Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 21
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Acta Pharmacol Sin ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34522005

RESUMO

Behavioral sensitization is a progressive increase in locomotor or stereotypic behaviours in response to drugs. It is believed to contribute to the reinforcing properties of drugs and to play an important role in relapse after cessation of drug abuse. However, the mechanism underlying this behaviour remains poorly understood. In this study, we showed that mTOR signaling was activated during the expression of behavioral sensitization to cocaine and that intraperitoneal or intra-nucleus accumbens (NAc) treatment with rapamycin, a specific mTOR inhibitor, attenuated cocaine-induced behavioural sensitization. Cocaine significantly modified brain lipid profiles in the NAc of cocaine-sensitized mice and markedly elevated the levels of phosphatidylinositol-4-monophosphates (PIPs), including PIP, PIP2, and PIP3. The behavioural effect of cocaine was attenuated by intra-NAc administration of LY294002, an AKT-specific inhibitor, suggesting that PIPs may contribute to mTOR activation in response to cocaine. An RNA-sequencing analysis of the downstream effectors of mTOR signalling revealed that cocaine significantly decreased the expression of SynDIG1, a known substrate of mTOR signalling, and decreased the surface expression of GluA2. In contrast, AAV-mediated SynDIG1 overexpression in NAc attenuated intracellular GluA2 internalization by promoting the SynDIG1-GluA2 interaction, thus maintaining GluA2 surface expression and repressing cocaine-induced behaviours. In conclusion, NAc SynDIG1 may play a negative regulatory role in cocaine-induced behavioural sensitization by regulating synaptic surface expression of GluA2.

2.
Biochem Pharmacol ; 177: 113926, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32217098

RESUMO

BACKGROUND AND PURPOSE: Indoleamine 2, 3-dioxygenase 1 (IDO1) has been linked to neuropathic pain and IDO1 inhibitors have been shown to reduce pain in animals. Some studies have indicated that IDO1 expression increased after neuropathic pain in hippocampus and spinal cord, whether these changes existing in anterior cingulate cortex (ACC) and amygdala remains obscure and how IDO1 inhibition leads to analgesia is largely unknown. Here, we evaluated the antinociceptive effect of PCC0208009, an indirect IDO1 inhibitor, on neuropathic pain and examined the related neurobiological mechanisms. EXPERIMENTAL APPROACH: The effects of PCC0208009 on pain, cognition and anxiogenic behaviors were evaluated in a rat model of neuropathic pain. Motor disorder, sedation and somnolence were also assessed. Biochemical techniques were used to measure IDO1-mediated signaling changes in ACC and amygdala. KEY RESULTS: In rats receiving spinal nerve ligation (SNL), IDO1 expression level was increased in ACC and amygdala. PCC0208009 attenuated pain-related behaviors in the formalin test and SNL model and increased cognition and anxiogenic behaviors in SNL rats at doses that did not affect locomotor activity and sleeping. PCC0208009 inhibited IDO1 expression in ACC and amygdala by inhibiting the IL-6-JAK2/STAT3-IDO1-GCN2-IL-6 pathway. In addition, PCC0208009 reversed synaptic plasticity at the functional and structural levels by suppressing NMDA2B receptor and CDK5/MAP2 or CDK5/Tau pathway in ACC and amygdala. CONCLUSION AND IMPLICATIONS: These results support the role of IDO1-mediated molecular mechanisms in neuropathic pain and suggest that the IDO1 inhibitor PCC0208009 demonstrates selective pain suppression and could be a useful pharmacological therapy for neuropathic pain.


Assuntos
Tonsila do Cerebelo/metabolismo , Analgésicos/uso terapêutico , Giro do Cíngulo/metabolismo , Indolamina-Pirrol 2,3,-Dioxigenase/antagonistas & inibidores , Neuralgia/tratamento farmacológico , Plasticidade Neuronal/efeitos dos fármacos , Tetrazóis/uso terapêutico , Analgésicos/farmacocinética , Animais , Comportamento Animal/efeitos dos fármacos , Comorbidade , Modelos Animais de Doenças , Formaldeído/farmacologia , Hiperalgesia/tratamento farmacológico , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neuralgia/metabolismo , Medição da Dor , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Tetrazóis/farmacocinética
3.
Eur J Med Chem ; 161: 364-377, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30384042

RESUMO

Hederagenin is a naturally occurring pentacyclic triterpenoids compound with multiple pharmacological activities. We recently showed that H6, a synthetic derivative of hederagenin, could enhance the anticancer activity of paclitaxel in drug-resistant cells in vitro and in vivo, but showed poor solubility. With the aim of improving the drug resistant reversal activity of H6, here we designed and synthesized a series of novel H6 analogues. Our results showed that compound 10 at the concentration of 5 µM significantly enhanced the cytotoxicity of paclitaxel to drug-resistant KBV cells and sensitized cells to paclitaxel in arresting cells in G2/M phase and inducing apoptosis. We found that compound 10 might block the drug efflux of P-gp via stimulating P-gp ATPase activity. Importantly, compound 10 enhanced the efficacy of paclitaxel against KBV cancer cell-derived xenograft tumors. Finally, we summarized a preliminary structure-activity relationship of hederagenin by the drug resistant reversal activity of H6 analogues in vitro and compound 10 and H6in vivo. This study highlights the importance of nitrogen-containing derivatives of hederagenin C-28 in the development of novel drug resistance reversal agents.


