Harpephyllum caffrum fruit (wild plum) facilitates glucose uptake and modulates metabolic activities linked to neurodegeneration in isolated rat brain: An in vitro and in silico approach.

Alteration in brain glucose metabolism due to glucose uptake reduction has been described in the onset of certain neurodegenerative disorders. This study determined Harpephyllum caffrum fruit's potential ability to improve glucose uptake and its modulatory effects on intrinsic antioxidant, glucogenic, cholinergic, and nucleotide-hydrolyzing enzyme activities in isolated rat brain. Consequently, the bioactive compounds of the fruits were identified with LC-MS. The fruit significantly improved brain glucose uptake following coincubation with glucose and brain tissue. The fruit extract also elevated GSH level, SOD, catalase, glycogen phosphorylase, and ENTPDase activities while simultaneously suppressing NO and malonaldehyde levels and fructose-1,6-bisphosphatase, ATPase, acetylcholinesterase and butyrylcholinesterase activities. LC-MS analysis revealed S-methylcysteine sulfoxide, dihydroquercetin, 3,4-dimethyl-2,5-bis(3,4,5-trimethoxyphenyl) tetrahydrofuran (MTHF), nobiletin, puerarin, quercetin 3-rutinoside, 8-D-glucosyl-4',5,7-trihydroxyflavone, asperulosidic acid, 1,2,4,6-tetragalloylglucose, and phellamurin. This study suggests the neuroprotective effects of H. caffrum fruit due to its ability to enhance glucose uptake, attenuate glucose-induced oxidative stress while modulating glucogenic, cholinergic, and nucleotide-hydrolyzing enzyme activities in normal brain tissues. PRACTICAL APPLICATIONS: Available scientific evidence describes oxidative stress as one of the physiological processes contributing to aging-associated neurodegeneration in humans. In this regard, commonly consumed natural products from plants have attracted much interest due to their ability to mitigate redox imbalance-related pathologies that affect various organs in the body such as the brain. Harpephyllum caffrum or bush mango is an evergreen plant native to the South African vegetation. The fruit from the plant is consumed locally as food or specifically for improving the nutritional quality of meals as deserts or condiments. While previous findings described the high antioxidant properties of the fruits, this study reported possible mechanisms via which the plant may exhibit ameliorative effects against oxidative stress-related neurological disorders in the brain. Hence, findings from the current work present another justification for the significance of fruits as a safer nutraceutical alternative for therapy in neurological disease management.