RESUMO
The Scandinavian region is home to a unique biome with endemic plant species. The aim of this study was to explore this natural diversity and identify plant extracts providing positive skin barrier effects. Six plant extracts were identified as starting material. Following biochemical screening, two candidates outperformed the rest: Betula alba (BA) and Empetrum nigrum (EN). Quantitative PCR analysis showed that BA and EN upregulated barrier genes, when used individually and in combination. Betula alba increased AQP3 and OCLN protein expression, something niacinamide was incapable of. Additionally, the skin barrier was strengthened, evidenced by inhibition of KLK5 and hyaluronidase and showed strong antioxidant and anti-inflammatory activity through DPPH and COX2 inhibition, respectively. A first split-face clinical study was conducted using the combination of extracts versus placebo. There was a significantly better skin restructuring effect and corneocyte cohesion on the side treated with combined extracts. A second split-face clinical study assessed the combined extracts versus 3% niacinamide. Significant variations in skin hydration and TEWL were observed in favor of the extract treated side. In conclusion, we identified a natural alternative to niacinamide for improving skin barrier health, in Scandinavian plant extracts, which yield strong performance, but at a lower concentration.
Assuntos
Ericaceae , Casca de Planta , Antioxidantes , Betula , Ciclo-Oxigenase 2/genética , Sucos de Frutas e Vegetais , Hialuronoglucosaminidase , Niacinamida/farmacologia , Extratos Vegetais/farmacologiaRESUMO
BACKGROUND: High demand on anti-aging skin care encourage the improvement and development of more personalized formulations with additional benefits for general skin health and age associated skin signs. The skin aging physical and biological phenotypes manifest differently between diverse ethnic populations. A highly polluted environment can be viewed as an extrinsic factor accelerating the skin aging process. AIM: To develop a unique formula with active complexes, having multifunctional effects for anti-pollution, brightening and anti-aging/barrier strengthening purposes with confirmed activities in vitro and ex vivo skin models, suitable for polluted skin. METHODS: In vitro culture model with primary human skin cells, ex vivo studies with full-thickness human skin, melanocyte 3D coculture model, gene expression of epidermal and dermal genes, anti-glycation, proteasomal activity, melanin, and cytokine assays. RESULTS: In vitro and ex vivo studies clearly demonstrated that diglucosyl gallic acid (active A) and the formulation complex inhibited pollution mediated MMP1 protein, CYP1A1 gene expression, and IL-6 protein secretion, while caprylic/capric triglyceride, diacetyl boldine (active B) had anti-melanogenic effect in in vitro primary melanocyte monoculture and 3D spheroid model. Another active compound, acetyl dipeptide 1 cetyl ester (active D), significantly upregulated epidermal barrier genes (Aquaporin 3 [AQP3], Filaggrin [FLG], caspase 14, and keratin 10) in human primary keratinocytes. Interestingly, both acetyl dipeptide 1 cetyl ester (active D) and niacinamide (active C) improved dermal gene expression (fibrillin-1, Collagen type 1 alpha 1, Decorin, Lysyl oxidase-like 1) and, moreover, had significant anti-glycant and proteasomal promoter activity in human primary fibroblasts. CONCLUSION: Considering consumers need in heavily polluted areas, we developed a multipurpose formulation comprised of unique active complexes toward pollution, pollution induced inflammation, skin brightening, and antiaging concerns with beneficial results demonstrated by in vitro and ex vivo studies.
Assuntos
Cosmecêuticos/farmacologia , Envelhecimento da Pele/efeitos dos fármacos , Higiene da Pele/métodos , Pigmentação da Pele/efeitos dos fármacos , Pele/efeitos dos fármacos , Poluentes Atmosféricos/efeitos adversos , Células Cultivadas , Técnicas de Cocultura , Proteínas Filagrinas , Humanos , Queratinócitos , Melanócitos , Cultura Primária de Células , Pele/citologia , Pele/metabolismoRESUMO
BACKGROUND: Fractional exhaled nitric oxide is elevated in allergen-provoked asthma. The cellular and molecular source of the elevated fractional exhaled nitric oxide is, however, uncertain. OBJECTIVE: To investigate whether fractional exhaled nitric oxide is associated with increased airway epithelial inducible nitric oxide synthase (iNOS) in allergen-provoked asthma. METHODS: Fractional exhaled nitric oxide was measured in healthy controls (n = 14) and allergic asthmatics (n = 12), before and after bronchial provocation to birch pollen out of season. Bronchoscopy was performed before and 24 hours after allergen provocation. Bronchial biopsies and brush biopsies were processed for nitric oxide synthase activity staining with nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d), iNOS immunostaining, or gene expression analysis of iNOS by real-time PCR. NADPH-d and iNOS staining were quantified using automated morphometric analysis. RESULTS: Fractional exhaled nitric oxide and expression of iNOS mRNA were significantly higher in un-provoked asthmatics, compared to healthy controls. Allergic asthmatics exhibited a significant elevation of fractional exhaled nitric oxide after allergen provocation, as well as an accumulation of airway eosinophils. Moreover, nitric oxide synthase activity and expression of iNOS was significantly increased in the bronchial epithelium of asthmatics following allergen provocation. Fractional exhaled nitric oxide correlated with eosinophils and iNOS expression. CONCLUSION: Higher fractional exhaled nitric oxide concentration among asthmatics is associated with elevated iNOS mRNA in the bronchial epithelium. Furthermore, our data demonstrates for the first time increased expression and activity of iNOS in the bronchial epithelium after allergen provocation, and thus provide a mechanistic explanation for elevated fractional exhaled nitric oxide in allergen-provoked asthma.