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: Kyung-Min Lim, SeungJin Bae, Jung Eun Koo, Eun-Sun Kim, Ok-Nam Bae, Joo Young Lee
• Journal: Archives of dermatological research (Arch Dermatol Res) Vol. 307 Issue 3 Pg. 219-27 (Apr 2015) ISSN: 1432-069X [Electronic] Germany
• PMID: 25501505 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Caffeic Acids
• NF-kappa B
• Tumor Necrosis Factor-alpha
• Oxazolone
• Immunoglobulin E
• Propolis
• Cyclooxygenase 2
• caffeic acid phenethyl ester
• Phenylethyl Alcohol
• Tetradecanoylphorbol Acetate

Topics

• Acute Disease
• Animals
• Caffeic Acids (administration & dosage, metabolism)
• Cell Line
• Chronic Disease
• Cyclooxygenase 2 (metabolism)
• Dermatitis, Atopic (drug therapy, immunology)
• Disease Models, Animal
• Humans
• Immunoglobulin E (blood)
• Inflammation (chemically induced, drug therapy, immunology)
• Keratinocytes (drug effects, immunology)
• Mice
• Mice, Inbred Strains
• NF-kappa B (antagonists & inhibitors)
• Oxazolone (metabolism)
• Phenylethyl Alcohol (administration & dosage, analogs & derivatives, metabolism)
• Propolis (metabolism)
• Skin (drug effects, immunology, pathology)
• Tetradecanoylphorbol Acetate (metabolism)
• Tumor Necrosis Factor-alpha (immunology)
• Water Loss, Insensible (drug effects)