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

  • J Nat Med. 2018 Mar;72(2):464-473. doi: 10.1007/s11418-017-1170-x.
Toshio Morikawa  1  2 ,  Ikuko Hachiman  3 ,  Kiyofumi Ninomiya  3  4 ,  Hiroki Hata  5 ,  Kaoru Sugawara  5 ,  Osamu Muraoka  3  4 ,  Hisashi Matsuda  6
Affiliations
  • 1. Pharmaceutical Research and Technology Institute, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka, 577-8502, Japan. [email protected].
  • 2. Antiaging Center, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka, 577-8502, Japan. [email protected].
  • 3. Pharmaceutical Research and Technology Institute, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka, 577-8502, Japan.
  • 4. Antiaging Center, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka, 577-8502, Japan.
  • 5. Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto, 607-8412, Japan.
  • 6. Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto, 607-8412, Japan. [email protected].
PMID: 29336005 DOI: 10.1007/s11418-017-1170-x
Abstract

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.

Keywords
Degranulation inhibitor; Maceneolignan; Myristica fragrans; Neolignan; Type I allergy.
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