RESUMEN
Irradiation of keratinocytes by ultraviolet B induces cytokine production, which in turn activates fibroblasts to produce cytokines and increase matrix metallopeptidase (MMP)1 protein expression. The present study investigated the effect and potential mechanisms of scopoletin on the regulation of MMP1 expression in fibroblasts. Scopoletin was isolated from Artemisia capillaris crude extract. Treatment of fibroblasts with scopoletin resulted in a decrease in the protein expression of MMP1 following stimulation with human keratinocyte (HaCaT) conditioned medium. To further explore the mechanism underlying this effect, the expression levels of proteins in the mitogenactivated protein kinase (MAPK) and nuclear factorκB (NFκB) signaling pathways were evaluated via western blot analysis. The mRNA expression levels of interleukin (IL)1α and tumor necrosis factor (TNF) α were evaluated via reverse transcriptionquantitative polymerase chain reaction. The effect of scopoletin on cell viability was assessed with the MTT assay. The results demonstrated that scopoletin treatment markedly decreased MMP1, IL1α and TNFα mRNA expression in fibroblasts stimulated with HaCaT conditioned medium (40 mJ/cm2), without any apparent cell cytotoxicity, and in a dosedependent manner. In addition, western blot analysis demonstrated that scopoletin reduced the phosphorylation of p38 MAPK in fibroblasts. In summary, the present study demonstrated that scopoletin inhibited MMP1 and proinflammatory cytokine expression by inhibiting p38 MAPK phosphorylation. These findings suggest that scopoletin may have potential as a therapeutic agent to prevent and treat photoaging of the skin.
Asunto(s)
Regulación hacia Abajo/efectos de los fármacos , Fibroblastos/metabolismo , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Metaloproteinasa 1 de la Matriz/biosíntesis , Escopoletina/farmacología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Línea Celular , Fibroblastos/patología , Humanos , Fosforilación/efectos de los fármacos , Envejecimiento de la Piel/efectos de los fármacos , Envejecimiento de la Piel/patologíaRESUMEN
Woohwangcheongsimwon (WHC) is a mixture of herbal medicines that is widely prescribed in Korean traditional medicine. SIRT1 is known for its regulatory roles in energy metabolism, oxidative stress, and circadian rhythms. This study was designed to determine whether WHC can increase and mimic the biological reactions of SIRT1 activation. Ten-month-old male mice were divided into four groups: nontreated normal diet (ND), nontreated high-fat diet (HFD), WHC-treated ND, and WHC-treated HFD. Body weight and cognitive functions were evaluated after treatment. The hippocampal expressions of SIRT1 and PGC-1α were also measured. The components of WHC were identified by liquid chromatography. High-fat diet-fed mice gained more weight and demonstrated greater deficits in short-term and long-term cognitive functions. WHC suppressed the deleterious effects of a HFD on weight gain and cognitive decline, but showed no prominent effects on animals fed NDs. The herbal treatment also increased the expression of SIRT1 and PGC-1α in the hippocampus. Despite the induction of hippocampal SIRT1 expression by WHC, resveratrol was not present among the natural compounds identified. This expression might have contributed to the suppression of high-fat diet-induced memory deficits in mice treated with the herbal mixture.
Asunto(s)
Dieta Alta en Grasa/efectos adversos , Trastornos de la Memoria/tratamiento farmacológico , Extractos Vegetales/administración & dosificación , Sirtuina 1/metabolismo , Animales , Peso Corporal/efectos de los fármacos , Cognición , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Humanos , Masculino , Medicina Tradicional Coreana , Trastornos de la Memoria/etiología , Trastornos de la Memoria/metabolismo , Trastornos de la Memoria/psicología , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos ICR , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Plantas Medicinales/química , Sirtuina 1/genéticaRESUMEN
We report here a mitochondria-targetable pH-sensitive probe that allows for a quantitative measurement of mitochondrial pH changes, as well as the real-time monitoring of pH-related physiological effects in live cells. This system consists of a piperazine-linked naphthalimide as a fluorescence off-on signaling unit, a cationic triphenylphosphonium group for mitochondrial targeting, and a reactive benzyl chloride subunit for mitochondrial fixation. It operates well in a mitochondrial environment within whole cells and displays a desirable off-on fluorescence response to mitochondrial acidification. Moreover, this probe allows for the monitoring of impaired mitochondria undergoing mitophagic elimination as the result of nutrient starvation. It thus allows for the monitoring of the organelle-specific dynamics associated with the conversion between physiological and pathological states.
Asunto(s)
Materiales Biocompatibles/química , Colorantes Fluorescentes/química , Mitocondrias/química , Compuestos de Bencilo/química , Transporte de Electrón , Células HeLa , Humanos , Concentración de Iones de Hidrógeno , Potencial de la Membrana Mitocondrial , Mitocondrias/metabolismo , Naftalimidas/química , Compuestos de Organoselenio/química , Piperazina , Piperazinas/químicaRESUMEN
We herein report a fluorescence probe 1 capable of detecting water-soluble oligomeric Aß aggregates and Aß fibrils. Upon injection into Aß42-challenged mouse brains, probe 1 shows increased fluorescence intensity, indicating its facile binding to extracellular Aß fibrils in brain tissues.