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. 2017 Sep 29;22(10):1639.
doi: 10.3390/molecules22101639.

N-(4-bromophenethyl) Caffeamide Protects Skin from UVB-Induced Inflammation Through MAPK/IL-6/NF-κB-Dependent Signaling in Human Skin Fibroblasts and Hairless Mouse Skin

Yueh-Hsiung Kuo  1   2 , Po-Yuan Wu  3   4 , Chien-Wen Chen  5 , Ping Lin  6 , Kuo-Ching Wen  7 , Chien-Yih Lin  8 , Hsiu-Mei Chiang  9
Affiliations

N-(4-bromophenethyl) Caffeamide Protects Skin from UVB-Induced Inflammation Through MAPK/IL-6/NF-κB-Dependent Signaling in Human Skin Fibroblasts and Hairless Mouse Skin

Yueh-Hsiung Kuo et al. Molecules. .

Abstract

Long-term exposure to ultraviolet (UV) irradiation causes skin inflammation and aging. N-(4-bromophenethyl) caffeamide (K36H) possesses antioxidant and antimelanogenic properties. The present study investigated the effects of K36H on UVB-induced skin inflammation in human skin fibroblasts and hairless mice and evaluated the underlying mechanisms. The in vitro results indicated that K36H reduced UVB-induced mitogen-activated protein kinase (MAP kinase) expression. Furthermore, K36H treatment reduced cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) protein expression in UVB-irradiated fibroblasts by regulating IκB and nuclear factor-kappa B (NF-κB) expression. In the animal study, topically applied K36H markedly reduced inflammation and skin thickness and prevented photodamage to the skin of hairless mice. In addition, K36H inhibited the levels of UV-upregulated inflammation-related proteins levels such as IL-1, iNOS, and NF-κB in the dermis of hairless mice. Our findings demonstrated the antioxidant and anti-inflammatory properties of K36H in human skin fibroblasts and hairless mice. Therefore, K36H can be developed as an antiphotodamage and antiphotoinflammation agent.

Keywords: IL-6; N-(4-bromophenethyl) caffeamide; NF-κB; photoinflammation; propolis.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
The structure of N-(4-bromophenethyl) caffeamide (K36H).
Figure 2
Figure 2
Human skin fibroblast viability (%) after treatment with K36H. K36H was not toxic to Hs68 cells.
Figure 3
Figure 3
1,1-Diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity of K36H. Significant difference versus nontreatment group: **, p < 0.01; ***, p < 0.001.
Figure 4
Figure 4
Intracellular reactive oxygen species (ROS) level measurement with 2′,7′-dichlorofluorescin diacetate (DCFDA) reagent after K36H treatment in ultraviolet (UV) B–irradiated human fibroblasts. Ascorbic acid was used as positive control. Significant difference versus nonirradiation group: ###, p < 0.001. Significant difference versus nontreatment group: *, p < 0.05; **, p < 0.01.
Figure 5
Figure 5
Effect of K36H on the UVB-induced phosphorylation of mitogen-activated protein (MAP) kinases in human fibroblasts. Significant difference versus nonirradiation group: ##, p < 0.01. Significant difference versus nontreatment group: *, p < 0.05; **, p < 0.01.
Figure 6
Figure 6
UVB-induced inducible nitric oxide synthase (iNOS) and COX-2 expression levels in human fibroblasts. Significant difference versus nonirradiation group: ##, p < 0.01; ###, p < 0.001. Significant difference versus nontreatment group: *, p < 0.05; **, p < 0.01; ***, p < 0.001.
Figure 7
Figure 7
Effect of K36H on UVB-induced p-IκBα and IκBα expression in human fibroblasts. Significant difference versus nonirradiation group: ###, p < 0.001. Significant difference versus nontreatment group: *, p < 0.05; **, p < 0.01.
Figure 8
Figure 8
Effect of K36H on UVB-induced activation of NF-κB P65 in human fibroblasts. K36H inhibited the UVB-induced translocation of NF-κB into the nucleus.
Figure 9
Figure 9
Effect of K36H on transepidermal water loss (TEWL) in chronic UVB-irradiated hairless mice at 12 weeks.
Figure 10
Figure 10
Light micrographs of histological sections stained with hematoxylin and eosin (H&E) in hairless mice.
Figure 11
Figure 11
Effect of K36H on the epidermal thickness in UVB-exposed hairless mice. Significant difference versus normal group: ### p < 0.001. Significant difference versus UVB group: *** p < 0.001.
Figure 12
Figure 12
Immunohistochemical staining of IL-6 expression on mice skin slices. K36H inhibited UVB-induced IL-6 overexpression in mice skin.
Figure 13
Figure 13
Immunohistochemical staining of iNOS expression on mice skin slices. K36H inhibited UVB-induced iNOS overexpression in mice skin.
Figure 14
Figure 14
Immunohistochemical staining of NF-κB expression on mice skin slices. K36H inhibited UVB-induced NF-κB overexpression in mice skin.
See this image and copyright information in PMC

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