Assuntos
Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Ácido Oleanólico/análogos & derivados , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Estrutura Molecular , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Ácido Oleanólico/síntese química , Ácido Oleanólico/química , Ácido Oleanólico/farmacologia , Relação Estrutura-Atividade , Células Tumorais Cultivadas
4.
Clin Respir J ; 10(4): 477-85, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25515647

RESUMO

BACKGROUND: Poor sleep is often associated with a series of health problems in patients with chronic obstructive pulmonary disease (COPD), but the relationship between sleep quality and functional exercise capacity has not been previously investigated. AIMS: To evaluate the relationship between quality of sleep and functional exercise capacity in clinically stable COPD. METHODS: One hundred three consecutive subjects with stable COPD were recruited. The subjects were assessed with the Pittsburgh Sleep Quality Index (PSQI) and divided into poor sleep group (PSQI >5) and good sleep group (PSQI ≤5). Subjects were also assessed with spirometry, 6-min walk distance (6MWD), oxygen saturation (SP O2 ), the Epworth Sleepiness Scale, Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, COPD Assessment Test (CAT), Modified Medical Research Council dyspnea scale and quadriceps muscle function. RESULTS: Poor sleep was present in 43.69% of the patients with COPD. Subjects with poor sleep had shorter 6MWD (t = -3.588, P < 0.001), greater age (t = 2.519, P = 0.013), worse quality of life (t = 5.487, P < 0.001) and more depression (t = 6.576, P < 0.001) or anxiety (t = 4.245, P < 0.001) symptoms. 6MWD showed significant negative correlations with the PSQI global score (r = -0.373, P < 0.001). Multiple stepwise regresion analysis showed that PSQI global score was an independent psychological predictor of 6MWD, and 6MWD was the only physical predictor of PSQI total score in patients with COPD. CONCLUSION: There is a close relationship between sleep quality and functional exercise capacity in patients with COPD.


Assuntos
Tolerância ao Exercício/fisiologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Transtornos do Sono-Vigília/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Teste de Esforço , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/psicologia , Qualidade de Vida/psicologia , Transtornos do Sono-Vigília/prevenção & controle , Transtornos do Sono-Vigília/psicologia , Espirometria , Inquéritos e Questionários
5.
J Thorac Dis ; 7(7): 1142-50, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26380729

RESUMO

BACKGROUND: Dynamic hyperinflation (DH) is a major contributor to exercise limitation in chronic obstructive pulmonary disease (COPD). Therefore, we aimed to elucidate the physiological factors responsible for DH development during the 6-minute walk test (6MWT) in COPD patients and compare ventilatory response to the 6MWT in hyperinflators and non-hyperinflators. METHODS: A total of 105 consecutive subjects with stable COPD underwent a 6MWT, and the Borg dyspnea scale, oxygen saturation (SpO2), breathing pattern, and inspiratory capacity (IC) were recorded before and immediately after walking. The change in IC was measured, and subjects were divided into hyperinflators (ΔIC >0.0 L) and non-hyperinflators (ΔIC ≤0.0 L). Spirometry, the Modified Medical Research Council (MMRC) dyspnea scale and St George's Respiratory Questionnaire (SGRQ) were also assessed. RESULTS: DH was present in 66.67% of subjects. ΔIC/IC was significantly and negatively correlated with the small airway function. On multiple stepwise regression analysis forced expiratory flow after exhaling 50% of the forced vital capacity (FEF50%) was the only predictor of ΔIC/IC. Non-hyperinflators had a higher post-walking VT (t=2.419, P=0.017) and post-walking VE (t=2.599, P=0.011) than the hyperinflators did. Age and resting IC were independent predictors of the 6-minute walk distance (6MWD) in hyperinflators. CONCLUSIONS: DH was considerably common in subjects with COPD. Small airway function may partly contribute to the DH severity during walking. The ventilator response to the 6MWT differed between hyperinflators and non-hyperinflators. Resting hyperinflation is an important predictor of functional exercise capacity in hyperinflators.

6.
Life Sci ; 124: 136-43, 2015 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-25640758

RESUMO

AIMS: The aim of the study is to evaluate the neuroprotective effects of continuous dopaminergic stimulation (CDS) by rotigotine-loaded microspheres (RoMS) in a mouse model of MPTP-induced Parkinson's disease (PD) and to elucidate the potential mechanism underlying these effects. MAIN METHODS: Male C57BL/6 mice were treated either intramuscularly once with RoMS or twice daily for two weeks with rotigotine, and from the 9th day, MPTP (30 mg/kg, i.p.) was injected for the last 5 days. Following treatment, Parkinsonism scores were calculated and oxidative stress-related indicators in the striatum were performed. Neuroinflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) were detected in the striatum. Expression of apoptosis-related proteins B-cell leukemia/lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (BAX) was measured in the striatum by Western blot. Nigral tyrosine hydroxylase (TH)-positive neurons and microglial cell markers, i.e., ionized calcium binding adaptor molecule-1 (Iba-1) and neuronal synaptosomes, were quantified to assess the neuroprotective efficacy of RoMS. KEY FINDINGS: The administration of rotigotine significantly improved the Parkinsonism score, protected dopaminergic neurons with antioxidants, reduced microglial cell activation and the release of neuroinflammatory cytokines, and balanced the expression of Bcl-2 and Bax in MPTP-treated mice. Interestingly, the neuroprotective properties of rotigotine were remarkably amplified by CDS treatment with RoMS. SIGNIFICANCE: These results suggest that CDS therapy can play a neuroprotective role in an MPTP mouse model. Neuroprotective disease-modifying therapy may have the potential benefits of early treatment by normalizing compensatory mechanisms and may also help to delay dyskinesia in the later stages of PD.


