Inhibitory effects of an ellagic acid glucoside, okicamelliaside, on antigen-mediated degranulation in rat basophilic leukemia RBL-2H3 cells and passive cutaneous anaphylaxis reaction in mice

Degranulation inhibitors in plants are widely used for prevention and treatment of immediate-type allergy. We previously isolated a new ellagic acid glucoside, okicamelliaside (OCS), from Camellia japonica leaves for use as a potent degranulation inhibitor. Crude extracts from leaves also suppressed...

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Published in:	International immunopharmacology Vol. 12; no. 4; pp. 675 - 681
Main Authors:	Kuba-Miyara, Megumi, Agarie, Kengo, Sakima, Rina, Imamura, Shihoko, Tsuha, Kazuyo, Yasumoto, Takeshi, Gima, Shinichi, Matsuzaki, Goro, Ikehara, Tsuyoshi
Format:	Journal Article
Language:	English
Published:	Kidlington Elsevier B.V 01-04-2012 Elsevier
Subjects:	Allergy Animals Anti-Allergic Agents - pharmacology Antigens - immunology Biological and medical sciences Calcium - immunology Cell Degranulation - drug effects Cell Line, Tumor Cyclooxygenase 2 - genetics Cytokines - genetics Degranulation Dinitrobenzenes - immunology Down-Regulation Ellagic Acid - analogs & derivatives Ellagic Acid - pharmacology Ellagic acid glucoside Gene Expression Regulation - drug effects Glucosides - pharmacology Hematologic and hematopoietic diseases Immunoglobulin E - immunology Intracellular Signaling Peptides and Proteins - immunology Leukemia, Basophilic, Acute - immunology Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Male Medical sciences Mice Mice, Inbred ICR Okicamelliaside Oligonucleotide Array Sequence Analysis Passive cutaneous anaphylaxis Passive Cutaneous Anaphylaxis - drug effects Passive Cutaneous Anaphylaxis - immunology Pharmacology. Drug treatments Protein-Tyrosine Kinases - immunology Rats RBL-2H3 Syk Kinase Degranulation Allergy Passive cutaneous anaphylaxis Okicamelliaside Ellagic acid glucoside RBL-2H3 Antineoplastic agent Hemostatic Rat Granulocyte Myeloproliferative syndrome Ellagic acid Tumor cell Immunopathology Antimutagen Basophilic leukemia Rodentia Glucoside Malignant hemopathy Antigen Vertebrata Mammalia Mouse Animal Cancer
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Summary:	Degranulation inhibitors in plants are widely used for prevention and treatment of immediate-type allergy. We previously isolated a new ellagic acid glucoside, okicamelliaside (OCS), from Camellia japonica leaves for use as a potent degranulation inhibitor. Crude extracts from leaves also suppressed allergic conjunctivitis in rats. In this study, we evaluated the in vivo effect of OCS using a pure sample and performed in vitro experiments to elucidate the mechanism underlying the extraordinary high potency of OCS and its aglycon. The IC50 values for degranulation of rat basophilic leukemia cells (RBL-2H3) were 14nM for OCS and 3μM for aglycon, indicating that the two compounds were approximately 2 to 3 orders of magnitude more potent than the anti-allergic drugs ketotifen fumarate, DSCG, and tranilast (0.17, 3, and >0.3mM, respectively). Antigen-induced calcium ion (Ca2+) elevation was significantly inhibited by OCS and aglycon at all concentrations tested (p<0.05). Upstream of the Ca2+ elevation in the principle signaling pathway, phosphorylation of Syk (Tyr525/526) and PLCγ-1 (Tyr783 and Ser1248) were inhibited by OCS and aglycon. In DNA microarray-screening test, OCS inhibited expression of proinflammatory cytokines [interleukin (IL)-4 and IL-13], cytokine-producing signaling factors, and prostaglandin-endoperoxidase 2, indicating that OCS broadly inhibits allergic inflammation. During passive cutaneous anaphylaxis in mice, OCS significantly inhibited vascular hyperpermeability by two administration routes: a single intraperitoneal injection at 10mg/kg and per os at 5mg/kg for 7days (p<0.05). These results suggest the potential for OCS to alleviate symptoms of immediate-type allergy. ► Okicamelliaside (OCS) is a degranulation inhibitor isolated from Camellia japonica. ► Preventive oral administration of OCS suppressed immediate-type allergy in mice. ► OCS and its aglycon inhibited Syk-phosphorylation and calcium increase in mast cells. ► OCS also suppressed the expression of proinflammatory cytokines and cycloxygenase 2. ► OCS may be a valuable source for functional foods and lead compounds in medicine.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1567-5769 1878-1705
DOI:	10.1016/j.intimp.2012.01.013