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 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)-Δ(8')-7-hydroxy-3,4-methylenedioxy-3',5'-dimethoxy-8-O-4'-neolignan (11), (-)-(8R)-Δ(8')-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).

Degranulation inhibitors from the arils of Myristica fragrans in antigen-stimulated rat basophilic leukemia cells.

A methanol extract of mace, the aril of Myristica fragrans (Myristicaceae), was found to inhibit the release of ß-hexosaminidase, a marker of antigen-IgE-stimulated degranulation in rat basophilic leukemia cells (RBL-2H3, IC50 = 45.7 µg/ml). From the extract, three new 8-O-4' type neolignans, maceneolignans I-K (1-3), were isolated, and the stereostructures of 1-3 were elucidated based on spectroscopic and chemical evidence. Among the isolates, maceneolignans A (5), D (6), and H (8), (-)-(8R)-∆8'-4-hydroxy-3,3',5'-trimethoxy-8-O-4'-neolignan (13), (-)-(8R)-∆8'-3,4,5,3',5'-pentamethoxy-8-O-4'-neolignan (14), (-)-erythro-(7R,8S)-∆8'-7-acetoxy-3,4-methylenedioxy-3',5'-dimethoxy-8-O-4'-neolignan (17), (+)-licarin A (20), nectandrin B (24), verrucosin (25), and malabaricone C (29) were investigated as possible degranulation inhibitors (IC50 = 20.7-63.7 µM). These inhibitory activities were more potent than those of the antiallergic agents tranilast (282 µM) and ketotifen fumalate (158 µM). Compounds 5, 25, and 29 also inhibited antigen-stimulated tumor necrosis factor-α production (IC50 = 39.5-51.2 µM), an important process in the late phase of type I allergic reactions.