The extract of Sclerocarya birrea , Nauclea latifolia , and Piper longum mixture ameliorates diabetes-associated cognitive dysfunction

Diabetes-associated cognitive dysfunction is linked to chronic hyperglycemia, oxidative stress, inflammation, cholinergic dysfunction, and neuronal degeneration. We investigated the antidiabetic and neuroprotective activity of a mixture of Sclerocarya birrea, Nauclea latifolia, and Piper longum (SNP) in type 2 diabetic (T2D) rat model-induced memory impairment. Fructose (10%) and streptozotocin (35 mg/kg) were used to induce T2D in male Wistar rats. Diabetic animals received distilled water, metformin (200 mg/kg), or SNP mixture (75, 150, or 300 mg/kg). HPLC–MS profiling of the mixture was performed. Behavioral testing was conducted using the Y-maze, NORT, and Morris water mazes to assess learning and memory. Biochemical markers were evaluated, including carbohydrate metabolism, oxidative/nitrative stress, pro-inflammatory markers, and acetylcholinesterase activity. Histopathological examination of the pancreas and hippocampus was also performed. Fructose/STZ administration resulted in T2D, impaired short- and long-term memory, significantly increased oxidative/nitrative stress, pro-inflammatory cytokine levels, acetylcholinesterase activity (AChE), hippocampal neuronal loss and degeneration in CA1 and CA3 subfields, and neuronal vacuolation in DG. SNP mixture at 150 and 300 mg/kg significantly improved blood glucose and memory function in diabetic rats. The mixture reduced oxidative/nitrative stress and increased endogenous antioxidant levels. It also reduced serum IL-1β, INF-γ and TNF-α levels and ameliorated AChE activity. Histologically, SNP protected hippocampus neurons against T2D-induced neuronal necrosis and degeneration. We conclude that the aqueous extract of SNP mixture has antidiabetic and neuroprotective activities thanks to active metabolites identified in the plant mixture, which consequently normalized blood glucose, protected hippocampus neurons, and improved memory function in diabetic rats. Graphical abstract