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.

RETRACTED ARTICLE: Notoginsenoside R1 alleviates TNF-α-induced pancreatic β-cell Min6 apoptosis and dysfunction through up-regulation of miR-29a

“…Cell activity was raised, whereas apoptosis was cut down after NGR1 administration, indicating that NGR1 could promote Min6 cell growth. Consistently, NGR1 treatment ameliorates the diabetes-induced apoptosis of podocytes [9].…”

“…Various reports supported our results. For example, NGR1 treatment induced actuation of the PI3K/AKT signalling way in rats [9]. miR-29a activated Wnt/b-catenin signalling way in pancreatic cancer cells [36].…”

“…Importantly, studies have proved that NGR1 has potential effects of antidiabetes. For example, NGR1 ameliorated podocyte injury in rats with diabetic nephropathy through actuating phosphatidylinositol 3'-kinase (PI3K)/protein kinase B (AKT) signal ways [9]. Recent studies showed that NGR1 provided a novel treatment for diabetic kidney disease [10], and NGR1 could ameliorate diabetic encephalopathy [11].…”

YAP and TAZ mediate steroid-induced alterations in the trabecular meshwork cytoskeleton in human trabecular meshwork cells

“…Finally, the transfection efficiency was detected using western blot analysis. For the knockdown of YAP and TAZ genes, HTM cells were transfected with YAP siRNA, TAZ siRNA or scrambled siRNA at 33 nM using DharmaFect transfection reagent with SMARTpool ON-TARGET siRNA (GE Healthcare Dharmacon, Inc., Lafayette, CO, USA) according to the manufacturer's instructions ( 22 ). The transfected cells were used for subsequent experiments 24 h later.…”

<p>Focus on Notoginsenoside R1 in Metabolism and Prevention Against Human Diseases</p>

“…73 Consistently, NG-R1 ameliorates podocyte injury by activation of PI3K/AKT signaling pathway and inhibition of inflammation and apoptosis, as indicated by increased phosphorylation of PI3K and AKT and decreased phosphorylation of p65 in streptozotocininduced rat diabetic nephropathy. 74 Furthermore, NG-R1 promotes the activity of the PI3K/AKT/mTOR signaling pathway and protects podocytes from high glucose-induced apoptosis 75 ( Figure 3).…”