PMID- 26712211 OWN - NLM STAT- MEDLINE DCOM- 20170227 LR - 20181113 IS - 1993-0402 (Electronic) IS - 1672-0415 (Linking) VI - 22 IP - 12 DP - 2016 Dec TI - Panax notoginseng saponins protect kidney from diabetes by up-regulating silent information regulator 1 and activating antioxidant proteins in rats. PG - 910-917 AB - 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 beta1 (TGF-beta1) 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 kappaB (NF-kappaB) P65 were determined by western blotting. The concentration of MCP-1, TGF-beta1 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-beta1 (P<0.05) and MCP-1 (P<0.05). PNS could also reverse the increased acetylation of NF-kappaB 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-beta1, as well as activating antioxidant proteins. FAU - Du, Yue-Guang AU - Du YG AD - Department of Pathyology, Zhejiang Chinese Medical University, Hangzhou, 310053, China. FAU - Wang, Li-Pei AU - Wang LP AD - Department of Pathyology, Zhejiang Chinese Medical University, Hangzhou, 310053, China. FAU - Qian, Jun-Wen AU - Qian JW AD - National Clinical Research Center of Traditional Chinese Medicine, Zhejiang Chinese Medical University, Hangzhou, 310053, China. FAU - Zhang, Ke-Na AU - Zhang KN AD - Department of Pathyology, Zhejiang Chinese Medical University, Hangzhou, 310053, China. FAU - Chai, Ke-Fu AU - Chai KF AD - National Clinical Research Center of Traditional Chinese Medicine, Zhejiang Chinese Medical University, Hangzhou, 310053, China. ckf666@163.com. LA - eng PT - Journal Article DEP - 20151228 PL - China TA - Chin J Integr Med JT - Chinese journal of integrative medicine JID - 101181180 RN - 0 (Antioxidants) RN - 0 (Blood Glucose) RN - 0 (Bone Morphogenetic Protein 7) RN - 0 (Chemokine CCL2) RN - 0 (Lipids) RN - 0 (Plasminogen Activator Inhibitor 1) RN - 0 (Protective Agents) RN - 0 (Saponins) RN - 0 (Transcription Factor RelA) RN - 0 (Transforming Growth Factor beta1) RN - 4Y8F71G49Q (Malondialdehyde) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - EC 3.5.1.- (Sirtuin 1) SB - IM MH - Acetylation/drug effects MH - Animals MH - Antioxidants/*metabolism MH - Blood Glucose/metabolism MH - Bone Morphogenetic Protein 7/metabolism MH - Chemokine CCL2/metabolism MH - Diabetes Mellitus, Experimental/blood/*drug therapy/genetics/physiopathology MH - Gene Knockdown Techniques MH - Immunohistochemistry MH - Kidney/drug effects/*pathology MH - Kidney Function Tests MH - Lipids/blood MH - Male MH - Malondialdehyde/metabolism MH - Mesangial Cells/drug effects/metabolism MH - Oxidative Stress/drug effects MH - Panax notoginseng/*chemistry MH - Plasminogen Activator Inhibitor 1/genetics/metabolism MH - Protective Agents/pharmacology/*therapeutic use MH - Rats, Sprague-Dawley MH - Saponins/pharmacology/*therapeutic use MH - Sirtuin 1/*genetics MH - Superoxide Dismutase/metabolism MH - Transcription Factor RelA/metabolism MH - Transcription, Genetic/drug effects MH - Transforming Growth Factor beta1/metabolism MH - Up-Regulation/*drug effects OTO - NOTNLM OT - Chinese medicine OT - Panax notoginseng saponins OT - diabetic nephropathy OT - inflammation OT - nuclear factor kappaB OT - silent information regulator 1 EDAT- 2015/12/30 06:00 MHDA- 2017/02/28 06:00 CRDT- 2015/12/30 06:00 PHST- 2015/03/04 00:00 [received] PHST- 2015/12/30 06:00 [pubmed] PHST- 2017/02/28 06:00 [medline] PHST- 2015/12/30 06:00 [entrez] AID - 10.1007/s11655-015-2446-1 [pii] AID - 10.1007/s11655-015-2446-1 [doi] PST - ppublish SO - Chin J Integr Med. 2016 Dec;22(12):910-917. doi: 10.1007/s11655-015-2446-1. Epub 2015 Dec 28.