Gallic acid ameliorates LPS-induced memory decline by modulating NF-κB, TNF-α, and Caspase 3 gene expression and attenuating oxidative stress and neuronal loss in the rat hippocampus.

Abstract

Neuroinflammation and apoptosis play critical roles in the pathogenesis of Alzheimer's disease (AD), which is responsible for most cases of dementia in the elderly people. Gallic acid is a phenolic compound with radical scavenging, anti-inflammatory and anti-apoptotic activities. This study aimed to explore the protective effects of gallic acid on LPS-induced spatial memory impairment and find the underlying mechanisms. Gallic acid was orally administered (100 mg/kg) to male Wistar rats for 12 days. LPS was injected intraperitoneally at a dose of 1 mg/kg on days 8-12. Morris water maze paradigm was used to evaluate spatial learning and memory. The mRNA level of nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α) and Caspase 3, lipid peroxidation and total thiol level was assessed in the rat hippocampus. Neuronal loss and histological changes were also evaluated in the brain. LPS treatment resulted in spatial learning and memory impairment, upregulation of NF-κB, TNF-α, and Caspase 3 mRNA expression, increased lipid peroxidation, decreased total thiol level, and neuronal loss in the hippocampus. Moreover, treatment with gallic acid at a dosage of 100 mg/kg ameliorated memory decline, reduced the mRNA level of NF-κB, TNF-α, and Caspase 3, decreased lipid peroxidation and increased total thiol level in the hippocampus. Gallic acid also prevented LPS-induced neuronal loss and histological changes in the brain. Conclusively, our study demonstrated that gallic acid exerts neuroprotective effect against LPS-induced memory decline in rats. This outcome could be due to anti-inflammatory, antioxidant, and anti-apoptotic activities of gallic acid.