title: Berberine ameliorates chronic kidney injury caused by atherosclerotic renovascular disease through the suppression of NFκB signaling pathway in rats.
abstract: OBJECTIVE
  Impaired renal function in atherosclerotic renovascular disease (ARD) may be the result of crosstalk between atherosclerotic renovascular stenosis and amplified oxidative stress, inflammation and fibrosis. Berberine (BBR) regulates cholesterol metabolism and exerts antioxidant effects. Accordingly, we hypothesized that BBR treatment may ameliorate ARD-induced kidney injury through its cholesterol-lowering effect and also suppression of the pathways involved in oxidative stress, inflammation and NFκB activation.
  
  
  METHODS
  Male rats were subjected to unilateral renal artery stenosis with silver-irritant coil, and then fed with 12-week hypercholesterolemic diet. Rats with renal artery stenosis were randomly assigned to two groups (n = 6 each) - ARD, or ARD+BBR - according to diet alone or in combination with BBR. Similarly, age-matched rats underwent sham operation and were also fed with hypercholesterolemic diet alone or in combination with BBR as two corresponding controls. Single-kidney hemodynamic metrics were measured in vivo with Doppler ultrasound to determine renal artery flow. The metrics reflecting hyperlipidemia, oxidative stress, renal structure and function, inflammation and NFκB activation were measured, respectively.
  
  
  RESULTS
  Compared with control rats, ARD rats had a significant increase in urinary albumin, plasma cholesterol, LDL and thiobarbituric acid reactive substances (TBARS) and a significant decrease in SOD activity. When exposed to 12-week BBR, ARD rats had significantly lower levels in blood pressure, LDL, urinary albumin, and TBARS. In addition, there were significantly lower expression levels of iNOS and TGF-β in the ARD+BBR group than in the ARD group, with attenuated NFκB-DNA binding activity and down-regulated protein levels of subunits p65 and p50 as well as IKKβ.
  
  
  CONCLUSIONS
  We conclude that BBR can improve hypercholesterolemia and redox status in the kidney, eventually ameliorating chronic renal injury in rats with ARD, and that BBR can act against proinflammatory and profibrotic responses through suppression of the NFκB signaling pathway.
authors.affiliation: Division of Nephrology, Department of Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wan
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhao
authors.forename: Wen-Juan
authors.initials: WJ
authors.lastname: Huang
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.forename: Gang-Gang
authors.initials: GG
authors.lastname: Miao
authors.forename: Wen
authors.initials: W
authors.lastname: Chen
authors.forename: Hong-Guang
authors.initials: HG
authors.lastname: Xie
authors.forename: Chang-Chun
authors.initials: CC
authors.lastname: Cao
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D050197:Atherosclerosis / Q000188:drug therapy* / Q000378:metabolism; D001599:Berberine / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D005355:Fibrosis / Q000473:pathology; D007249:Inflammation; D008297:Male; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D012078:Renal Artery Obstruction / Q000473:pathology; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy*; D015398:Signal Transduction; D013599:Systole; D017392:Thiobarbituric Acid Reactive Substances; D018608:Ultrasonography, Doppler
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D016328:NF-kappa B; D017392:Thiobarbituric Acid Reactive Substances; D001599:Berberine
references.citation: Hypertension. 2011 Apr;57(4):788-94
references.pmid: 21321301
references.citation: J Am Soc Nephrol. 2010 Jun;21(6):993-1002
references.pmid: 20360313
references.citation: Nat Rev Immunol. 2008 Nov;8(11):837-48
references.pmid: 18927578
references.citation: Hypertension. 2005 May;45(5):934-9
references.pmid: 15837840
references.citation: Nat Med. 2004 Dec;10(12):1344-51
references.pmid: 15531889
references.citation: J Pathol. 2009 Jul;218(3):360-9
references.pmid: 19334049
references.citation: Metabolism. 2011 Feb;60(2):298-305
references.pmid: 20304443
references.citation: Am J Physiol Regul Integr Comp Physiol. 2011 Mar;300(3):R635-43
references.pmid: 21178122
references.citation: Eur J Pharm Sci. 2010 Apr 16;40(1):1-8
references.pmid: 20149867
references.citation: J Cell Biochem. 2010 Sep 1;111(1):104-10
references.pmid: 20506155
references.citation: Diabetes. 2006 Aug;55(8):2256-64
references.pmid: 16873688
references.citation: J Am Soc Nephrol. 2004 Apr;15(4):958-66
references.pmid: 15034098
references.citation: Mol Cell Endocrinol. 2011 Jan 1;331(1):34-40
references.pmid: 20674665
references.citation: Nat Rev Nephrol. 2009 Dec;5(12):677-89
references.pmid: 19935815
references.citation: Am J Physiol Renal Physiol. 2009 Jan;296(1):F118-26
references.pmid: 18971213
references.citation: Circulation. 2007 Jul 3;116(1):85-97
references.pmid: 17606856
references.citation: Antioxid Redox Signal. 2012 Jan 15;16(2):139-52
references.pmid: 21895524
references.citation: Nat Clin Pract Nephrol. 2006 Oct;2(10):582-93
references.pmid: 17003837
references.citation: Circ Res. 2007 Aug 3;101(3):227-9
references.pmid: 17673681
references.citation: Can J Physiol Pharmacol. 2010 Mar;88(3):369-78
references.pmid: 20393601
references.citation: Circ Res. 2007 Aug 3;101(3):268-76
references.pmid: 17585070
references.citation: N Engl J Med. 1999 Jan 14;340(2):115-26
references.pmid: 9887164
references.citation: Am J Physiol Endocrinol Metab. 2009 Apr;296(4):E955-64
references.pmid: 19208854
references.citation: Am J Physiol Renal Physiol. 2010 Jul;299(1):F135-40
references.pmid: 20462971
references.citation: Am J Physiol Renal Physiol. 2009 Oct;297(4):F895-903
references.pmid: 19656915
references.citation: Proc Natl Acad Sci U S A. 2010 May 25;107(21):9795-800
references.pmid: 20448200
references.citation: Metabolism. 2005 Jun;54(6):788-92
references.pmid: 15931616
references.citation: J Am Soc Nephrol. 2012 Mar;23(3):458-69
references.pmid: 22223877
references.citation: Circulation. 2002 Aug 27;106(9):1165-71
references.pmid: 12196346
references.citation: J Am Soc Nephrol. 2005 Apr;16(4):1005-12
references.pmid: 15716331
references.citation: Prog Cardiovasc Dis. 2009 Nov-Dec;52(3):196-203
references.pmid: 19917330
references.citation: Nephrol Dial Transplant. 2010 Nov;25(11):3615-22
references.pmid: 20501460
references.citation: Am J Physiol Renal Physiol. 2009 Feb;296(2):F298-305
references.pmid: 19073636
references.citation: PLoS One. 2011;6(9):e24028
references.pmid: 21949690