Assuntos
Agonistas de Dopamina/farmacologia , Intoxicação por MPTP/prevenção & controle , Fármacos Neuroprotetores/farmacologia , Transtornos Parkinsonianos/tratamento farmacológico , Tetra-Hidronaftalenos/farmacologia , Tiofenos/farmacologia , Animais , Antioxidantes/metabolismo , Western Blotting , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/patologia , Citocinas/metabolismo , Modelos Animais de Doenças , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microesferas , Estresse Oxidativo/efeitos dos fármacos , Transtornos Parkinsonianos/fisiopatologia
7.
Respir Care ; 59(5): 654-66, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24170916

RESUMO

OBJECTIVE: This meta-analysis was performed to evaluate the efficacy and safety of the addition of tiotropium to standard treatment regimens for inadequately controlled asthma. METHODS: A systematic search was made of PubMed, EMBASE, MEDLINE, and CENTRAL databases, and ClinicalTrials.gov, and a hand search of leading respiratory journals. Randomized, double-blind clinical trials on the treatment of inadequately controlled asthma for ≥ 4 weeks with the addition of tiotropium, compared with placebo, were reviewed. Studies were pooled to odds ratio (OR) and weighted mean differences (WMDs), with 95% CI. RESULTS: Six trials met the inclusion criteria. The addition of tiotropium, compared with placebo, significantly improved all spirometric indices, including morning and evening peak expiratory flow (WMD 20.59 L/min, 95% CI 15.36-25.81 L/min, P < .001; and WMD 24.95 L/min, 95% CI 19.22-30.69 L/min, P < .001, respectively), trough and peak FEV1 (WMD 0.13 L, 95% CI 0.09-0.18 L, P < .001; and WMD 0.10 L, 95% CI 0.06-0.14 L, P < .001, respectively), the area under the curve of the first 3 h of FEV1 (WMD 0.13 L, 95% CI 0.08-0.18 L, P < .001), trough and peak FVC (WMD 0.1 L, 95% CI 0.05-0.15 L, P < .001; and WMD 0.08 L, 95% CI 0.04-0.13 L, P < .001, respectively), the area under the curve of the first 3 h of FVC (WMD 0.11 L, 95% CI 0.06-0.15 L, P < .001). The mean change in the 7-point Asthma Control Questionnaire score (WMD -0.12, 95% CI -0.21 to -0.03, P = .01) was markedly lower in tiotropium group, but not clinically important. There were no significant differences in Asthma Quality of Life Questionnaire score (WMD 0.09, 95% CI -0.01 to 0.20, P = .09), night awakenings (WMD 0.00, 95% CI -0.05 to 0.05, P = .99) or rescue medication use (WMD -0.18, 95% CI -0.36 to 0.00, P = .06). No significant increase was noticed in adverse events in the tiotropium group (OR 0.80, 95% CI 0.62-1.03, P = .08). CONCLUSIONS: The addition of tiotropium to standard treatment regimens has significantly improved lung function without increasing adverse events in patients with inadequately controlled asthma. Long-term trials are required to assess the effects of the addition of tiotropium on asthma exacerbations and mortality.


Assuntos
Asma/tratamento farmacológico , Broncodilatadores/uso terapêutico , Derivados da Escopolamina/uso terapêutico , Asma/fisiopatologia , Broncodilatadores/efeitos adversos , Quimioterapia Combinada , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Placebos/uso terapêutico , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Derivados da Escopolamina/efeitos adversos , Índice de Gravidade de Doença , Espirometria , Brometo de Tiotrópio , Capacidade Vital/efeitos dos fármacos
8.
Artigo em Inglês | MEDLINE | ID: mdl-23125868

RESUMO

Doxorubicin (DOX) is considered as one of the best antineoplastic agents. However, its clinical use is restricted by its associated cardiotoxicity, which is mediated by the production of reactive oxygen species. In this study, 20(S)-ginsenoside Rh2 (Rh2) was explored whether it had protective effects against DOX-induced cardiotoxicity. In vitro study on H9C2 cell line, as well as in vivo investigation in one mouse and one rat model of DOX-induced cardiomyopathy, was carried out. The results showed that pretreatment with Rh2 significantly increased the viability of DOX-injured H9C2 cells. In the mouse model, Rh2 could suppress the DOX-induced release of the cardiac enzymes into serum and improved the occurred pathological changes through ameliorating the decreased antioxidant biomolecules and the cumulated lipid peroxidation malondialdehyde in heart tissues. In the rat model, Rh2 could attenuate the change of ECG resulting from DOX administration. Furthermore, Rh2 enhanced the antitumor activity of DOX in A549 cells. Our findings thus demonstrated that Rh2 pretreatment could effectively alleviate heart injury induced by DOX, and Rh2 might act as a novel protective agent in the clinical usefulness of DOX.

