title: Suppression of skin inflammation in keratinocytes and acute/chronic disease models by caffeic acid phenethyl ester.
abstract: Skin inflammation plays a central role in the pathophysiology and symptoms of diverse chronic skin diseases including atopic dermatitis (AD). In this study, we examined if caffeic acid phenethyl ester (CAPE), a skin-permeable bioactive compound from propolis, was protective against skin inflammation using in vitro cell system and in vivo animal disease models. CAPE suppressed TNF-α-induced NF-κB activation and expression of inflammatory cytokines in human keratinocytes (HaCaT). The potency and efficacy of CAPE were superior to those of a non-phenethyl derivative, caffeic acid. Consistently, topical treatment of CAPE (0.5 %) attenuated 12-O-tetradecanoylphorbol-13-acetate(TPA)-induced skin inflammation on mouse ear as CAPE reduced ear swelling and histologic inflammation scores. CAPE suppressed increased expression of pro-inflammatory molecules such as TNF-α, cyclooxygenase-2 and inducible NO synthase in TPA-stimulated skin. TPA-induced phosphorylation of IκB and ERK was blocked by CAPE suggesting that protective effects of CAPE on skin inflammation is attributed to inhibition of NF-κB activation. Most importantly, in an oxazolone-induced chronic dermatitis model, topical application of CAPE (0.5 and 1 %) was effective in alleviating AD-like symptoms such as increases of trans-epidermal water loss, skin thickening and serum IgE as well as histologic inflammation assessment. Collectively, our results propose CAPE as a promising candidate for a novel topical drug for skin inflammatory diseases.
authors.affiliation: College of Pharmacy, Ewha Womans University, Seoul, Korea.
authors.forename: Kyung-Min
authors.initials: KM
authors.lastname: Lim
authors.forename: SeungJin
authors.initials: S
authors.lastname: Bae
authors.forename: Jung Eun
authors.initials: JE
authors.lastname: Koo
authors.forename: Eun-Sun
authors.initials: ES
authors.lastname: Kim
authors.forename: Ok-Nam
authors.initials: ON
authors.lastname: Bae
authors.forename: Joo Young
authors.initials: JY
authors.lastname: Lee
mesh_terms: D000208:Acute Disease; D000818:Animals; D002109:Caffeic Acids / Q000008:administration & dosage* / Q000378:metabolism; D002460:Cell Line; D002908:Chronic Disease; D051546:Cyclooxygenase 2 / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D015603:Keratinocytes / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D010081:Oxazolone / Q000378:metabolism; D010626:Phenylethyl Alcohol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism; D011429:Propolis / Q000378:metabolism; D012867:Skin / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014870:Water Loss, Insensible / Q000187:drug effects
chemical_list: D002109:Caffeic Acids; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D010081:Oxazolone; D007073:Immunoglobulin E; D011429:Propolis; D051546:Cyclooxygenase 2; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol; D013755:Tetradecanoylphorbol Acetate