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1.
Int J Cosmet Sci ; 46(1): 24-38, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37562497

RESUMEN

OBJECTIVE: Facial skin undergoes major structural and functional changes as a result of intrinsic and extrinsic factors. The goal of the current work is to demonstrate L-4-thiazolylalaine (L4, Protinol), a non-proteinogenic amino acid shown to stimulate the production of dermal proteins by fibroblasts, is an alternative efficacious topical ingredient for visible signs of ageing. METHODS: In vitro studies using 3D human skin tissue models were performed to show changes in protein and gene expression of key dermal markers in samples treated with 0.3% L4 compared to vehicle control. In vivo evaluation of skin turnover was measured in volunteers after treatment with L4 compared to retinol. Skin biopsies (n = 30) were taken to investigate epidermal and dermal changes in cases treated with L4 and compared to retinol. Finally, a clinical evaluation (n = 28) was conducted to assess the efficacy of L4 over a base formulation using various ageing parameters within a population of women 46-66 years old with mild-to-moderate wrinkles. RESULTS: In vitro studies on 3D tissues displayed significant changes in the dermal matrix via an increase in HA and pro-collagen I production and a decrease in the expression of inflammatory genes. In vivo biopsy studies demonstrated that L4 and retinol independently increased epidermal thickness and collagen remodelling significantly more compared with the base formula. Clinical evaluation showed firmer and smoother skin at day 28 post-treatment with L4 over the vehicle control without causing side effects such as redness or irritation. CONCLUSION: L4 is a novel, multi-functional ingredient which offers a superior alternative to currently available technologies for improving epidermal and dermal parameters that change during ageing and photodamage.


OBJECTIF: La peau du visage est sujet à des changements majeurs structuraux et fonctionnels dus à des facteurs intrinsèques et extrinsèques. Dans cette étude, nous montrons que l'acide aminé non-protéinogène L-4-thiazolylalanine (L4, Protinol) est une alternative intéressante pour une application topique. MÉTHODES: Des modèles 3D de peaux ont été utilisés pour mesurer les changements d'expressions géniques et protéiques de marqueurs clés du derme à partir d'échantillons traités avec L4 comparés à une condition contrôle. In vivo, après un traitement L4, le renouvellement cutané a été mesuré chez les volontaires et comparé à un traitement au rétinol. Des biopsies de peaux (n = 30) traitées soit à L4 soit au rétinol ont été isolées afin d'évaluer les changements au niveau du derme et de l'épiderme. Pour finir, une étude clinique (n = 28) a été menée pour évaluer l'efficacité de L4 par rapport à une formulation de base en utilisant différents paramètres de vieillissement au sein d'une population de femmes de 46 à 66 ans présentant des rides légères à modérées. RÉSULTATS: Les études in vitro sur tissues 3D ont montré des changements dans la matrice du derme avec une augmentation de la production d'acide hyaluronique et de procollagène I et une diminution d'expression de gènes pro-inflammatoires. Les études menées in vivo sur biopsies ont démontré que L4 et rétinol augmentaient indépendamment tous deux significativement l'épaisseur de l'épiderme et le remodelage du collagène par rapport à leur base seule. Pour finir, une peau plus ferme et plus lisse a été mesurée cliniquement après 28 jours de traitement L4 par rapport au véhicule et cela sans effets indésirables tels que rougeur et irritation. CONCLUSION: L4 est un ingrédient, innovant et multifonctionnel. Il offre une sérieuse alternative aux technologies actuellement disponibles dans les traitements contre le vieillissement de la peau ou le photodommage.