9.
Eur J Pharmacol ; 640(1-3): 75-81, 2010 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-20470770

RESUMO

The present study was to investigate the neuroprotective efficacy and mechanism of Forsythoside B. Male Sprague-Dawley rats were subjected to middle cerebral artery occlusion for 1 h followed by reperfusion for 23 h. Rats received an intravenous bolus injection of Forsythoside B at 15 min after reperfusion. The results showed that Forsythoside B at doses higher than 8 mg/kg produced a significant neuroprotective potential in cerebral ischemia and reperfusion rats. Forsythoside B (20 mg/kg) demonstrated significant neuroprotective activity even after delayed administration at 1 h, 3 h and 5 h after cerebral ischemia and reperfusion. Forsythoside B 20 mg/kg attenuated histopathological damage as demonstrated by smaller brain infarct size and brain edema, decreased cerebral Evans blue extravasation and myeloperoxidase (MPO) activity, inhibited cerebral phosphor-IkappaB-alpha and nuclear transcription factors kappaB (NF-kappaB) expression. Meanwhile, NF-kappaB expression with immunohistochemical staining was reduced, while circulating polymorphonuclear leukocytes was increased. All of these findings suggested that Forsythoside B exerted potent neuroprotective effects with a favorable therapeutic time-window, reduce of cerebral ischemia and reperfusion injury degree, attenuating blood-brain barrier (BBB) breakdown, and its protective effects may be due to inhibition of inflammatory response.


Assuntos
Anti-Inflamatórios/farmacologia , Isquemia Encefálica/tratamento farmacológico , Ácidos Cafeicos/farmacologia , Glucosídeos/farmacologia , Glicosídeos/farmacologia , Fármacos Neuroprotetores/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/toxicidade , Antígenos Nucleares/metabolismo , Infarto Encefálico/complicações , Infarto Encefálico/tratamento farmacológico , Infarto Encefálico/metabolismo , Infarto Encefálico/patologia , Isquemia Encefálica/complicações , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Ácidos Cafeicos/uso terapêutico , Ácidos Cafeicos/toxicidade , Modelos Animais de Doenças , Azul Evans/metabolismo , Extravasamento de Materiais Terapêuticos e Diagnósticos , Glucosídeos/uso terapêutico , Glucosídeos/toxicidade , Glicosídeos/uso terapêutico , Glicosídeos/toxicidade , Leucócitos/efeitos dos fármacos , Masculino , NF-kappa B/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/imunologia , Neurônios/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Fármacos Neuroprotetores/toxicidade , Peroxidase/metabolismo , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia
10.
Phytother Res ; 24(4): 547-52, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20041427

RESUMO

This study was conducted to investigate the efficacy of cornin, an iridoid glycoside, in an experimental cerebral ischemia induced by middle cerebral artery occlusion (MCAO) and reperfusion (I/R), and to elucidate the potential mechanism. Adult male Sprague-Dawley rats were subjected to MCAO for 1 h, then reperfusion for 23 h. Behavioral tests were used to evaluate the damage to central nervous system. The cerebral infarct volume and histopathological damage were assessed to evaluate the brain pathophysiological changes. Spectrophotometric assay methods were used to determine the activities of superoxide dismutase (SOD) and glutathione-peroxidase (GPx). Contents of malondialdehyde (MDA), the generation of reactive oxygen species (ROS) as well as respiratory control ratio and respiratory enzymes of the brain mitochondria were also determined. The results showed that cornin significantly decreased neurological deficit scores, and reduced cerebral infarct volume and degenerative neurons. Meanwhile, cornin significantly increased the brain ATP content, improved mitochondrial energy metabolism, inhibited the elevation of MDA content and ROS generation, and attenuated the decrease of SOD and GPx activities in brain mitochondria. These findings indicate that cornin has protective potential against cerebral ischemia injury and its protective effects may be due to amelioration of cerebral mitochondrial function and its antioxidant property.


Assuntos
Infarto da Artéria Cerebral Média/tratamento farmacológico , Iridoides/uso terapêutico , Fitoterapia , Verbena , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Cálcio/metabolismo , Respiração Celular/efeitos dos fármacos , Transporte de Elétrons/efeitos dos fármacos , Glutationa Peroxidase/metabolismo , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/patologia , Glicosídeos Iridoides , Masculino , Malondialdeído/metabolismo , Fluidez de Membrana/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Membranas Mitocondriais/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Fosfolipídeos/metabolismo , Extratos Vegetais/uso terapêutico , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Superóxido Dismutase/metabolismo , Água/metabolismo
11.
Phytomedicine ; 17(3-4): 282-8, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19524418

RESUMO

This study was carried out to investigate whether rosmarinic acid (RA) has antifibrotic effect on experimental liver fibrosis in vitro and in vivo and its possible mechanism. Culture of hepatic stellate cells (HSCs) determine proliferation and expression of transforming growth factor-beta1 (TGF-beta1), connective transforming growth factor (CTGF) and alpha-smooth muscle actin (alpha-SMA). In carbon tetrachloride (CCL(4))-induced rat liver fibrosis model, determined biochemical indicator, liver fibrosis grade and histopathological changes, immunohistochemical detected liver TGF-beta1 and CTGF expression. The results indicated that RA could inhibit HSCs proliferation, inhibit TGF-beta1, CTGF and alpha-SMA expression in cultured HSCs. It has marked evident in reducing fibrosis grade, ameliorating biochemical indicator and histopathological morphology, reducing liver TGF-beta1 and CTGF expression in CCL(4)-induced liver fibrosis. These findings suggest that RA has potentially conferring antifibrogenic effects.


