Ann Dermatol.  2017 Oct;29(5):548-558. 10.5021/ad.2017.29.5.548.

Effects of VitabridC¹² on Skin Inflammation

• Lee JH
• Jeon YJ
• Choi JH
• Kim HY
• Kim TY

• KMID: 2388905
• DOI: http://doi.org/10.5021/ad.2017.29.5.548

Abstract

BACKGROUND
VitabridC¹² is newly developed and composed of vitamin C and Vitabrid (lamellar, hydrated zinc oxide).
OBJECTIVE
In this study, we aimed to investigate the effects of VitabridC¹² on psoriasis and atopic dermatitis.
METHODS
Mice with imiquimod-induced psoriasis or Dermatophagoides farinae-induced atopic dermatitis were applied with VitabridC¹². The effects of VitabridC¹² were evaluated by clinical features, histology, and immunologic features by examining cytokines and chemokines.
RESULTS
In psoriasis model, VitabridC¹² decreased epidermal thickness and reduced inflammatory cell infiltration. In atopic dermatitis model, VitabridC¹² decreased dermal infiltration of inflammatory cells, epidermal hyperplasia, and hyperkeratosis. VitabridC¹² reduced the expression levels of proinflammatory mediators such as interleukin (IL)-1β, IL-6, IL-8, IL-17A, IL-22, tumor necrosis factor-α, CXCL1, CCL17, and CCL20 as well as COX-2 in imiquimod-induced psoriatic skin lesions. Likewise, VitabridC¹² reduced the expression levels of IL-4, IL-5, IL-13, thymic stromal lymphopoietin, and CCL4 in D. farinae-induced skin lesions, and decreased the serum immunoglobulin E level in the atopic dermatitis mouse model. Particularly, the VitabridC¹²-treated mice showed downregulated expressions of mitogen-activated protein kinase (MAPK), including extracellular signal-regulated kinase (ERK), p38, and MAPK/ERK kinase, as well as inhibited phosphorylation of nuclear factor-κB p65.
CONCLUSION
Taken together, these findings indicate that VitabridC¹² exhibits anti-inflammatory activities and is a promising candidate as a treatment option for psoriasis or atopic dermatitis.

Keyword

Ascorbic acid; Atopic dermatitis; Inflammation; Psoriasis

MeSH Terms

Animals
Ascorbic Acid
Chemokines
Cytokines
Dermatitis, Atopic
Hyperplasia
Immunoglobulin E
Immunoglobulins
Inflammation*
Interleukin-13
Interleukin-17
Interleukin-4
Interleukin-5
Interleukin-6
Interleukin-8
Interleukins
Mice
Necrosis
Phosphorylation
Phosphotransferases
Protein Kinases
Psoriasis
Pyroglyphidae
Skin*
Zinc
Ascorbic Acid
Chemokines
Cytokines
Immunoglobulin E
Immunoglobulins
Interleukin-13
Interleukin-17
Interleukin-4
Interleukin-5
Interleukin-6
Interleukin-8
Interleukins
Phosphotransferases
Protein Kinases
Zinc

Figure

• 

  Fig. 1 Effect of VitabridC12 on imiquimod-induced psoriasiform inflammation in BALB/c mice. (A) Skin lesions of psoriasiform inflammation. Images of skin lesions were taken in the 8th week. (B) H&E stained skin recovered in the 8th weeks (×100). VitabridC12 reduced acanthosis and inflammatory cell infiltration in the imiquimod skin lesions. (C) Epidermis thickness and dermal edema were evaluated at the 8th week. Vitabrid and VitabridC12 decreased skin thickness. Representative clinical presentations of the mice from the control group, imiquimod group, Vitabrid group, and VitabridC12 group are shown. These results are representative of 3 independent experiments (n=5 for each group). Each data represents the mean value±standard error of three independent experiments. *p<0.05.

• 

  Fig. 2 VitabridC12 alleviated the Dermatophagoides farinae body (Dfb)-induced atopic dermatitis (AD)-like inflammation in the mouse model. (A) Skin lesions of AD-like skin inflammation. Images of skin lesions were taken in the 3rd week. (B) H&E stained skin recovered in the 3 weeks (×100). (C) Epidermal and dermal thickness were evaluated. VitabridC12 markedly decreased skin thickness; VitabridC12 reduced acanthosis and inflammatory cell infiltration in the AD-like skin lesions. Representative clinical presentations of the mice from the control group, Dfb group, Vitabrid group, and VitabridC12 group are shown. Data represent mean values±standard error (n=5). *p<0.05. The data shown are representative of three independent experiments.

• 

  Fig. 3 The number of mast cells in the dorsal skin in Nc/Nga mice. (A) Histological assessment was performed by toluidine blue staining (×100). Purple colored cells were counted. (B) The number of mast cells in atopic dermatitis-like skin lesions and VitabridC12-treated skin lesions were determined. Purple cells (arrows) were counted. The number of cells at ×400 magnification was counted for each section using 3 randomly selected fields. Data represent mean values±standard error (n=5). *p<0.05. The data shown are representative of three independent experiments.

• 

  Fig. 4 VitabridC12 inhibited imiquimod-induced inflammatory responses in the mouse skin. Total RNA was isolated from the skin lesions of imiquimod-induced mice, and quantitative real-time polymerase chain reaction was performed to examine psoriasis-specific cytokines. VitabridC12 decreased the mRNA expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-8, IL-17A, IL-22, CXCL1, CCL20, and CCL17, and thereby ameliorated imiquimod-induced psoriasiform inflammation in the skin lesion. Data represent mean values±standard error (n=5). *p<0.05. The data shown are representative of three independent experiments.

• 

  Fig. 5 VitabridC12 inhibited Dermatophagoides farinae body (Dfb)-induced inflammatory responses in the Nc/Nga mouse skin. (A) Total RNA was isolated from the skin lesions of Dfb-treated mice, and quantitative real-time polymerase chain reaction was performed to examine atopic dermatitis-specific cytokines. VitabridC12 decreased the mRNA expression levels of thymic stromal lymphopoietin (TSLP), CCL4, interleukin (IL)-4, IL-5, and IL-13. Data represent mean values±standard error (SE) (n=5). *p<0.05. The data shown are representative of three independent experiments. (B) Immunoglobulin E (IgE) was quantified by performing an enzyme-linked immunosorbent assay. Representative clinical presentations of the mice from the control group, Dfb group, Vitabrid group, and VitabridC12 group are shown. Data represent mean values±SE (n=5). *p<0.05. The data shown are representative of three independent experiments.

• 

  Fig. 6 VitabridC12 inhibited cutaneous inflammation via the nuclear factor-κB signaling pathway. Protein extracts were prepared, and western blot analysis was performed with antibodies specific for the molecules indicated. pERK, p-p38, pMEK, p-p65, and COX-2 expression levels increased in psoriatic skin. The protein levels of pERK (44, 48 kDa), p-p38 (38 kDa), pMEK (44, 45 kDa), p-p65 (65 kDa), and COX-2 (75 kDa) decreased after treatment with VitabridC12. ERK: extracellular signal-regulated kinase, MEK: mitogen-activated protein kinase/ERK kinase, GAPDH: glyceraldehyde-3-phosphate dehydrogenase.

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