Changes of hepatic proteome in bile duct ligated rats with hepatic fibrosis following treatment with Yin-Chen-Hao-Tang

Chang²,

Lo³

et al. 2010

Int J Mol Med

Abstract. Obesity is associated with a complex systemic inflammatory state that has been implicated in the development of hepatic steatosis. This study was to test the efficacy of Yin-Chen-Hao-Tang (YCHT), an agent that improves hepatic triglyceride metabolism in its ability to modulate pathways implicated in hepatic steatosis. Mice were fed with high-fat diet for fifteen weeks. The therapeutic mechanism of YCHT likely enhanced adiponectin and endothelial progenitor cells, and up-regulation of peroxisome proliferator-activated receptor Á might be responsible for fatty liver diseases. In addition, YCHT anti-oxidative stress effect might be associated with inhibition of hepatic free fatty acid concentrations and elevation of the glutathione levels in hepatic tissues. Furthermore, YCHT action mechanisms might promote senescence marker protein-30 metabolism that increase resistance to hepatic oxidative stress. These findings suggest a novel therapeutic approach for fatty liver progression in obesity mice.

“…Changes in GSH/GSSG were determined by HPLC (16). Two-dimensional-PAGE was performed according to our previous study to detect various proteosomal changes (15).…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Alleviation of hepatic oxidative stress by Chinese herbal medicine Yin-Chen-Hao-Tang in obese mice with steatosis

Chang²,

Lo³

et al. 2010

Int J Mol Med

“…On the other hand, tissue proteome analysis has been successfully applied to investigate the molecular effects of drugs and to obtain information regarding their mode of action and therapeutic mechanism [13]. Indeed, proteomic technologies have been applied to murine models for the study of changes in the levels of liver proteins [14,15].…”

Section: Introductionmentioning

confidence: 99%

Modulation of the cannabinoid receptors by andrographolide attenuates hepatic apoptosis following bile duct ligation in rats with fibrosis

Chang

2010

Apoptosis

Bile acid-induced apoptosis plays an important role in the pathogenesis of cholestatic liver disease, and its prevention is of therapeutic interest. The aim of this study was to test whether the andrographolide limits the evolution of apoptosis in a murine model of bile duct ligation (BDL)-induced hepatic fibrosis. Male Sprague-Dawley rats were divided into four groups and hepatic apoptosis was induced by BDL for 2 weeks. The BDL animals were also treated with andrographolide (50, 100, and 200 mg/kg, i.p.) during the same time period. BDL-induced liver injury was associated with apoptosis and fibrosis, and the latter was significantly reduced in animals receiving andrographolide. The increase in serum alanine aminotransferase, asparate aminotransferase, tumor necrosis factor-alpha and IL-1beta levels caused by BDL were also significantly reduced by treatment with andrographolide. Andrographolide decreased the intrahepatic protein levels of cannabinoid receptor 1 (CB1), Bax, and cytochrome c, along with of alpha-smooth muscle actin (alpha-SMA) and transforming growth factor-beta (TGF-beta), two markers of fibrogenesis. This effect was mediated by the inactivation of the c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK1/2) phosphorylation cascade, but it did not affect the p38 mitogen-activated protein kinase pathway. Additionally, andrographolide reduced the generation of hepatic lipid peroxidation and enhance senescence marker protein-30 levels to resist the hepatic oxidative stress in the presence of BDL. In conclusion, this study has identified AP as a potent protector against cholestasis-induced apoptosis in vivo. Its anti-apoptotic action largely relies on the inhibition of the oxidative stress pathway.

“…Chemiluminescence (ECL; Amersham, Piscataway, NJ) in conjunction with video densitometry was used to quantify protein expression. Twodimensional-PAGE was performed according to our previous study to detect various proteosomal changes (15).…”

Section: Western Blotting and 2-d Gel Electrophoresismentioning

confidence: 99%

Longdan Xiegan Tang has immunomodulatory effects on CD4+CD25+ T cells and attenuates pathological signs in MRL/lpr mice

Chang²

2010

Int J Mol Med

Abstract. Longdan Xiegan Tang (LXT) is a Chinese herbal medicine that is prescribed as an anti-inflammatory aid, a hepato-protectant, and an immunostimulant. In this study, we examined the biological effects of LXT administration in MRL/lpr mice. MRL/lpr mice provide a good model of systemic lupus erythematosus (SLE). These mice develop immunological disturbances and dysregulation in Th1 and Th2 cytokine production. Female mice were randomly separated into two groups. The experimental group received LXT (250 mg/kg/day, po) from 19 to 21 weeks of age. Splenic CD3 + CD4 + , CD3 + CD8 + , and CD4 + CD25 + T cells were increased in the LXT-administered mice compared to MRL/lpr controls, and this was associated with splenomegaly. There was a marked reduction in IFN-Á, TNF-·, anti-dsDNA antibody, and there were reduced IgG immune complex deposits in the glomeruli. LXT also restored kidney glutathione levels, thereby limiting the toxic effects of the inflammatory mediators iNOS and COX-2, which are overproduced in MRL/lpr mice. Two-dimensional gel electrophoresis was used to analyze proteome changes. LXT protected MRL/lpr mice against developing the lupus syndrome through upregulation of phosphoglycerate kinase 1 and down-regulation of ferritin light chain 1, selenium-binding protein 2, and ·-enolase. This study indicates that LXT at this dose and time course of administration was effective in reducing oxidative stress associated with disease progression in MRL/lpr mice. LXT could be useful as adjunctive therapy for reducing distress in SLE.