Guo_2024_J.Chem.Neuroanat__102404

Alzheimer's disease (AD) is a degenerative neurological disorder with unclear pathogenesis. Single-target drugs have very limited efficacy in treating AD, but synthetic multi-target drugs have poor efficacy and safety. Therefore, finding suitable natural multi-target drugs against AD is of great interest for research studies. We chose two flavonols, myricetin and morin, for the relevant study. In this study, we used microinjection of Abeta(1-42) oligomers into the CA1 region of rat hippocampus, combined with gavage of Aluminum chloride hexahydrate (AlCl(3).6H(2)O) solution to establish AD rat models, and myricetin and morin were selected as intervening drugs to explore the protective effects against neurological impairment. Experimental results showed that myricetin or morin could reduce the production of Abeta, Tubulin-associated unit (Tau), and Phosphorylated tubulin-associated unit (p-Tau), down-regulate the expression of relevant inflammatory factors, reduce hippocampal cell apoptosis in rats. There was a significant increase in the activity of adenosine triphosphatase, catalase, total superoxide dismutase, and the content of glutathione in the brain tissue. However, the content of malondialdehyde, inducible nitric oxide synthase, and the activity of acetylcholinesterase were decreased in the brain tissue. These two flavonols can regulate the imbalance of monoamine and amino acid neurotransmitter levels. In conclusion, Myricetin or morin can effectively improve learning and memory dysfunction in AD rats induced by Abeta(1-42)/Al(3+) through anti-oxidative stress and anti-apoptotic features.