Neolignans from the Arils of <i>Myristica fragrans</i> as Potent Antagonists of CC Chemokine Receptor 3

CC chemokine receptor 3 (CCR3) is expressed selectively in eosinophils, basophils, and some Th2 cells and plays a major role in allergic diseases. A methanol extract from the arils of <i>Myristica fragrans</i> inhibited CC chemokine ligand 11-induced chemotaxis in CCR3-expressing L1.2 cells at 100 μg/mL. From this extract, eight new neolignans, maceneolignans A–H (<b>1</b>–<b>8</b>), were isolated, and their stereostructures were elucidated from their spectroscopic values and chemical properties. Of those constituents, compounds <b>1</b>, <b>4</b>, <b>6</b>, and <b>8</b> and (+)-<i>erythro</i>-(7<i>S</i>,8<i>R</i>)-Δ^8′-7-hydroxy-3,4-methylenedioxy-3′,5′-dimethoxy-8-<i>O</i>-4′-neolignan (<b>11</b>), (−)-(8<i>R</i>)-Δ^8′-3,4-methylenedioxy-3′,5′-dimethoxy-8-<i>O</i>-4′-neolignan (<b>17</b>), (+)-licarin A (<b>20</b>), nectandrin B (<b>25</b>), verrucosin (<b>26</b>), and myristicin (<b>27</b>) inhibited CCR3-mediated chemotaxis at a concentration of 1 μM. Among them, <b>1</b> (EC₅₀ 1.6 μM), <b>6</b> (1.5 μM), and <b>8</b> (1.4 μM) showed relatively strong activities, which were comparable to that of a synthetic CCR3 selective antagonist, SB328437 (0.78 μM)

Neolignans from the Arils of <i>Myristica fragrans</i> as Potent Antagonists of CC Chemokine Receptor 3

CC chemokine receptor 3 (CCR3) is expressed selectively in eosinophils, basophils, and some Th2 cells and plays a major role in allergic diseases. A methanol extract from the arils of <i>Myristica fragrans</i> inhibited CC chemokine ligand 11-induced chemotaxis in CCR3-expressing L1.2 cells at 100 μg/mL. From this extract, eight new neolignans, maceneolignans A–H (<b>1</b>–<b>8</b>), were isolated, and their stereostructures were elucidated from their spectroscopic values and chemical properties. Of those constituents, compounds <b>1</b>, <b>4</b>, <b>6</b>, and <b>8</b> and (+)-<i>erythro</i>-(7<i>S</i>,8<i>R</i>)-Δ^8′-7-hydroxy-3,4-methylenedioxy-3′,5′-dimethoxy-8-<i>O</i>-4′-neolignan (<b>11</b>), (−)-(8<i>R</i>)-Δ^8′-3,4-methylenedioxy-3′,5′-dimethoxy-8-<i>O</i>-4′-neolignan (<b>17</b>), (+)-licarin A (<b>20</b>), nectandrin B (<b>25</b>), verrucosin (<b>26</b>), and myristicin (<b>27</b>) inhibited CCR3-mediated chemotaxis at a concentration of 1 μM. Among them, <b>1</b> (EC₅₀ 1.6 μM), <b>6</b> (1.5 μM), and <b>8</b> (1.4 μM) showed relatively strong activities, which were comparable to that of a synthetic CCR3 selective antagonist, SB328437 (0.78 μM)