Assuntos
Antioxidantes/uso terapêutico , Intoxicação por Tetracloreto de Carbono/tratamento farmacológico , Cinamatos/uso terapêutico , Depsídeos/uso terapêutico , Células Estreladas do Fígado/efeitos dos fármacos , Cirrose Hepática/tratamento farmacológico , Fígado/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Actinas/metabolismo , Animais , Antioxidantes/farmacologia , Intoxicação por Tetracloreto de Carbono/complicações , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Cinamatos/farmacologia , Fator de Crescimento do Tecido Conjuntivo/antagonistas & inibidores , Depsídeos/farmacologia , Modelos Animais de Doenças , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/etiologia , Cirrose Hepática/metabolismo , Masculino , Fitoterapia , Extratos Vegetais/farmacologia , Ratos , Ratos Sprague-Dawley , Fator de Crescimento Transformador beta1/antagonistas & inibidores
12.
Pharmacology ; 84(3): 162-70, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19696522

RESUMO

Cornuside, a secoiridoid glucoside compound, was isolated from the fruit of Cornus officinalis Sieb. et Zucc. The present study elucidates the effects of cornuside on cultured rat cortical neuron damage induced by oxygen-glucose deprivation. The results show that cornuside treatment obviously attenuates apoptosis and ameliorates mitochondrial energy metabolism in rat cortical neurons by increasing the cell survival rate, mitochondrial antioxidant enzyme activities, mitochondrial respiratory enzyme activity, mitochondrial respiratory control ratio and the ATP content, and by decreasing the mitochondrial malondialdehyde content, lactate dehydrogenase leakage rate, intracellular Ca(2+) level and caspase-3 activity in a concentration-dependent manner. These findings indicate that cornuside has protective potential against cerebral ischemic injury, and its protective effects may be due to the suppression of intracellular Ca(2+) elevation and caspase-3 activity, and improvements in mitochondrial energy metabolism and antioxidant properties.


Assuntos
Apoptose/efeitos dos fármacos , Cornus/química , Metabolismo Energético/efeitos dos fármacos , Glucosídeos/farmacologia , Piranos/farmacologia , Animais , Antioxidantes/administração & dosagem , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Isquemia Encefálica/prevenção & controle , Cálcio/metabolismo , Caspase 3/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Relação Dose-Resposta a Droga , Frutas , Glucosídeos/administração & dosagem , Glucosídeos/isolamento & purificação , Técnicas In Vitro , L-Lactato Desidrogenase/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Piranos/administração & dosagem , Piranos/isolamento & purificação , Ratos , Ratos Sprague-Dawley
13.
Planta Med ; 75(14): 1470-5, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19644810

RESUMO

Astilbin, a flavonoid compound, was isolated from the rhizome of Smilax glabra Roxb. This study was conducted to investigate the efficacy of astilbin on experimental diabetic nephropathy (DN) in vivo and in vitro and its possible mechanisms. Astilbin was added in high glucose stimulated HK-2 cells, streptozotocin-induced experimental DN, randomized to receive intragastric ( I. G.) astilbin to observe its anti-renal lesion effect. Results showed that astilbin inhibited high glucose stimulated HK-2 cell production of transforming growth factor-beta1 (TGF-beta1) and connective tissue growth factor (CTGF) in vitro, especially CTGF; analogic results was also found in vivo. I. G. of astilbin 2.5 mg/kg or 5 mg/kg significantly ameliorated renal function, reduced kidney index, while it increased body weight and survival time in animals. In addition there was no significant difference in blood glucose level between the STZ-treated group and the astilbin groups. Furthermore, astilbin ameliorated the pathological progress of renal morphology. Astilbin can exert an early renal protective role to DN, inhibit production of TGF-beta1 and especially of CTGF. We suggest that astilbin inhibition of CTGF may be a potential target in DN therapy. This work provides the first evidence for astilbin as a new candidate of DN therapeutic medicine.


Assuntos
Antioxidantes/uso terapêutico , Diabetes Mellitus Experimental/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Flavonóis/uso terapêutico , Rim/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Smilax/química , Animais , Antioxidantes/farmacologia , Peso Corporal/efeitos dos fármacos , Linhagem Celular , Fator de Crescimento do Tecido Conjuntivo/antagonistas & inibidores , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Experimental/fisiopatologia , Nefropatias Diabéticas/patologia , Nefropatias Diabéticas/fisiopatologia , Flavonóis/isolamento & purificação , Flavonóis/farmacologia , Glucose/metabolismo , Humanos , Rim/patologia , Rim/fisiopatologia , Longevidade/efeitos dos fármacos , Masculino , Modelos Animais , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Rizoma , Fator de Crescimento Transformador beta1/antagonistas & inibidores
14.
Basic Clin Pharmacol Toxicol ; 105(1): 64-71, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19371254