Asunto(s)
Envejecimiento de la Piel , Vitamina A , Humanos , Femenino , Persona de Mediana Edad , Anciano , Vitamina A/farmacología , Aminoácidos , Piel/metabolismo , Epidermis/metabolismo , Colágeno/metabolismo
2.
Photodermatol Photoimmunol Photomed ; 35(6): 408-414, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30951225

RESUMEN

BACKGROUND: The epidermis is the outermost layer of skin and is composed of cells primarily containing keratin. It consists of about ten layers of living cells (keratinocytes) and ten layers of dead cells (corneocytes). Thinning of the epidermis and decreased proliferation of its cells are associated with aging related changes in skin, including wrinkling and laxity. Fluorescence excitation spectroscopy is a noninvasive method of monitoring characteristic excitation-emission peaks in skin that have been related to the epidermal and dermal composition. The magnitude of the peak that occurs at 295nm excitation (F295) has been linked to changes in epidermal thickness, proliferation, and skin aging. AIM: The goal of this study is to correlate changes in the F295 signal with proliferation of cells and thickening of the epidermis induced by cosmetic formulations. We hypothesize that two commonly used cosmetic ingredients, retinol and glycolic acid, will increase these markers that have been implicated in skin anti-aging. METHODS: In a placebo-controlled study subjects' forearms were treated with formulations containing retinol or glycolic acid under occlusive patch for a period of 21 days. Skin fluorescence was measured at baseline and after treatment, and biopsies were taken following treatment for histological analysis of epidermal thickness and cell proliferation. RESULTS: After 21 days of treatment retinol and glycolic acid formulas significantly increased F295 (by 265.1±33.5% and 162.2±18.7% respectively), whereas the placebo control formula did not induce a change from baseline. Furthermore, retinol and glycolic acid treatments significantly increased epidermal thickness (by 63.1% and 7.8% respectively) and keratinocyte proliferation (by 236.9% and 62.8% respectively) versus placebo control. CONCLUSION: Increases in F295 were found to correlate with epidermal renewal, but more so with increased cell proliferation than epidermal thickness. We conclude that the F295 signal is a fast and reliable early indicator of epidermal remodeling in skin that can be used to distinguish between formulations with different cosmetic ingredients.


Asunto(s)
Proliferación Celular/efectos de los fármacos , Epidermis/efectos de los fármacos , Glicolatos/farmacología , Queratinocitos/fisiología , Vitamina A/farmacología , Administración Cutánea , Anciano , Cosméticos/farmacología , Epidermis/patología , Femenino , Fluorescencia , Glicolatos/administración & dosificación , Humanos , Queratolíticos/farmacología , Persona de Mediana Edad , Envejecimiento de la Piel/fisiología , Espectrometría de Fluorescencia , Vitamina A/administración & dosificación , Vitaminas/farmacología
3.
Skin Res Technol ; 25(5): 606-611, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30874339

RESUMEN

BACKGROUND: Contractile films that smooth the surface of skin upon drying are popular among consumers due to their "instant" effect and perceivable smoothing benefits. The objective of our study was to correlate an in vitro measurement of contractile force with in vivo smoothing performance, thereby enabling rapid screening of film-forming technologies for impactful cosmetic results. METHODS: We introduce and characterize an in vitro method to measure drying stress of film-containing formulations. This method is used to measure the drying stresses of seven different cosmetic film formulations. We then evaluate these formulas in a blinded clinical study, measuring their effect on under-eye and Crow's Feet area smoothing through bioinstrumentation (3D PRIMOS imaging) and blinded expert grading of images. RESULTS: The in vitro drying stress measurement was found to be repeatable and sensitive enough to detect differences between formulations with typical amounts of film-forming agents. Significant correlation was found between the in vitro drying stress measurements and under-eye smoothing measured by 3D imaging (R2  = 0.71). Expert grading confirmed that film formulas deliver perceivable smoothing in the under-eye and Crow's Feet regions 15 minutes after application. CONCLUSION: The in vitro method described here can be used to predict the efficacy of formulations that deliver smoothing benefits to consumers. For consumer use, the esthetic properties of a formula should be balanced with film performance, guided by this model which predicts skin smoothing efficacy.


