Protective effect of fisetin alone and in combination with lactobacillus using experimental model of diabetes associated cognitive impairment in rats.

Type 2 diabetes mellitus (T2DM), which occurs due to frequent consumption of a high-fat diet (HFD), is recognized as a significant risk factor for progressive cognitive decline. The present study investigates the potential neuroprotective effects of fisetin, alone and in combination with Lactobacillus, in an HFD-STZ-induced T2DM rat model. Diabetes was induced by feeding HFD and a single dose of STZ injection of 45 mg/kg intraperitoneally in albino Wistar rats. After confirmation of the diabetic state, rats were administered fisetin (25, 50 mg/kg) orally, in combination with Lactobacillus at 1.5 × 109 CFU/mL. Cognition and memory were analyzed by NORT, MWM, EPM, biochemical markers, neurotransmitters, and molecular (NF-κB via immunohistochemistry) assessments, along with histopathological analysis of tissues, were performed. Fisetin, alone and in combination with Lactobacillus, treatment restored cognitive deficits and glucose level, as well as attenuated lipid profile, biochemical, and neurochemical abnormalities in rats (p < 0.05 vs. STZ-HFD group). Further, the combination of fisetin (50 mg/kg/p.o.) with Lactobacillus (1.5 × 109 CFU/mL) significantly achieved a protective effect as compared to treatment with fisetin alone in diabetic rats (p < 0.05 vs. STZ-HFD Fisetin 25 and 50 mg/kg/ p.o. group). Results of the study revealed that the combination of fisetin with Lactobacillus exhibits impressive anti-oxidant, modulates neurotransmitter levels, and suppresses the NF-κB pathway, promising a strategy for treating diabetes-associated cognitive problems.