Article

Effects of berberine on matrix accumulation and NF-kappa B signal pathway in alloxan-induced diabetic mice with renal injury.

School of Pharmaceutical Sciences, Sun Yat-Sen University, Wai Huan Dong Road 132, Guangzhou Higher Education Mega Center, Guangzhou 510006, Guangdong, China.
European journal of pharmacology (Impact Factor: 2.68). 07/2010; 638(1-3):150-5. DOI: 10.1016/j.ejphar.2010.04.033
Source: PubMed

ABSTRACT One of the main pathological changes in diabetic nephropathy is the renal fibrosis, which includes glomerulosclerosis and tubulointerstitial fibrosis. In vivo and in vitro studies demonstrated that berberine could ameliorate renal dysfunction in diabetic rats with nephropathy and inhibit fibronectin expression in mesangial cells cultured under high glucose. However, the molecular mechanisms have not been fully elucidated. The purpose of the present study was to investigate the effects of berberine on the nuclear factor-kappa B (NF-kappaB) activation, intercellular adhesion molecule-1, transforming growth factor-beta1 and fibronectin protein expression in renal tissue from alloxan-induced diabetic mice with renal damage. The distribution of NF-kappaB p65 in glomerulus and the degradation of I kappaB-alpha in renal cortex were examined by immunohistochemistry and Western blot, respectively. The protein expression of intercellular adhesion molecule-1, transforming growth factor-beta 1 and fibronectin in renal cortex were also detected by Western blot. Our results revealed that in alloxan-induced diabetic mice, the nuclear staining of NF-kappaB p65 was increased in glomerulus, whereas renal I kappaB-alpha protein was significantly reduced. The protein levels of intercellular adhesion molecule-1, transforming growth factor-beta 1 and fibronectin were upregulated in kidney from diabetic mice. After berberine treatment, the immunostaining of NF-kappaB was decreased, and the reduced degradation of I kappaB-alpha level was partially restored. The protein levels of intercellular adhesion molecule-1, transforming growth factor-beta 1 and fibronectin were all downregulated by berberine compared with diabetic model group. In conclusion, the ameliorative effects of berberine on extracellular matrix accumulation might associate with its inhibitory function on NF-kappaB signal pathway.

0 Followers
 · 
120 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Diabetes and diabetic nephropathy are complex diseases affected by genetic and environmental factors. Identification of the susceptibility genes and investigation of their roles may provide useful information for better understanding of the pathogenesis and for developing novel therapeutic approaches. Intercellular adhesion molecule 1 (ICAM1) is a cell surface glycoprotein expressed on endothelial cells and leukocytes in the immune system. The ICAM1 gene is located on chromosome 19p13 within the linkage region of diabetes. In the recent years, accumulating reports have implicated that genetic polymorphisms in the ICAM1 gene are associated with diabetes and diabetic nephropathy. Serum ICAM1 levels in diabetes patients and the icam1 gene expression in kidney tissues of diabetic animals are increased compared to the controls. Therefore, ICAM1 may play a role in the development of diabetes and diabetic nephropathy. In this review, we present genomic structure, variation, and regulation of the ICAM1 gene, summarized genetic and biological studies of this gene in diabetes and diabetic nephropathy and discussed about the potential application using ICAM1 as a biomarker and target for prediction and treatment of diabetes and diabetic nephropathy.
    Frontiers in Endocrinology 01/2012; 3:179. DOI:10.3389/fendo.2012.00179
  • Source
    Diabetic Nephropathy, 04/2012; , ISBN: 978-953-51-0543-5
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: O-GlcNAcylation is an O-linked β-N-acetylglucosamine (O-GlcNAc) moiety linked to the serine or threonine residues in proteins. O-GlcNAcylation is a dynamic post-translational modification involved in a wide range of biological processes and diseases such as cancer. This modification can increase and decrease the activity of enzymes as well as interfere with protein stability and interaction. The modulatory capacity of O-GlcNAcylation, as well as protein phosphorylation, is of paramount importance in the regulation of metabolism and intracellular signaling of tumor cells. Thus, understanding the regulation of O-GlcNAcylation in tumor cells and their difference compared to non-tumor cells may elucidate new mechanisms related to tumor generation and development, could provide a new marker to diagnosis and prognosis in patients with cancer and indicate a new target to cancer chemotherapy.
    Frontiers in Oncology 06/2014; 4:132. DOI:10.3389/fonc.2014.00132