RESUMEN
Neuroinflammation activated by microglia affects inflammatory pain development. This study aimed to explore the anti-inflammatory properties and mechanisms of 1,6,7-trihydroxy-2-(1,1-dimethyl-2-propenyl)-3-methoxyxanthone (THMX) from Cudrania tricuspidata in microglia activation-mediated inflammatory pain. In RAW 264.7 and BV2 cells, THMX has been shown to reduce lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and pro-inflammatory mediators and cytokines, including nitric oxide (NO), prostaglandin (PG) E2, interleukin (IL)-6, and tumor necrosis factor alpha (TNF-α). THMX also decreased LPS-induced phosphorylation of mitogen-activated protein kinase (MAPK) and the activation of p65 nuclear factor kappa B (NF-κB). Interestingly, THMX also activated heme oxygenase (HO)-1 expression. These findings suggest that THMX is a promising biologically active compound against inflammation through preventing MAPKs and NF-ĸB and activating HO-1 signaling pathways.
Asunto(s)
Moraceae , FN-kappa B , FN-kappa B/metabolismo , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Lipopolisacáridos/farmacología , Antiinflamatorios/farmacología , Antiinflamatorios/metabolismo , Transducción de Señal , Microglía/metabolismo , Interleucina-6/metabolismo , Dolor/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Ciclooxigenasa 2/metabolismoRESUMEN
OBJECTIVE: The prenylated xanthones compounds, macluraxanthone B (MCXB) was isolated from the MeOH extracts of Cudrania tricuspidata. In this study, we investigated the effect of MCXB on inflammatory response. MATERIALS AND METHODS: Anti-inflammatory effects of MCXB were examined in lipopolysaccharide (LPS)-stimulated RAW264.7 and BV2 cells. We observed their anti-inflammatory effects by ELISA, western blot analysis, and immunofluorescence. RESULTS: MCXB significantly inhibited the LPS-stimulated production of nitric oxide (NO), prostaglandin E2 (PGE2), interleukin-6 (IL-6), and tumor necrosis factor (TNF)-α in RAW264.7 and BV2 cells. MCXB also reduced the LPS-induced expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 proteins. Incubating cells with MCXB prevented subsequent activation of the nuclear factor kappa B (NF-κB) signaling pathway by inhibiting the nuclear localization and DNA-binding activity of the p65 subunit induced by LPS. MCXB inhibited the phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 mitogen-activated protein kinases (MAPKs) in RAW264.7 and BV2 cells. MCXB induced the expression of heme oxygenase (HO)-1 protein, and the inhibitory effect of MCXB on nitric oxide production was partially reversed by a selective HO-1 inhibitor. DISCUSSION AND CONCLUSIONS: Our results suggested that the anti-inflammatory effect of MCXB is partly regulated by HO-1 induction. In conclusion, MCXB could be a useful candidate for the development of therapeutic and preventive agents to treat inflammatory diseases.
Asunto(s)
Lipopolisacáridos , Xantonas , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacología , Ciclooxigenasa 2/metabolismo , Lipopolisacáridos/toxicidad , Sistema de Señalización de MAP Quinasas , Ratones , FN-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Células RAW 264.7 , Transducción de Señal , Xantonas/farmacologíaRESUMEN
A prenylated flavonoid, cudraflavanone B, is isolated from Cudrania tricuspidata. In this study, we investigated its anti-inflammatory and anti-neuroinflammatory effects in lipopolysaccharide (LPS)-induced RAW264.7 and BV2 cells. In our initial study of the anti-inflammatory effects of cudraflavanone B the production of nitric oxide and prostaglandin E2 was attenuated in LPS-stimulated RAW264.7 and BV2 cells. These inhibitory effects were related to the downregulation of inducible nitric oxide synthase and cyclooxygenase-2. In addition, cudraflavanone B suppressed the production of pro-inflammatory cytokines such as interleukin-6 and tumor necrosis factor-α in LPS-induced RAW264.7 and BV2 cells. Moreover, the evaluation of the molecular mechanisms underlying the anti-inflammatory effects of cudraflavanone B revealed that the compound attenuated the nuclear factor-kappa B signaling pathway in LPS-induced RAW264.7 and BV2 cells. In addition, cudraflavanone B inhibited the phosphorylation of extracellular signal-regulated kinase mitogen-activated protein kinase signaling pathways in these LPS-stimulated cells. Thus, cudraflavanone B suppressed nuclear factor-κB, and extracellular signal-regulated kinase mitogen-activated protein kinase mediated inflammatory pathways, demonstrating its potential in the treatment of neuroinflammatory conditions.
