Vernonia Amygdalina Del. stimulated glucose uptake in brain tissues enhances antioxidative activities; and modulates functional chemistry and dysregulated metabolic pathways

Brain glucose uptake is usually reduced in type 2 diabetes owing to downregulation of brain glucose transporters. The ability of Vernonia amygdalina to stimulate glucose uptake as well as ameliorate glucose-induced oxidative stress and proinflammation were investigated in rat brain. Hot infusion of V. amygdalina leaves was incubated with rat brain tissues for 2 h in the presence of glucose. Another incubation with glucose only, served as negative control while metformin served as positive control. Incubation of brain tissues with V. amygdalina led to significant (p < 0.05) increase in glucose uptake, reduced glutathione, nitric oxide and non-thiol proteins levels, superoxide dismutase, catalase and ATPase activities, while concomitantly decrease in myeloperoxidase activity and malondialdehyde level compared to the negative control. Incubation with glucose only, led to the development of nitrate, amide II and amide I functional groups which were removed on incubation with the infusion. LC-MS analysis revealed depletion of oxidative stress-induced 2-keto-glutaramic acid and cysteinyl-tyrosine metabolites in brain tissues, with concomitant generation of S-formylglutathione and adenosine tetraphosphate by the infusion. Pathway analysis of the metabolites revealed an activation of pyruvate metabolism pathway in the negative control, with the infusion reducing the intensity fold. LC-MS analysis of the infusion revealed the presence of l–serine, l-cysteine, l-proline, nicotinic acid, cumidine, salicylic acid, isoquinoline, 3-methyl-, and γ-octalactone. Except for l–serine, l-cysteine and l-proline, the other compounds were predicted to be permeable across the blood brain barrier. These results indicate the brain glucose uptake stimulatory and neuroprotective effect of V. amygdalina.