Nobiletin, a polymethoxy flavonoid, exerts anti-allergic effect by suppressing activation of phosphoinositide 3-kinase

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• 作者：Sayo Onishi ; Kosuke Nishi ; Sho Yasunaga ; Ayako Muranaka ; Kazutaka Maeyama ; Ayumu Kadota ; Takuya Sugahara
• 关键词：BMMC ; bone marrow-derived mast cell ; BSA ; bovine serum albumin ; [Ca2+]i ; intracellular Ca2+ concentration ; DMEM ; Dulbecco&rsquo ; s modified Eagle&rsquo ; s medium ; DMSO ; dimethyl sulphoxide ; DNP ; dinitrophenol ; FBS ; fetal bovine serum ; Fc蔚RI ; high-affinity IgE receptor ; HRP ; horseradish peroxidase ; HSA ; human serum albumin ; PBS ; phosphate-buffered saline ; PBS-T ; PBS containing 0.05% Tween 20 ; PCA ; passive cutaneous anaphylaxis ; PI3K ; phosphoinositide 3-kinase ; PLC ; phospholipase C ; SD ; standard de
• 刊名：Journal of Functional Foods
• 出版年：January, 2014
• 年：2014
• 卷：6
• 期：Complete
• 页码：606-614
• 全文大小：776 K

文摘

Nobiletin is a polymethoxy flavonoid present in fruit tissues of citrus species and has been reported to suppress degranulation of RBL-2H3 cells. However, the detailed mechanism is still unknown. In this study the mechanism of suppressive effect of nobiletin on degranulation of RBL-2H3 cells was examined. Nobiletin suppressed degranulation of both RBL-2H3 cells and bone marrow-derived mast cells induced by antigen stimulation. Nobiletin also suppressed degranulation stimulated by the calcium ionophore A23187 and thapsigargin, a specific inhibitor of the Ca²⁺-dependent ATPase. Elevation of intracellular free Ca²⁺ concentration was also suppressed by nobiletin when RBL-2H3 cells were stimulated by either antigen or A23187. Immunoblot analysis revealed that the inhibitory effect results from down-regulated phosphorylation of both phosphatidylinositol 3-kinase (PI3K) and phospholipase C纬1 in the signaling pathways related to degranulation stimulated by antigen. Furthermore, oral administration of nobiletin suppressed vascular permeability in passive cutaneous anaphylaxis model mice. The tendency in all experiments obtained by treating with nobiletin was highly similar to that obtained by wortmannin, a specific inhibitor of PI3K. These findings suggest that nobiletin suppresses Ca²⁺ influx and consequently exerts the anti-allergy activity in a similar way to wortmannin.