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: 2.59). 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.

  • [Show abstract] [Hide abstract]
    ABSTRACT: RhoA/Rho kinase (ROCK) signaling has been suggested to be involved in diabetic nephropathy (DN) pathogenesis. Altered expression of connexin43 (Cx43) has been found in kidneys of diabetic animals. Both of them have been found to regulate nuclear factor kappa-B (NF-κB) activation in high glucose-treated glomerular mesangial cells (GMCs). The aim of this study was to investigate the relationship between RhoA/ROCK signaling and Cx43 in the DN pathogenesis. We found that upregulation of Cx43 expression inhibited NF-κB p65 nuclear translocation induced by RhoA/ROCK signaling in GMCs. Inhibition of RhoA/ROCK signaling attenuated the high glucose-induced decrease in Cx43. F-actin accumulation and an enhanced interaction between zonula occludens-1 (ZO-1) and Cx43 were observed in high glucose-treated GMCs. ZO-1 depletion or disruption of F-actin formation also inhibited the reduction in Cx43 protein levels induced by high glucose. In conclusion, activated RhoA/ROCK signaling induces Cx43 degradation in GMCs cultured in high glucose, depending on F-actin regulation. Increased F-actin induced by RhoA/ROCK signaling promotes the association between ZO-1 and Cx43, which possibly triggered Cx43 endocytosis, a mechanism of NF-κB activation in high glucose-treated GMCs.
    Experimental Cell Research 07/2014; · 3.37 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cisplatin is a potent anti-tumor compound. Nephrotoxicity-inducing oxidative stress is a common side effect. This study was conducted to find out whether, the triterpenoid saponin of Terminalia arjuna (TA), Arjunolic acid which is a natural antioxidant, could prevent cisplatin-induced renal toxicity and if so, explore its possible renoprotective mechanism.
    Clinical and Experimental Nephrology 11/2014; · 1.71 Impact Factor
  • 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. 01/2014; 4:132.