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1.
Eur J Pharmacol ; 829: 1-11, 2018 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-29625084

RESUMO

Chronic low-grade inflammation plays a major role in the development of insulin resistance. The potential role and underlying mechanism of vitamin C, an antioxidant and anti-inflammatory agent, was investigated in tumor necrosis factor-α (TNF-α)-induced insulin resistance. Gulonolactone oxidase knockout (Gulo-/-) mice genetically unable to synthesize vitamin C were used to induce insulin resistance by continuously pumping small doses of TNF-α for seven days, and human liver hepatocellular carcinoma cells (HepG2 cells) were used to induce insulin resistance by treatment with TNF-α. Vitamin C deficiency aggravated TNF-α-induced insulin resistance in Gulo-/- mice, resulting in worse glucose tolerance test (GTT) results, higher fasting plasma insulin level, and the inactivation of the protein kinase B (AKT)/glycogen synthase kinase-3ß (GSK3ß) pathway in the liver. Vitamin C deficiency also worsened liver lipid accumulation and inflammation in TNF-α-treated Gulo-/- mice. In HepG2 cells, vitamin C reversed the TNF-α-induced reduction of glucose uptake and glycogen synthesis, which were mediated by increasing GLUT2 levels and the activation of the insulin receptor substrate (IRS-1)/AKT/GSK3ß pathway. Furthermore, vitamin C inhibited the TNF-α-induced activation of not only the mitogen-activated protein kinase (MAPKs), but also nuclear factor-kappa B (NF-κB) signaling. Taken together, vitamin C is essential for preventing and improving insulin resistance, and the supplementing with vitamin C may be an effective therapeutic intervention for metabolic disorders.


Assuntos
Deficiência de Ácido Ascórbico/metabolismo , Resistência à Insulina , Fator de Necrose Tumoral alfa/farmacologia , Animais , Ácido Ascórbico/farmacologia , Deficiência de Ácido Ascórbico/patologia , Ativação Enzimática/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Glucose/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Células Hep G2 , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Quinase I-kappa B/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
2.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-676846

RESUMO

Objective To develop a method for the simultaneous separation and determination of 10 kinds of sedative hypnotica drugs in the functional food with high performance liquid chromatography mass spectrometry system.Methods The mobile phase consisted of acetonitrile and 15 mmol/L ammonium acetate solution(0.1% formic acid ),chromatographic column was Zobax SB C 18.Identification was based on the compound's absolute retention time,protonated molecular ion,and representative fragment ion by multiple reaction monitoring.The condition of determination was investigated and optimized.Results With this method,the linear range for the 10 drugs was 10-1 080 ?g/kg,the average recoveries ranged from 80.5%-97.1% and the detection limits were from 0.35-12.0?g/kg respectively.Conclusion The method established in the present paper is applicable to monitoring sedative hypnotica drug in the functional food.

3.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-289340

RESUMO

OBJECTIVE: To evaluate the pharmacological effects of Liangyuan Pipagao on cough reflex and ciliary action. Liangyuan Pipagao is a compound preparation of traditional Chinese medicine. METHODS: Cough was induced by aerosol citric acid in guinea pigs and aerosol capsacin in mice. Excretion function of the airway in mice was determined by phenol red method. Ciliary movement function of frog esophagus was examined by a migration method of charcoal granules. RESULTS: Liangyuan Pipagao inhibited both the citric acid-induced cough in guinea pigs and capsacin-induced cough in mice. ID(50)value 2.64 g/kg (95%Cl1.12 approximately 6.19) and 11.40 g/kg (95%Cl5.76 approximately 22.58) respectively. Further, Liangyuan Pipagao increased phenol red excretion in mice airways and stimulated ciliary action of frog esophagusin a dose-dependent fashion. ED(50) value 7.70 g/kg (95%Cl 4.62 approximately 12.83) and EC(25) value 1.07 X 10(-4) (95% Cl 0.394 approximately 2.92x10(-4)) respectively. CONCLUSION: Liangyuan Pipagao a traditional Chinese medicine may have anti-tussive as well as expectorant actions.

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