RESUMEN
AIM: Metergoline is an ergot-derived psychoactive drug that acts as a ligand for serotonin and dopamine receptors. The aim of this study was to investigate the regulatory effects of metergoline on the neuronal Nav1.2 voltage-dependent Na(+) channels in vitro. METHODS: Xenopus oocytes were injected with cRNAs encoding rat brain Nav1.2 α and ß1 subunits. Voltage-activated Na(+) currents were recorded using two-electrode voltage clamp technique. Drugs were applied though perfusion. RESULTS: Both metergoline and lidocaine reversibly and concentration-dependently inhibited the peak of Na(+) currents with IC50 values of 3.6 ± 4.2 and 916.9 ± 98.8 µmol/L, respectively. Metergoline (3 µmol/L) caused a 6.8 ± 1.2 mV depolarizing shift of the steady-state activation curve of the Na(+) currents, and did not alter the inactivation curve. In contrast, lidocaine (3 µmol/L) caused a 12.7 ± 1.2 mV hyperpolarizing shift of the inactivation curve of the Na(+) currents without changing the steady-state activation curve. Both metergoline and lidocaine produced tonic and use-dependent inhibition on the peak of Na(+) currents. CONCLUSION: Metergoline exerts potent inhibition on the activity of neuronal Nav1.2 channels, which may contribute to its actions on the central nervous system.
Asunto(s)
Metergolina/farmacología , Bloqueadores del Canal de Sodio Activado por Voltaje/farmacología , Animales , Expresión Génica , Canal de Sodio Activado por Voltaje NAV1.2/genética , Canal de Sodio Activado por Voltaje NAV1.2/metabolismo , Oocitos/efectos de los fármacos , Oocitos/metabolismo , Ratas , Xenopus laevisRESUMEN
Asthma is a potentially life-threatening inflammatory disease of the lung characterized by the presence of large numbers of CD4+ T cells. These cells produce the Th2 and Th17 cytokines that are thought to orchestrate the inflammation associated with asthma. Bee venom (BV) has traditionally been used to relieve pain and to treat chronic inflammatory diseases. Recent reports have suggested that BV might be an effective treatment for allergic diseases. However, there are still unanswered questions related to the efficacy of BV therapy in treating asthma and its therapeutic mechanism. In this study, we evaluated whether BV could inhibit asthma and whether BV inhibition of asthma could be correlated with regulatory T cells (Treg) activity. We found that BV treatment increased Treg populations and suppressed the production of Th1, Th2 and Th17-related cytokines in an in vitro culture system, including IL2, IL4, and IL17. Interestingly, production of IL10, an anti-inflammatory cytokine secreted by Tregs, was significantly augmented by BV treatment. We next evaluated the effects of BV treatment on allergic asthma in an ovalbumin (OVA)-induced mouse model of allergic asthma. Cellular profiling of the bronchoalveolar lavage (BAL) and histopathologic analysis demonstrated that peribronchial and perivascular inflammatory cell infiltrates were significantly lowered following BV treatment. BV also ameliorated airway hyperresponsiveness, a hallmark symptom of asthma. In addition, IL4 and IL13 levels in the BAL fluid were decreased in the BV treated group. Surprisingly, the beneficial effects of BV treatment on asthma were eradicated following Treg depletion by anti-CD25 antibody injection, suggesting that the major therapeutic targets of BV were Tregs. These results indicate that BV efficiently diminishes bronchial inflammation in an OVA-induced allergic asthma murine model, and that this effect might correlate with Tregs, which play an important role in maintaining immune homeostasis and suppressing the function of other T cells to limit the immune response. These results also suggest that BV has potential therapeutic value for controlling allergic asthma responses.
