Full Text:   <1656>

CLC number: R692.6

On-line Access: 

Received: 2008-01-20

Revision Accepted: 2008-04-26

Crosschecked: 0000-00-00

Cited: 12

Clicked: 4048

Citations:  Bibtex RefMan EndNote GB/T7714

-   Go to

Article info.
1. Reference List
Open peer comments

Journal of Zhejiang University SCIENCE B 2008 Vol.9 No.11 P.885~894

http://doi.org/10.1631/jzus.B0820024


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


Author(s):  Xi-sheng XIE, Man YANG, Heng-cuang LIU, Chuan ZUO, Zi LI, Yao DENG, Jun-ming FAN

Affiliation(s):  Department of Nephrology, West China Hospital, Sichuan University, Chengdu 610041, China; more

Corresponding email(s):   junmingfan2007@yahoo.com.cn

Key Words:  Ginsenoside Rg1, Renal fibrosis, Tubular epithelial-myofibroblast transition (TEMT), Thrombospondin-1 (TSP-1), Transforming growth factor-&beta, 1 (TGF-&beta, 1)


Xi-sheng XIE, Man YANG, Heng-cuang LIU, Chuan ZUO, Zi LI, Yao DENG, Jun-ming FAN. Influence of ginsenoside Rg1, a panaxatriol saponin from Panax notoginseng, on renal fibrosis in rats with unilateral ureteral obstruction[J]. Journal of Zhejiang University Science B, 2008, 9(11): 885~894.

@article{title="Influence of ginsenoside Rg1, a panaxatriol saponin from Panax notoginseng, on renal fibrosis in rats with unilateral ureteral obstruction",
author="Xi-sheng XIE, Man YANG, Heng-cuang LIU, Chuan ZUO, Zi LI, Yao DENG, Jun-ming FAN",
journal="Journal of Zhejiang University Science B",
volume="9",
number="11",
pages="885~894",
year="2008",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B0820024"
}

%0 Journal Article
%T Influence of ginsenoside Rg1, a panaxatriol saponin from Panax notoginseng, on renal fibrosis in rats with unilateral ureteral obstruction
%A Xi-sheng XIE
%A Man YANG
%A Heng-cuang LIU
%A Chuan ZUO
%A Zi LI
%A Yao DENG
%A Jun-ming FAN
%J Journal of Zhejiang University SCIENCE B
%V 9
%N 11
%P 885~894
%@ 1673-1581
%D 2008
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B0820024

TY - JOUR
T1 - Influence of ginsenoside Rg1, a panaxatriol saponin from Panax notoginseng, on renal fibrosis in rats with unilateral ureteral obstruction
A1 - Xi-sheng XIE
A1 - Man YANG
A1 - Heng-cuang LIU
A1 - Chuan ZUO
A1 - Zi LI
A1 - Yao DENG
A1 - Jun-ming FAN
J0 - Journal of Zhejiang University Science B
VL - 9
IS - 11
SP - 885
EP - 894
%@ 1673-1581
Y1 - 2008
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B0820024


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-&beta;1 (TGF-&beta;1), 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 1)%29&ck%5B%5D=abstract&ck%5B%5D=keyword'>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.

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1] Chan, R.Y., Chen, W.F., Dong, A., Guo, D., Wong, M.S., 2002. Estrogen-like activity of ginsenoside Rg1 derived from Panax notoginseng. J. Clin. Endocrinol. Metab., 87(8):3691-3695.

[2] Daniel, C., Takabatake, Y., Mizui, M., Isaka, Y., Kawashi, H., Rupprecht, H., Imai, E., Hugo, C., 2003. Antisense oligonucleotides against thrombospondin-1 inhibit activation of TGF-beta in fibrotic renal disease in the rat in vivo. Am. J. Pathol., 163(3):1185-1192.

[3] Daniel, C., Wiede, J., Krutzsch, H.C., Ribeiro, S.M., Roberts, D.D., Murphy-Ullrich, J.E., Hugo, C., 2004. Thrombospondin-1 is a major activator of TGF-beta in fibrotic renal disease in the rat in vivo. Kidney. Int., 65(2):459-468.

[4] Fan, J.M., Ng, Y.Y., Hill, P.A., Nikolic-Paterson, D.J., Mu, W., Atkins, R.C., Lan, H.Y., 1999. Transforming growth factor-beta regulates tubular epithelial-myofibroblast transdifferentiation in vitro. Kidney. Int., 56(4):1455-1467.

[5] Fu, P., Liu, F., Su, S., Wang, W., Huang, X.R., Entman, M.L., Schwartz, R.J., Wei, L., Lan, H.Y., 2006. Signaling mechanism of renal fibrosis in unilateral ureteral obstructive kidney disease in ROCK1 knockout mice. J. Am. Soc. Nephrol., 17(11):3105-3114.

[6] Guo, G., Morrissey, J., McCracken, R., Tolley, T., Liapis, H., Klahr, S., 2001. Contributions of angiotensin II and tumor necrosis factor-alpha to the development of renal fibrosis. Am. J. Physiol. Renal. Physiol., 280(5):F777-F785.

[7] Hugo, C., 2003. The thrombospondin 1-TGF-beta axis in fibrotic renal disease. Nephrol. Dial. Transplant., 18(7):1241-1245.

[8] Hugo, C., Kang, D.H., Johnson, R.J., 2002. Sustained expression of thrombospondin-1 is associated with the development of glomerular and tubulointerstitial fibrosis in the remnant kidney model. Nephron, 90(4):460-470.

