Macrocyclic <i>bis</i>-quinolizidine alkaloids from <i>Xestospongia muta</i>

<p>A new stereoisomer <i>Meso</i>-araguspongine C together with nine reported macrocyclic <i>bis</i>-quinolizidine alkaloids araguspongines A, C, E, L, N−P, petrosin, and petrosin A were isolated from marine sponge <i>Xestospongia muta</i>. Stereochemistry of <i>meso</i>-araguspongine C (<b>2</b>) and araguspongines N-P (<b>3</b>−<b>5</b>) were established by their NMR data and conformational analyses. Both araguspongine C (<b>1</b>) and <i>meso</i>-araguspongine C (<b>2</b>) exhibited great cytotoxic activity towards HepG-2, HL-60, LU-1, MCF-7, and SK-Mel-2 human cancer cells (IC₅₀ in the range of 0.43–1.02 μM). At a concentration of 20 μM, isolated compounds (<b>1</b>−<b>10</b>) also showed modest inhibitory effects (from 7.6 to 40.8%) on the NO production in LPS activated RAW264.7 macrophages.</p

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 PGE₂ concentrations were determined using Griess reaction and PGE₂ 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 PGE₂ production in LPS-stimulated BV2 cells, with IC₅₀ 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