PKCι is a target of 7,8,4'-trihydroxyisoflavone for the suppression of UVB-induced MMP-1 expression.

The soy isoflavone daidzein is bioconverted to 7,8,4'-trihydroxyisoflavone (7,8,4'-THIF) by microorganisms. Here, we investigated the matrix metalloproteinase (MMP)-1 inhibitory properties of 7,8,4'-THIF that arise through the suppression of UVB-induced MMP-1 expression. 7,8,4'-THIF reduced UVB-induced MMP-1 expression at the transcriptional level in primary human dermal fibroblasts and inhibited UVB-induced transcriptional activity of AP-1, a major activator of MMP-1 expression. Additionally, it was observed that the mitogen-activated protein kinase (MAPK) pathway, a crucial signalling cascade for MMP-1 expression, was suppressed by 7,8,4'-THIF. Protein kinase C iota (PKCι) was suspected to be a direct target of 7,8,4'-THIF. The direct interaction between 7,8,4'-THIF and PKCι was confirmed using pull-down assays and immobilized metal ion affinity-based fluorescence polarization assays. Finally, we observed that 7,8,4'-THIF inhibited UVB-induced MMP-1 expression in a human skin equivalent model. Taken together, these results suggest that 7,8,4'-THIF, a bioconversion product of daidzein, suppresses UVB-induced MMP-1 expression.

Theobroma cacao extract attenuates the development of Dermatophagoides farinae-induced atopic dermatitis-like symptoms in NC/Nga mice.

Cacao beans from Theobroma cacao are an abundant source of polyphenols, particularly flavonoids. Previous studies demonstrated that cacao flavanols decrease pro-inflammatory cytokines resulting in the alleviation of allergic symptoms. We sought to investigate the effects of cacao extract (CE) on Dermatophagoides farinae extract (DFE)-induced atopic dermatitis (AD)-like symptoms. CE attenuated DFE-induced AD-like symptoms as assessed by skin lesion analyses, dermatitis score, and skin thickness. Histopathological analysis revealed that CE suppressed DFE-induced immune cell infiltration into the skin. These observations occurred concomitantly with the downregulation of inflammatory markers including serum immunoglobulin (Ig) E, chemokine; thymus and activation-regulated chemokine and macrophage-derived chemokine as well as the skin-derived cytokines interleukin (IL)-4, IL-5, and interferon-γ. CE also significantly alleviated transepidermal water loss and increased skin hydration. These results suggest that CE, a natural phytochemical-rich food, has potential therapeutic efficacy for the treatment of AD.

Oral Supplementation with Cocoa Extract Reduces UVB-Induced Wrinkles in Hairless Mouse Skin.

Cacao beans contain various bioactive phytochemicals that could modify the pathogeneses of certain diseases. Here, we report that oral administration of cacao powder (CP) attenuates UVB-induced skin wrinkling by the regulation of genes involved in dermal matrix production and maintenance. Transcriptome analysis revealed that 788 genes are down- or upregulated in the CP supplemented group, compared with the UVB-irradiated mouse skin controls. Among the differentially expressed genes, cathepsin G and serpin B6c play important roles in UVB-induced skin wrinkle formation. Gene regulatory network analysis also identified several candidate regulators responsible for the protective effects of CP supplementation against UVB-induced skin damage. CP also elicited antiwrinkle effects via inhibition of UVB-induced matrix metalloproteinases-1 expression in both the human skin equivalent model and human dermal fibroblasts. Inhibition of UVB-induced activator protein-1 via CP supplementation is likely to affect the expression of matrix metalloproteinases-1. CP supplementation also downregulates the expression of cathepsin G in human dermal fibroblasts. 5-(3',4'-Dihydroxyphenyl)-γ-valerolactone, a major in vivo metabolite of CP, showed effects similar to CP supplementation. These results suggest that cacao extract may offer a protective effect against photoaging by inhibiting the breakdown of dermal matrix, which leads to an overall reduction in wrinkle formation.

Cocoa Flavanol Supplementation Influences Skin Conditions of Photo-Aged Women: A 24-Week Double-Blind, Randomized, Controlled Trial.

