Optimization of red yeast rice fermentation for enhanced Monacolin K accumulation and assessment of α-amylase inhibitory activity for antihyperglycemic potential

Monascus sp. can break down starch-based substrates into bioactive metabolites with antibacterial, anticancer, antidiabetic, and anti-obesity effects. Combining Monacolin K (MK) and other compounds produced by Red Yeast Rice products reduces inflammation and insulin resistance, thereby minimizing the adverse effects of Advanced Glycation End products (AGEs) on pancreatic function, which is associated with various chronic diseases, including diabetes and atherosclerosis. This study aimed to determine the optimal fermentation conditions for Monascus purpureus to produce RYR with high red pigment intensity, Monacolin K, and low citrinin content, and to assess the inhibition of α-amylase activity. The study applied Response Surface Methodology with a Box-Behnken design to optimize fermentation parameters. The experimental matrix was generated by JMP software, allowing systematic analysis of variable interactions and identification of optimal conditions. The LC-MS/MS method was used to analyze the citrinin and Monacolin K content. Additionally, the α-amylase inhibitory activity of the extract was evaluated. The optimal fermentation conditions for the rice substrate are a temperature of 24°C, with a fungal biomass inoculum size of 8% and an incubation period of 12 days. Triplicate analyses showed that the concentration of Monacolin K was 288.44 ± 3.88ppm without citrinin. The α-amylase inhibitory activity of the RYR extract varied with concentration, which ranged from 5.39% to 79.44%. The IC₅₀ value was calculated to be 119.36 μg/mL. These results are essential for evaluating RYR extract α-amylase inhibitory capacity and suggest that it can be used to lower cholesterol and support the prevention of diseases related to obesity.