Asunto(s)
Cosméticos/farmacología , Fármacos Dermatológicos/farmacología , Envejecimiento de la Piel/efectos de los fármacos , Administración Cutánea , Cosméticos/administración & dosificación , Cara , Humanos , Técnicas In Vitro , Albúmina Sérica Bovina/farmacología , Cuidados de la Piel , Estrés Fisiológico/fisiología
4.
Int J Cosmet Sci ; 40(6): 589-595, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30428143

RESUMEN

OBJECTIVE: This paper presents in vivo an in vitro studies demonstrating the induction of pigmentation in human skin by visible light which can be blocked by using formulation containing the correct amount of yellow iron oxide (YIO). METHODS: An in vitro absorption method was developed to determine the protection provided by a test formulation containing 4.5% YIO using an IPD UVA-VIS action spectrum. Following the development of the in vitro method and in vivo study with 10 normal healthy volunteers with Fitzpatrick skin phototypes IV to VI was conducted to verify if the predictive model. RESULTS: The in vitro model for visible light protection provided a protection factor of 2.5 using the in vitro absorption spectrum of 4.5% of YIO with a very similar result from the in vivo study with a protection factor of 3.0. Multiple daily exposures of visible light have shown increase in skin pigmentation and the application of YIO provide less development of pigmentation when compared to unprotected skin. CONCLUSION: In vitro testing of the absorbance of the pigmented formulation using a proposed action spectrum for immediate pigment darkening (IPD) response in the visible light range supports the in vivo protection observations for persistent pigment darkening (PPD) and can be used as predictor for skin pigmentation induced by visible light.


Asunto(s)
Luz/efectos adversos , Protectores contra Radiación/farmacología , Pigmentación de la Piel/efectos de la radiación , Relación Dosis-Respuesta a Droga , Voluntarios Sanos , Humanos , Protectores contra Radiación/administración & dosificación
5.
PLoS One ; 10(6): e0130949, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26121474

RESUMEN

Visible light (400-700 nm) lies outside of the spectral range of what photobiologists define as deleterious radiation and as a result few studies have studied the effects of visible light range of wavelengths on skin. This oversight is important considering that during outdoors activities skin is exposed to the full solar spectrum, including visible light, and to multiple exposures at different times and doses. Although the contribution of the UV component of sunlight to skin damage has been established, few studies have examined the effects of non-UV solar radiation on skin physiology in terms of inflammation, and limited information is available regarding the role of visible light on pigmentation. The purpose of this study was to determine the effect of visible light on the pro-pigmentation pathways and melanin formation in skin. Exposure to visible light in ex-vivo and clinical studies demonstrated an induction of pigmentation in skin by visible light. Results showed that a single exposure to visible light induced very little pigmentation whereas multiple exposures with visible light resulted in darker and sustained pigmentation. These findings have potential implications on the management of photo-aggravated pigmentary disorders, the proper use of sunscreens, and the treatment of depigmented lesions.


Asunto(s)
Adaptación Fisiológica/efectos de la radiación , Luz , Melaninas/biosíntesis , Piel/efectos de la radiación , Absorción de Radiación , Adulto , Femenino , Regulación de la Expresión Génica/efectos de la radiación , Humanos , Persona de Mediana Edad , Monofenol Monooxigenasa/metabolismo , Pigmentación de la Piel/efectos de la radiación , Análisis Espectral
6.
J Invest Dermatol ; 132(7): 1901-7, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22318388

RESUMEN

Daily skin exposure to solar radiation causes cells to produce reactive oxygen species (ROS), which are a primary factor in skin damage. Although the contribution of the UV component to skin damage has been established, few studies have examined the effects of non-UV solar radiation on skin physiology. Solar radiation comprises <10% of UV, and thus the purpose of this study was to examine the physiological response of skin to visible light (400-700 nm). Irradiation of human skin equivalents with visible light induced production of ROS, proinflammatory cytokines, and matrix metalloproteinase (MMP)-1 expression. Commercially available sunscreens were found to have minimal effects on reducing visible light-induced ROS, suggesting that UVA/UVB sunscreens do not protect the skin from visible light-induced responses. Using clinical models to assess the generation of free radicals from oxidative stress, higher levels of free radical activity were found after visible light exposure. Pretreatment with a photostable UVA/UVB sunscreen containing an antioxidant combination significantly reduced the production of ROS, cytokines, and MMP expression in vitro, and decreased oxidative stress in human subjects after visible light irradiation. Taken together, these findings suggest that other portions of the solar spectrum aside from UV, particularly visible light, may also contribute to signs of premature photoaging in skin.


