Protective effects of isoquercitrin on streptozotocin-induced neurotoxicity

Alzheimer's disease (AD) is characterized by irreversible and progressive memory loss and has no effective treatment. Recently, many small molecule nature products have been identified with neuroprotective functions and shown beneficial effects to AD patients. In the current study, we thus performed a small scale screening to determine the protective effects of natural compounds on streptozotocin (STZ)-induced neurotoxicity and Alzheimer's disease (AD). We found that a lead flavonoid compound, isoquercitrin (ISO) display the most effective anti-cytotoxic activities via inhibiting STZ-induced apoptosis, mitochondria dysfunction and oxidative stress. Treatment with ISO largely rescues STZ-induced differentiation inhibition and enhances neurite outgrowth of Neuro2a (N2a) cells in vitro. Moreover, oral administration of ISO protects hippocampal neurons from STZ-induced neurotoxicity and significantly improves the cognitive and behavioural impairment in STZ-induced AD rats. In general, our screening identifies ISO as an effective therapeutic candidate against STZ-induced neurotoxicity and AD-like changes.