AUTHOR=Yang Meixia , Yan Caishan , Ospondpant Dusadee , Wang Lisong , Lin Shengying , Tang Wai Lun , Dong Tina Tingxia , Tong Penger , Xu Qin , Tsim Karl Wah Keung 

TITLE=Unveiling the therapeutic potential of Lobaria extract and its depsides/depsidones in combatting Aβ42 peptides aggregation and neurotoxicity in Alzheimer’s disease

JOURNAL=Frontiers in Pharmacology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1426569

DOI=10.3389/fphar.2024.1426569

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> The development of effective inhibitors that can inhibit amyloid <italic>β</italic> (A<italic>β</italic>) peptides aggregation and promote neurite outgrowth is crucial for the possible treatment of Alzheimer’s disease (AD). <italic>Lobaria</italic> (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.</p><p><bold>Methods:</bold><italic>Lobaria</italic> extracts were analyzed using HPLC to identify DEPs and establish standards. The inhibitory effects of <italic>Lobaria</italic> on A<italic>β</italic>42 fibrillization and depolymerization were assessed using various approaches with biophysical and cellular methods. The neuroprotective activity of <italic>Lobaria</italic> extracts and its DEPs aganist A<italic>β</italic>-mediated cytotoxicity was also evaluated.</p><p><bold>Results:</bold> Norstictic and stictic acid were found in the water extract, while norstictic, stictic, and gyrophoric acid were detected in the ethanol extract of <italic>Lobaria</italic>. Both extracts, and their DEPs effectively inhibited A<italic>β</italic>42 fibrillation and disaggregate mature A<italic>β</italic>42 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 A<italic>β</italic>42 aggregation species significantly protected neuronal cells from A<italic>β</italic>42-induced cell damage and promoted neurite outgrowth.</p><p><bold>Conclusion:</bold> This study is the first to investigate the effect of <italic>Lobaria</italic> on A<italic>β</italic>42 and neuronal cell in AD. Given that <italic>Lobaria</italic> is commonly used in ethnic medicine and food with good safety records, our findings propose that <italic>Lobaria</italic> extracts and DEPs have potential as neuroprotective and therapeutic agents for AD patients.</p>