RESUMO
The atopic dermatitis (AD) complex pathogenesis mechanism reveals marked changes of certain signaling factors as well as some morphological alterations in the epidermis. Reduced resilience against environmental factors and oxidative stress often makes the treatment with corticosteroids or tacrolismus ointments indispensable. In view of the correlation between oxidative stress and AD pathological factors, antioxidants can be incorporated into AD management strategies. This study investigates a curly kale, apple and green tea-containing natural extract rich in antioxidants for its effects on signaling inflammatory molecules and skin barrier enhancement in human epidermal keratinocytes- (NHEKs) based cell assays. Furthermore, the skin penetration on porcine ears was measured ex vivo using Raman micro spectroscopy. Finally, in a double-blind half-side, placebo-controlled clinical study, the effects of a formulation containing this extract were analyzed for the influence of lesion severity, epidermal barrier function, and pruritus in mild to moderately AD patients. Summarizing our results: The extract reduces expression of inflammatory cytokines in keratinocytes and increases barrier-related molecules. The verum formulation with a very high antioxidant capacity used in AD patients with mild to moderate lesions reduces itching, local SCORAD, and improves barrier function and the hydration of skin lesions.
RESUMO
Two differently designed, spatially resolved reflectance spectroscopy-based scanners and two-photon tomography were used for noninvasive in vivo determination of cutaneous carotenoids, and collagen I/elastin aging index of dermis, respectively, in the skin of 29 healthy female volunteers between 40 and 56 years of age. The volunteers received a supplement in the form of a carotenoid-rich natural curly kale extract containing 1650 µg of carotenoids in total (three capsules of 550 µg), once a day. Measurements were taken before, after 5 months and after 10 months of daily supplementation. The results showed significantly increased values for the cutaneous carotenoids and the collagen I/elastin aging index of dermis 5 and 10 months after the beginning of the study. The obtained results show that a natural carotenoid-rich extract could prevent the aging-related collagen I degradation in the dermis and improve the extracellular matrix.
Assuntos
Brassica/química , Carotenoides/administração & dosagem , Colágeno Tipo I/metabolismo , Elastina/metabolismo , Extratos Vegetais/administração & dosagem , Envelhecimento da Pele/efeitos dos fármacos , Pele/efeitos dos fármacos , Adulto , Suplementos Nutricionais , Matriz Extracelular/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , Pele/metabolismoRESUMO
Type 2 diabetes mellitus (T2DM) is a common and increasingly prevalent metabolic disorder, and effective preventive strategies against this disease are needed. The aim of the present study was to evaluate the potential antidiabetic properties of a dietary apple/kale extract (AKE), which was rich in phlorizin and flavonoids, in laboratory mice. Mice were fed a control diet, a Western-type high-sugar, high-fat diet (WTD), or a WTD plus AKE for 10 weeks. Body weight, food and energy intake, body composition, and blood glucose level were recorded in addition to the postprandial rise in blood glucose concentration after a single administration of glucose (oral glucose tolerance test, OGTT). Furthermore, changes in glucose-induced short-circuit current (ISC) in response to AKE and phlorizin administration were evaluated in situ in intestinal tissues with Ussing chambers. In addition, the in vitro inhibition of α-glucosidase by AKE was determined. The present data suggest that supplementation of an AKE to a WTD significantly improved both blood glucose levels and OGTT in mice. Furthermore, in situ uptake of glucose was significantly inhibited by AKE. Finally, we showed that AKE significantly inhibits α-glucosidase activity in vitro. We conclude that AKE exhibits antidiabetic properties by a dual mechanism, including the inhibition of α-glucosidase and sodium-dependent glucose transporter 1 (SGLT1). Thus, AKE has the potential to serve as a natural plant bioactive compound for dietary prevention strategies against T2DM.
Assuntos
Brassica/química , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Malus/química , Extratos Vegetais/administração & dosagem , Animais , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Dieta Hiperlipídica/efeitos adversos , Feminino , Flavonoides/administração & dosagem , Teste de Tolerância a Glucose , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Florizina/administração & dosagem , Transportador 1 de Glucose-Sódio/genética , Transportador 1 de Glucose-Sódio/metabolismo , alfa-Glucosidases/genética , alfa-Glucosidases/metabolismoRESUMO
Ion transporters are emerging targets of increasing importance to the pharmaceutical industry because of their relevance to a wide range of numerous indications of cardiovascular, metabolic, and inflammatory diseases. However, traditional ion transporter assay technologies using radioactive or fluorescent ligands and substrates or manual patch clamping suffer from several problems: limited sensitivity and robustness, significant numbers of false positives and false negatives, and cost. The authors describe a novel method for the measurement of ion transporters using cell-free electrophysiology based on the SURFE (2) R (surface electrogenic event reader) technology platform. The main advantages of the method described here are high sensitivity and simple handling. Material for assays is mainly a simple membrane preparation, which can be stored over weeks and months. Thus, the application of the method does not depend on a permanently running cell-culture lab. The application of the technology itself uses a bench-top system and chips loaded with membrane fragments. The SURFE (2) R technology was used to establish an Na+/Ca2+-exchanger assay. The assay performance, as judged by the Z' value of 0.73 and the signal-to-background ratio of 7.6, suggests that this is a reliable and robust assay. The authors compared the technology with patch-clamp experiments: The measurement of activity of 17 different inhibitors and the determination of an IC (50)value indicated a good correlation between SURFE (2) R technology and patch clamp results. Using the SURFE (2) R technology, results were obtained with 20 times higher throughput and required less-qualified personnel compared with manual patch clamping.
