title: Notoginsenoside R1 ameliorates podocyte injury in rats with diabetic nephropathy by activating the PI3K/Akt signaling pathway.
abstract: The present study was designed to examine the protective effect of notoginsenoside R1 (NR1) on podocytes in a rat model of streptozotocin (STZ)‑induced diabetic nephropathy (DN), and to explore the mechanism responsible for NR1-induced renal protection. Diabetes was induced by a single injection of STZ, and NR1 was administered daily at a dose of 5 mg/kg (low dose), 10 mg/kg (medium) and 20 mg/kg (high) for 16 weeks in Sprague-Dawley rats. Blood glucose levels, body weight and proteinuria were measured every 4 weeks, starting on the day that the rats received NR1. Furthermore, on the day of sacrifice, blood, urine and kidneys were collected in order to assess renal function according to general parameters. Pathological staining was performed to evaluate the renal protective effect of NR1, and the expression of the key slit diaphragm proteins, namely neprhin, podocin and desmin, were evaluated. In addition, the serum levels of inflammatory cytokines [tumor necrosis factor-α (TNF-α), tumor growth factor-β1 (TGF-β1), interleukin (IL)-1 and IL-6] as well as an anti-inflammatory cytokine (IL-10) were assessed, and the apoptosis of podocytes was quantified. Finally, the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway and the involvement of nuclear factor-κB (NF-κB) inactivation was further analyzed. In this study, NR1 improved renal function by ameliorating histological alterations, increasing the expression of nephrin and podocin, decreasing the expression of desmin, and inhibiting both the inflammatory response as well as the apoptosis of podocytes. Furthermore, NR1 treatment increased the phosphorylation of both PI3K (p85) and Akt, indicating that activation of the PI3K/Akt signaling pathway was involved. Moreover, NR1 treatment decreased the phosphorylation of NF-κB (p65), suggesting the downregulation of NF-κB. This is the first study to the best of our knowledge, to clearly demonstrate that NR1 treatment ameliorates podocyte injury by inhibiting both inflammation and apoptosis through the PI3K/Akt signaling pathway.
authors: Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi 530011, P.R. China.
authors: Guodong
authors: G
authors: Huang
authors: Guangxi University of Chinese Medicine, Nanning, Guangxi 530001, P.R. China.
authors: Jianzhen
authors: J
authors: Lv
authors: Guangxi University of Chinese Medicine, Nanning, Guangxi 530001, P.R. China.
authors: Tongyu
authors: T
authors: Li
authors: Department of Biomedical Engineering, Medical School of the University of Electronic Science and Technology of China, Chengdu, Sichuan 610054, P.R. China.
authors: Guoli
authors: G
authors: Huai
authors: Department of Biomedical Engineering, Medical School of the University of Electronic Science and Technology of China, Chengdu, Sichuan 610054, P.R. China.
authors: Xiang
authors: X
authors: Li
authors: Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi 530011, P.R. China.
authors: Shaowei
authors: S
authors: Xiang
authors: Guangxi University of Chinese Medicine, Nanning, Guangxi 530001, P.R. China.
authors: Longlong
authors: L
authors: Wang
authors: Guangxi University of Chinese Medicine, Nanning, Guangxi 530001, P.R. China.
authors: Zhenlin
authors: Z
authors: Qin
authors: Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi 530011, P.R. China.
authors: Jianli
authors: J
authors: Pang
authors: Department of Gynecology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, P.R. China.
authors: Bingyu
authors: B
authors: Zou
authors: Department of Pharmacy, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, P.R. China.
authors: Yi
authors: Y
authors: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003893:Desmin / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D036145:Ginsenosides / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D050199:Podocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use; D011507:Proteinuria / Q000097:blood / Q000150:complications / Q000188:drug therapy; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D001786:Blood Glucose; D016207:Cytokines; D003893:Desmin; D036145:Ginsenosides; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein; D020011:Protective Agents; C113267:nephrin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C072936:notoginsenoside R1