RESUMEN
BACKGROUND: Oily skin condition is caused by an excessive sebaceous gland activity, resulting in an overproduction of sebum, giving the skin an undesired shiny, oily appearance. AIMS: To identify an active substance that reduces sebum production in human sebaceous glands by regulating fat metabolism in a natural way. PATIENTS/METHODS: The effects of L-carnitine on ß-oxidation and intracellular lipid content were investigated in vitro using the human sebaceous cell line SZ95. Penetration experiments utilizing pig skin as a model system were performed with a cosmetic formulation containing radioactively labeled L-carnitine. To determine the in vivo effects, a vehicle-controlled, randomized study was carried out using a cosmetic formulation containing 2%l-carnitine for 3 weeks. Sebum production was investigated utilizing the lipid-absorbent Sebutape(®). RESULTS: SZ95 cells treated with 0.5% or 1% L-carnitine demonstrated a significant concentration-dependent increase in ß-oxidation compared to control cells. Following the treatment with L-carnitine, intracellular lipid concentrations decreased significantly in a dose-dependent manner compared with untreated control cells. In skin penetration experiments, topically applied L-carnitine reached the dermis. In addition, topical in vivo application of a formulation containing 2% L-carnitine for 3 weeks significantly decreased the sebum secretion rate compared to the treatment with vehicle. CONCLUSIONS: Our results show that the treatment of human sebocytes with L-carnitine significantly augments ß-oxidation and significantly decreases intracellular lipid content in human sebocytes. Topically applied L-carnitine is bioavailable and leads to a significant sebum reduction in vivo. In conclusion, L-carnitine represents a valuable compound, produced naturally within the body, for the topical treatment of oily skin in humans.
Asunto(s)
Carnitina/farmacología , Glándulas Sebáceas/efectos de los fármacos , Glándulas Sebáceas/metabolismo , Sebo/metabolismo , Complejo Vitamínico B/farmacología , Administración Cutánea , Adulto , Animales , Carnitina/farmacocinética , Células Cultivadas , Relación Dosis-Respuesta a Droga , Cara , Femenino , Humanos , Metabolismo de los Lípidos/efectos de los fármacos , Persona de Mediana Edad , Oxidación-Reducción , Sebo/efectos de los fármacos , Porcinos , Complejo Vitamínico B/farmacocinética , Adulto JovenRESUMEN
BACKGROUND: The dermal extracellular matrix provides stability and structure to the skin. With increasing age, however, its major component collagen is subject to degeneration, resulting in a gradual decline in skin elasticity and progression of wrinkle formation. Previous studies suggest that the reduction in cellular energy contributes to the diminished synthesis of cutaneous collagen during aging. AIMS: To investigate the potential of topically applied creatine to improve the clinical signs of skin aging by stimulating dermal collagen synthesis in vitro and in vivo. PATIENTS/METHODS: Penetration experiments were performed with a pig skin ex vivo model. Effects of creatine on dermal collagen gene expression and procollagen synthesis were studied in vitro using cultured fibroblast-populated collagen gels. In a single-center, controlled study, 43 male Caucasians applied a face-care formulation containing creatine, guarana extract, and glycerol to determine its influence on facial topometric features. RESULTS: Cultured human dermal fibroblasts supplemented with creatine displayed a stimulation of collagen synthesis relative to untreated control cells both on the gene expression and at the protein level. In skin penetration experiments, topically applied creatine rapidly reached the dermis. In addition, topical in vivo application of a creatine-containing formulation for 6 weeks significantly reduced the sagging cheek intensity in the jowl area as compared to baseline. This result was confirmed by clinical live scoring, which also demonstrated a significant reduction in crow's feet wrinkles and wrinkles under the eyes. CONCLUSIONS: In summary, creatine represents a beneficial active ingredient for topical use in the prevention and treatment of human skin aging.
Asunto(s)
Colágeno/biosíntesis , Creatina/farmacocinética , Creatina/uso terapéutico , Envejecimiento de la Piel/efectos de los fármacos , Piel/efectos de los fármacos , Piel/metabolismo , Adulto , Anciano , Animales , Células Cultivadas , Colágeno/genética , Creatina/farmacología , Elasticidad/efectos de los fármacos , Fibroblastos/metabolismo , Expresión Génica , Glicerol/farmacología , Glicerol/uso terapéutico , Humanos , Técnicas In Vitro , Masculino , Persona de Mediana Edad , Paullinia , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Procolágeno/biosíntesis , Absorción Cutánea , Estadísticas no Paramétricas , PorcinosRESUMEN
A formal validation study was performed, in order to investigate whether the commercially-available reconstructed human epidermis (RHE) models, EPISKIN, EpiDerm and SkinEthic, are suitable for in vitro skin absorption testing. The skin types currently recommended in the OECD Test Guideline 428, namely, ex vivo human epidermis and pig skin, were used as references. Based on the promising outcome of the prevalidation study, the panel of test substances was enlarged to nine substances, covering a wider spectrum of physicochemical properties. The substances were tested under both infinite-dose and finite-dose conditions, in ten laboratories, under strictly controlled conditions. The data were subjected to independent statistical analyses. Intra-laboratory and inter-laboratory variability contributed almost equally to the total variability, which was in the same range as that in preceding studies. In general, permeation of the RHE models exceeded that of human epidermis and pig skin (the SkinEthic RHE was found to be the most permeable), yet the ranking of substance permeation through the three tested RHE models and the pig skin reflected the permeation through human epidermis. In addition, both infinite-dose and finite-dose experiments are feasible with RHE models. The RHE models did not show the expected significantly better reproducibility, as compared to excised skin, despite a tendency toward lower variability of the data. Importantly, however, the permeation data showed a sufficient correlation between all the preparations examined. Thus, the RHE models, EPISKIN, EpiDerm and SkinEthic, are appropriate alternatives to human and pig skin, for the in vitro assessment of the permeation and penetration of substances when applied as aqueous solutions.