RESUMO

The present study was carried out to investigate the effects of paeoniflorin in cultured RAW264.7 cell line as well as in an experimental model of sepsis induced by cecal ligation and puncture, and intraperitoneal injection (i.p.) of lipopolysaccharide in rats. Results showed that paeoniflorin concentration-dependently down-regulated the levels of TNF-alpha, IL-6 and high-mobility group-box 1 protein in lipopolysaccharide-induced RAW264.7 cell, inhibited the IkappaB kinase pathway and modulated NF-kappaB. Intravenous injection (i.v.) of paeoniflorin alone or in combination with imipenem reduced i.p. of lipopolysaccharide or cecal ligation and puncture-induced lethality in rats. In addition, serum levels of TNF-alpha, IL-6, high-mobility group-box 1 protein, triggering receptor expressed on myeloid cells and endotoxin were down-regulated; by contrast, serum levels of IL-10 were up-regulated. Amelioration of hemodynamics, decrease of enzyme levels, decrease of myeloperoxidase in lung, liver, and small intestine were also found after paeoniflorin injection. These data indicate that the anti-sepsis effect of paeoniflorin was mediated by decreasing local and systemic levels of a wide spectrum of inflammatory mediators. This work provides the first evidence that paeoniflorin has the capacity to inactivate inflammatory response in sepsis and the anti-inflammatory mechanism of paeoniflorin may inhibit activation of the NF-kappaB pathway by inhibiting IkappaB kinase activity.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Benzoatos/farmacologia , Hidrocarbonetos Aromáticos com Pontes/farmacologia , Glucosídeos/farmacologia , Inflamação/patologia , Choque Séptico/mortalidade , Animais , Antibacterianos/farmacologia , Nitrogênio da Ureia Sanguínea , Ceco/lesões , Ceco/cirurgia , Linhagem Celular , Ensaios Enzimáticos Clínicos , Proteínas de Ligação a DNA/análise , Endotoxinas/sangue , Endotoxinas/toxicidade , Hemodinâmica/fisiologia , Imipenem/farmacologia , Mediadores da Inflamação/sangue , Mediadores da Inflamação/fisiologia , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/enzimologia , Ácido Láctico/sangue , Fígado/efeitos dos fármacos , Fígado/enzimologia , Pulmão/efeitos dos fármacos , Pulmão/enzimologia , Macrófagos/química , Macrófagos/efeitos dos fármacos , Masculino , Glicoproteínas de Membrana/sangue , Camundongos , Monoterpenos , Peroxidase/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores Imunológicos/sangue , Choque Séptico/induzido quimicamente , Receptor Gatilho 1 Expresso em Células Mieloides
15.
Planta Med ; 75(6): 614-9, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19263342

RESUMO

This study was conducted to investigate the efficacy of cornuside, a secoiridoid glucoside compound, in cultured macrophages as well as in an experimental model of sepsis induced by cecal ligation and puncture (CLP) in rats. Cornuside was added to cultured macrophages at different concentrations, and all CLP rats were randomized to receive an intravenous injection of the corresponding drug followed by observation of its antisepsis effect. Our results showed that cornuside downregulated the levels of TNF- alpha, IL-6, and NO production in a dose-dependent manner in activated macrophages, while it upregulated the level of IL-10. Intravenous injection of cornuside or imipenem alone or in combination reduced CLP-induced lethality in rats after CLP. In addition, serum levels of TNF- alpha, IL-6, triggering receptor expressed on myeloid cells, and endotoxin were downregulated. On the other hand, the serum levels of IL-10 were upregulated. Decreased bacterial counts in blood, peritoneum, spleen, liver, and mesenteric lymph nodes and decreased myeloperoxidase in lung, liver, and small intestine also were found after cornuside injection. These data indicate that the antisepsis therapeutic effect of cornuside is mediated by decreased local and systemic levels of a wide spectrum of inflammatory mediators. This work provides first evidence for the clinic use of cornuside as a new immunomodulatory drug that has the capacity to inhibit the inflammatory response in sepsis.


Assuntos
Antibacterianos/uso terapêutico , Cornus/química , Glucosídeos/uso terapêutico , Fatores Imunológicos/uso terapêutico , Mediadores da Inflamação/sangue , Extratos Vegetais/uso terapêutico , Piranos/uso terapêutico , Sepse/tratamento farmacológico , Animais , Antibacterianos/farmacologia , Contagem de Colônia Microbiana , Citocinas/sangue , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Regulação para Baixo , Quimioterapia Combinada , Endotoxinas/sangue , Frutas , Glucosídeos/isolamento & purificação , Glucosídeos/farmacologia , Imipenem/farmacologia , Imipenem/uso terapêutico , Fatores Imunológicos/farmacologia , Macrófagos/efeitos dos fármacos , Masculino , Células Mieloides/efeitos dos fármacos , Óxido Nítrico/sangue , Peroxidase/metabolismo , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Piranos/isolamento & purificação , Piranos/farmacologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Sepse/sangue , Regulação para Cima
16.
Shock ; 32(6): 608-13, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19295475

