Ultraviolet radiation (UV) induces an increase in multiple cutaneous inflammatory mediators. Ellagic acid (EA) and rosmarinic acid (RA) are natural anti-inflammatory and immunomodulatory compounds found in many plants, fruits, and nuts. We assessed the ability of EA and RA to modulate IL-1β, IL-6, IL-8, IL-10, MCP-1, and TNF-α gene expression in HaCaT cells after UVB irradiation. Cells were treated with UVB (100 mJ/cm2) and simultaneously with EA (5 μM in 0.1% DMSO) or RA (2.7 μM in 0.5% DMSO). Moreover, these substances were added to the UVB-irradiated cells 1 h or 6 h before harvesting, depending on the established UVB-induced cytokine expression peak. Cytokine gene expression was examined using quantitative real time polymerase chain reaction. RA produced a significant reduction in UVB-induced expression of IL-6, IL-8, MCP-1, and TNF-α when applied at the same time as irradiation. EA showed milder effects compared with RA, except for TNF-α. Both substances decreased IL-6 expression, also when applied 5 h after irradiation, and always produced a significant increase in UVB-induced IL-10 expression. Our findings suggest that EA and RA are able to prevent and/or limit the UVB-induced inflammatory cascade, through a reduction in proinflammatory mediators and the enhancement of IL-10, with its protective function.

(PD98059) or Akt inhibitor (LY294002). Both PD98059 and LY294002 abolished the inhibition of melanin synthesis by clotrimazole ( Figure S3b). Moreover, PD98059 and LY294002 attenuated the inhibition of tyrosinase expression by clotrimazole ( Figure S3c). Taken together, these results indicate that clotrimazole suppressed melanogenesis through the proteasomal degradation of tyrosinase and that this may be associated with the activation of the ERK and Akt signalling pathways. ConclusionsHerein, we have demonstrated a novel role for the antimycotic agent clotrimazole in the inhibition of melanogenesis by accelerating ERK and PI3K-/Akt-mediated tyrosinase degradation, which is a novel mechanism. These findings indicate that clotrimazole is a safe depigmenting agent that is suitable for the topical treatment of hyperpigmentary disorders related to fungal infection and of other sources of inflammation. Acknowledgements Author contributionsBYC wrote the manuscript; SYK performed the research; JMJ assisted in writing the manuscript; CHW, JHC and MWL analysed the data; and SEC supervised the study and the manuscript. Conflict of interestsThe authors have declared no conflicting interests. Supporting InformationAdditional supporting data may be found in the supplementary information of this article. Data S1. Materials and methods. Figure S1. Cell viability assay of clotrimazole. Figure S2. Clotrimazole inhibits melanogenesis in Mel-Ab cells. Figure S3. The effects of clotrimazole on melanogenesis are related to ERK and Akt signalling pathways. Abstract: Human follicle dermal papilla cells (FDPC) are a specialized population of mesenchymal cells located in the skin. They regulate hair follicle (HF) development and growth, and represent a reservoir of multipotent stem cells. Growing evidence supports the hypothesis that HF cycling is associated with vascular remodeling. Follicular keratinocytes release vascular endothelial growth factor (VEGF) that sustains perifollicular angiogenesis leading to an increase of follicle and hair size. Furthermore, several human diseases characterized by hair loss, including Androgenetic Alopecia, exhibit alterations of skin vasculature. However, the molecular mechanisms underlying HF vascularization remain largely unknown. In vitro coculture approaches can be successfully employed to greatly improve our knowledge and shed more light on this issue. Here we used Transwell-based co-cultures to show that FDPC promote survival, proliferation and tubulogenesis of human microvascular endothelial cells (HMVEC) more efficiently than fibroblasts. Accordingly, FDPC enhance the endothelial release of VEGF and IGF-1, two well-known proangiogenic growth factors. Collectively, our data suggest a key role of papilla cells in vascular remodeling of the hair follicle.

Euxyl K 400 is a preservative for cosmetics and toiletries containing 2 active ingredients, 1,2-dibromo-2,4-dicyanobutan and 2-phenoxyethanol. 2057 consecutive patients with contact dermatitis were patch tested with Euxyl K 400 2.5% pet. and ethanol. A positive patch test occurred in 24 patients (1.2%). The source of sensitization was traced in 8 patients to their cosmetics. Both leave-on and rinse-off products were responsible. Further patch tests with Euxyl K 400 0.5% pet. and phenoxyethanol 5% pet. were performed in 11 patients. A positive patch test to phenoxyethanol was detected in 1 of them. Only 3 patients showed a mild reaction to Euxyl K 400 0.5%. A provocative use test with a lotion preserved with Euxyl K 400 0.1% was positive in 5 of these 11 patients. Patients with Euxyl K 400 sensitivity showed a high prevalence of positive patch tests to other common ingredients of cosmetics. Since the use of Euxyl K 400 in cosmetic products is rapidly increasing, it should be included in the patch test series for patients with suspected cosmetic allergy.

The anti-inflammatory effects and antioxidant activities of individual isoflavones are well established although little is known about the photoprotective effect of their combination. The aim of this study was to investigate the photoprotective effects of different concentrations of genistein and daidzein individually or combined. We measured the expression levels of the cyclo-oxygenase-2 (COX-2) and growth arrest and DNA-damage inducible (Gadd45) genes, which are involved in inflammation and DNA repair, respectively, in BJ-5ta human skin fibroblasts irradiated with 60 mJ/cm2 UVB. We also determined the cellular response to UVB-induced DNA damage by Comet assay. We report that genistein and daidzein when administered combined, and at a specific concentration and ratio, exerted a synergistic photoprotective effect that was greater than the effect obtained with each isoflavone alone. The results reported herein suggest that low concentrations of genistein and daidzein combined may be good candidate ingredients for protective agents against UV-induced photodamage.

Many natural compounds having antioxidant and anti-inflammatory activity are a potential target for new therapies against chronic inflammatory syndromes. The oral administration of functional herbal supplements may become a prevention strategy or therapy adjuvant for susceptible patients. A case study is our milk thistle (Silybum marianum) extract rich in silymarin complex. A water-soluble microencapsulated powder system was developed by a spray drying technique to improve the poor silymarin bioactivity after oral administration. Sodium carboxymethylcellulose (NaCMC) was employed as coating/swelling polymer matrix and sodium lauryl sulfate (SLS) as the surfactant (1:1:0.05 w/w/w). A H2O/EtOH/acetone (50/15/35 v/v/v) solvent system was used as liquid feed. The microsystems were capable of improving the in vitro dissolution and permeation rates, suggesting an enhancement of bioactivity after oral administration. The microsystems protect the antioxidant activity of silymarin after harsh storage conditions period and do not affect the anti-inflammatory properties of the raw extract (efficient already at lower concentrations of 0.312 mg/mL) to reduce dendritic cells (DCs) inflammatory cytokine secretion after lipopolysaccharide administration. This approach allows managing particle size, surface properties and release of bioactive agents improving the bioactivity of a herbal supplement and is also possibly applicable to many other similar natural products.