Anti-Neuroinflammatory Effects of Compounds Isolated from Quercus acuta Thunb. Fruits via NF-κB Signaling Inhibition in BV2 Microglia

Aging is a major risk factor for neurodegenerative diseases in which microglia-driven neuroinflammation plays a critical role in neuronal dysfunction and disease progression. In this study, we sought to isolate bioactive metabolites from <i>Quercus acuta</i> Thunb. fruits-which have traditionally been used in oriental medicine but are chemically and pharmacologically underexplored-and evaluate their anti-neuroinflammatory potential. A total of 14 compounds were isolated from an ethanol extract of <i>Q. acuta</i> fruits through bioactivity-guided isolation, and their structures were identified by NMR spectroscopy. Notably, this study is the first to demonstrate that 3,5,7,2',6'-pentahydroxyflavanone and 2,5-dihydroxybenzaldehyde, among the compounds isolated from <i>Q. acuta</i> fruits, exhibit significant anti-neuroinflammatory activities. Both compounds reduced the production of proinflammatory mediators, including IL-6 and TNF-α, while inhibiting the expression of iNOS and COX-2. Moreover, they significantly inhibited NF-κB activation in lipopolysaccharide-induced BV2 microglia. Collectively, these findings indicate that <i>Q. acuta</i> fruits contain bioactive constituents with previously unreported anti-neuroinflammatory properties, supporting their potential as a natural source for the development of therapeutic agents targeting age-related neuroinflammation.