Anti-Neuroinflammatory Eremophilane Sesquiterpenoids from Marine-Derived Fungus Phoma sp. DXH009

Three new eremophilane sesquiterpenoids (1–3), together with six known analogues, were isolated from the marine-derived fungus Phoma sp. DXH009. Their structures were elucidated through detailed NMR and MS spectroscopic analysis, and the absolute configurations of 1–4 were determined by conformational analysis and quantum chemical TDDFT-ECD calculation. Their anti-neuroinflammatory activities were evaluated using the lipopolysaccharide (LPS)-induced BV2 microglial cells. The results indicated that compound 5 (dihydrosporogen AO-1) exhibited significant inhibitory effects on the production of nitric oxide (NO) levels (EC50 = 3.11 μM) with less cytotoxicity, leading to a reversal effect in inducing microphage polarization in LPS-treated BV2 microglial cells. These were correlated with suppressions of the canonical NF-κB pathway as well as the expression levels of key neuroinflammatory markers, including COX2, TNF-α, IL-6, and IL-1β. Correspondingly, treating 5 in LPS-induced mice efficiently ameliorated neuroinflammation in the tissues of the cortex and hippocampus. These findings suggest that eremophilane sesquiterpenoid 5 could be a potential candidate for the development of anti-neuroinflammatory drugs.