Kolaviron stimulates glucose uptake with concomitant modulation of metabolic activities implicated in neurodegeneration in isolated rat brain, without perturbation of tissue ultrastructural morphology
Abstract
Reduced glucose uptake usually occurs in type 2 diabetes due to down-regulation of brain glucose transporters. The potential of kolaviron, a biflavonoid from Garcinia kola to stimulate glucose uptake and suppress glucose-induced oxidative toxicity were investigated in rat brain. Its molecular interactions with the target proteins were investigated in silico. Kolaviron was incubated with excised rat brain in the presence of glucose for 2 h, with metformin serving as a positive control. Kolaviron caused a significant (p < 0.05) increase in glucose uptake, glutathione level, superoxide dismutase, catalase, ATPase, ENTPDase and 5'-nucleotidase activities, while concomitantly depleting malondialdehyde level, acetylcholinesterase and butyrylcholinesterase activities compared to brains incubated with glucose only. Electron microscopy (SEM and TEM) analysis revealed kolaviron had little or no effect on the ultrastructural morphology of brain tissues as evidenced by the intact dendritic and neuronal network, blood vessels, mitochondria, synaptic vesicles, and pre-synaptic membrane. SEM-EDX analysis revealed a restorative effect of glucose-induced alteration in brain elemental concentrations, with total depletion of aluminum and zinc. MTT analysis revealed kolaviron had no cytotoxic effect on HT-22 cells. Molecular docking revealed a potent interaction between kolaviron and catalase at the SER114 and MET350 residues, with a binding energy of 12 kcal/mol. Taken together, these results…
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