Anti-hyperglycemic activity of myricetin, through inhibition of DPP-4 and enhanced GLP-1 levels, is attenuated by co-ingestion with lectin-rich protein.

Dipeptidyl peptidase-4 (DPP-4) is a proteolytic enzyme responsible for the rapid degradation of Glucagon-like peptide 1 (GLP-1) that is required for the secretion of insulin. DPP-4
also influences activation of node like receptor family, pyrin domain containing 3 (NLRP3)
inflammasome under diabetic conditions. Although several polyphenols are reported for various bioactivities, they are consumed as part of the food matrix and not in isolation. Horsegram (Macrotyloma uniflorum) is a rich source of myricetin (Myr) (35 μg/g flour), reported for
its anti-hyperglycemic effect. In this investigation, we aimed to study the effect of Myr, singly,
and in the presence of co-nutrient horsegram protein (HP) on DPP-4 activity and its consequential impact on GLP-1, insulin, and NLRP3 inflammasome in high-fat diet and single low
dose streptozotocin (STZ)-induced diabetic male Wistar rats. In diabetic control (DC), the
activity of DPP-4 and its expression were higher compared to treated groups. The consequential decrease in the circulating GLP-1 levels in the DC group, but not treated groups,
further indicated the effectiveness of our test molecules under diabetic conditions. Specifically, Myr decreased DPP-4 activity and its expression levels with enhanced circulating
GLP-1 and insulin levels. Myr administration also resulted in a lessening of diabetes-induced
NLRP3 inflammasome activation and enhanced antioxidant enzyme activities. HP also
proved to be efficient in reducing elevated blood glucose levels and enhancing antioxidant
enzyme activities. However, Myr, in the presence of HP as a co-nutrient, had diminished
capacity to inhibit DPP-4 and, consequently, reduced potential in ameliorating diabetic conditions. Myr proved to be a potent inhibitor of DPP-4 in vitro and in vivo, resulting in
enhanced circulating GLP-1 and insulin levels, thereby improving diabetic conditions.
Though Myr and HP, individually ameliorate diabetic conditions, their dietary combination
had reduced efficiency.