Anti-Inflammatory Phenolic Metabolites from the Edible Fungus Phellinus baumii in LPS-Stimulated RAW264.7 Cells

Abstract

The edible fungus <i>Phellinus baumii</i> Pilat (Hymenochaetaceae) has been used in Korean traditional medicines for strengthening health and prolonging life. An extract of the fruiting bodies of <i>P. baumii</i> was subjected to bioassay-guided fractionation based on its anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The resulting fractions were chemically investigated, leading to isolation of three phenolic compounds (<b>1</b>-<b>3</b>), a sesquiterpene (<b>4</b>), two steroids (<b>5</b>-<b>6</b>), a fatty acid (<b>7</b>), and a cerebroside (<b>8</b>). Spectroscopic analyses including 1D and 2D NMR spectroscopy and LC/MS were used to determine their chemical structures. Compounds <b>2</b>, <b>4</b>, <b>5</b>, <b>7</b> and <b>8</b> were identified in <i>P. baumii</i> for the first time. Since all compounds were isolated from active fractions with anti-inflammatory activity, their ability to inhibit LPS-stimulated nitric oxide (NO) production in RAW264.7 cells were evaluated in vitro. Compounds <b>1</b>, <b>2</b>, <b>3</b>, <b>5</b> and <b>7</b> inhibited LPS-stimulated NO production, and compounds <b>1</b>-<b>3</b> had IC₅₀ values <10 μM. Treatment of LPS-stimulated RAW264.7 cells with compounds <b>1</b>-<b>3</b> inhibited phosphorylation of IKKα and IκBα. In addition, treatment of compounds <b>1</b>-<b>3</b> reduced LPS-induced increases of nuclear factor-kappa B (NF-κB) p65, iNOS and COX-2 protein expressions. Collectively, compounds <b>1</b>-<b>3</b> inhibited NF-κB-dependent inflammation in RAW264.7 cells. Thus, <i>P. baumii</i> is a potential source of natural anti-inflammatory agents, and active compounds <b>1</b>-<b>3</b> could be promising lead compounds for the development of novel anti-inflammatory agents.