Glucose absorption promoters perform insulin mimic functions to enhance blood glucose transport to skeletal muscle cells and accelerate glucose consumption, thereby reducing blood glucose levels. In our screening exploration of food ingredients for improving glucose transportation and metabolism, we found that the saponins in American ginseng (Panaxquinquefolius L.) showed potential activity to promote glucose uptake, which can be used for stabilizing levels of postprandial blood glucose. The aim of this study was to identify key components of American ginseng with glucose uptake-promoting activity and to elucidate their metabolic regulatory mechanisms. Bio-guided isolation using zebrafish larvae and 2-NBDG indicator identified ginsenoside Rb1 (GRb1) as the most potential promotor of glucose uptake. Using UPLC-QTOF-MS/MS combined with RT-qPCR and phenotypic verification, we found that riboflavin metabolism is the hinge for GRb1-mediated facilitation of glucose transport. GRb1-induced restoration of redox homeostasis was mediated by targeting riboflavin transporters (SLC52A1 and SLC52A3) and riboflavin kinase (RFK).
