title: Rhododendrin ameliorates skin inflammation through inhibition of NF-κB, MAPK, and PI3K/Akt signaling.
abstract: 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-κB (NF-κB) by inhibiting phosphorylation of NF-κB, inhibitor of NF-κB(IκBα), and IκBα kinase(IKKα/β). 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-1α (IL-1α), IL-1β, IL-6, IL-8, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), chemokine (C-X-C) motif ligand 1 (CXCL1), and chemokine (C-C motif) ligand 17 (CCL17) in TNF-α/IFN-γ-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.
authors.affiliation: Department of Dermatology, College of Medicine, The Catholic University of Korea, Seoul 137-040, South Korea.
authors.forename: Yoon-Jae
authors.initials: YJ
authors.lastname: Jeon
authors.forename: Byung-Hak
authors.initials: BH
authors.lastname: Kim
authors.forename: Sunghwan
authors.initials: S
authors.lastname: Kim
authors.forename: Ikhoon
authors.initials: I
authors.lastname: Oh
authors.forename: Sooryun
authors.initials: S
authors.lastname: Lee
authors.forename: Jongheon
authors.initials: J
authors.lastname: Shin
authors.forename: Tae-Yoon
authors.initials: TY
authors.lastname: Kim
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D002460:Cell Line; D006027:Glycosides / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D010636:Phenols / Q000494:pharmacology* / Q000627:therapeutic use; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D018515:Plant Leaves / Q000737:chemistry; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D029793:Rhododendron / Q000737:chemistry; D012867:Skin / Q000187:drug effects* / Q000473:pathology*
chemical_list: C580978:3'-keto rhododendrin; D000893:Anti-Inflammatory Agents; D006027:Glycosides; D016328:NF-kappa B; D010636:Phenols; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: Anti-inflammatory activity; Inflammatory skin disease; Keratinocyte; Rhododendrin