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Lee T.-Y.,Chang Gung University | Chang H.-H.,Chang Gung University | Chang H.-H.,Center for Traditional Chinese Medicine
International Journal of Molecular Medicine | Year: 2010

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-γ, TNF-α, 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 α-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.

Lee T.-Y.,Chang Gung University | Chang H.-H.,Chang Gung University | Chang H.-H.,Center for Traditional Chinese Medicine | Lo W.-C.,Chang Gung University | Lin H.-C.,Taipei Veterans General Hospital
International Journal of Molecular Medicine | Year: 2010

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 γ 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.

Liou C.-J.,Chang Gung University | Cheng P.-Y.,Chang Gung University | Huang W.-C.,Chang Gung University | Chan C.-C.,Chang Gung University | And 4 more authors.
Allergy, Asthma and Immunology Research | Year: 2014

Purpose: Lovastatin is an effective inhibitor of cholesterol synthesis. A previous study demonstrated that lovastatin can also suppress airway hyperresponsiveness (AHR) in murine model of asthma. We aimed to investigate the effect of lovastatin on mucus secretion and inflammation-associated gene expression in the lungs of murine model of asthma. Methods: Female BALB/c mice were sensitized and challenged with ovalbumin (OVA) by intraperitoneal injection, and orally administered lovastatin from days 14 to 27 post-injection. Gene expression in lung tissues was analyzed using real-time polymerase chain reaction. AHR and goblet cell hyperplasia were also examined. BEAS-2B human bronchial epithelial cells were used to evaluate the effect of lovastatin on the expression of cell adhesion molecules, chemokines, and proinflammatory cytokines in vitro. Results: We showed that lovastatin inhibits the expression of Th2-associated genes, including eotaxins and adhesion molecules, in the lungs of murine model of asthma. Mucin 5AC expression, eosinophil infiltration and goblet cell hyperplasia were significantly decreased in the lung tissue of murine model of asthma treated with lovastatin. Furthermore, lovastatin inhibited AHR and expression of Th2-associated cytokines in bronchoalveolar lavage fluid. However, a high dose (40 mg/kg) of lovastatin was required to decrease specific IgE to OVA levels in serum, and suppress the expression of Th2-associated cytokines in splenocytes. Activated BEAS-2B cells treated with lovastatin exhibited reduced IL-6, eotaxins (CCL11 and CCL24), and intercellular adhesion molecule-1 protein expression. Consistent with this, lovastatin also suppressed the ability of HL-60 cells to adhere to inflammatory BEAS-2B cells. Conclusions: These data suggest that lovastatin suppresses mucus secretion and airway inflammation by inhibiting the production of eotaxins and Th2 cytokines in murine model of asthma. © The Korean Academy of Asthma, Allergy and Clinical Immunology. The Korean Academy of Pediatric Allergy and Respiratory Disease.

Lee T.-Y.,Chang Gung University | Chang H.-H.,Chang Gung University | Chang H.-H.,Center for Traditional Chinese Medicine | Chang H.-H.,China Medical University at Taichung | And 3 more authors.
Journal of Ethnopharmacology | Year: 2014

Ethnopharmacological relevance Liver fibrosis is a complex disease in which several pathological processes, such as inflammation and angiogenesis, are closely integrated.Materials and methods We hypothesised that treatment with the pharmacological agent, andrographolide (AP), which has multiple mechanisms of action, will provide a greater understanding of the role of AP during the multiple pathological processes that occur in advanced liver disease.Results Liver fibrogenesis was induced in mice using thioacetamide (TAA), which was administrated for 6 weeks. Andrographolide (5, 20 or 100 mg/kg) was then given once daily following TAA injection. Liver collagen was examined using hydroxyproline and α-SMA, while the inflammatory response was quantified by Western blot and RT-PCR assays. Liver angiogenesis, neutrophil infiltration and hypoxia were assessed using CD11b+, vWF and HIF-1α immunostaining. Mice with liver injuries that were treated with andrographolide showed improved inflammatory response and diminished angiogenesis and hepatic fibrosis. Andrographolide treatment inhibited liver neutrophil infiltration, while a decreased in TNF-α and COX-2 signalling indicated macrophage activation. Andrographolide decreased overall liver hypoxia, as shown by the downregulation of hypoxia-inducible cascade genes, such as VEGF. Andrographolide treatment resulted in a significant decrease in hepatic fibrogenesis, α-SMA abundance, and TGF-βR1 expression.Conclusions The present results suggest that multi-targeted therapies directed against angiogenesis, inflammation, and fibrosis should be considered for the treatment of advanced liver injury. They further suggest that andrographolide treatment may be a novel therapeutic agent for the treatment of liver disease. © 2014 Elsevier Ireland Ltd. All rights reserved.

Yang S.,Center for Traditional Chinese Medicine | Yang S.,Chang Gung University | Chen H.,Center for Traditional Chinese Medicine | Lin Y.,Center for Traditional Chinese Medicine | And 2 more authors.
Evidence-based Complementary and Alternative Medicine | Year: 2012

Pattern, or zheng, differentiation is the essential guide to treatment with traditional Chinese medicine (TCM). However, the considerable variability between TCM patterns complicates evaluations of TCM treatment effectiveness. The aim of this study was to explore and characterize the relationship between patterns and the core patterns of allergic rhinitis. We summarized 23 clinical trials of allergic rhinitis with mention of pattern differentiation; association rule mining was used to analyze TCM patterns of allergic rhinitis. A total of 205 allergic rhinitis patients seen at Chang Gung Memorial Hospital from March to June 2005 were included for comparison. Among the 23 clinical trials evaluated, lung qi deficiency and spleen qi deficiencies were the core patterns of allergic rhinitis, accounting for 29.50% and 28.98% of all patterns, respectively. A higher prevalence of lung or spleen qi deficiency (93.7%) was found in Taiwan. Additionally, patients with lung or spleen qi deficiency were younger (27.99 ± 12.94 versus 58.54 ± 12.96 years) and the severity of nasal stuffiness was higher than among patients with kidney qi deficiency (1.35 ± 0.89 versus 0.62 ± 0.65; P < 0.05). Lung and spleen qi deficiencies are the core patterns of allergic rhinitis and determining the severity of nasal stuffiness is helpful in differentiating the TCM patterns. © Copyright 2012 Sienhung Yang et al.

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