Neolignans from the Arils of Myristica fragrans 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 Myristica fragrans inhibited CC chemokine ligand 11-induced chemotaxis in CCR3-expressing L1.2 cells at 100 mu g/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)-Delta(8)'-7-hydroxy-3,4-methylenedioxy-3,5'-dimethoxy-8-O-4'-neolignan (11), (-)- (8R)-Delta(8,)-3,4-methylene dioxy-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 mu M. Among them, 1 (EC50 1.6 mu M), 6 (1.5 mu M), and 8 (1.4 mu M) showed relatively strong activities, which were comparable to that of a synthetic CCR3 selective antagonist, SB328437 (0.78 mu M).