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Journal of Natural Medicines

, Volume 72, Issue 2, pp 464–473 | Cite as

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

  • Toshio MorikawaEmail author
  • Ikuko Hachiman
  • Kiyofumi Ninomiya
  • Hiroki Hata
  • Kaoru Sugawara
  • Osamu Muraoka
  • Hisashi MatsudaEmail author
Original Paper

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 (13), were isolated, and the stereostructures of 13 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

Myristica fragrans Degranulation inhibitor Type I allergy Neolignan Maceneolignan 

Notes

Acknowledgements

This work was supported by the MEXT-Supported Program for the Strategic Research Foundation at Private Universities, 2014–2018, Japan (S1411037, T. M.), as well as the JSPS KAKENHI, Japan, grant nos. 15K08008 (T. M.), 15K08009 (K. N.), and 16K08313 (O. M.).

Supplementary material

11418_2017_1170_MOESM1_ESM.doc (72 kb)
Supplementary material 1 (DOC 72 kb)

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Copyright information

© The Japanese Society of Pharmacognosy and Springer Japan KK, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Pharmaceutical Research and Technology InstituteKindai UniversityOsakaJapan
  2. 2.Antiaging Center, Kindai UniversityOsakaJapan
  3. 3.Kyoto Pharmaceutical UniversityKyotoJapan

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