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2.
Oxid Med Cell Longev ; 2018: 9524657, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29643980

RESUMEN

The skin covers the outer surface of the body, so the epidermal keratinocytes within it are susceptible to reactive oxygen species (ROS) generated by environmental pollutants such as benzo(a)pyrene (BaP), a potent activator of aryl hydrocarbon receptor (AHR). Antioxidant activity is generally mediated by the nuclear factor-erythroid 2-related factor-2 (NRF2) and heme oxygenase-1 (HO1) axis in human keratinocytes. Perillaldehyde is the main component of Perilla frutescens, which is a medicinal antioxidant herb traditionally consumed in East Asia. However, the effect of perillaldehyde on the AHR/ROS and/or NRF2/HO1 pathways remains unknown. In human keratinocytes, we found that perillaldehyde (1) inhibited BaP-induced AHR activation and ROS production, (2) inhibited BaP/AHR-mediated release of the CCL2 chemokine, and (3) activated the NRF2/HO1 antioxidant pathway. Perillaldehyde is thus potentially useful for managing inflammatory skin diseases or disorders related to oxidative stress.


Asunto(s)
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/antagonistas & inhibidores , Queratinocitos/efectos de los fármacos , Monoterpenos/farmacología , Factor 2 Relacionado con NF-E2/metabolismo , Receptores de Hidrocarburo de Aril/antagonistas & inhibidores , Antioxidantes/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Benzo(a)pireno/farmacología , Línea Celular , Núcleo Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Supervivencia Celular/efectos de los fármacos , Quimiocina CCL2/biosíntesis , Citocromo P-450 CYP1A1/antagonistas & inhibidores , Citocromo P-450 CYP1A1/biosíntesis , Hemo-Oxigenasa 1/antagonistas & inhibidores , Hemo-Oxigenasa 1/metabolismo , Humanos , Queratinocitos/citología , Queratinocitos/metabolismo , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Especies Reactivas de Oxígeno/metabolismo , Receptores de Hidrocarburo de Aril/metabolismo , Transducción de Señal/efectos de los fármacos
3.
J Invest Dermatol ; 137(10): 2217-2226, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28552542

RESUMEN

Wound healing is an elaborate process composed of overlapping phases, such as proliferation and remodeling, and is delayed in several circumstances, including diabetes. Although several treatment strategies for chronic wounds, such as growth factors, have been applied, further alternatives are required. The skin, especially keratinocytes, is continually exposed to UV rays, which impairs wound healing. 6-Formylindolo[3,2-b]carbazole (FICZ) is a tryptophan photoproduct formed by UV exposure, indicating that FICZ might be one of the effectors of UV radiation. In contrast, treatment with tryptophan, the precursor for FICZ, promoted wound closure in keratinocytes. Therefore, the aim of our study was to determine the role of FICZ in wound healing. Here we showed that FICZ enhanced keratinocyte migration through mitogen-activated protein kinase/extracellular signal-regulated kinase activation, and promoted wound healing in various mouse models, including db/db mice, which exhibit wound healing impairments because of type 2 diabetes. Moreover, FICZ, the endogenous ligand of an aryl hydrocarbon receptor, accelerated migration even in the aryl hydrocarbon receptor knockdown condition and also promoted wound healing in DBA/2 mice, bearing a low-affinity aryl hydrocarbon receptor, suggesting that FICZ enhanced keratinocyte migration in a mitogen-activated protein kinase/extracellular signal-regulated kinase-dependent, but aryl hydrocarbon receptor-independent, manner. The function of FICZ might indicate the possibility of its clinical use for intractable chronic wounds.


Asunto(s)
Carbazoles/farmacología , Diabetes Mellitus Experimental , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Receptores de Hidrocarburo de Aril/metabolismo , Piel/patología , Cicatrización de Heridas/efectos de los fármacos , Animales , Línea Celular , Movimiento Celular , Humanos , Queratinocitos/metabolismo , Ratones , Ratones Endogámicos DBA , Piel/efectos de los fármacos , Piel/metabolismo
4.
J Dermatol Sci ; 85(1): 36-43, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27720465

RESUMEN

BACKGROUND: Dioxins and other environmental pollutants are toxic and remain in biological tissues for a long time leading to various levels of oxidative stress. Although the toxicity of these agents has been linked to activation of the aryl hydrocarbon receptor (AHR), no effective treatment has been developed. OBJECTIVE: To explore novel phytochemicals that inhibit AHR activation in keratinocytes. METHODS: Keratinocytes were used in this study because the skin is one of the organs most affected by dioxin and other environmental pollutants. HaCaT cells, which are a human keratinocyte cell line, and normal human epidermal keratinocytes were stimulated with benzo[a]pyrene to induce AHR activation, and the effects of traditional Japanese Kampo herbal formulae were analyzed. Quantification of mRNA, western blotting, immunofluorescence localization of molecules, siRNA silencing, and visualization of oxidative stress were performed. RESULTS: Cinnamomum cassia extract and its major constituent cinnamaldehyde significantly inhibited the activation of AHR. Cinnamaldehyde also activated the NRF2/HO1 pathway and significantly alleviated the production of reactive oxygen species in keratinocytes. The inhibition of AHR signaling and the activation of antioxidant activity by cinnamaldehyde operated in a mutually independent manner as assessed by siRNA methods In addition, AHR signaling was effectively inhibited by traditional Kampo formulae containing C. cassia. CONCLUSION: Cinnamaldehyde has two independent biological activities; namely, an inhibitory action on AHR activation and an antioxidant effect mediated by NRF2/HO1 signaling. Through these dual functions, cinnamaldehyde may be beneficial for the treatment of disorders related to oxidative stress such as dioxin intoxication, acne, and vitiligo.


Asunto(s)
Acroleína/análogos & derivados , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Cinnamomum aromaticum/química , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo/efectos de los fármacos , Receptores de Hidrocarburo de Aril/metabolismo , Transducción de Señal/efectos de los fármacos , Acroleína/farmacología , Antioxidantes/farmacología , Benzo(a)pireno/metabolismo , Línea Celular , Dioxinas/toxicidad , Contaminantes Ambientales/toxicidad , Células Epidérmicas , Epidermis/efectos de los fármacos , Epidermis/metabolismo , Hemo-Oxigenasa 1/metabolismo , Humanos , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Medicina Kampo , Factor 2 Relacionado con NF-E2/genética , Oxidación-Reducción/efectos de los fármacos , Extractos Vegetales/farmacología , Interferencia de ARN , Especies Reactivas de Oxígeno/metabolismo
5.
Nat Mater ; 14(3): 330-6, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25485987

RESUMEN

Organic compounds that exhibit highly efficient, stable blue emission are required to realize inexpensive organic light-emitting diodes for future displays and lighting applications. Here, we define the design rules for increasing the electroluminescence efficiency of blue-emitting organic molecules that exhibit thermally activated delayed fluorescence. We show that a large delocalization of the highest occupied molecular orbital and lowest unoccupied molecular orbital in these charge-transfer compounds enhances the rate of radiative decay considerably by inducing a large oscillator strength even when there is a small overlap between the two wavefunctions. A compound based on our design principles exhibited a high rate of fluorescence decay and efficient up-conversion of triplet excitons into singlet excited states, leading to both photoluminescence and internal electroluminescence quantum yields of nearly 100%.

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