ABSTRACT Objective This study examined whether diet supplemented with African star apple fruit pulp (FP) can mitigate the effect of high blood pressure on brain neurochemicals, histopathology and expression of genes linked with neuroinflammation. Methods Rats were administered with cyclosporine (25 mg/kg.bw) to induce hypertension and were fed with or without FP supplemented diet. Purinergic (Nucleoside triphosphate diphosphohydrolases [NTPdase] and adenosine deaminase [ADA]) cholinergic (acetylcholinesterase [AChE]) and monoaminergic (monoamine oxidase-B) enzymes were assessed in treated and untreated hypertensive rats’ brains. Oxidative stress biomarkers (catalase, glutathione-S-transferase, thiols, reactive oxygen species [ROS] and malondialdehyde [MDA]), as well as AChE, tumour necrosis factor and receptor (TNF-α and TNF-α-R) expression, were also determined. Results FP supplemented diet significantly reduced NTPdase and ADA activities and increased Na+/K+-ATPase activities in hypertensive rats’ brains compared to the untreated group. Furthermore, FP reduced acetylcholinesterase and monoamine oxidase-B activities compared to the hypertensive group. Redox imbalance was observed in hypertensive rats with inhibition of antioxidant enzymes and high levels of ROS and MDA. However, FP supplemented diet improved antioxidant enzymes, reduced ROS and MDA production in the brain of hypertensive rats. High blood pressure also triggered upregulation of AChE, TNF-α and TNF-α-R while feeding with FP supplemented diet downregulated the genes. Conclusion This study demonstrates the neuroprotective role of FP supplemented diet against alterations in neurochemicals associated with Alzheimer’s disease, oxidative stress-induced neuronal damage and expression of genes linked with neuroinflammation. Moreover, studies on animal behaviour and human subjects are required to confirm these beneficial effects.