Investigating the hypoglycaemic potential of processed apple and acarbose combination in vitro, ex vivo, and in vivo: the role of quercetin-3-glucoside in steering α-glucosidase inhibition

This study investigated the interaction between apple juice (AJ) and acarbose (A) in modulating glycaemic responses, with the aim of validating in vivo results previously observed in vitro. When administered to rats, AJ alone reduced the glycemic curve, but the combination of AJ with increasing doses of A resulted in higher glycemic responses, suggesting an antagonistic interaction in alpha-glucosidase inhibition. To explore this mechanism, quercetin-3-glucoside (Q-3-G), a major phenolic compound in AJ, was tested for alpha-glucosidase inhibition in vitro. Q-3-G and A together showed reduced inhibitory efficacy compared to either compound alone, consistent with in vivo findings. Ex vivo studies in Caco-2 cells further supported this antagonism. Sucrose hydrolysis experiments showed that low concentrations of Q-3-G increased residual sucrose when combined with moderate concentrations of A, but higher concentrations of Q-3-G favoured sucrose hydrolysis regardless of A levels. The results highlight the antagonistic interaction between Q-3-G and A in inhibiting alpha-glucosidase and emphasise the need to combine in vitro, ex vivo and in vivo studies to evaluate food-drug interactions. This comprehensive approach is essential before advocating the use of functional foods alongside pharmacological therapies.