The effects of Monascus purpureus fermentation on metabolic profile, α-glucosidase inhibitory action, and in vitro digestion of mulberry leaves flavonoids

Mulberry leaves (MLs) were considered to have great hypoglycemic potential because of their rich flavonoid compounds. To enhance the hypoglycaemic effect of MLs, we exploited the fermentation potential of Monascus purpureus to improve its flavonoid profile. Targeted metabolomics analysis showed that we optimized flavonoid composition by subjecting MLs to M. purpureus fermentation. Significant improvements in flavonoid content were observed, with both solid-state fermentation (SSF) and submerged fermentation (SMF) enhancing the flavonoid profiles. Specifically, kaempferol and quercetin were significantly upregulated, whereas astragalin, isoquercetin, and rutin were downregulated, suggesting enhanced antidiabetic properties. Our investigation revealed the metabolic pathways that emphasize the importance of flavonoid biosynthesis. Enhanced α-glucosidase (AG) inhibitory activities were identified in fermented MLs, which are essential for diabetes management. The IC50 values for the inhibitory activities of SSF-MLs and SMF-MLs against AG reached 112.80 ± 1.29 μg/mL and 123.90 ± 0.96 μg/mL, respectively. The types of AG inhibition by the seven major flavonoids were revealed by enzyme inhibition kinetics. Molecular docking revealed the interaction mechanisms underlying AG inhibition. Furthermore, our study demonstrated that SMF optimizes the bioavailability of flavonoids during in vitro digestion. This study presents M. purpureus-assisted MLs fermentation as an relevant strategy, enriching its therapeutic potential for diabetes.