Crocin Improves Cognitive Impairment in LPS-treated Rats through Anti-Apoptotic, Anti-Inflammatory, and Antioxidant Activities

Abstract

Brain inflammation and oxidative stress play critical roles in neuronal apoptosis and memory dysfunction in Alzheimer's disease. Crocin, a natural carotenoid in the stigma of saffron, possesses radical scavenging, anti-inflammatory, and anti-apoptotic properties. This study investigates the protective impact of crocin on neuronal apoptosis, oxidative stress, neuroinflammation, and memory deficits induced by lipopolysaccharide (LPS) in rats. Male Wistar rats received 100 mg/kg of crocin for 12 days, with LPS (1 mg/kg, ip) injected on days 8-12. Spatial learning and memory were evaluated in the Morris water maze two hours after LPS injection. Gene expression of nuclear factor kappa B (NF-kappaB), tumor necrosis factor-alpha (TNF-alpha), caspase 3, and lipid peroxidation was assessed in hippocampal homogenates at the end of the behavioral test. Histopathological changes in the hippocampus and cerebral cortex were evaluated using H&E staining. The results indicated that LPS administration caused spatial learning and memory dysfunction (P = 0.001, P < 0.01) accompanied by upregulation of Nfkb, Tnfalpha, and Casp3 mRNA expression (P < 0.0001), increased TNF-alpha (P < 0.01) and lipid peroxidation level (P < 0.01), decreased total thiol concentration (P < 0.05), tissue damage and neuronal loss in the hippocampus (P < 0.0001). Furthermore, crocin treatment at a dosage of 100 mg/kg attenuated learning and memory impairments (P = 0.001, P < 0.01), downregulated Nfkb, Tnfalpha, and Casp3 mRNA expression (P < 0.0001), decreased TNF-alpha level (P < 0.01) and lipid peroxidation (P < 0.05) and increased total thiol level (P < 0.05) in the hippocampus. Crocin also ameliorated LPS-induced pathological changes and neuronal loss in the hippocampus (P < 0.001) and cerebral cortex (P < 0.01). In conclusion, the neuroprotective effects of crocin against LPS-induced histopathological and behavioral changes could be attributed to its anti-apoptotic, anti-inflammatory, and radical-scavenging activities in the rat brain.