Abstract Title:

Nobiletin and tangeretin ameliorate scratching behavior in mice by inhibiting the action of histamine and the activation of NF-κB, AP-1 and p38.

Abstract Source:

Int Immunopharmacol. 2013 Nov ;17(3):502-7. Epub 2013 Aug 9. PMID: 23938254

Abstract Author(s):

Se-Eun Jang, Kwon-Ryeol Ryu, Sung-Hwan Park, Suna Chung, Yuto Teruya, Myung Joo Han, Je-Tae Woo, Dong-Hyun Kim

Article Affiliation:

Se-Eun Jang


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 proteinkinase 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.

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