Multi-Mechanistic In Vitro Evaluation of Antihyperglycemic, Antioxidant and Antiglycation Activities of Three Phenolic-Rich Indian Red Rice Genotypes and In Silico Evaluation of Their Phenolic Metabolites

The study evaluated the antidiabetic potential of three traditional Indian red rice genotypes/RR (Kattuyanam/KA, Chennangi/CH & Karungkuruvai/KU) using a combination of in vitro, metabolomics (Quadrupole-Time of Flight-Liquid chromatography-Mass spectrometry/Q-TOF-LC-MS/MS), and in silico techniques. In terms of antihyperglycemic potential, KA exhibited the highest inhibitory activity against α-amylase; CH against α-glucosidase; and KU against DPPIV and PTP1B enzymes. KA exhibited the highest antioxidant activity (DPPH, FRAP, and ABTS) and greater inhibition of protein glycation compared to other RR indicating its potential to mitigate diabetic complications. The metabolomic analysis confirmed the presence of 99 phenolics in the sample extracts (KU-71, KA-70, CH-68). Molecular docking studies revealed seven metabolites to be good inhibitors of the four target enzymes and activators of insulin receptor substrate/IRS. The antihyperglycemic and oxidation-glycation reduction composite index revealed KA to have the highest overall antidiabetic potential. Hence, the RR could be utilized in functional foods with a multi-barrelled strategy for diabetes prevention/management.