Rhododendrin ameliorates skin inflammation through inhibition of NF-¦ÊB, MAPK, and PI3K/Akt signaling

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• 作者：Yoon-Jae Jeon ; Byung-Hak Kim ; Sunghwan Kim ; Ikhoon Oh ; Sooryun Lee ; Jongheon Shin ; Tae-Yoon Kim
• 关键词：Rhododendrin ; Keratinocyte ; Inflammatory skin disease ; Anti-inflammatory activity
• 刊名：European Journal of Pharmacology
• 出版年：2013
• 出版时间：15 August, 2013
• 年：2013
• 卷：714
• 期：1-3
• 页码：7-14
• 全文大小：1572 K

文摘

A wide range of active compounds isolated from nature is used in clinical applications and as a source of lead compounds for drug development. Rhododendron brachycarpum has been used as an oriental herbal medicine for skin inflammatory diseases. In this study, we isolated rhododendrin from Rhododendron brachycarpum leaves and investigated its molecular mechanisms for anti-inflammatory effect. Rhododendrin showed intracellular reactive oxygen species scavenging activity and suppressed nuclear translocation of nuclear factor-¦ÊB (NF-¦ÊB) by inhibiting phosphorylation of NF-¦ÊB, inhibitor of NF-¦ÊB(I¦ÊB¦Á), and I¦ÊB¦Á kinase(IKK¦Á/¦Â). Furthermore, rhododendrin inhibited mitogen-activated protein kinases (MAPKs), including ERK1/2, p38, and decreased c-Jun N-terminal kinase (JNK) and phosphoinositide 3-kinase (PI3K)/Akt signaling. As a result, rhododendrin reduced expression of pro-inflammatory mediators, such as cyclooxygenase-2 (COX-2), intracellular adhesion molecule-1 (ICAM-1), interleukin-1¦Á (IL-1¦Á), IL-1¦Â, IL-6, IL-8, tumor necrosis factor-¦Á (TNF-¦Á), interferon-¦Ã (IFN-¦Ã), chemokine (C-X-C) motif ligand 1 (CXCL1), and chemokine (C-C motif) ligand 17 (CCL17) in TNF-¦Á/IFN-¦Ã-stimulated keratinocytes. Notably, we demonstrated that topically applied rhododendrin alleviated skin inflammation in trinitrochlorobenzene (TNCB)-treated mouse ear skins. Collectively, these results indicate that rhododendrin is a biologically active compound that exhibits anti-inflammatory activity and is a promising candidate molecule to treat inflammatory skin diseases, such as psoriasis.