Asunto(s)
Asma/tratamiento farmacológico , Asma/inmunología , Venenos de Abeja/farmacología , Linfocitos T Reguladores/efectos de los fármacos , Animales , Asma/fisiopatología , Venenos de Abeja/uso terapéutico , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , Antígenos CD4/biosíntesis , Modelos Animales de Enfermedad , Inmunoglobulina E/sangre , Interleucina-10/inmunología , Interleucina-17/inmunología , Interleucina-2/inmunología , Subunidad alfa del Receptor de Interleucina-2/biosíntesis , Subunidad alfa del Receptor de Interleucina-2/inmunología , Interleucina-4/inmunología , Pulmón/inmunología , Pulmón/patología , Ratones , Ovalbúmina , Linfocitos T Reguladores/inmunologíaRESUMEN
BACKGROUND: In this study, we evaluated the anti-inflammatory effect of PM014 on cigarette smoke induced lung disease in the murine animal model of chronic obstructive pulmonary disease (COPD). METHODS: Mice were exposed to cigarette smoke (CS) for 2 weeks to induce COPD-like lung inflammation. Two hours prior to cigarette smoke exposure, the treatment group was administered PM014 via an oral injection. To investigate the effects of PM014, we assessed PM014 functions in vivo, including immune cell infiltration, cytokine profiles in bronchoalveolar lavage (BAL) fluid and histopathological changes in the lung. The efficacy of PM014 was compared with that of the recently developed anti-COPD drug, roflumilast. RESULTS: PM014 substantially inhibited immune cell infiltration (neutrophils, macrophages, and lymphocytes) into the airway. In addition, IL-6, TNF-α and MCP-1 were decreased in the BAL fluid of PM014-treated mice compared to cigarette smoke stimulated mice. These changes were more prominent than roflumilast treated mice. The expression of PAS-positive cells in the bronchial layer was also significantly reduced in both PM014 and roflumilast treated mice. CONCLUSIONS: These data suggest that PM014 exerts strong therapeutic effects against CS induced, COPD-like lung inflammation. Therefore, this herbal medicine may represent a novel therapeutic agent for lung inflammation in general, as well as a specific agent for COPD treatment.
Asunto(s)
Nicotiana/efectos adversos , Extractos Vegetales/farmacología , Neumonía/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Humo/efectos adversos , Animales , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Quimiocina CCL2/análisis , Quimiocina CCL2/metabolismo , Femenino , Células Caliciformes/efectos de los fármacos , Hiperplasia/patología , Interleucina-6/análisis , Interleucina-6/metabolismo , Pulmón/efectos de los fármacos , Pulmón/patología , Ratones , Ratones Endogámicos BALB C , Extractos Vegetales/uso terapéutico , Neumonía/inducido químicamente , Neumonía/metabolismo , Sustancias Protectoras/farmacología , Sustancias Protectoras/uso terapéutico , Factor de Necrosis Tumoral alfa/análisis , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
It has long been believed that mast cells play a crucial role in the development of many physiological changes during immediate allergic responses. This study was conducted to evaluate the anti-inflammation mechanism of Schizonepeta tenuifolia (ST) extract and ST purified chemicals on the PMA plus A23187-induced stimulation of HMC-1 human mast cells. ST, rosmarinic acid, pulegone, and 2α,3α,24-thrihydrooxylen-12en-28oic acid treatment of HMC-1 cells led to significant suppression of pro-inflammatory cytokines (IL-6, IL-8, and TNF-α) in a dose dependent manner. In addition, the results of the microarray and real-time RT-PCR analyses revealed that ST regulates several pathways, including the cytokine-cytokine receptor interaction (CCRI), MAPK, and the Toll-like receptor (TLR) signaling pathways. ST may be useful for the treatment of inflammation disease via anti-inflammation activity that occurs through inhibition of the CCRI, MAPK, and TLR signaling pathways.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Lamiaceae , Mastocitos/efectos de los fármacos , Calcimicina/farmacología , Ionóforos de Calcio/farmacología , Línea Celular , Cinamatos/farmacología , Monoterpenos Ciclohexánicos , Citocinas/biosíntesis , Depsidos/farmacología , Perfilación de la Expresión Génica , Humanos , Mastocitos/metabolismo , Monoterpenos/farmacología , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/farmacología , Análisis de Secuencia por Matrices de Oligonucleótidos , Extractos Vegetales/farmacología , Transducción de Señal/efectos de los fármacos , Ácido RosmarínicoRESUMEN
This study was conducted to compare the effects of low frequency electroacupuncture (EA) and high frequency EA at acupoint ST36 on the production of IgE and Th1/Th2 cytokines in BALB/c mice that had been immunized with 2,4-dinitrophenylated keyhole limpet protein (DNP-KLH), as well as to investigate the difference in the immunomodulatory effects exerted by EA stimulations at acupoint ST36 and at a non-acupoint (tail). Female BALB/c mice were divided into seven groups: normal (no treatments), IM (immunization only), ST36-PA (IM + plain acupuncture at ST36), ST36-LEA (IM + low frequency (1 Hz) EA at ST36), ST36-HEA (IM + high frequency (120 Hz) EA at ST36), NA-LEA (IM + low frequency (1 Hz) EA at non-acupoint) and NA-HEA (IM + high frequency (120 Hz) EA at non-acupoint). EA stimulation was performed daily for two weeks, and total IgE, DNP-KLH specific IgE, IL-4 and IFN-γ levels were measured at the end of the experiment. The results of this study showed that the IgE and IL-4 levels were significantly suppressed in the ST36-LEA and ST36-HEA groups, but not in the NA-LEA and NA-HEA groups. However, there was little difference in the immunomodulatory effects observed in the ST36-LEA and ST36-HEA groups. Taken together, these results suggest that EA stimulation-induced immunomodulation is not frequency dependent, but that it is acupoint specific.