Assuntos
Proteínas de Transporte/fisiologia , Eletrofisiologia/métodos , Farmacologia , Animais , Técnicas Biossensoriais , Linhagem Celular , Cricetinae , Humanos , Transporte de Íons , Técnicas de Patch-ClampRESUMO
In the last decade, cutaneous carotenoid measurements have become increasingly popular, as carotenoids were found to be a biomarker of nutrition rich in fruits and vegetables, permitting monitoring of the influence of various stress factors. For such measurements, in addition to the specific and selective resonance Raman spectroscopy (RRS), newly developed low expensive small and mobile sensors that are based on spatially resolved reflectance spectroscopy (SRRS) are used for cutaneous carotenoid measurements. Human volunteers of different age exhibiting skin types I to III were investigated using RRS and two SRRS-based sensors to determine the influence of these parameters on the measuring results. In two studies on volunteers of either the same age or skin type, however, the respective other parameter being varied and no significant influences of age or skin type could be detected. Furthermore, the kinetic changes resulting from the intake and discontinued intake of a vegetable extract rich in carotenoids showed a good correlation among the three sensors and with the detected blood carotenoids. This illustrates that the SRRS-based sensors and RRS device provide reliable cutaneous carotenoid values independent of age and skin types I to III of the volunteers.
Assuntos
Carotenoides/sangue , Dieta , Pele/química , Análise Espectral Raman , Verduras , Adulto , Idoso , Biomarcadores/sangue , Biomarcadores/química , Carotenoides/administração & dosagem , Carotenoides/análise , Carotenoides/farmacocinética , Desenho de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacocinética , Pele/irrigação sanguínea , Análise Espectral Raman/instrumentação , Análise Espectral Raman/métodos , Adulto JovemRESUMO
SCOPE: There is a growing interest in food constituents that could reduce intestinal glucose absorption to prevent overshooting plasma glucose and insulin levels in patients with prediabetes and diabetes mellitus type 2. METHODS AND RESULTS: We here demonstrate that an extract and individual polyphenols from apple diminish sodium-coupled glucose transporter 1 (SGLT1) mediated glucose uptake in vitro and in vivo. Inhibition of transport of sugars by SGLT1 was shown in Xenopus oocytes and in mice jejunal segments. Strongest inhibition was observed for phlorizin with IC50 values for transport inhibition of 0.46 ± 0.19 and 4.1 ± 0.6 µM in oocytes and intestinal segments, respectively. An oral glucose tolerance test performed in volunteers with prior administration of the apple extract reduced venous blood glucose and plasma insulin levels, similar to findings obtained in C57BL/6N mice. Analysis of human urine samples revealed that the extract increased modestly renal glucose loss that is most likely a result of inhibition of renal glucose reabsorption by phloretin derivatives found in plasma of the volunteers. CONCLUSION: Although the apple extract substantially decreased intestinal glucose absorption in all test systems, the finding that there are systemic effects that relate to inhibition of glucose transport processes beyond the intestine addresses safety issues that need further exploitation.
Assuntos
Glicemia/metabolismo , Hipoglicemiantes/farmacologia , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Transportador 1 de Glucose-Sódio/antagonistas & inibidores , Adulto , Animais , Feminino , Glicosúria/tratamento farmacológico , Humanos , Masculino , Malus , Camundongos Endogâmicos C57BL , Oócitos/efeitos dos fármacos , Florizina/farmacologia , Polifenóis/análise , Período Pós-Prandial/efeitos dos fármacos , Transportador 1 de Glucose-Sódio/genética , Transportador 1 de Glucose-Sódio/metabolismo , Xenopus laevis , Adulto JovemRESUMO
Skin functions and structure are significantly influenced by nutrients. Antioxidants protect the supportive layer of the skin against any damaging irradiation effects and the action of free radicals. A lack of suitable methods means that the pharmacokinetic properties of systemically applied carotenoids transferred into the skin remain poorly understood. In this study, a natural kale extract or placebo oil were given orally to 22 healthy volunteers for 4 weeks. Carotenoid bioaccessibility was evaluated using non-invasive resonance Raman spectroscopy on the palm and forehead skin. For the analysis of the blood serum, the standard HPLC method was used. The blood and skin levels of the carotenoids increased significantly during the study but compared to the blood serum values, increases in skin were delayed and depended on the dermal area as well as on the carotenoid. Lycopene, measured as being low in the extract, increases more in the skin compared to the blood indicating that the natural mixture of the extract stabilizes the antioxidative network in the skin. After supplementation had ended, the carotenoids decreased much faster in the blood than in the skin. The delayed decrease in the skin may indicate a peripheral buffer function of the skin for carotenoids.