Asunto(s)
Luz , Metaloproteinasas de la Matriz/biosíntesis , Especies Reactivas de Oxígeno/metabolismo , Piel/efectos de la radiación , Antioxidantes/farmacología , Células Cultivadas , Citocinas/biosíntesis , Receptores ErbB/fisiología , Quinasas MAP Reguladas por Señal Extracelular/fisiología , Humanos , Mediciones Luminiscentes , Dímeros de Pirimidina/biosíntesis , Transducción de Señal/efectos de la radiación , Piel/metabolismo , Rayos Ultravioleta
7.
Arch Dermatol Res ; 303(8): 551-62, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21465312

RESUMEN

The human body has its own innate electrical system that regulates the body's functions via communications among organs through the well-known neural system. While the effect of low-level electrical stimulation on wound repair has been reported, few studies have examined the effect of electric potential on non-wounded, intact skin. A galvanic couple comprised of elemental zinc and copper was used to determine the effects of low-level electrical stimulation on intact skin physiology using a Dermacorder device. Zn-Cu induced the electrical potential recorded on intact skin, enhanced H(2)O(2) production and activated p38 MAPK and Hsp27 in primary keratinocytes. Treatment with Zn-Cu was also found to reduce pro-inflammatory cytokines, such as IL-1α, IL-2, NO and TNF-α in multiple cell types after stimulation with PHA or Propionibacterium acnes bacteria. The Zn-Cu complex led to a dose-dependent inhibition of TNF-α-induced NF-κB levels in keratinocytes as measured by a dual-luciferase promoter assay, and prevented p65 translocation to the nucleus observed via immunofluorescence. Suppression of NF-κB activity via crosstalk with p38 MAPK might be one of the potential pathways by which Zn-Cu exerted its inflammatory effects. Topical application of Zn-Cu successfully mitigated TPA-induced dermatitis and oxazolone-induced hypersensitivity in mice models of ear edema. Anti-inflammatory activity induced by the Zn-Cu galvanic couple appears to be mediated, at least in part, by production of low level of hydrogen peroxide since this activity is reversed by the addition of Catalase enzyme. Collectively, these results show that a galvanic couple containing Zn-Cu strongly reduces the inflammatory and immune responses in intact skin, providing evidence for the role of electric stimulation in non-wounded skin.


Asunto(s)
Cobre/uso terapéutico , Terapia por Estimulación Eléctrica , Respuesta Galvánica de la Piel/fisiología , Inflamación/prevención & control , Nanopartículas del Metal/uso terapéutico , Fenómenos Fisiológicos de la Piel , Zinc/uso terapéutico , Adulto , Animales , Células Cultivadas , Cobre/administración & dosificación , Dermatitis/etiología , Dermatitis/fisiopatología , Dermatitis/prevención & control , Dinoprostona/metabolismo , Modelos Animales de Enfermedad , Edema/etiología , Edema/fisiopatología , Edema/prevención & control , Femenino , Humanos , Peróxido de Hidrógeno/metabolismo , Inflamación/inmunología , Inflamación/fisiopatología , Queratinocitos/citología , Queratinocitos/metabolismo , Masculino , Nanopartículas del Metal/administración & dosificación , Ratones , Persona de Mediana Edad , FN-kappa B/metabolismo , Piridinas/efectos adversos , Especies Reactivas de Oxígeno/metabolismo , Zinc/administración & dosificación , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
8.
Toxicol In Vitro ; 24(7): 2021-9, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20688150

