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Neolignans from the Arils of Myristica fragrans as Potent Antagonists of CC Chemokine Receptor 3

Morikawa, Toshio, Hachiman, Ikuko, Matsuo, Kazuhiko, Nishida, Eriko, Ninomiya, Kiyofumi, Hayakawa, Takao, Yoshie, Osamu, Muraoka, Osamu, Nakayama, Takashi
Journal of natural products 2016 v.79 no.8 pp. 2005-2013
CCR3 receptor, Myristica fragrans, antagonists, aril, basophils, beta chemokines, chemotaxis, eosinophils, ligands, lignans, median effective concentration, methanol, physicochemical properties, spectroscopy
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 Myristica fragrans 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 (1–8), were isolated, and their stereostructures were elucidated from their spectroscopic values and chemical properties. Of those constituents, compounds 1, 4, 6, and 8 and (+)-erythro-(7S,8R)-Δ⁸′-7-hydroxy-3,4-methylenedioxy-3′,5′-dimethoxy-8-O-4′-neolignan (11), (−)-(8R)-Δ⁸′-3,4-methylenedioxy-3′,5′-dimethoxy-8-O-4′-neolignan (17), (+)-licarin A (20), nectandrin B (25), verrucosin (26), and myristicin (27) inhibited CCR3-mediated chemotaxis at a concentration of 1 μM. Among them, 1 (EC₅₀ 1.6 μM), 6 (1.5 μM), and 8 (1.4 μM) showed relatively strong activities, which were comparable to that of a synthetic CCR3 selective antagonist, SB328437 (0.78 μM).