Unveiling the therapeutic potential of extract and its depsides/depsidones in combatting A42 peptides aggregation and neurotoxicity in Alzheimer's disease.

The development of effective inhibitors that can inhibit amyloid (A) peptides aggregation and promote neurite outgrowth is crucial for the possible treatment of Alzheimer's disease (AD). (Schreb.) Hoffm., a traditional Chinese medicine used in Himalaya region for inflammatory diseases, contains depsides/depsidones (DEPs) such as gyrophoric acid, norstictic acid, and stictic acid known for their anti-cancer and anti-inflammation properties. extracts were analyzed using HPLC to identify DEPs and establish standards. The inhibitory effects of on A42 fibrillization and depolymerization were assessed using various approaches with biophysical and cellular methods. The neuroprotective activity of extracts and its DEPs aganist A-mediated cytotoxicity was also evaluated. Norstictic and stictic acid were found in the water extract, while norstictic, stictic, and gyrophoric acid were detected in the ethanol extract of . Both extracts, and their DEPs effectively inhibited A42 fibrillation and disaggregate mature A42 fibrils. Notably, the ethanol extract showed superior inhibitory effect compared to the water extract, with gyrophoric acid being the most effective DEPs. Additionally, herbal extract-treated A42 aggregation species significantly protected neuronal cells from A42-induced cell damage and promoted neurite outgrowth. This study is the first to investigate the effect of on A42 and neuronal cell in AD. Given that is commonly used in ethnic medicine and food with good safety records, our findings propose that extracts and DEPs have potential as neuroprotective and therapeutic agents for AD patients.