RESUMEN

Three-dimensional in vitro skin models provide an alternative to animal testing for assessing tissue damage caused by chemical or physical agents and for the identification and characterization of agents formulated to mitigate this damage. The StrataTest® human skin model made with pathogen-free NIKS® keratinocyte progenitors is a fully-stratified tissue containing epidermal and dermal components that possesses barrier function as determined by measurements of electrical impedance. Independent batches of skin tissues responded consistently to known chemical irritants even after refrigerated storage for up to 7 days. Reactive oxygen species (ROS) were detected after exposure of skin tissues to ozone, cigarette smoke or ultraviolet (UV) irradiation. Pretreatment with the antioxidant parthenolide-depleted (PD)-Feverfew extract prevented cigarette smoke-induced or UV irradiation-mediated increases in ROS. Interleukin (IL)-1α and IL-1 receptor antagonist (IL-1RA) secretion increased in a dose dependent manner following UV irradiation but cytokine release was abrogated by pretreatment with a UVA/UVB sunscreen. Similarly, immunohistochemical detection showed increased thymidine dimer formation in UV-irradiated skin tissue that was prevented with sunscreen pretreatment. These results demonstrate that the StrataTest® human skin model is broadly applicable to a wide range of in vitro toxicological assays.


Asunto(s)
Modelos Biológicos , Piel/efectos de los fármacos , Pruebas de Toxicidad/métodos , Alternativas a las Pruebas en Animales/métodos , Antioxidantes/farmacología , Relación Dosis-Respuesta a Droga , Humanos , Ozono/toxicidad , Especies Reactivas de Oxígeno/metabolismo , Refrigeración , Piel/metabolismo , Piel/efectos de la radiación , Protectores Solares/farmacología , Contaminación por Humo de Tabaco/efectos adversos , Rayos Ultravioleta/efectos adversos
9.
J Invest Dermatol ; 130(10): 2448-56, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20505747

RESUMEN

Prostaglandin D(2) (PGD(2)) is known to have antipruritic activity by suppressing histamine release. However, agents that can topically induce PGD(2) for itch relief are not well established. The antimycotic sertaconazole nitrate (STZ) has been shown to exhibit anti-itch properties; however, the mechanism for this activity has not been elucidated. STZ mitigated degranulation of RBL-2H3 (rat basophilic leukemia) mast cells induced by compound 48/80, a pruritogenic agent known to promote the release of histamine, and augmented PGD(2) production in mast cells and macrophages. Addition of exogenous PGD(2) abrogated compound 48/80-induced degranulation by acting through the prostanoid D receptor 1 (DP1). STZ induced p38 mitogen-activated protein kinase (MAPK) phosphorylation in mast cells and a pharmacological inhibitor of p38 MAPK, SB203580, resulted in the attenuation of PGD(2) levels. Finally, in a murine model of pruritus, the scratching behavior induced by compound 48/80 was mitigated by topical application of STZ. This effect was reversed by the addition of the cyclooxygenase inhibitor, ibuprofen, or a DP1 receptor antagonist (MK0524). Collectively, these results suggest that STZ mediates its anti-itch effects by boosting the antipruritic agent, PGD(2), by the activation of the p38-MAPK pathway. This is the first report to demonstrate a promising approach to topically induce PGD(2) for improving pruritus.


Asunto(s)
Imidazoles/farmacología , Macrófagos/efectos de los fármacos , Mastocitos/efectos de los fármacos , Prostaglandina D2/metabolismo , Prurito/tratamiento farmacológico , Tiofenos/farmacología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Administración Tópica , Animales , Antifúngicos/farmacología , Degranulación de la Célula/efectos de los fármacos , Línea Celular , Interacciones Farmacológicas , Histamina/metabolismo , Indoles/farmacología , Macrófagos/citología , Macrófagos/metabolismo , Mastocitos/citología , Mastocitos/metabolismo , Ratones , Ratones Endogámicos ICR , Prostaglandina D2/farmacología , Prurito/inducido químicamente , Prurito/metabolismo , Ratas , Receptores de Prostaglandina/metabolismo , p-Metoxi-N-metilfenetilamina/farmacología
10.
Arch Dermatol Res ; 300(10): 569-74, 2008 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-18461339