RESUMEN
BACKGROUND: The molecular and biological mechanisms by which many antidepressants function are based on the monoamine depletion hypothesis. However, the entire cascade of mechanisms responsible for the therapeutic effect of antidepressants has not yet been elucidated. RESULTS: We used a genome-wide microarray system containing 30,000 clones to evaluate total RNA that had been isolated from the brains of treated rats to identify the genes involved in the therapeutic mechanisms of various antidepressants, a tricyclic antidepressant (imipramine). a selective serotonin reuptake inhibitor (fluoxetine), a monoamine oxidase inhibitor (phenelzine) and psychoactive herbal extracts of Nelumbinis Semen (NS). To confirm the differential expression of the identified genes, we analyzed the amount of mRNA that was isolated from the hippocampus of rats that had been treated with antidepressants by real-time RT-PCR using primers specific for selected genes of interest. These data demonstrate that antidepressants interfere with the expression of a large array of genes involved in signaling, survival and protein metabolism, suggesting that the therapeutic effect of these antidepressants is very complex. Surprisingly, unlike other antidepressants, we found that the standardized herbal medicine, Nelumbinis Semen, is free of factors that can induce neurodegenerative diseases such as caspase 8, α-synuclein, and amyloid precursor protein. In addition, the production of the inflammatory cytokine, IFNγ, was significantly decreased in rat hippocampus in response to treatment with antidepressants, while the inhibitory cytokine, TGFß, was significantly enhanced. CONCLUSIONS: These results suggest that antidepressants function by regulating neurotransmission as well as suppressing immunoreactivity in the central nervous system.
Asunto(s)
Antidepresivos/farmacología , Trastorno Depresivo/tratamiento farmacológico , Trastorno Depresivo/genética , Perfilación de la Expresión Génica , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , Animales , Antidepresivos Tricíclicos/farmacología , Perfilación de la Expresión Génica/métodos , Estudio de Asociación del Genoma Completo/métodos , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Ratas , Ratas Sprague-DawleyRESUMEN
To evaluate the direct effects of Cyperi Rhizoma (CR), a plant water extract, on Th1/Th2 lineage development in vitro, this study was conducted. Sorted CD4(+) T cells obtained from the splenocytes of BALB/c mice were activated with anti-CD3/anti-CD28 and then cultured in medium that contained CR medium under Th1 inducing or Th2 inducing conditions. Subsequently, IFN-gamma or IL-4 secreting cells were quantitated using flow cytometry analysis. In addition, IFN-gamma and IL-4 protein secretions were detected by ELISA analysis, after which, IFN-gamma and T-bet transcripts, key players in the Th1 immune function, and also, IL-4 and GATA-3, which are primary components in the Th2 immune mechanism, were quantitated by real-time RT-PCR. CR had no mitogenic effects on un-stimulated CD4(+) T cells, however, it increased the CD4(+) T cell population. Th1/Th2 polarization experiments revealed that CR enhanced IFN-gamma secretion in Th1 cells, but reduced the IL-4 in Th2 cells, and this occurred in a dose-dependent manner and showed significances. In addition, under Th1/Th2 skewed conditions, the transcription levels of IFN-gamma and T-bet were considerably increased, while the expressions of IL-4 and GATA-3 were relatively decreased with CR treatment. These findings suggest that CR enhances Th1 lineage development by increasing Th1 specific cytokine expression and secretion and reduces Th2 lineage development by repressing Th2 specific cytokine productions. Therefore, CR extract may be useful for preventing the onset of allergies or improving allergic symptoms.
