Influence of ginsenoside Rg1, a panaxatriol saponin from Panax notoginseng, on renal fibrosis in rats with unilateral ureteral obstruction

Abstract

Total saponins of Panax notoginseng (PNS) have been shown to ameliorate renal interstitial fibrosis. Ginsenoside Rg1, a panaxatriol saponin, is one of the major active molecules from PNS. The present study was undertaken to investigate the effect of ginsenoside Rg1 on renal fibrosis in rats with unilateral ureteral obstruction (UUO). The rats were randomly divided into 3 groups: sham-operation (n=15), UUO (n=15) and UUO with ginsenoside Rg1 treatment (n=15, 50 mg per kg body weight, intraperitoneally (i.p.) injected). The rats were sacrificed on Days 7 and 14 after the surgery. Histological examination demonstrated that ginsenoside Rg1 significantly inhibited interstitial fibrosis including tubular injury as well as collagen deposition. α-smooth muscle actin (α-SMA) and E-cadherin are two markers of tubular epithelial-myofibroblast transition (TEMT). Interestingly, ginsenoside Rg1 notably decreased α-SMA expression and simultaneously enhanced E-cadherin expression. The messenger RNA (mRNA) of transforming growth factor-β1 (TGF-β1), a key mediator to regulate TEMT, in the obstructed kidney increased dramatically, but was found to decrease significantly after administration of ginsenoside Rg1. Further study showed that ginsenoside Rg1 considerably decreased the levels of both active TGF-β1 and phosphorylated Smad2 (pSmad2). Moreover, ginsenoside Rg1 substantially suppressed the expression of thrombospondin-1 (TSP-1), a cytokine which can promote the transcription of TGF-β1 mRNA and the activation of latent TGF-β1. These results suggest that ginsenoside Rg1 inhibits renal interstitial fibrosis in rats with UUO. The mechanism might be partly related to the blocking of TEMT via suppressing the expression of TSP-1.

Astragalus mongholicus ameliorates renal fibrosis by modulating HGF and TGF-β in rats with unilateral ureteral obstruction

“…Ten separate fields of each section were scanned at 400× magnification and put into digital form using imaging software (Photoshop, Adobe, San Jose, California). The number of points covering the blue collagen staining was counted and the extent of collagen deposition was evaluated (Mizuguchi et al, 2004;Xie et al, 2008).…”

“…Paraffin-embedded sections (5 μm) were deparaffinized, washed with phosphate-buffered saline (PBS), treated with 3% (v/v) H 2 O 2 for 5 min, blocked with 10% (w/v) normal goat serum for 1 h, and then incubated with primary antibodies, including rabbit antibodies to α-SMA (ABCAM, UK), rabbit antibodies to HGF (Santa Cruz Biotechnology, Santa Cruz, CA, USA), rabbit antibodies to TGF-β1 (Santa Cruz Biotechnology), rabbit antibodies to collagen I (colI), and rabbit antibodies to fibronectin (FN) (Boshide Biological Technology Co., Ltd., Wuhan, China), at 4 °C overnight as described previously (Xie et al, 2008). Slides then were incubated with appropriate biotin-conjugated secondary immunoglobulin G, and treated with reagents from a Vecta-Elite streptavidin-peroxidase kit (Vector Laboratories, Burlingame, CA, USA).…”

“…The cDNA was synthesized and real-time PCR was run as described previously (Xie et al, 2008). Primers and probes of α-SMA, TGF-β1, HGF, fibronectin, collagen I, and the internal calibrator glyceraldehyde-3-phosphate dehydrogenase (GAPDH, synthesized by Sangon, Shanghai, China) were listed in Table 1.…”

“…The thermocycles of PCR reaction were performed as reported previously (Xie et al, 2008). PCR products then went through agarose-gel electrophoretic analysis, and fluorescence signal were collected to calculate Ct (cycles of threshold).…”

Ginsenoside-Rg1 inhibits endoplasmic reticulum stress-induced apoptosis after unilateral ureteral obstruction in rats

“…11,12 In addition, Xie et al elaborated that G-Rg1 ameliorated renal interstitial fibrosis by inhibiting the tubular epithelial-myofibroblast transition 27 and decreasing the expression of thrombospondin-1.…”