Anti-inflammatory coumarins from <i>Paramignya trimera</i>

<p><b>Context:</b><i>Paramignya trimera</i> (Oliv.) Burkill (Rutaceae) has been used to treat liver diseases and cancer. However, the anti-inflammatory effects of this medicinal plant and its components have not been elucidated.</p> <p><b>Objective:</b> This study investigated chemical constituents of the <i>P. trimera</i> stems and evaluated anti-inflammatory effects of isolated compounds.</p> <p><b>Materials and methods:</b> Cytotoxicity of isolated compounds (5–40 μM) toward BV2 cells was tested using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) for 24 h. Inhibitory effects of isolated compounds (5-40 μM) on nitrite and PGE<sub>2</sub> concentrations were determined using Griess reaction and PGE<sub>2</sub> ELISA kit, respectively (pretreated with the compounds for 3 h and then stimulated for 18 h with LPS). Inhibitory effects of compounds (5-40 μM) on iNOS and COX-2 protein expression were evaluated by Western blot analysis (pretreated with the compounds for 3 h and then stimulated for 24 h with LPS).</p> <p><b>Results:</b> Seven coumarins were isolated and identified as: ostruthin (<b>1</b>), ninhvanin (<b>2</b>), 8-geranyl-7-hydroxycoumarin (<b>3</b>), 6-(6′,7′-dihydroxy-3′,7′-dimethylocta-2′-enyl)-7-hydroxycoumarin (<b>4</b>), 6-(7-hydroperoxy-3,7-dimethylocta-2,5-dienyl)-7-hydroxycoumarin (<b>5</b>), 6-(2-hydroxyethyl)-2,2-dimethyl-2<i>H</i>-1-benzopyran (<b>6</b>), and luvangetin (<b>7</b>). Compounds <b>1</b>–<b>4</b> and <b>7</b> inhibited NO and PGE<sub>2</sub> production in LPS-stimulated BV2 cells, with IC<sub>50</sub> values ranging from 9.8 to 46.8 and from 9.4 to 52.8 μM, respectively. Ostruthin (<b>1</b>) and ninhvanin (<b>2</b>) were shown to suppress LPS-induced iNOS and COX-2 protein expression.</p> <p><b>Discussion and conclusion:</b> The present study provides a scientific rationale for the use of <i>P. trimera</i> in the prevention and treatment of neuroinflammatory diseases. Ostruthin and ninhvanin might have potential therapeutic effects and should be considered for further development as new anti-neuroinflammatory agents.</p>