Abstract

Millions of people worldwide are suffering from Alzheimer’s disease (AD) due to the accumulation of senile plaques and neurofibrillary tangles in the brain, which results in neuronal death. Till now, there is no reliable medication. Therefore, prevention and management through phytochemicals offers a more promising strategy for the early onset of disease and management of symptoms. With this dual targeting objective, we herein focus on heterocyclic alkaloids, which have always been a great source for brain-associated diseases. We report isolation and in-vitro evaluation of indoquinoline alkaloid cryptolepine from Sida acuta Burm. f. It is isolated with good purity, with 92.60%. The present study demonstrates that cryptolepine exhibits potent multi-targeted activity for AD. It significantly inhibits acetylcholinesterase, showing 82.2% inhibition at 2.5μM. Furthermore, cryptolepine displayed compelling anti-aggregation and anti-hyperphosphorylation properties. It effectively inhibited amyloid (25-35) neurotoxicity in SHY5Y cell lines, achieving 70.89% protection at 0.5μM. Crucially, it also demonstrated potent inhibition of tau hyperphosphorylation in the N2a cell model, with 71.45% inhibition at a remarkably low concentration of 0.01 μM. Based on its impressive multi-target inhibition profile, cryptolepine represents a compelling lead compound with significant potential for development in Alzheimer's disease prevention and treatment strategies.

Key words: Alzheimer’s disease, Cryptolepine, AChE, Tau, Amyloid.