Synergic effect of phenolic compounds by concentration dependence of andrographolide against carbohydrate digestive enzyme (α-glucosidase and α-amylase) by <i>in vitro</i>, <i>in silico,</i> and fluorescence analysis

Abstract Diabetes mellitus (DM) is a chronic metabolic disorder caused by insufficient insulin secretion and function. One suggested treatment for type 2 DM (T2DM) is inhibiting carbohydrate digestive enzymes to decrease blood glucose levels. Moreover, combination drugs are also recommended for T2DM management. This research investigated the inhibition potential of phenolic compounds (syringic acid and vanillin) and andrographolide (AGL) and the combination of syringic acid/AGL and vanillin/AGL against α-glucosidase and α-amylase by in vitro, in silico, and fluorescence analysis. The results revealed that the inhibition potential of AGL against α-glucosidase and α-amylase was higher than that of syringic acid and vanillin. Furthermore, these compounds’ inhibition of α-glucosidase appears more potent than α-amylase. The combination of syringic acid/AGL and vanillin/AGL shows a synthetic effect on α-glucosidase and α-amylase when increasing AGL. The fluorescence technique has confirmed that compounds alone and the combination have binding at the active sites of α-glucosidase and α-amylase. AGL’s lowest inhibition constant (Ki) and highest binding affinity suggest that this compound has stronger binding interactions with the amino acids in the active sites of α-glucosidase and α-amylase than syringic acid and vanillin. Our findings indicate that the combination of syringic acid/AGL and vanillin/AGL is recommended for applications in T2DM treatment.