Asunto(s)
Linaje de la Célula/efectos de los fármacos , Cyperus/química , Extractos Vegetales/farmacología , Rizoma/química , Células TH1/citología , Células Th2/citología , Animales , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Eugenol/análisis , Factor de Transcripción GATA3/genética , Factor de Transcripción GATA3/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Interferón gamma/genética , Interferón gamma/metabolismo , Interleucina-4/genética , Interleucina-4/metabolismo , Ratones , Extractos Vegetales/análisis , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteínas de Dominio T Box/genética , Proteínas de Dominio T Box/metabolismo , Células TH1/efectos de los fármacos , Células TH1/metabolismo , Células Th2/efectos de los fármacos , Células Th2/metabolismoRESUMEN
AIM: The rhizome of turmeric, Curcuma longa (CL), is a herbal medicine used in many traditional prescriptions. It has previously been shown that CL treatment showed greater than 47% recovery from cisplatin-induced cell damage in human kidney HEK 293 cells. This study was conducted to evaluate the recovery mechanisms of CL that occur during cisplatin induced nephrotoxicity by examining the genome wide mRNA expression profiles of HEK 293 -cells. METHOD: Recovery mechanisms of CL that occur during cisplatin-induced nephrotoxicity were determined by microarray, real-time PCR, immunofluorescent confocal microscopy and Western blot analysis. RESULTS: The results of microarray analysis and real-time PCR revealed that NFκB pathway-related genes and apoptosis-related genes were down-regulated in CL-treated HEK 293 cells. In addition, immunofluorescent confocal microscopy and Western blot analysis revealed that NFκB p65 nuclear translocation was inhibited in CL-treated HEK 293 cells. Therefore, the mechanism responsible for the effects of CL on HEK 293 cells is closely associated with regulation of the NFκB pathway. CONCLUSION: CL possesses novel therapeutic agents that can be used for the prevention or treatment of cisplatin-induced renal disorders.
Asunto(s)
Antineoplásicos/toxicidad , Línea Celular/metabolismo , Cisplatino/toxicidad , Curcuma/química , Enfermedades Renales/inducido químicamente , FN-kappa B/metabolismo , Extractos Vegetales/farmacología , Regulación hacia Abajo , Perfilación de la Expresión Génica , Genoma/efectos de los fármacos , Humanos , Enfermedades Renales/genética , Análisis por Micromatrices , FN-kappa B/genética , Reacción en Cadena de la Polimerasa/métodosRESUMEN
BACKGROUND/AIMS: This study was conducted to evaluate the anti-inflammatory mechanisms of Erigeron canadensis (EC) on the tumor necrosis factor-alpha (TNF-alpha)-, interleukin (IL)-4- and IL-1beta-induced stimulation of A549 cells. METHODS: In the present study, the anti-inflammatory effects of EC on TNF-alpha-, IL-4- and IL-1beta-induced A549 cells were determined by analyzing eotaxin secretion using ELISA. In addition, the effects of ECon gene expression profiles in stimulated A549 cells were evaluated by microarray analysis. RESULTS: Oligonucleotide microarray analysis revealed that inflammatory-related genes such as NOS1, NOS2A, IL-1beta, IL-8 and CSF2 and cell adhesion-related genes such as SELE, MMP3, VCAM1, ICAM1, ITGA7 and ITGB2 were downregulated in EC-treated A549 cells that had been pretreated with TNF-alpha, IL-4 and IL-1beta. In addition, significant decreases in Eotaxin, ICAM, VCAM and IL-8 gene expression were observed in EC-treated A549 cells. CONCLUSIONS: EC has an anti-inflammatory effect in stimulated A549 cells. Microarray-based genomic survey is a high-throughput approach that is suitable for the evaluation of gene expression in cell lines that have been treated with EC.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Citocinas/inmunología , Células Epiteliales/efectos de los fármacos , Erigeron , Regulación de la Expresión Génica/efectos de los fármacos , Extractos Vegetales/farmacología , Alveolos Pulmonares/citología , Algoritmos , Análisis de Varianza , Línea Celular Tumoral , Quimiocina CCL11/metabolismo , Suplementos Dietéticos , Células Epiteliales/inmunología , Células Epiteliales/metabolismo , Humanos , Molécula 1 de Adhesión Intercelular/genética , Molécula 1 de Adhesión Intercelular/metabolismo , Interleucina-1beta/inmunología , Interleucina-4/inmunología , Interleucina-8/genética , Interleucina-8/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Análisis de Secuencia por Matrices de Oligonucleótidos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Necrosis Tumoral alfa/inmunología , Molécula 1 de Adhesión Celular Vascular/genética , Molécula 1 de Adhesión Celular Vascular/metabolismoRESUMEN
