid content using Liquid Chromatography-Mass Spectrometry (LC-MS). To investigate the antidiabetic activity, the sample extract was tested for its effect on the in vitro amylase enzyme and inhibition of glycated haemoglobin. Moreover, advanced techniques such as in silico analysis and molecular docking are used to elucidate the molecular mechanism behind the antidiabetic effects of insulin leaves. The results of our study revealed that plant extracts, particularly those rich in flavonoids such as luteolin, genistein, and hispidulin, are potent inhibitors of the α-amylase enzyme and the formation of glycated haemoglobin. The Inhibition Concentration 50% (IC₅₀) value of flavonoids was found to be lower than that of glibenclamide, suggesting their superior efficacy in stabilizing blood sugar levels. Docking analysis further confirmed the strong interactions between flavonoids and key enzyme residues and haemoglobin, while Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) predictions indicated favourable absorption and distribution profiles. Both experimental and computational approaches show the importance of flavonoids in the antidiabetic activity of insulin leaf extracts, highlighting their contribution to its effectiveness.