RESUMEN

Oatmeal has been used for centuries as a soothing agent to relieve itch and irritation associated with various xerotic dermatoses; however few studies have sought to identify the active phytochemical(s) in oat that mediate this anti-inflammatory activity. Avenanthramides are phenolic compounds present in oats at approximately 300 parts per million (ppm) and have been reported to exhibit anti-oxidant activity in various cell-types. In the current study we investigated whether these compounds exert anti-inflammatory activity in the skin. We found that avenanthramides at concentrations as low as 1 parts per billion inhibited the degradation of inhibitor of nuclear factor kappa B-alpha (IkappaB-alpha) in keratinocytes which correlated with decreased phosphorylation of p65 subunit of nuclear factor kappa B (NF-kappaB). Furthermore, cells treated with avenanthramides showed a significant inhibition of tumor necrosis factor-alpha (TNF-alpha) induced NF-kappaB luciferase activity and subsequent reduction of interleukin-8 (IL-8) release. Additionally, topical application of 1-3 ppm avenanthramides mitigated inflammation in murine models of contact hypersensitivity and neurogenic inflammation and reduced pruritogen-induced scratching in a murine itch model. Taken together these results demonstrate that avenanthramides are potent anti-inflammatory agents that appear to mediate the anti-irritant effects of oats.


Asunto(s)
Avena , Flavonoides/uso terapéutico , Inflamación/tratamiento farmacológico , Fenoles/uso terapéutico , Fitoterapia , Prurito/tratamiento farmacológico , ortoaminobenzoatos/uso terapéutico , Animales , Células Cultivadas , Dermatitis por Contacto/tratamiento farmacológico , Dermatitis por Contacto/etiología , Dermatitis por Contacto/metabolismo , Modelos Animales de Enfermedad , Diterpenos/efectos adversos , Flavonoides/farmacología , Humanos , Inflamación/etiología , Inflamación/metabolismo , Interleucina-8/metabolismo , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Ratones , Ratones Endogámicos ICR , FN-kappa B/metabolismo , Oxazolona/efectos adversos , Fenoles/farmacología , Polifenoles , Prurito/etiología , Prurito/metabolismo , Transducción de Señal/fisiología , ortoaminobenzoatos/farmacología
11.
Pigment Cell Melanoma Res ; 21(2): 172-83, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18426410

RESUMEN

The protease-activated receptor-2 (PAR-2) is a seven transmembrane G-protein-coupled receptor that could be activated by serine protease cleavage or by synthetic peptide agonists. We showed earlier that activation of PAR-2 with Ser-Leu-Ile-Gly-Arg-Leu-NH(2) (SLIGRL), a known PAR-2 activating peptide, induces keratinocyte phagocytosis and increases skin pigmentation, indicating that PAR-2 regulates pigmentation by controlling phagocytosis of melanosomes. Here, we show that Leu-Ile-Gly-Arg-NH(2) (LIGR) can also induce skin pigmentation. Both SLIGRL and LIGR increased melanin deposition in vitro and in vivo, and visibly darkened human skins grafted onto severe combined immuno-deficient (SCID) mice. Both SLIGRL and LIGR stimulated Rho-GTP activation resulting in keratinocyte phagocytosis. Interestingly, LIGR activates only a subset of the PAR-2 signaling pathways, and unlike SLIGRL, it does not induce inflammatory processes. LIGR did not affect many PAR-2 signaling pathways, including [Ca(2+)] mobilization, cAMP induction, the induction of cyclooxgenase-2 (COX-2) expression and the secretion of prostaglandin E2, interleukin-6 and -8. PAR-2 siRNA inhibited LIGR-induced phagocytosis, indicating that LIGR signals via PAR-2. Our data suggest that LIGR is a more specific regulator of PAR-2-induced pigmentation relative to SLIGRL. Therefore, enhancing skin pigmentation by topical applications of LIGR may result in a desired tanned-like skin color, without enhancing inflammatory processes, and without the need of UV exposure.