AIM OF THE STUDY: The therapeutic application of bee venom (BV) has been used in traditional medicine to treat diseases such as arthritis, rheumatism and pain. Macrophages produce molecules that are known to play roles in inflammatory responses. MATERIAL AND METHODS: We performed microarray analysis to evaluate the global gene expression profiles of RAW264.7 macrophage cells treated with BV. In addition, six genes were subjected to real-time PCR to confirm the results of the microarray. The cells were treated with lipopolysaccharide (LPS) or BV plus LPS for 30 min or 1h. RESULTS: 124 genes were found to be up-regulated and 158 were found to be down-regulated in cells that were treated with BV plus LPS for 30 min, whereas 211 genes were up-regulated and 129 were down-regulated in cells that were treated with BV plus LPS for 1h when compared with cells that were treated with LPS alone. Furthermore, the results of real-time PCR were similar to those of the microarray. BV inhibited the expression of specific inflammatory genes that were up-regulated by nuclear factor-kappa B in the presence of LPS, including mitogen-activated protein kinase kinase kinase 8 (MAP3K8), TNF, TNF-alpha-induced protein 3 (TNFAIP3), suppressor of cytokine signaling 3 (SOCS3), TNF receptor-associated factor 1 (TRAF1), JUN, and CREB binding protein (CBP). CONCLUSIONS: These results demonstrate the potent activity of BV as a modulator of the LPS-mediated nuclear factor-kappaB (NF-kappaB)/MAPK pathway in activated macrophages. In addition, these results can be used to understand other effects of BV treatment.
Asunto(s)
Venenos de Abeja/farmacología , Macrófagos/efectos de los fármacos , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Animales , Regulación hacia Abajo/efectos de los fármacos , Perfilación de la Expresión Génica/métodos , Lipopolisacáridos/farmacología , Macrófagos/metabolismo , Ratones , Proteínas Quinasas Activadas por Mitógenos/efectos de los fármacos , Proteínas Quinasas Activadas por Mitógenos/metabolismo , FN-kappa B/efectos de los fármacos , FN-kappa B/metabolismo , Reacción en Cadena de la Polimerasa , Factores de Tiempo , Regulación hacia Arriba/efectos de los fármacosRESUMEN
This study was conducted to quantitatively evaluate the recovery effects of herbal medicines on acetaminophen-induced nephrotoxicity. In the present study, the recovery effects of 251 herb medicines on HEK 293 cells that had been damaged by acetaminophen were evaluated using an MTS assay. HEK 293 cells were cultured in 96-well plates and then pretreated with or without 20µM acetaminophen (IC(50) value: 17.5±1.9) for 1h. Next, different herbal medicines were added to the wells, after which the cells were reincubated at 37°C for 24h. After the first round of screening, the candidate herbal medicines were selected based on a recovery rate of greater than 20% and their efficacy were then determined by dose response kinetic analysis. Among these extracts, 8 herbal medicines (Ledebouriella divaricata, Sparganium simplex, Panax ginseng, Aster tataricus, Citrus aurantium, Sanguisorba officianlis, Arisaema consanguineum, and Polygonum aviculare) had a strong recovery effect on acetaminophen-induced damage in HEK 293 cells. Dose response non-linear regression analysis demonstrated that P. aviculare showed the best recovery rate (98%), and that its EC(50) (0.1ng/mL) was the smallest among the screened candidate herbal medicines. Additional studies of these herbal medicines should be conducted to determine if they possess novel therapeutic agents for the prevention or treatment of renal disorders.
RESUMEN
A major satiety hormone, cholecystokinin (CCK) is well known to be released by electroacupuncture (EA) stimulation at certain body sites which elicits profound psychophysiological responses. Previous clinical and animal studies have shown that EA stimulation reduces food intake and body weight in both normal and obese subjects. The aim of the present study was to elucidate the satiety effect of EA stimulation and its mechanism related to CCK in rats. Here we show that EA stimulation at "Zusanli" (ST36) acupoint significantly reduced 30-min and 60-min food intake in 48-h fasted Sprague-Dawley rats, and such effect was reversed by a lorglumide (CCK-1 receptor antagonist, 10mg/kg, i.p.) pretreatment. The ST36 EA stimulation-induced satiety was not observed in CCK-1 receptor knockout, Otsuka Long-Evans Tokushima Fatty rats, but in their controls, Long-Evans Tokushima Otsuka rats. Subdiaphragmatic vagotomy also blocked the satiety effect of ST36 EA stimulation in Sprague-Dawley rats. These results suggest that ST36 EA stimulation elicits satiety in rats and this is mediated by the endogenous CCK signaling pathway.