BACKGROUND: The consumption of dietary antioxidants is considered to be a good strategy against photo-aging. However, the results of previous clinical trials that investigated the effects of oral consumption of high-flavanol cocoa products on skin photo-aging have been contradictory. OBJECTIVE: The aim of this study was to investigate whether high-flavanol cocoa supplementation would improve the moderately photo-aged facial skin of female participants, by assessing skin wrinkles and elasticity. METHODS: We performed a 24-wk, randomized, double-blind, placebo-controlled study to evaluate the effects of oral supplementation of cocoa flavanols on cutaneous photo-aging. All participants were moderately photo-aged Korean women with visible facial wrinkles (age range: 43-86 y). Participants were randomly assigned to receive a placebo beverage or cocoa beverage that contained 320 mg total cocoa flavanols/d. We measured wrinkles, skin elasticity, and hydration at baseline and at 12 and 24 wk. The primary endpoint was the mean percentage change in the average roughness value (Rz) at 24 wk. RESULTS: At 24 wk, the mean percentage change in Rz (primary endpoint) was significantly lower in the cocoa group than in the placebo group (-8.7 percentage points; 95% CI: -16.1, -1.3 percentage points; P = 0.023). The mean percentage changes in gross elasticity, as determined by a cutometer, also differed between the groups at 12 wk (9.1 percentage points; 95% CI: 1.5, 16.7 percentage points; P = 0.020) and 24 wk (8.6 percentage points; 95% CI: 1.0, 16.2 percentage points; P = 0.027). However, there were no significant differences in skin hydration and barrier integrity between the 2 groups. CONCLUSIONS: In moderately photo-aged women, regular cocoa flavanol consumption had positive effects on facial wrinkles and elasticity. Cocoa flavanol supplementation may contribute to the prevention of the progression of photo-aging. This trial was registered at clinicaltrials.gov as NCT02060097.

Chlorella vulgaris Attenuates Dermatophagoides Farinae-Induced Atopic Dermatitis-Like Symptoms in NC/Nga Mice.

Atopic dermatitis (AD) is a chronic and inflammatory skin disease that can place a significant burden on quality of life for patients. AD most frequently appears under the age of six and although its prevalence is increasing worldwide, therapeutic treatment options are limited. Chlorella vulgaris (CV) is a species of the freshwater green algae genus chlorella, and has been reported to modulate allergy-inducible factors when ingested. Here, we examined the effect of CV supplementation on AD-like symptoms in NC/Nga mice. CV was orally administrated for six weeks while AD-like symptoms were induced via topical application of Dermatophagoides farinae extract (DFE). CV treatment reduced dermatitis scores, epidermal thickness, and skin hydration. Histological analysis also revealed that CV treatment reduced DFE-induced eosinophil and mast cell infiltration into the skin, while analysis of serum chemokine levels indicated that CV treatment downregulated thymus- and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC) levels. In addition, CV treatment downregulated mRNA expression levels of IL-4 and IFN-γ. Taken together, these results suggest that CV extract may have potential as a nutraceutical ingredient for the prevention of AD.

Brown Pine Leaf Extract and Its Active Component Trans-Communic Acid Inhibit UVB-Induced MMP-1 Expression by Targeting PI3K.

Japanese red pine (Pinus densiflora) is widely present in China, Japan, and Korea. Its green pine leaves have traditionally been used as a food as well as a coloring agent. After being shed, pine leaves change their color from green to brown within two years, and although the brown pine leaves are abundantly available, their value has not been closely assessed. In this study, we investigated the potential anti-photoaging properties of brown pine leaves for skin. Brown pine leaf extract (BPLE) inhibited UVB-induced matrix metalloproteinase-1 (MMP-1) expression to a greater extent than pine leaf extract (PLE) in human keratinocytes and a human skin equivalent model. HPLC analysis revealed that the quantity of trans-communic acid (TCA) and dehydroabietic acid (DAA) significantly increases when the pine leaf color changes from green to brown. BPLE and TCA elicited reductions in UVB-induced MMP-1 mRNA expression and activator protein-1 (AP-1) transactivation by reducing DNA binding activity of phospho-c-Jun, c-fos and Fra-1. BPLE and TCA also inhibited UVB-induced Akt phosphorylation, but not mitogen activated protein kinase (MAPK), known regulators of AP-1 transactivation. We additionally found that BPLE and TCA inhibited phosphoinositide 3-kinase (PI3K), the upstream kinase of Akt, in vitro. In summary, both BPLE and its active component TCA exhibit protective effects against UVB-induced skin aging. Taken together, these findings underline the potential for BPLE and TCA to be utilized as anti-wrinkling agents and cosmetic ingredients, as they suppress UVB-induced MMP-1 expression.

