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1.
Zhen Ci Yan Jiu ; 48(8): 812-7, 2023 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-37614140

RESUMO

OBJECTIVE: To observe the effects of transcutaneous auricular vagus nerve stimulation (taVNS) on plasma melatonin (MLT) content and insulin receptor expression in the liver, the skeletal muscles, and the pancreas of Zucker diabetic fatty (ZDF) rats, so as to explore the hypoglycemic mechanism of taVNS. METHODS: Thirty male ZDF rats were randomly divided into model group, taVNS group and sham-taVNS group, with 10 rats in each group; besides, 10 male Zucker lean rats of the same strain were collected for the blank control group. ZDF rats were fed with high-fat diet to induce type 2 diabetes mellitus (T2DM) rat model. In the taVNS group, HANS-100A electroacupuncture instrument was used to stimulate the cavum conchae of both sides. The stimulation sites of rats in the sham-taVNS were the same as the taVNS group, but without electricity delivered. The above interventions were performed 30 min each time, once daily, lasting for 6 weeks. Fasting blood glucose (FBG) was measured weekly in each group, the plasma metatonin (MLT) content was detected by ELISA, and the insulin receptor expression level in the liver, the skeletal muscle and the pancreas was determined by Western blot. RESULTS: Compared with the blank control group, the level of FBG of rats were increased (P<0.01), the plasma MLT content was decreased (P<0.01) and the insulin receptor expression level in the pancreatic tissue was decreased (P<0.01) in the model group. In the taVNS gruop, FBG was decreased (P<0.05, P<0.01), the plasma MLT content was increased (P<0.01), and the insulin receptor expression level in the liver, the skeletal muscle and the pancreas was increased (P<0.05, P<0.01, P<0.001) when compared with the model group. Compared with the taVNS group, FBG was increased (P<0.05, P<0.01), the plasma MLT content was decreased (P<0.01), and the expression level of insulin receptors in the skeletal muscle and the pancreas was decreased (P<0.01, P<0.001) in the sham-taVNS group. CONCLUSION: The taVNS can improve the insulin resistance and ultimately obtain the antihyperglycemic effect through regulating MLT concentration.


Assuntos
Diabetes Mellitus Tipo 2 , Melatonina , Estimulação do Nervo Vago , Animais , Masculino , Ratos , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/terapia , Hipoglicemiantes , Ratos Zucker , Receptor de Insulina
2.
Biomed Res Int ; 2020: 4816209, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32461991

RESUMO

This thesis is aimed at shedding light on the effects of the Zhenwu decoction (ZWD) on the activities and mRNA expressions of seven CYP450 isoenzymes. In the first step, we determined the main chemical compounds of ZWD by high-performance liquid chromatography (HPLC). Next, 48 male (SD) rats were randomly divided into the normal saline (NS) group and the ZWD low- (2.1875 g/kg), medium- (4.375 g/kg), and high- (8.75 g/kg) dose groups (12 per group). All rats were gavaged once daily for 28 consecutive days. A mixed solution of seven probe drugs was injected into 24 rats through the caudal vein after the last intragastric administration. Lastly, a validated cocktail method and real-time quantitative reverse-transcription polymerase chain reaction (RT-qPCR) were used to detect pharmacokinetic parameters and mRNA expressions, respectively. Compared with the NS group, ZWD at medium- and high-dose groups could significantly induce CYP2C6 (P < 0.05) activity, while the mRNA expression (P < 0.05) increased only in the high-dose group. Additionally, CYP2C11 activity was induced and consistent with mRNA expression (P < 0.05). Moreover, ZWD could induce the activity of CYP3A1 (P < 0.05), but the mRNA expression showed no significant differences except in high-dose groups. Additionally, ZWD has no effects on CYP1A2, CYP2B1, CYP2C7, and CYP2D2. In conclusion, the significant inductive effects of ZWD on three CYP450 isoenzymes indicated that when ZWD was coadministrated with drugs mediated by these enzymes, not only should the potential herb-drug interactions (HDIs) be observed, but the dosage adjustment and tissue drug concentration should also be considered. Furthermore, the approach described in this article can be applied to study the importance of gender, age, and disease factors to HDI prediction.


Assuntos
Sistema Enzimático do Citocromo P-450 , Medicamentos de Ervas Chinesas/farmacologia , Testes de Toxicidade/métodos , Animais , Cromatografia Líquida de Alta Pressão , Sistema Enzimático do Citocromo P-450/análise , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Expressão Gênica/efeitos dos fármacos , Interações Ervas-Drogas , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , Modelos Químicos , Preparações Farmacêuticas/administração & dosagem , Preparações Farmacêuticas/sangue , Preparações Farmacêuticas/metabolismo , RNA Mensageiro/análise , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem
3.
Med Oncol ; 23(4): 553-62, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17303915

RESUMO

Excessive and inappropriate action of transforming growth factor (TGF)-beta has been implicated in the pathogenesis of several disease processes, especially cancer and fibrosis. To identify antagonists of the TGF- beta ligand-binding domain that may have therapeutic potential, we screened the National Cancer Institute open access chemical repository for molecules that inhibited binding of TGF-beta to the type II receptor (TbetaRII). About 30,000 molecules were screened resulting in the identification of five structurally related molecules that reduced binding of TGF-beta1 to soluble TbetaRII with an ED50 of approx 10 microM. The chemicals blocked inhibition of Mv1Lu cell growth by TGF-beta, TGF-beta - induced expression of luciferase driven by the TGF-beta response element, and induction of plasminogen inhibitor mRNA detected by Northern blot. In contrast, the chemicals did not block activin-induced inhibition of cell growth. Our results identify a novel chemical group that blocks binding of TGF-beta to its receptor and may result in novel treatment for disease.


Assuntos
Receptores de Fatores de Crescimento Transformadores beta/antagonistas & inibidores , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Fator de Crescimento Transformador beta1/antagonistas & inibidores , Fator de Crescimento Transformador beta1/metabolismo , Ativinas/metabolismo , Animais , Northern Blotting , Células CHO , Linhagem Celular Tumoral , Cricetinae , Cricetulus , Avaliação Pré-Clínica de Medicamentos , Expressão Gênica/efeitos dos fármacos , Humanos , Ligação Proteica/efeitos dos fármacos , Receptores de Fatores de Crescimento Transformadores beta/isolamento & purificação , Fator de Crescimento Transformador beta1/isolamento & purificação
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