Sinigrin as a Therapeutic Agent for Diabetes: A Combined In Vitro and In Silico Investigation.

Abstract

Type 2 diabetes continues to have a detrimental influence on the health of millions. Insulin resistance, or the inability to respond to insulin and eliminate blood glucose, is a major pathogenic driver of the disease. Skeletal muscle is the principal tissue responsible for maintaining glucose homeostasis through glucose uptake via insulin-dependent and insulin-independent processes. Natural products are a rich source of chemicals for drug discovery, as has long been known. Many groups of secondary metabolites, including glucosinolates are found to possess medicinal properties. Sinigrin which belongs to Brassicaceae family of glucosides is examined for its antidiabetic properties.  The effect of sinigrin on the viability of L6 myotubes was evaluated by MTT assay at different sinigrin concentrations. There was more than 95% viability at concentrations of sinigrin up to 100 µM indicating its non-toxic nature of sinigrin. Sinigrin enhanced glucose uptake as a percentage compared to control cells, 106%, 111%, 121%, 132%, and 156%   concentrations, 20,40,60, 80 and 100 µM respectively. In addition, glucose uptake was reduced in the presence of LY294002 (PI-3 kinase inhibitor) indicating a major mechanism involving the induction of GLUT4 membrane translocation via the activation of both PI3K/Akt pathway. Sinigrin enhances the uptake of glucose in rat L6 myotubes independent of insulin through the PI 3 kinase signaling pathway.  According to computational analysis, sinigrin's interactions and binding energy with PEPCK and G6 pase indicate that the compound has the ability to inhibit both gluconeogenic enzymes. The study fully understands the mechanism of action of sinigrin, and these findings show that sinigrin could be developed into an effective antidiabetic medicine