RESUMO

The present study was to investigate the effects of rosmarinic acid (RA) in cultured RAW264.7 cells and experimental model of sepsis induced by cecal ligation and puncture in rats and the potential mechanism. Results showed that RA concentration dependently down-regulated the levels of TNF-alpha, IL-6, and high-mobility group box 1 protein in LPS-induced RAW264.7 cells, inhibited the IkappaB kinase pathway, and modulated nuclear factor-kappaB. Intravenous injection of RA alone or in combination with imipenem reduced cecal ligation and puncture-induced lethality in rats. In addition, serum levels of TNF-alpha, IL-6, high-mobility group box 1 protein, triggering receptor expressed on myeloid cells, and endotoxin were down-regulated; in contrast, serum level of IL-10 was up-regulated. Amelioration of hemodynamics and decrease in serum enzyme activities and myeloperoxidase in lung, liver, and small intestine were also observed after RA injection. These data indicate that the antisepsis effect of RA was mediated by decreasing local and systemic levels of a wide spectrum of inflammatory mediators. This article provides the first evidence that RA has the capacity to inactivate inflammatory response in sepsis. The anti-inflammatory mechanism of RA may inhibit activation of the nuclear factor- kappaB pathway by inhibiting IkappaB kinase activity.


Assuntos
Cinamatos/farmacologia , Depsídeos/farmacologia , Regulação da Expressão Gênica , Hemodinâmica , Inflamação/patologia , Sepse/tratamento farmacológico , Animais , Antibacterianos/farmacologia , Modelos Animais de Doenças , Endotoxinas/metabolismo , Humanos , Imipenem/farmacologia , Masculino , Camundongos , Células Mieloides/citologia , Ratos , Ratos Sprague-Dawley , Sepse/prevenção & controle , Tretinoína
17.
Biol Pharm Bull ; 30(1): 44-7, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17202657

RESUMO

Previous research has shown that salvianic acid A [2-(3,4-dihydroxyphenyl)-2-hydroxy-propanoic acid, SA] extracted from Salvia miltiorrhiza BGE (Danshen) markedly inhibits lipid peroxidation of mitochondrial membrane of hepatic cells in vitro. The present study was conducted to examine protective effect of SA on liver injury induced by carbon tetrachloride (CCl4) and its possible mechanism in vivo. Male Sprague-Dawley rats weighing 180-200 g were used in the experiments. Five mmol/kg CCl4 in olive oil was given to rats i.p. Spectrophotometrical method was used to measure activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum, activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) as well as malondialdehyde (MDA) level in hepatic tissue and the rate of superoxide anion (O2*-) generation in hepatic submitochondrial particles. Hepatic histological structure was observed under light microscopy. CCl4 caused significant changes of activities of the enzymes, MDA level, and the rate of O2*- generation and histopathological changes of acute hepatic injury were noted. SA reversed the significant changes induced by CCl4. These results demonstrate that SA produces protective action on acute hepatic injury induced by CCl4 via an antioxidative mechanism.


Assuntos
Antioxidantes/farmacologia , Ácidos Cafeicos/farmacologia , Tetracloreto de Carbono , Lactatos/farmacologia , Hepatopatias/prevenção & controle , Fígado/efeitos dos fármacos , Alanina Transaminase/sangue , Animais , Antioxidantes/isolamento & purificação , Antioxidantes/uso terapêutico , Aspartato Aminotransferases/sangue , Ácidos Cafeicos/isolamento & purificação , Ácidos Cafeicos/uso terapêutico , Catalase/metabolismo , Doença Hepática Induzida por Substâncias e Drogas , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/química , Glutationa Peroxidase/metabolismo , Lactatos/isolamento & purificação , Lactatos/uso terapêutico , Fígado/metabolismo , Fígado/patologia , Hepatopatias/sangue , Hepatopatias/metabolismo , Hepatopatias/patologia , Masculino , Malondialdeído/metabolismo , Necrose , Extratos Vegetais , Ratos , Ratos Sprague-Dawley , Salvia miltiorrhiza , Superóxido Dismutase/metabolismo , Superóxidos/metabolismo
18.
J Asian Nat Prod Res ; 7(4): 607-13, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16087635

RESUMO

The therapeutic effects of hydroxysafflor yellow A (HSYA), extracted from Carthamus tinctorius. L, on focal cerebral ischemic injury in rats and its related mechanisms have been investigated. Focal cerebral ischemia in rats were made by inserting a monofilament suture into internal carotid artery to block the origin of the middle cerebral artery and administrated by HSYA via sublingular vein injection in doses of 1.5, 3.0, 6.0 mg kg(-1) at 30 min after the onset of ischemia, in comparison with the potency of nimodipine at a dose of 0.2 mg kg(-1). Then, 24 h later, the evaluation for neurological deficit scores of the rats were recorded and postmortem infarct areas determined by quantitative image analysis. At the end of the experiment, blood samples were taken to determine plasma 6-Keto-PGF1alpha/TXB2 by radioimmunoassays and blood rheological parameters. The effects exerted by HSYA on thrombosis formation by artery vein by-pass method and ADP-induced platelet aggregation in vivo and in vitro were investigated, respectively. The results indicated that more than 30% of the area of ischemic cerebrum was observed in the ischemic model group. HSYA dose-dependently improved the neurological deficit scores and reduced the cerebral infarct area, and HSYA bore a similarity in potency of the therapeutic effects on focal cerebral ischemia to nimodipine. The inhibition rates of thrombosis formation by HSYA at the designated doses were 20.3%, 43.6% and 54.2%, respectively, compared with saline-treated group. Inhibitory activities of HSYA were observed on ADP-induced platelets aggregation in a dose-dependent manner, and the maximum inhibitory aggregation rate of HSYA was 41.8%. HSYA provided a suppressive effect on production of TXA2 without significant effect on plasma PGI2 concentrations. Blood rheological parameters were markedly improved by HSYA, such as whole blood viscosity (from 21.71 +/- 4.77 to 11.61 +/- 0.90 mPa.s), plasma viscosity (from 2.73 +/- 0.53 to 1.42 +/- 0.07 mPa.s), deformability (from 0.66 +/- 0.26 to 0.77 +/- 0.33) and aggregation of erythrocyte (from 3.24 +/- 0.41 to 2.57 +/- 0.30), but no significant effect of HSYA on homatocrit was found (from 51.38 +/- 4.68% to 49.91 +/- 2.32%). HSYA appears to be a good potential agent to treat focal cerebral ischemia, and the underlying mechanisms exerted by HSYA might be involved in its inhibitory effects on thrombosis formation and platelet aggregation as well as its beneficial action on regulation of PGI2/TXA2 and blood rheological changes in rats.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Chalcona/análogos & derivados , Infarto da Artéria Cerebral Média/complicações , Quinonas/farmacologia , Animais , Isquemia Encefálica/veterinária , Chalcona/farmacologia , Relação Dose-Resposta a Droga , Epoprostenol/sangue , Infarto da Artéria Cerebral Média/veterinária , Ratos , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/veterinária
19.
Zhongguo Zhong Yao Za Zhi ; 30(6): 466-8, 2005 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-15810458

