ABSTRACT
Diabetes, the cause of colossal economic and disease burden, is a key area of research in drug discovery programs. Elevated blood glucose levels in diabetes lead to several adverse consequences due to the formation of advanced glycation end products and free radicals. Vitamin C, a potent antioxidant, protects the body's cells and tissues from oxidative damage and dysfunctions. Glucose is the precursor of Vitamin C synthesis in plants and some mammals. L-gulono lactone oxidase (GULO) is the rate-limiting enzyme in producing Vitamin C. However, it is not synthesized in bats, primates, humans, and guinea pigs because of the pseudogene. Several phytomolecules having antioxidant properties are hypothesized to be promising and selective activators of GULO. Therefore, the present study focused on screening agonists of GULO from phytomolecules as an effective augmentor for Vitamin C synthesis, thereby suppressing the sequela of diabetic events. The 3D structure of GULO was generated by the ab-initio method. Subsequently, molecular docking explored the possible binding patterns of GULO protein with different plant phenolic compounds, followed by supplementation of the potent phytomolecules to diabetic guinea pigs. It is noteworthy that Resveratrol and Hydroxytyrosol showed better binding affinity. The molecular simulation also confirmed that Resveratrol is an activator of the GULO enzyme. Interestingly, it was also established that Vitamin C levels were improved in diabetic guinea pigs supplemented with the phytomolecules and comparatively Resveratrol modulates the concentration of glucose and Vitamin C levels substantially, thereby alleviating hyperglycemia. However, further studies are warranted to study the mechanisms.Communicated by Ramaswamy H. Sarma.
