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 β-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.