Isorhapontigenin prevents β-amyloid-associated cognitive impairments through activation of the PI3K/AKT/GSK-3β pathway

Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disease that is the most common cause of dementia in the elderly. A beta 1-42 is significantly associated with memory deficits and it can increase the level of acetylcholine, promote the activity of acetylcholinesterase (AChE), and cause cognitive dysfunction. Isorhapontigenin (ISO) is a stilbene derivative that has antioxidant, anti-tumor, and anti-inflammatory effects. However, it is still unclear whether ISO can affect beta-amyloid-associated cognitive impairments. In this study, we found that ISO improved cognitive dysfunction induced by A beta 1-42 in rats. It inhibited the A beta-induced activation of M1 microglia and reduced the release of inflammatory cytokines. It alleviated amyloid beta-induced oxidative stress and led to an overall improvement in AD symptoms. Cellularly, we found that ISO alleviated A beta-induced inflammation and oxidative stress by activating the PI3K/AKT/GSK-3 beta pathway and ultimately improved cognitive dysfunction in AD rats.