title: Effects of berberine on matrix accumulation and NF-kappa B signal pathway in alloxan-induced diabetic mice with renal injury.
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.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-Sen University, Wai Huan Dong Road 132, Guangzhou Higher Education Mega Center, Guangzhou 510006, Guangdong, China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Liu
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhang
authors.forename: Peiqing
authors.initials: P
authors.lastname: Liu
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Shen
authors.forename: Tian
authors.initials: T
authors.lastname: Lan
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Li
authors.forename: Qin
authors.initials: Q
authors.lastname: Jiang
authors.forename: Xi
authors.initials: X
authors.lastname: Xie
authors.forename: Heqing
authors.initials: H
authors.lastname: Huang
mesh_terms: D000818:Animals; D001599:Berberine / Q000494:pharmacology / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000276:immunology*; D015536:Down-Regulation / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects*; D005353:Fibronectins / Q000378:metabolism; D005355:Fibrosis; D020672:I-kappa B Proteins / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D005353:Fibronectins; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; C000606206:Nfkbia protein, rat; D053773:Transforming Growth Factor beta1; D001599:Berberine; D018799:Intercellular Adhesion Molecule-1; D000072000:NF-KappaB Inhibitor alpha