In-silico Kinetic Modelling of Polyphenol-Inhibited Starch Digestion in Diabetic Patients

Abstract

Polyphenols are naturally occurring plant-derived secondary metabolites that play a significant role in regulating postprandial blood glucose levels by modulating carbohydrate digestion and absorption. Among these, flavonoids and phenolic acids have been extensively studied for their ability to reduce glycemic response through multiple mechanisms, including inhibition of digestive enzymes, reduction of oxidative stress, and modulation of glucose transport pathways. Given the increasing prevalence of prediabetes and type 2 diabetes or Diabetes Mellitus, there is a growing interest in exploring dietary polyphenols as potential nutraceutical agents for glycemic control. The present study investigates the inhibitory effects of selected dietary polyphenols – tannic acid and gallic acid- on enzymatic starch hydrolysis using a mathematically developed in silico gastrointestinal digestion model. This model is designed to simulate physiological digestion conditions relevant to prediabetic and diabetic individuals. Computational simulations were carried out using MATLAB, enabling the dynamic modeling of starch breakdown and subsequent glucose formation under conditions that closely mimic the human gastrointestinal environment. The inhibitory effect of polyphenols was studied to evaluate their influence on the catalytic efficiency of the major carbohydrate-digesting enzymes, namely α-amylase and α-glucosidase. Simulation results demonstrated that these polyphenols significantly inhibit enzymatic starch degradation in a competitive inhibition manner, leading to a reduced rate of glucose release and a moderated postprandial glycemic response. The extent of inhibition was concentration-dependent, with higher concentrations producing more pronounced effects, interfering with substrate–enzyme interactions and thereby slowing the catalytic process of starch hydrolysis. Kinetic modeling based on rate-law equations and Michaelis–Menten dynamics provided further insights into the mechanism of inhibition. In addition to enzyme inhibition, the model also predicts that polyphenols may influence intestinal glucose transport mechanisms, potentially reducing glucose absorption across the intestinal epithelium and further contributing to glycemic control. Overall, the results demonstrate the capacity of dietary polyphenols to modulate starch digestion kinetics and attenuate postprandial hyperglycemia. The integration of computational modeling with biochemical insights provides a useful framework for evaluating nutraceutical strategies aimed at diabetes management and supports the potential role of polyphenol-rich foods in glycemic control.