ABSTRACT
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.
Subject(s)
Down-Regulation/drug effects , Fibroblasts/metabolism , Gene Expression Regulation, Enzymologic/drug effects , Matrix Metalloproteinase 1/biosynthesis , Scopoletin/pharmacology , p38 Mitogen-Activated Protein Kinases/metabolism , Cell Line , Fibroblasts/pathology , Humans , Phosphorylation/drug effects , Skin Aging/drug effects , Skin Aging/pathologyABSTRACT
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.
Subject(s)
Diet, High-Fat/adverse effects , Memory Disorders/drug therapy , Plant Extracts/administration & dosage , Sirtuin 1/metabolism , Animals , Body Weight/drug effects , Cognition , Hippocampus/drug effects , Hippocampus/metabolism , Humans , Male , Medicine, Korean Traditional , Memory Disorders/etiology , Memory Disorders/metabolism , Memory Disorders/psychology , Mice , Mice, Inbred C57BL , Mice, Inbred ICR , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Plants, Medicinal/chemistry , Sirtuin 1/geneticsABSTRACT
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.
Subject(s)
Biocompatible Materials/chemistry , Fluorescent Dyes/chemistry , Mitochondria/chemistry , Benzyl Compounds/chemistry , Electron Transport , HeLa Cells , Humans , Hydrogen-Ion Concentration , Membrane Potential, Mitochondrial , Mitochondria/metabolism , Naphthalimides/chemistry , Organoselenium Compounds/chemistry , Piperazine , Piperazines/chemistryABSTRACT
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.
