title: Simiao pill ameliorates renal glomerular injury via increasing Sirt1 expression and suppressing NF-κB/NLRP3 inflammasome activation in high fructose-fed rats.
abstract: BACKGROUND
  Simiao pill is one of the most frequently prescriptions in traditional Chinese medicine to treat hyperuricemia and gout. This study was to investigate the protective effects of Simiao pill on renal glomerular injury in a rat model of high fructose intake.
  
  
  METHODS
  Sprague-Dawley male rats were given 10% fructose in drinking water and standard laboratory chow for 4 weeks to induce hyperuricemia and metabolic syndrome. Then fructose-fed animals were randomly divided into four groups receiving water, Simiao pill (78.87 and 157.74 mg/kg) and allopurinol (5mg/kg) daily for next 6 weeks, respectively. Serum levels of uric acid, creatinine, triglyceride, total cholesterol, low density lipoprotein, blood urea nitrogen, insulin, as well as urinary albumin were measured. Oral glucose tolerance test (OGTT) was carried out. Kidney pathological changes were detected using periodic-acid schiff-stained (PAS) staining and transmission electron microscopy (TEM) analysis. Glomerular protein levels of nephrin, podocin, CD2-associated protein (CD2AP), interleukin (IL)-1β, sirtuin 1 (Sirt1), nuclear factor kappaB (NF-κB) and pyrin domain containing 3 (NLRP3) inflammasome were measured by Western blot.
  
  
  RESULTS
  Simiao pill effectively restored high fructose-induced hyperuricemia and metabolic syndrome in rats. Simiao pill significantly increased protein levels of nephrin, podocin and CD2AP in renal glomeruli, improved renal inflammatory cell infiltration into interstitium and glomerular injury in high fructose-fed rats with reduction of urine albumin levels. Furthermore, Simiao pill up-regulated Sirt1 protein levels and suppressed NF-κB/NLRP3 inflammasome activation to reduce IL-1β in renal glomeruli of high fructose-fed rats.
  
  
  CONCLUSIONS
  The renal protective effects of Simiao pill may be associated with up-regulation of Sirt1 expression and suppression of NF-κB/NLRP3 inflammasome activation to reduce renal glomerular injury in high fructose-fed rats with metabolic syndrome.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing 210023, People's Republic of China.
authors.forename: Chun-Hua
authors.initials: CH
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing 210023, People's Republic of China.
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Kang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing 210023, People's Republic of China.
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Ren
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing 210023, People's Republic of China.
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing 210023, People's Republic of China. Electronic address: kongld@nju.edu.cn.
authors.forename: Ling-Dong
authors.initials: LD
authors.lastname: Kong
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000419:Albuminuria / Q000150:complications / Q000188:drug therapy; D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D005632:Fructose / Q000008:administration & dosage* / Q000494:pharmacology; D033461:Hyperuricemia / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D058847:Inflammasomes / Q000187:drug effects* / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D051381:Rats; D056564:Sirtuin 1 / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C114545:CD2-associated protein; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D004365:Drugs, Chinese Herbal; D058847:Inflammasomes; D053583:Interleukin-1beta; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D016328:NF-kappa B; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C407223:NPHS2 protein; C573346:Nlrp3 protein, rat; C113267:nephrin; C000590843:simiaowan; D005632:Fructose; D056564:Sirtuin 1
keywords: Fructose; NF-κB; NLRP3 inflammasome; Renal glomerular injury; Simiao pill; Sirt1