Asunto(s)
Administración Tópica , Péptidos/farmacología , Receptor PAR-2 , Pigmentación de la Piel/efectos de los fármacos , Animales , Western Blotting , Células Cultivadas , Femenino , Silenciador del Gen , Humanos , Inflamación , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Ratones , Ratones SCID , Péptidos/genética , Fagocitosis , Receptor PAR-2/genética , Receptor PAR-2/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal/efectos de los fármacos , Trasplante de Piel , Porcinos , Trasplante Heterólogo
12.
Arch Dermatol Res ; 300(2): 69-80, 2008 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-18071724

RESUMEN

The skin is under continual assault from a variety of damaging environmental factors such as ultraviolet irradiation and atmospheric pollutants, and as organisms age the cumulative damage exceeds the capacity of endogenous antioxidant defenses resulting in chronic inflammation and premature aging. Botanical extracts such as Feverfew containing naturally occurring antioxidants could replenish the depleted cutaneous stores and perhaps forestall these degenerative changes. A parthenolide-depleted extract of Feverfew (PD-Feverfew), which was free of sensitization potential, was found to possess free radical scavenging activity against a wide range of reactive oxygen species and with greater activity than Vitamin C. In vitro, PD-Feverfew restored cigarette smoke-mediated depletion of cellular thiols, attenuated the formation of UV-induced hydrogen peroxide and reduced pro-inflammatory cytokine release. In vivo, topical PD-Feverfew reduced UV-induced epidermal hyperplasia, DNA damage and apoptosis. In a clinical study PD-Feverfew treatment significantly reduced erythema versus placebo 24 h post-UV exposure. Through the ability to scavenge free radicals, preserve endogenous antioxidant levels, reduce DNA damage and induce DNA repair enzymes, which can help repair damaged DNA, parthenolide-depleted extract of Feverfew may protect skin from the numerous external aggressions encountered daily by the skin and reduce the damage to oxidatively challenged skin.


Asunto(s)
Exposición a Riesgos Ambientales/efectos adversos , Eritema/prevención & control , Hiperplasia/prevención & control , Extractos Vegetales/uso terapéutico , Piel/patología , Piel/efectos de la radiación , Tanacetum parthenium , Rayos Ultravioleta/efectos adversos , Administración Tópica , Animales , Estudios de Casos y Controles , Células Cultivadas , Reparación del ADN , Eritema/etiología , Femenino , Depuradores de Radicales Libres/uso terapéutico , Humanos , Peróxido de Hidrógeno/antagonistas & inhibidores , Peróxido de Hidrógeno/efectos de la radiación , Hiperplasia/etiología , Inflamación , Masculino , Ratones , Ratones Pelados , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Sesquiterpenos/aislamiento & purificación , Sesquiterpenos/metabolismo , Piel/inmunología , Envejecimiento de la Piel/efectos de la radiación , Fumar/efectos adversos , Porcinos
13.
J Invest Dermatol ; 128(2): 336-44, 2008 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-17637821

RESUMEN

Sertaconazole nitrate is an antifungal agent that exhibits anti-inflammatory activity; however, the mechanism for this action was unknown. We investigated the cellular mechanisms by which sertaconazole exerts its anti-inflammatory activity in keratinocytes and human peripheral blood mononuclear cells (PBMCs). Paradoxically, sertaconazole was found to activate the proinflammatory p38 mitogen-activated protein kinase. Treatment with sertaconazole also resulted in the induction of cyclooxygenase-2 (COX-2) and the subsequent release of prostaglandin E2 (PGE2). Knocking down p38 in keratinocytes using small interfering RNA resulted in an inhibition of sertaconazole-induced PGE2 release confirming that activation of p38 was required for PGE2 production. Additionally, in stimulated keratinocytes and human PBMCs, sertaconazole was found to suppress the release of cytokines. Treatment with anti-PGE2 antiserum or the COX-2 inhibitor NS398 reversed the inhibitory effects of sertaconazole on the release of proinflammatory cytokines, linking endogenous PGE2 with the anti-inflammatory effects. Finally, in an in vivo mouse model of tetradecanoyl phorbol acetate (TPA)-induced dermatitis, the sertaconazole-mediated inhibition of TPA-induced ear edema was reversed by NS398. Biochemical analysis of tissue biopsies revealed increase in PGE2 levels in sertaconazole-treated mice. Thus, activation of the p38-COX-2-PGE2 pathway by agents such as sertaconazole provides anti-inflammatory therapeutic benefits.