Asunto(s)
Flavonoides/farmacología , Mediadores de Inflamación/antagonistas & inhibidores , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Macrófagos/efectos de los fármacos , Microglía/efectos de los fármacos , FN-kappa B/antagonistas & inhibidores , Animales , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo/efectos de los fármacos , Regulación hacia Abajo/fisiología , Flavonoides/aislamiento & purificación , Mediadores de Inflamación/metabolismo , Lipopolisacáridos/toxicidad , Sistema de Señalización de MAP Quinasas/fisiología , Macrófagos/metabolismo , Ratones , Microglía/metabolismo , Moraceae , FN-kappa B/metabolismo , Corteza de la Planta , Células RAW 264.7RESUMEN
BACKGROUND: Obesity in adolescence can continue up to adulthood and lead to various complications. There has been a continuous increase in the obesity incidence among adolescents, which is an emerging social issue. Studies have reported that decreased sleep duration in adolescents can have negative effects on health, leading to obesity. Therefore, in the present study, we aimed to investigate the relationship between sleep duration and body mass index among South Korean middle and high school students aged 12-18 years. METHODS: The participants of the Sixth National Health and Nutrition Survey conducted during 2013-2015 were screened. We selected 1,177 adolescents aged between 12 and 18 years who were enrolled in middle and high school or on leave of absence and had available data for sleep duration and body mass index (BMI) in the survey. Analyses of variance and covariance were performed after adjusting for confounding variables, including age, gender, waist circumference, and drinking experience, that showed significant correlations in univariate logistic regression. RESULTS: The analysis of covariance revealed that an increase in sleep duration led to a corresponding decrease in the mean BMI among all students and middle school students. CONCLUSION: Significant negative correlations were confirmed between sleep duration and BMI in all students and middle school students.
RESUMEN
Brain cell damage that results from oxidative toxicity contributes to neuronal degeneration. The transcription factor nuclear factorE2related factor 2 (Nrf2) regulates the expression of heme oxygenase (HO)1 and glutathione (GSH), and serves a key role in the pathogenesis of neurological diseases. Brassica rapa is a turnip that is unique to Ganghwa County, and is used mainly for making kimchi, a traditional Korean food. In the current study, brassicaphenanthrene A (BrPA) from B. rapa was demonstrated to exhibit protective effects against neurotoxicity induced by glutamate via Nrf2mediated HO1 expression. Similarly, BrPA increased the expression of cellular glutathione and glutaminecysteine ligase genes. Furthermore, BrPA caused the nuclear translocation of Nrf2 and increased antioxidant response element (ARE) promoter activity. Nrf2 also mediated HO1 induction by BrPA through the PI3K/Akt and JNK regulatory pathways. The results of the present study indicated the neuroprotective effect of BrPA, a natural food component from B. rapa.
Asunto(s)
Brassica rapa/química , Hemo-Oxigenasa 1/genética , Factor 2 Relacionado con NF-E2/genética , Fenantrenos/farmacología , Animales , Elementos de Respuesta Antioxidante/genética , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Ratones , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Fármacos Neuroprotectores/farmacología , Fenantrenos/químicaRESUMEN
The extract of Sappan Lignum, the heartwood of Caesalpinia sappan L., has been used in medicine to improve blood circulation. Recently, the application of microwave extraction methods has been a major focus of research into the extraction of components from natural sources. In this experiment, we compared the antiinflammatory effects of Sappan Lignum prepared by heat70% EtOH extraction (CSEH70E) and microwave70% EtOH extraction (CSEMW70E). Highperformance liquid chromatography analysis was used to identify the compounds in these extracts. The heat70% EtOH and microwave70% EtOH extracts of Sappan Lignum had different chromatograms. CSEMW70E significantly inhibited the protein expression of iNOS and COX2, PGE2, TNFα, and reduced NO and IL1ß production in macrophages exposed to LPS, whereas, only high concentrations of CSEH70E (20 µg/ml) resulted in any effects. Furthermore, CSEMW70E upregulated heme oxygenase1 (HO1) expression. In addition, the use of tin protoporphyrin, an inhibitor of HO1, confirmed the inhibitory effects of CSEMW70E on proinflammatory mediators. These results suggested that the CSEMW70Emediated upregulation of HO1 played an important role in the antiinflammatory effects of macrophages. Therefore, these findings showed that microwave extraction can be utilized to improve the extraction efficiency and biological activity of Sappan Lignum.
