title: Panax notoginseng saponins protect kidney from diabetes by up-regulating silent information regulator 1 and activating antioxidant proteins in rats.
abstract: OBJECTIVE
  To explore the mechanism of the protective effects of Panax notoginseng saponins (PNS) on kidney in diabetic rats.
  
  
  METHODS
  Diabetic rat model was obtained by intravenous injection of alloxan, and the rats were divided into model, PNS-100 mg/(kg day) and PNS-200 mg/(kg day) groups, 10 each. Another 10 rats injected with saline were served as control. Periodic acid-Schiff staining and immunological histological chemistry were used to observe histomorphology and tissue expression of bone morphogenetic protein-7 (BMP-7). Silent information regulator 1 (SIRT1) was silenced in rat mesangial cells by RNA interference. The mRNA expressions of SIRT-1, monocyte chemoattractant protein-1 (MCP-1), transforming growth factor β1 (TGF-β1) and plasminogen activator inhibitor-1 (PAI-1) were analyzed by reverse transcription polymerase chain reaction. The protein expressions of SIRT1 and the acetylation of nuclear factor κB (NF-κB) P65 were determined by western blotting. The concentration of MCP-1, TGF-β1 and malondialdehyde (MDA) in culture supernatant were detected by enzyme-linked immuno sorbent assay. The activity of superoxide dismutase (SOD) was detected by the classical method of nitrogen and blue four.
  
  
  RESULTS
  In diabetic model rats, PNS could not only reduce blood glucose and lipid (P<0.01), but also increase protein level of BMP-7 and inhibit PAI-1 expression for suppressing fibrosis of the kidney. In rat mesangial cells, PNS could up-regulate the expression of SIRT1 (P<0.01) and in turn suppress the transcription of TGF-β1 (P<0.05) and MCP-1 (P<0.05). PNS could also reverse the increased acetylation of NF-κB p65 by high glucose. In addition, redox regulation factor MDA was down-regulated (P<0.05) and SOD was up-regulated (P<0.01), which were both induced by SIRT1 up-regulation.
  
  
  CONCLUSIONS
  PNS could protect kidney from diabetes with the possible mechanism of up-regulating SIRT1, therefore inhibiting inflammation through decreasing the induction of inflammatory cytokines and TGF-β1, as well as activating antioxidant proteins.
authors.affiliation: Department of Pathyology, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
authors.forename: Yue-Guang
authors.initials: YG
authors.lastname: Du
authors.affiliation: Department of Pathyology, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
authors.forename: Li-Pei
authors.initials: LP
authors.lastname: Wang
authors.affiliation: National Clinical Research Center of Traditional Chinese Medicine, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
authors.forename: Jun-Wen
authors.initials: JW
authors.lastname: Qian
authors.affiliation: Department of Pathyology, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
authors.forename: Ke-Na
authors.initials: KN
authors.lastname: Zhang
authors.affiliation: National Clinical Research Center of Traditional Chinese Medicine, Zhejiang Chinese Medical University, Hangzhou, 310053, China. ckf666@163.com.
authors.forename: Ke-Fu
authors.initials: KF
authors.lastname: Chai
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D055419:Bone Morphogenetic Protein 7 / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D055785:Gene Knockdown Techniques; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects / Q000473:pathology*; D007677:Kidney Function Tests; D008055:Lipids / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D050527:Mesangial Cells / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D053723:Panax notoginseng / Q000737:chemistry*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000494:pharmacology / Q000627:therapeutic use*; D056564:Sirtuin 1 / Q000235:genetics*; D013482:Superoxide Dismutase / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D001786:Blood Glucose; D055419:Bone Morphogenetic Protein 7; D018932:Chemokine CCL2; D008055:Lipids; D017395:Plasminogen Activator Inhibitor 1; D020011:Protective Agents; D012503:Saponins; D051996:Transcription Factor RelA; D053773:Transforming Growth Factor beta1; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D056564:Sirtuin 1
keywords: Chinese medicine; Panax notoginseng saponins; diabetic nephropathy; inflammation; nuclear factor κB; silent information regulator 1