Synergistic Effect of Acarbose–Chlorogenic Acid on α-Glucosidase Inhibition: Kinetics and Interaction Studies Reveal Mixed-Type Inhibition and Denaturant Effect of Chlorogenic Acid

The α-glucosidase inhibitory mechanism of chlorogenic acid was evaluated in the presence of an antidiabetic drug, acarbose. Enzyme kinetics showed the mode of inhibition of the chlorogenic acid–acarbose combination to be either mixed inhibition (competitive and noncompetitive inhibition) or solely competitive inhibition, depending on the dominating inhibitor in the dual system. Despite weaker inhibition by chlorogenic acid, supplementation with acarbose exhibited a synergistic effect on α-glucosidase inhibition, with acarbose equivalent activity exceeding the concentration of acarbose present. Fluorescence quenching studies indicated an increased affinity of chlorogenic acid in the presence of acarbose with an effective quenching constant increasing from 1.6 ± 0.11 × 104 to 3.9 ± 0.32 × 104 M–1. Furthermore, acarbose did not affect the static binding mode or the number of chlorogenic acid bound per α-glucosidase molecule. This chlorogenic acid–acarbose dual inhibition system highlights the potential for antidiabetic nutraceuticals as adjuvant therapy for acarbose-based treatments in diabetes management and, to a broader extent, reveals that nutraceuticals can significantly modify or regulate drug-disease state dynamics.