Asunto(s)
Antiinflamatorios/farmacología , Fabaceae/química , Hemo-Oxigenasa 1/metabolismo , Microondas , FN-kappa B/metabolismo , Extractos Vegetales/farmacología , Animales , Cromatografía Líquida de Alta Presión , Ciclooxigenasa 2/metabolismo , Citocinas/metabolismo , ADN/metabolismo , Dinoprostona/metabolismo , Hemo-Oxigenasa 1/genética , Mediadores de Inflamación/metabolismo , Lipopolisacáridos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Metaloporfirinas/farmacología , Ratones , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Nitritos/metabolismo , Unión Proteica/efectos de los fármacos , Protoporfirinas/farmacología , Células RAW 264.7 , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
BACKGROUND: The preprocedural neutrophil-lymphocyte ratio (NLR) is related to adverse outcomes in patients with coronary artery disease. We hypothesized that high NLR is a predictor of cardiac death after percutaneous coronary intervention (PCI). The objective of this investigation was to assess the associations of NLR, high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B type natriuretic peptide (NT-proBNP) with the occurrence of cardiac death after PCI. MATERIALS AND METHODS: The NLR, hs-cTnT and NT-proBNP were analyzed in 372 patients who underwent PCI. The primary end point was cardiac death. RESULTS: The median NLR was 2.3 (interquartile range: 1.5-4.1). There were 21 cardiac death events during a mean follow-up duration of 25.8 months. With the NLR cutoff level set to 3.3 using the receiver-operating characteristic curve, the sensitivity and specificity for differentiating between the group with cardiac death and the group without cardiac death were 85.7% and 59.3%, respectively. Kaplan-Meier analysis revealed that the higher NLR group (≥3.3) had a significantly higher cardiac death rate than the lower NLR group (<3.3) (11.1% versus 1.4%, log-rank: P < 0.0001). This value was more useful in patients with heart failure (NT-proBNP ≥ 300ng/L) or myocardial injury (hs-cTnT ≥ 100ng/L). CONCLUSIONS: The outcomes of the current study demonstrate that high NLR is a predictor of cardiac death after PCI, especially in patients with heart failure or myocardial injury.
Asunto(s)
Linfocitos/metabolismo , Péptido Natriurético Encefálico/metabolismo , Neutrófilos/metabolismo , Fragmentos de Péptidos/metabolismo , Intervención Coronaria Percutánea/mortalidad , Troponina T/metabolismo , Anciano , Anciano de 80 o más Años , Muerte , Femenino , Humanos , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea/efectos adversos , República de Corea/epidemiologíaRESUMEN
In Vibrio vulnificus, the production of metalloprotease VvpE is controlled by Crp (cAMP-receptor protein) and SmcR (a quorum sensing regulator) at the transcription level, and by PilD-mediated type II general secretion system (TTGSS) at the extracellular secretion level. Iron is known to stimulate VvpE production but the related mechanisms remain unidentified. Iron stimulated vvpE transcription and extracellular VvpE production even in the background with a crp and/or smcR mutation. Iron stimulated the transcription of pilD encoding an essential element of TTGSS. Therefore, iron seems to stimulate vvpE transcription through factor(s) other than Crp and SmcR, and to facilitate extracellular VvpE production by increasing the activity of TTGSS.
Asunto(s)
Proteínas Bacterianas/genética , Regulación Enzimológica de la Expresión Génica , Hierro/metabolismo , Metaloproteasas/genética , Vibrio vulnificus/enzimología , Proteínas Bacterianas/metabolismo , Regulación Bacteriana de la Expresión Génica , Humanos , Metaloproteasas/metabolismo , Vibriosis/microbiología , Vibrio vulnificus/genética , Vibrio vulnificus/metabolismoRESUMEN
Among 1590 ORFs in the Helicobacter pylori genome, >250 have been identified as authentic genes by proteomic analysis. Low-abundance proteins need to be enriched to a minimal amount for MALDI-TOF analysis and salt precipitation has generally been used for protein enrichment. Here, a whole-cell extract of H. pylori strain 26695 was subjected to protein fractionation with stepwise concentrations of ammonium sulfate and the proteins were displayed by 2-DE. The protein spots were quantified using PDQUEST software and identified by peptide fingerprinting. The 2-DE profiles and intensities of individual protein spots differed among the protein fractions. Out of the 98 identified proteins, 61 were found in the stepwise ammonium sulfate fractions but not in the whole-cell extract. Out of these, 37 proteins, including KdsA, were found exclusively in a single fraction. In contrast, GroEL, UreA, UreB, TrxA, NapA, and FldA were ubiquitously present in all fractions. Iron-containing proteins such as NapA, SodB, CeuE, and Pfr were found predominantly in the 100% saturated ammonium sulfate precipitate. Additionally, 29 proteins were newly identified in this study. These data will facilitate the preparation of significant H. pylori proteins, as well as provide information about low-abundance proteins.