Discovery of Flazin, an Alkaloid Isolated from Cherry Tomato Juice, As a Novel Non-Enzymatic Protein Glycation Inhibitor via in Vitro and in Silico Studies

Both overproduced reactive oxygen species/reactive nitrogen species and hyperglycemic conditions accompany a significant increase in protein glycation and nitration that contribute to the initiation and progression of diabetic complications and neuronal disorders. In this study, 19 compounds, including steroidal saponins, alkaloids, cerebroside, phenolic compounds, sterols, and nucleosides, were isolated from cherry tomato (Solanum lycopersicum var. cerasiforme) juice, of which flazin showed good inhibition on monosaccharide-induced non-enzymatic bovine pancreas insulin and bovine serum albumin (BSA) glycation. Molecular dynamics simulations revealed that flazin continuously interacts with Phe1, Val2, Tyr26, and Lys29 insulin residues, which play a key role in insulin glycation/dimerization. In addition, depending upon the flazin dose, this blocked the tyrosine nitration of BSA via scavenging peroxynitrite anions. Taken together, our novel findings suggest that flazin could be a lead compound for the treatment of diabetes and neuronal disorders via the inhibition of non-enzymatic protein glycation and the elimination of peroxynitrite.