title: A flavanone derivative from the Asian medicinal herb (Perilla frutescens) potently suppresses IgE-mediated immediate hypersensitivity reactions.
abstract: Perilla frutescens is a dietary leafy herb consumed as a traditional Japanese condiment as well as used for Chinese medicine with anti-inflammatory activity. Here we report a hitherto-unrecognized P. frutescens phytochemical that potently suppresses IgE-mediated type I hypersensitivity reactions. Structural analysis reveals that the purified anti-allergic compound (Perilla-derived methoxyflavanone, PDMF) is identified as 8-hydroxy-5,7-dimethoxyflavanone. PDMF significantly inhibits IgE-mediated histamine release from RBL-2H3 rat basophilic leukemia cells as compared with those seen in known P. frutescens-derived anti-inflammatory polyphenols. We also show that oral administration of PDMF not only suppresses passive cutaneous anaphylaxis, but also prevents allergic rhinitis-like nasal symptoms in a murine model of Japanese cedar pollinosis. Mechanistically, PDMF negatively regulates Akt phosphorylation and intracellular Ca2+influx, both of which are essential for mast cell secretory granule translocation and its exocytosis upon high-affinity IgE receptor (FcεRI) cross-linking. These results represent PDMF as a new potent anti-allergic phytochemical useful for prevention of IgE-driven hypersensitivity reactions.
authors.affiliation: Hiroshima Research Center for Healthy Aging (HiHA), Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima, Japan.
authors.forename: Rikiya
authors.initials: R
authors.lastname: Kamei
authors.affiliation: Hiroshima Research Center for Healthy Aging (HiHA), Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Fujimura
authors.affiliation: Hiroshima Research Center for Healthy Aging (HiHA), Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Matsuda
authors.affiliation: Hiroshima Research Center for Healthy Aging (HiHA), Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Kakihara
authors.affiliation: Mishima Foods Co. Ltd., Hiroshima, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Hirakawa
authors.affiliation: Mishima Foods Co. Ltd., Hiroshima, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Baba
authors.affiliation: Hiroshima Research Center for Healthy Aging (HiHA), Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima, Japan; Faculty of Life Sciences, Hiroshima Institute of Technology, Hiroshima, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Ono
authors.affiliation: Hiroshima Research Center for Healthy Aging (HiHA), Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Arakawa
authors.affiliation: Hiroshima Research Center for Healthy Aging (HiHA), Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima, Japan. Electronic address: skawa@hiroshima-u.ac.jp.
authors.forename: Seiji
authors.initials: S
authors.lastname: Kawamoto
mesh_terms: D000818:Animals; D018926:Anti-Allergic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D045744:Cell Line, Tumor; D032485:Cryptomeria / Q000276:immunology; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D005260:Female; D044950:Flavanones / Q000008:administration & dosage* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects; D006969:Hypersensitivity, Immediate / Q000517:prevention & control*; D007073:Immunoglobulin E / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects; D031344:Perilla frutescens / Q000737:chemistry*; D010946:Plants, Medicinal / Q000737:chemistry*; D051381:Rats; D017455:Receptors, IgE / Q000276:immunology; D006255:Rhinitis, Allergic, Seasonal / Q000188:drug therapy* / Q000517:prevention & control
chemical_list: C000619507:8-hydroxy-5,7-dimethoxyflavanone; D018926:Anti-Allergic Agents; D004365:Drugs, Chinese Herbal; D044950:Flavanones; D017455:Receptors, IgE; D007073:Immunoglobulin E
keywords: Allergy; IgE; Mast cells; Perilla frutescens; Polyphenols