Asunto(s)
Colecistoquinina/metabolismo , Electroacupuntura , Saciedad/fisiología , Animales , Ayuno/fisiología , Masculino , Proglumida/análogos & derivados , Proglumida/farmacología , Ratas , Ratas Endogámicas OLETF , Ratas Sprague-DawleyRESUMEN
To investigate the effects of electro-acupuncture (EA) treatment on regions remote from the application, we measured cellular, enzymatic, and transcriptional activities in various internal tissues of healthy rats. The EA was applied to the well-identified acupoint ST36 of the leg. After application, we measured the activity of natural killer cells in the spleen, gene expression in the hypothalamus, and the activities of antioxidative enzymes in the hypothalamus, liver and red blood cells. The EA treatment increased natural killer cell activity in the spleen by approximately 44%. It also induced genes related to pain, including 5-Hydroxytryptamine (serotonin) receptor 3a (Htr3a) and Endothelin receptor type B (Ednrb) in the hypothalamus, and increased the activity of superoxide dismutase in the hypothalamus, liver, and red blood cells. These findings indicate that EA mediates its effects through changes in cellular activity, gene expression, and enzymatic activity in multiple remote tissues. The sum of these alterations may explain the beneficial effects of EA.
Asunto(s)
Puntos de Acupuntura , Electroacupuntura , Animales , Hipotálamo/enzimología , Células Asesinas Naturales/citología , Análisis de Secuencia por Matrices de Oligonucleótidos , Especificidad de Órganos , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Superóxido Dismutasa/metabolismo , Transcripción Genética , Regulación hacia ArribaRESUMEN
Bioassay-guided fractionation of the root extract of Asarum sieboldii led to the isolation of the four active compounds (-)-sesamin (1), (2E,4E,8Z,10E)-N-(2-methylpropyl)dodeca-2,4,8,10-tetraenamide (2), kakuol (3), and '3,4,5-trimethoxytoluene' (=1,2,3-trimethoxy-5-methylbenzene; 4), in terms of inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production. Compounds 1-4 showed potent inhibition of NO production, with IC(50) values in the low nanomolar-to-micromolar range. Also isolated were the known compounds methylkakuol (5), '3,5-dimethoxytoluene', safrole, asaricin, methyleugenol, and (-)-asarinin, which were found to be inactive in the above assay. Among the ten known isolates, compounds 1, 2, and 5 were found for the first time in this plant.
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Dioxoles/farmacología , Lignanos/farmacología , Lipopolisacáridos/antagonistas & inhibidores , Microglía/efectos de los fármacos , Óxido Nítrico/antagonistas & inhibidores , Alcamidas Poliinsaturadas/farmacología , Propiofenonas/farmacología , Tolueno/análogos & derivados , Animales , Aristolochiaceae/química , Línea Celular , Dioxoles/química , Dioxoles/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Lignanos/química , Lignanos/aislamiento & purificación , Lipopolisacáridos/farmacología , Ratones , Microglía/citología , Microglía/metabolismo , Estructura Molecular , Óxido Nítrico/biosíntesis , Raíces de Plantas/química , Alcamidas Poliinsaturadas/química , Alcamidas Poliinsaturadas/aislamiento & purificación , Propiofenonas/química , Propiofenonas/aislamiento & purificación , Estereoisomerismo , Relación Estructura-Actividad , Tolueno/química , Tolueno/aislamiento & purificación , Tolueno/farmacologíaRESUMEN
Our previous study demonstrated that successive electroacupuncture (EA) at ST36 acupoint reduces IgE production in BALB/c mice immunized with 2,4-dinitrophenylated keyhole limpet protein (DNP-KLH) by suppression of the Th2 cell lineage development. Here, we report that pretreatment of phentolamine (alpha-adrenoceptor antagonist, 10mg/kg, i.p.) completely blocks the EA-induced suppression of antigen-specific and total IgE levels in serum and IL-4 production in anti-CD3 mAb-activated splenocytes in DNP-KLH immunized mice. The results suggest that alpha-adrenoceptor play an important role in mediating the suppressive effects of EA on IgE production and Th2 cell response in DNP-KLH immunized mice.
