Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, 1, Hoegi, Dongdaemun-gu, Seoul 130-701 Korea; Department of Food and Nutrition, Kyung Hee University, 1, Hoegi, Dongdaemun-gu, Seoul 130-701, Korea.
Int Immunopharmacol. 2013 Nov;17(3):502-7. doi: 10.1016/j.intimp.2013.07.012. Epub 2013 Aug 9.
Nobiletin and tangeretin are polymethoxy flavonoids that are abundantly present in the pericarp of Citrus unshiu (family Rutaceae) and the fruit of Citrus depressa (family Rutaceae). They exhibit various biological activities, including anti-inflammatory and anti-asthmatic effects. To evaluate the anti-allergic effects of nobiletin and tangeretin, we measured their inhibitory effects in histamine- or compound 48/80-induced scratching behavioral mice. Nobiletin and tangeretin potently inhibited scratching behavior, as well as histamine-induced vascular permeability. Furthermore, they inhibited the expression of the allergic cytokines, IL-4 and TNF-α as well as the activation of their transcription factors NF-κB, AP-1 and p38 in histamine-stimulated skin tissues. They also inhibited the expression of IL-4 and TNF-α and the activation of NF-κB and c-jun in PMA-stimulated RBL-2H3 cells. Furthermore, nobiletin and tangeretin inhibited protein kinase C (PKC) activity and the IgE-induced degranulation of RBL-2H3 cells. These agents showed potent anti-histamine effect through the Magnus test when guinea pig ileum was used. Based on these results, nobiletin and tangeretin may ameliorate scratching behavioral reactions by inhibiting the action of histamine as well as the activation of the transcription factors NF-κB and AP-1 via PKC.
川陈皮素和桔皮素是多甲氧基黄酮类化合物，大量存在于橘（芸香科）果皮和椪柑（芸香科）果实中。它们具有多种生物活性，包括抗炎和抗哮喘作用。为了评估川陈皮素和桔皮素的抗过敏作用，我们测量了它们对组胺或化合物 48/80 诱导的搔抓行为小鼠的抑制作用。川陈皮素和桔皮素能强烈抑制搔抓行为以及组胺诱导的血管通透性。此外，它们还抑制了过敏细胞因子 IL-4 和 TNF-α的表达以及组胺刺激皮肤组织中 NF-κB、AP-1 和 p38 的转录因子的激活。它们还抑制了 PMA 刺激的 RBL-2H3 细胞中 IL-4 和 TNF-α的表达以及 NF-κB 和 c-jun 的激活。此外，川陈皮素和桔皮素抑制蛋白激酶 C（PKC）活性和 IgE 诱导的 RBL-2H3 细胞脱颗粒。当使用豚鼠回肠时，这些药物在 Magnus 试验中表现出强烈的抗组胺作用。基于这些结果，川陈皮素和桔皮素可能通过 PKC 抑制组胺的作用以及 NF-κB 和 AP-1 转录因子的激活来改善搔抓行为反应。
