The chalcone derivative Chana 1 protects against amyloid beta peptide-induced oxidative stress and cognitive impairment

초록

Alzheimer's disease (AD) is the most common neurodegenerative disease to cause dementia in the elderly. Amyloid beta (A beta)-peptide induced oxidative stress causes the initiation and progression of AD. Recently, new chalcone derivatives termed the Chana series were synthesized. Among them, Chana 1 showed high free radical scavenging activity (72.5%), as measured by a DPPH (1,1-diphenyl-2-picryl-hydrazyl) assay. In this study, we investigated the effect of Chana 1 against A beta-induced cytotoxicity and cognitive deficits. Additionally, we sought to estimate the lethal dose, 50% (LD50) of Chana I in mice using an acute oral toxicity test. We found that Chana 1 significantly protected against A beta-induced neuronal cell death in PC12 cells. Oral administration of Chana I at a dose of 50 mg/kg body weight/day significantly improved A beta-induced learning and memory impairment in mice, as measured in Y-maze and passive avoidance tests. In acute toxicity tests, the LD50 in mice was determined to be 520.44 mg/kg body weight. The data are valuable for future studies and suggest that Chana 1 has therapeutic potential for the management of neurodegenerative disease.

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