Asunto(s)
Antiinflamatorios/farmacología , Antifúngicos/farmacología , Dermatitis por Contacto/tratamiento farmacológico , Imidazoles/farmacología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/inmunología , Tiofenos/farmacología , Acné Vulgar/tratamiento farmacológico , Acné Vulgar/inmunología , Acné Vulgar/microbiología , Animales , Biopsia , Carcinógenos/farmacología , Línea Celular , Ciclooxigenasa 2/metabolismo , Citocinas/metabolismo , Dermatitis por Contacto/inmunología , Dermatitis por Contacto/patología , Dinoprostona/metabolismo , Activación Enzimática/efectos de los fármacos , Activación Enzimática/inmunología , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/inmunología , Humanos , Irritantes , Queratinocitos/citología , Queratinocitos/efectos de los fármacos , Queratinocitos/inmunología , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/inmunología , Ratones , Propionibacterium acnes , ARN Interferente Pequeño , Acetato de Tetradecanoilforbol/farmacología , Proteínas Quinasas p38 Activadas por Mitógenos/genética , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
14.
Arch Dermatol Res ; 298(4): 191-9, 2006 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-16868738

RESUMEN

Cutaneous fungal infections are frequently associated with an inflammatory component including irritated skin, itching and stinging/burning. Therapeutic anti-fungal agents that have anti-inflammatory activity have the potential to provide clinical benefit beyond fungus eradication. Recently, certain anti-fungal agents have been shown to have intrinsic anti-inflammatory activity, therefore we sought to determine the extent of the anti-inflammatory activity of these compounds. The anti-inflammatory activities of eight anti-fungal agents (butoconazole, ciclopirox olamine, fluconazole, miconazole nitrate, sertaconazole nitrate, terconazole, tioconazole and ketoconazole) were compared in a number of preclinical models of dermal inflammation and pruritus. While butoconazole, ciclopirox olamine, fluconazole, and miconazole nitrate were all found to have anti-inflammatory activity, only sertaconazole nitrate reduced the release of cytokines from activated lymphocytes and mitigated inflammation in animal models of irritant contact dermatitis and neurogenic inflammation. In addition, sertaconazole nitrate inhibited contact hypersensitivity and scratching responses in a murine model of pruritus. Furthermore, the in vitro and in vivo anti-inflammatory activity of sertaconazole nitrate was found to be greater than other topical anti-fungal agents examined. These studies demonstrate that topical administration of clinically relevant concentrations of sertaconazole nitrate resulted in an efficacious anti-inflammatory activity against a broad spectrum of dermal inflammation models and itch. The anti-inflammatory properties of sertaconazole may contribute to the efficacy of the drug in the treatment of cutaneous fungal conditions and provide greater anti-inflammatory activity compared with other anti-fungal agents.


Asunto(s)
Antifúngicos/farmacología , Citocinas/efectos de los fármacos , Dermatitis Irritante/tratamiento farmacológico , Imidazoles/farmacología , Prurito/tratamiento farmacológico , Linfocitos T/efectos de los fármacos , Tiofenos/farmacología , Animales , Antiinflamatorios/farmacología , Dermatomicosis/complicaciones , Dermatomicosis/tratamiento farmacológico , Humanos , Masculino , Ratones , Ratones Endogámicos , Modelos Animales , Prurito/etiología
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