[9] Iwano, M., Plieth, D., Danoff, T.M., Xue, C., Okada, H., Neilson, E.G., 2002. Evidence that fibroblasts derive from epithelium during tissue fibrosis. J. Clin. Invest., 110(3):341-350.

[10] Li, L., Sheng, Y.X., Zhang, J.L., Wang, S.S., Guo, D.A., 2006. High-performance liquid chromatographic assay for the active saponins from Panax notoginseng in rat tissues. Biomed. Chromatogr., 20(4):327-335.

[11] Liu, Y., 2004. Epithelial to mesenchymal transition in renal fibrogenesis: pathologic significance, molecular mechanism, and therapeutic intervention. J. Am. Soc. Nephrol., 15(1):1-12.

[12] Liu, Y., 2006. Renal fibrosis: new insights into the pathogenesis and therapeutics. Kidney. Int., 69(2):213-217.

[13] Ma, L.Q., Liang, B., Liu, B., Duan, L.P., Li, S.A., Dong, X.Q., Zhang, L., Zhan, E.Y., Yang, Z.W., Zhang, S.J., Wei, Y.M., Wu, X.J., Ji, D.G., 2007. Experimental study of Panaxsaponin Rg1 on hepatic fibrosis in rats. Chin. J. Integr. Tradit. Western Med. Dig., 15(3):165-168 (in Chinese).

[14] Mizuguchi, Y., Miyajima, A., Kosaka, T., Asano, T., Asano, T., Hayakawa, M., 2004. Atorvastatin ameliorates renal tissue damage in unilateral ureteral obstruction. J. Urol., 172(6 Pt 1):2456-2459.

[15] Morrissey, J.J., Klahr, S., 1998. Differential effects of ACE and AT1 receptor inhibition on chemoattractant and adhesion molecule synthesis. Am. J. Physiol., 274(3 Pt 2):F580-F586.

[16] Naito, T., Masaki, T., Nikolic-Paterson, D.J., Tanji, C., Yorioka, N., Kohno, N., 2004. Angiotensin II induces thrombospondin-1 production in human mesangial cells via p38 MAPK and JNK: a mechanism for activation of latent TGF-beta1. Am. J. Physiol. Renal Physiol., 286(2):F278-F287.

[17] Ng, T.B., 2006. Pharmacological activity of sanchi ginseng (Panax notoginseng). J. Pharm. Pharmacol., 58(8):1007-1019.

[18] Pfaffl, M.W., Horgan, G.W., Dempfle, L., 2002. Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic. Acids. Res., 30(9):e36.

[19] Strutz, F., Müller, G.A., 2006. Renal fibrosis and the origin of the renal fibroblast. Nephrol. Dial. Transplant., 21(12):3368-3370.

[20] Su, B.H., Li, Z., Fan, J.M., Wang, M., Tang, R., 2005. Effects of Panax notoginseng saponins on the process of renal interstitial fibrosis after unilateral ureteral obstruction in rats. Sichuan Da Xue Xue Bao Yi Xue Ban, 36(3):368-371 (in Chinese).

[21] Wang, M., Fan, J.M., Liu, X.Y., 2004. Effect of total saponins of Panax notoginseng on transdifferentiation of rats’ tubular epithelial cell induced by IL-1alpha. Chin. J. Integr. Tradit. Western Med. Dig., 24(8):722-725 (in Chinese).

[22] Wang, W., Koka, V., Lan, H.Y., 2005. Transforming growth factor-beta and Smad signalling in kidney diseases. Nephrology, 10(1):48-56.

[23] Wei, H.J., Yang, H.H., Chen, C.H., Lin, W.W., Chen, S.C., Lai, P.H., Chang, Y., Sung, H.W., 2007. Gelatin microspheres encapsulated with a nonpeptide angiogenic agent, ginsenoside Rg1, for intramyocardial injection in a rat model with infarcted myocardium. J. Control. Rel., 120(1-2):27-34.

[24] Wu, F., Zhang, S.S., Kang, G.F., 2003. Effects of Panax notoginseng saponins on the expression of tumor necrosis factor alpha and secretion phospholipase A2 in rats with liver fibrosis. Zhonghua Gan Zang Bing Za Zhi, 11(1):51-52 (in Chinese).

[25] Yang, J., Shultz, R.W., Mars, W.M., Wegner, R.E., Li, Y., Dai, C., Nejak, K., Liu, Y., 2002. Disruption of tissue-type plasminogen activator gene in mice reduces renal interstitial fibrosis in obstructive nephropathy. J. Clin. Invest., 110(10):1525-1538.

[26] Yevdokimova, N., Wahab, N.A., Mason, R.M., 2001. Thrombospondin-1 is the key activator of TGF-beta1 in human mesangial cells exposed to high glucose. J. Am. Soc. Nephrol., 12(4):703-712.

[27] Yung, S., Lee, C.Y., Zhang, Q., Lau, S.K., Tsang, R.C., Chan, T.M., 2006. Elevated glucose induction of thrombospondin-1 up-regulates fibronectin synthesis in proximal renal tubular epithelial cells through TGF-beta1 dependent and TGF-beta1 independent pathways. Nephrol. Dial. Transplant., 21(6):1504-1513.

[28] Zhang, H.S., Wang, S.Q., 2006. Ginsenoside Rg1 inhibits tumor necrosis factor-alpha (TNF-alpha)-induced human arterial smooth muscle cells (HASMCs) proliferation. J. Cell. Biochem., 98(6):1471-1481.

Open peer comments: Debate/Discuss/Question/Opinion

<1>

Please provide your name, email address and a comment





Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - Journal of Zhejiang University-SCIENCE