title: Berberine attenuates lipopolysaccharide-induced extracelluar matrix accumulation and inflammation in rat mesangial cells: involvement of NF-κB signaling pathway.
abstract: BACKGROUND
  Our previous studies demonstrated that berberine could improve the renal function in rats and mice with diabetic nephropathy (DN) and inhibit extracellular matrix (ECM) component, fibronectin (FN) expression in rat mesangial cells (MCs) cultured under high glucose. However, the molecular mechanisms have not been fully elucidated.
  
  
  OBJECTIVE
  To explore the potential mechanisms of berberine in the treatment of DN, we investigated the effects of berberine on lipopolysaccharide (LPS)-induced nuclear factor-kappa B (NF-κB) activation and its downstream inflammatory mediators, such as intercellular adhesion molecule-1 (ICAM-1), transforming growth factor-beta 1 (TGF-β1), inducible nitric oxide synthase (iNOS) and fibronectin (FN) protein expression in rat MCs.
  
  
  METHODS
  Cell proliferation was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The activation of NF-κB was detected by Western blot and confocal microscopy. The protein levels of ICAM-1, TGF-β1, iNOS and FN in rat MCs were detected by Western blot.
  
  
  RESULTS
  Our results revealed that berberine significantly suppressed LPS-induced cell proliferation and inhibited LPS-induced NF-κB nuclear translocation in MCs, as well as protein expression of ICAM-1, TGF-β1, iNOS and FN.
  
  
  CONCLUSIONS
  Berberine significantly repressed LPS-induced cell proliferation and FN expression in rat MCs through inhibiting the activation of NF-κB signaling pathway and protein expression of its downstream inflammatory mediators. The ameliorative effects of berberine on DN might be associated with this inhibition effect on NF-κB signaling pathway which was independent of its hypoglycemic effect.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-Sen University, Guagnzhou 510006, Guangdong, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Jiang
authors.forename: Peiqing
authors.initials: P
authors.lastname: Liu
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Wu
authors.forename: Weihua
authors.initials: W
authors.lastname: Liu
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Shen
authors.forename: Tian
authors.initials: T
authors.lastname: Lan
authors.forename: Suowen
authors.initials: S
authors.lastname: Xu
authors.forename: Jing
authors.initials: J
authors.lastname: Peng
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*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005353:Fibronectins / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D020672:I-kappa B Proteins / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D050527:Mesangial Cells / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D051996:Transcription Factor RelA / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D005353:Fibronectins; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; C000606206:Nfkbia protein, rat; D051996:Transcription Factor RelA; D053773:Transforming Growth Factor beta1; D001599:Berberine; D018799:Intercellular Adhesion Molecule-1; D000072000:NF-KappaB Inhibitor alpha; D052247:Nitric Oxide Synthase Type II