Anti-neuroinflammatory Potential of Dendrobium fimbriatum var. oculatum and Phenanthrene Derivatives in BV2 Microglial Cells

Neuroinflammation is one of the major pathological features of Alzheimer’s disease (AD). Microglial overactivation leads to excessive production of nitric oxide (NO) and other inflammatory mediators, contributing to neuronal damage. Dendrobium fimbriatum var. oculatum, a traditional medicinal herb, has been used to alleviate inflammatory conditions, yet its anti-neuroinflammatory potential remains underexplored. In this study, 90% ethanol extract of D. fimbriatum and its dichloromethane (DCM) fraction significantly inhibited LPS-induced NO production in a dose-dependent manner in BV2 microglial cells. Based on bioactivity-guided isolation, four phenanthrene derivatives were isolated and identified as flavanthridin (1), denthyrsinin (2), lusianthridin (3), and (1R,2R)-1,7-hydroxy-2,8-methoxy-2,3-dihydrophenanthrene (4) from the DCM fraction. Compounds 1, 3, and 4 showed potent effects on NO inhibition at non-cytotoxic concentrations, with corresponding reductions in iNOS expression. These compounds also significantly and dose-dependently inhibited the production of pro-inflammatory cytokines such as IL-6. These results suggest that phenanthrene derivatives from D. fimbriatum exhibit inhibitory activities on neuroinflammation. These findings support their potential as therapeutic agents for preventing or treating AD.