Asunto(s)
Electroacupuntura , Inmunoglobulina E/biosíntesis , Receptores Adrenérgicos alfa/inmunología , Células Th2/inmunología , Antagonistas Adrenérgicos alfa/farmacología , Animales , Ensayo de Inmunoadsorción Enzimática , Femenino , Hemocianinas/inmunología , Inmunoglobulina E/sangre , Interferón gamma/biosíntesis , Interferón gamma/inmunología , Interleucina-4/biosíntesis , Interleucina-4/inmunología , Ratones , Ratones Endogámicos BALB C , Fentolamina/farmacología , Receptores Adrenérgicos alfa/efectos de los fármacosRESUMEN
"Responder" Sprague-Dawley (SD) rats that were sensitive to electroacupuncture (EA) in an acute thermal pain test (i.e. tail flick latency [TFL] test) maintained sensitivity to EA in the warm allodynia test after peripheral nerve injury. Similarly, the "non-responder" SD rats that were insensitive to EA in the TFL test were also insensitive to EA in the allodynia test. The EA-induced analgesic effects in the TFL test were significantly higher in CCK-A receptor deficient, Otsuka Long-Evans Tokushima Fatty (OLETF) rats than in their littermates, Long-Evans Tokushima Otsuka (LETO) rats. Similarly, the anti-allodynic effects of EA were significantly greater in OLETF rats than in LETO rats. These results suggest that the individual differences in the sensitivity of acute pain behavior to EA were maintained in neuropathic pain behavior following peripheral nerve injury, and that CCK-A receptor expression plays an important role in mediating this phenomenon.
Asunto(s)
Electroacupuntura/métodos , Individualidad , Manejo del Dolor , Dolor/etiología , Enfermedades del Sistema Nervioso Periférico/complicaciones , Animales , Conducta Animal , Modelos Animales de Enfermedad , Masculino , Dimensión del Dolor , Ratas , Ratas Endogámicas OLETF , Ratas Long-Evans , Ratas Sprague-Dawley , Tiempo de Reacción/fisiología , Receptor de Colecistoquinina A/deficienciaRESUMEN
UNLABELLED: Eosinophils have been implicated in a broad range of diseases, most notably allergic conditions (e.g. asthma, rhinitis and atopic dermatitis) and inflammatory diseases. These diseases are characterized by an accumulation of eosinophils in the tissue. Defining the mechanisms that control eosinophil recruitment is fundamental to understanding how these diseases progress and may identify a novel target for drug therapy. Eotaxin is a potent eosinophil-specific chemokine that is released in the respiratory epithelium after allergic stimulation. AIM OF THE STUDY: In this study, we determined whether Moutan Cortex Radicis (MCR), a plant extract, effects eotaxin secretion from A549 epithelial cells and eosinophil chemotaxis, and then examined the mechanism involved. MATERIALS AND METHODS: Prior to assaying MCR's effects, A549 cells were stimulated with tumor necrosis factor-alpha (TNF-alpha), interleukin-4 (IL-4) and IL-1beta to induce expression of chemokines and adhesion molecules involved in eosinophil chemotaxis. In the presence of MCR, eotaxin, regulated on activation in normal T cells expressed and secreted (RANTES), IL-8, IL-16, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) transcripts were quantitated by real-time RT-PCR. RESULTS: As a result, 0.01, 1, and 100 microg/ml of MCR treatments reduced eotaxin expression significantly and 0.01, 0.1, 1, 10, and 100 microg/ml of MCR reduced significantly eotaxin secretion. In addition, MCR treatment significantly inhibited eosinophil migration toward A549 medium. And 100 microg/ml of MCR suppressed the activated of nuclear factor (NF)-kappaB. CONCLUSIONS: These findings indicate that suppressed eotaxin secretion by MCR treatment is due to the inhibition of NF-kappaB activation. Therefore, MCR might be of therapeutic value in treating asthma.