20-O-ß-D-glucopyranosyl-20(S)-protopanaxadiol-fortified ginseng extract attenuates the development of atopic dermatitis-like symptoms in NC/Nga mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginseng and ginsenosides are frequently used in the treatment of chronic inflammatory diseases. Recently, 20-O-ß-d-glucopyranosyl-20(S)-protopanaxadiol (GPD), the main metabolite of ginsenosides, was reported to have both anti-allergic and anti-pruritic effects. The immunomodulatory effects of GPD-fortified ginseng extract (GFGE) on atopic dermatitis (AD)-like symptoms in mice were investigated. This study was designed to investigate the preventive effect of GFGE on AD-like symptoms. MATERIALS AND METHODS: The effects of orally administered GFGE on Dermatophagoides farinae body extract (DFE)-induced AD-like symptoms in NC/Nga mice were assessed by analyzing dermatitis score, ear thickness, scratching time, skin histological changes, and serum level of macrophage-derived chemokine (MDC). In addition, splenocytes were isolated from the mice and stimulated with anti-CD3 and anti-CD28 monoclonal antibodies to produce cytokines. RESULTS: Oral administration of GFGE significantly attenuated DFE-induced increases in dermatitis score, ear thickness, scratching time, and severity of skin lesions in NC/Nga mice. GFGE treatment also reduced level of MDC in serum, infiltration of eosinophils and mast cells in skin, and production of cytokines in splenocytes. CONCLUSIONS: These results suggest that GFGE might ameliorate DFE-induced AD-like symptoms and be an alternative therapeutic agent for the prevention of AD.

7,3',4'-Trihydroxyisoflavone Ameliorates the Development of Dermatophagoides farinae-Induced Atopic Dermatitis in NC/Nga Mice.

Atopic dermatitis is an inflammatory and chronically relapsing skin disorder that commonly occurs in children; the number of atopic dermatitis patients is increasing. The cause and mechanism of atopic dermatitis have not been defined clearly, although many studies are ongoing. Epidemiological studies suggest that soybean and its isoflavones have immunoregulatory activities. Here, we report that 7,3',4'-trihydroxyisoflavone (7,3',4'-THIF), a major metabolite of daidzin, effectively inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO), tumor necrosis factor (TNF)- α , and interleukin (IL)-6 production in RAW 264.7 cells, and also reduced ß -hexosaminidase secretion in RBL-2H3 cells. Moreover, 7,3',4'-THIF significantly reduced scratching time, transepidermal water loss, and mast cell infiltration. It also decreased protease-activated receptor (PAR)-2 and IL-4 expression and increased filaggrin expression in skin lesions of NC/Nga mice. These results suggest that 7,3',4'-THIF improves Dermatophagoides farina body extract-induced atopic dermatitis in NC/Nga mice.

Persimmon peel extract attenuates PDGF-BB-induced human aortic smooth muscle cell migration and invasion through inhibition of c-Src activity.

The unregulated migration and invasion of human aortic smooth muscle cells (HASMCs) into the intima is a crucial step in the development of atherosclerosis. Recently, the oriental persimmon extract (Diospyros kaki Thunb. cv. Fuyu) has been investigated for its anti-atherogenic properties, but the molecular mechanisms involved remain unclear. We investigated the inhibitory effects of persimmon peel and flesh extract on the platelet-derived growth factor (PDGF) BB-induced MMP-1 expression using Western blot, and abnormal migration and invasion of HASMCs using a modified Boyden chamber assay and a wound healing assay. We also evaluated the inhibitory effects of persimmon peel extract on aortic vessel thickening using a rat aortic sprouting assay. Persimmon peel (PPE), but not flesh extract (PFE), inhibited PDGF-BB-induced MMP-1 expression, cell migration and invasion in HASMCs, while suppressing the rat aortic sprouting. Western blot and in vitro kinase assay data demonstrated that PPE inhibited Src kinase activity and subsequently attenuated PDGF-BB-induced phosphorylation of MAPK and Akt signalling pathways. Taken together, our results indicate that persimmon peel might possess a potential anti-atherogenic effect through attenuation of ASMCs migration and invasion and aortic sprouting by direct inhibition of the c-Src kinase activity.