RESUMO

OBJECTIVE: To study the protective effect of ligusticum chuanxiong phthalides on cerebral ischemia in rats and its related mechanism of action. METHOD: Middle cerebral artery occlusion (MCAO) model, thrombosis formation, platelet aggregation and hemorrheological parameters were measured to evaluate the protective effect of ligusticum chuanxiong phthalides. RESULT: Ligusticum chuanxiong phthalides could markedly decrease the infarct size and behavior deficits score, inhibit the thrombus formation and platelet aggregation, ameliorate hemorrheological parameters with a dose-dependent manner in rats. CONCLUSION: Ligusticum chuanxiong phthalides has protective effects on focal cerebral ischemia in rats, and its mechanism may be relevant to its inhibition of platelet-dependent thrombosis and amelioration of hemorrheological parameters.


Assuntos
Benzofuranos/farmacologia , Isquemia Encefálica/patologia , Ligusticum/química , Fármacos Neuroprotetores/farmacologia , Trombose Venosa/prevenção & controle , Animais , Benzofuranos/isolamento & purificação , Viscosidade Sanguínea/efeitos dos fármacos , Isquemia Encefálica/sangue , Relação Dose-Resposta a Droga , Hematócrito , Infarto da Artéria Cerebral Média/sangue , Infarto da Artéria Cerebral Média/patologia , Masculino , Plantas Medicinais/química , Agregação Plaquetária/efeitos dos fármacos , Ratos , Ratos Wistar
20.
Yao Xue Xue Bao ; 40(12): 1144-6, 2005 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-16496682

RESUMO

AIM: To investigate the protective effect of hydroxysafflor yellow A (HSYA), a soluble element extracted from Carthamus tinctorius L., on focal cerebral ischemia in rats. METHODS: Focal cerebral ischemia in male Wistar-Kyoto (WKY) rats were induced by permanent middle cerebral artery occlusion (MCAO). Three doses of 1.5, 3.0 and 6.0 mg x kg(-1) of HSYA were administrated to three groups of rats, separately, via sublingular vein injection 30 min after the onset of ischemia. 24 h after ischemia in rats, neurological deficit scores were evaluated and the infarction area of brain was assessed by quantitative image analysis. The in vitro neuroprotective effect of HSYA was tested in cultured fetal cortical neurons exposed to glutamate and sodium cyanide (NaCN). RESULTS: HSYA at doses of 3.0 and 6.0 mg x kg(-1) exerted significant neuroprotective effects on rats with focal cerebral ischemic injury as expressed by neurological deficit scores and reduced the infarct area as compared with saline group, and the potency of HSYA at dose of 6.0 mg x kg(-1) was similar to that of 0.2 mg x kg(-1) of nimodipine. In vitro studies, HSYA significantly inhibited neurons damage induced by exposure to glutamate and NaCN in cultured fetal cortical cells. CONCLUSION: HSYA has potential neuroprotective action against focal cerebral ischemia in rats and cultured rat fetal cortical neurons as well.


Assuntos
Isquemia Encefálica/patologia , Encéfalo/patologia , Carthamus tinctorius , Chalcona/análogos & derivados , Fármacos Neuroprotetores/farmacologia , Quinonas/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Isquemia Encefálica/etiologia , Isquemia Encefálica/fisiopatologia , Carthamus tinctorius/química , Células Cultivadas , Córtex Cerebral/citologia , Chalcona/isolamento & purificação , Chalcona/farmacologia , Ácido Glutâmico , Infarto da Artéria Cerebral Média/complicações , L-Lactato Desidrogenase/metabolismo , Masculino , Neurônios/citologia , Neurônios/metabolismo , Fármacos Neuroprotetores/isolamento & purificação , Plantas Medicinais/química , Quinonas/isolamento & purificação , Ratos , Ratos Endogâmicos WKY , Cianeto de Sódio/antagonistas & inibidores
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...