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Movimiento Celular/efectos de los fármacos , Quimiocinas/metabolismo , Medicamentos Herbarios Chinos/farmacología , Eosinófilos/efectos de los fármacos , Células Epiteliales/metabolismo , Western Blotting , Núcleo Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Supervivencia Celular/efectos de los fármacos , Quimiocina CCL5/metabolismo , Quimiotaxis de Leucocito/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Citocinas/metabolismo , ADN Complementario/biosíntesis , Ensayo de Inmunoadsorción Enzimática , Células Epiteliales/efectos de los fármacos , Humanos , Interleucina-1beta/antagonistas & inhibidores , Interleucina-1beta/farmacología , Interleucina-4/antagonistas & inhibidores , Interleucina-4/farmacología , Paeonia , ARN Mensajero/biosíntesis , ARN Mensajero/aislamiento & purificación , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
Aurantii Fructus (AF) is one of the most well-known traditional herbal medicines frequently used for the treatment of cardiovascular symptoms in Korea. The anti-ischemic effects of AF on ischemia-induced isolated rat heart were investigated through analyses of changes in perfusion pressure, aortic flow, coronary flow, and cardiac output. The subjects in this study were divided into two groups: an ischemia-induced group without any treatment, and an ischemia-induced group with AF treatment. There were no significant differences in perfusion pressure, aortic flow, coronary flow, and cardiac output between them before ischemia was induced. The supply of oxygen and buffer was stopped for 10 min to induce ischemia in isolated rat hearts, and AF was administered during ischemia induction. AF treatment significantly prevented decreases in perfusion pressure, aortic flow, coronary flow, and cardiac output under ischemic conditions (p < 0.01). These results suggest that AF has distinct anti-ischemic effects through recovery of contractile dysfunction in ischemic heart.
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Contracción Miocárdica/efectos de los fármacos , Isquemia Miocárdica/tratamiento farmacológico , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Extractos Vegetales/farmacología , Animales , Velocidad del Flujo Sanguíneo/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Gasto Cardíaco/efectos de los fármacos , Citrus , Circulación Coronaria/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Frutas , Frecuencia Cardíaca/efectos de los fármacos , Corea (Geográfico) , Masculino , Medicina Tradicional de Asia Oriental , Isquemia Miocárdica/fisiopatología , Daño por Reperfusión Miocárdica/fisiopatología , Extractos Vegetales/administración & dosificación , Ratas , Ratas Sprague-DawleyRESUMEN
The present study was performed to determine whether the expression levels of the hypothalamic cholecystokinin (CCK) and its receptors are associated with the responsiveness to high frequency electroacupuncture (EA) analgesia in rats. EA stimulation (100 Hz, 0.5 ms pulse width, 0.2-0.3 mA) was delivered to the Zusanli (ST36) acupoint of male Sprague-Dawley rats for 20 min without anesthetics or holder restraint. The analgesic effect of EA was quantified using a tail flick latency test, and subsequently animals were allocated to responder or non-responder groups. The hypothalamus of rats in each group was dissected and RNA was purified. The mRNA expressions of CCK, and CCK-A and -B receptor were determined by real-time RT-PCR. CCK mRNA levels were not significantly different in the two groups, whereas both CCK-A and -B receptors were significantly more expressed in non-responders. These results suggest that the level of CCK receptor mRNA expression in the hypothalamus, rather than CCK mRNA, has an important relationship with the individual variations to high frequency EA analgesia in rats.
Asunto(s)
Electroacupuntura , ARN Mensajero/metabolismo , Receptor de Colecistoquinina A/química , Receptor de Colecistoquinina B/química , Sincalida/química , Analgesia , Animales , Hipotálamo/metabolismo , Masculino , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sincalida/metabolismoRESUMEN
Administration of bee venom (BV) elicits anti-inflammatory, anti-nociceptive and anti-allergic effects in various animal models. This study was designed to evaluate the direct effects of BV on helper T cell activities and on Th1/Th2 lineage development using both in vitro and in vivo conditions. In the Th1 skewed condition, BV increased the expression of IFN-gamma mRNA and enhanced the expression of T-bet on purified CD4(+) T cells from splenocytes of BALB/c mice. On the other hand, BV treatment did not alter the expression of IL-4 or GATA-3 in a Th2 driven environment. To elucidate the effects of BV on Th1/Th2 lineage development under in vivo conditions, BV was given by intraperitonial injection to BALB/c mice. It significantly increased the CD4(+) T cell population and enhanced IFN-gamma expression, while IL-4 transcripts were not altered upon in vivo activation using an anti-CD3 antibody injection. Taken together, these results imply that BV induces Th1 lineage development from CD4(+) T cells by increasing the expression of a Th1-specific cytokine, IFN-gamma. In addition, this result may be mediated by inducing a Th1-specific transcription factor, T-bet.