Skip to main content

Advertisement

Log in

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

  • Published:
Journal of Zhejiang University SCIENCE B Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • 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. [doi:10.1210/jc.87.8.3691]

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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. [doi:10.1111/j.1523-1755.2004.00395.x]

    Article  PubMed  CAS  Google Scholar 

  • 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. [doi:10.1046/j.1523-1755.1999.00656.x]

    Article  PubMed  CAS  Google Scholar 

  • 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. [doi:10.1681/ASN.2005121366]

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • Hugo, C., 2003. The thrombospondin 1-TGF-beta axis in fibrotic renal disease. Nephrol. Dial. Transplant., 18(7): 1241–1245. [doi:10.1093/ndt/gfg159]

    Article  PubMed  CAS  Google Scholar 

  • 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. [doi:10.1159/000054735]

    Article  PubMed  CAS  Google Scholar 

  • 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. [doi:10.1172/JCI200215518]

    PubMed  CAS  Google Scholar 

  • 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. [doi:10.1002/bmc.567]

    Article  PubMed  CAS  Google Scholar 

  • 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. [doi:10.1097/01.ASN.0000106015.29070.E7]

    Article  PubMed  CAS  Google Scholar 

  • Liu, Y., 2006. Renal fibrosis: new insights into the pathogenesis and therapeutics. Kidney. Int., 69(2):213–217. [doi:10.1038/sj.ki.5000054]

    Article  PubMed  CAS  Google Scholar 

  • 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).

    CAS  Google Scholar 

  • 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. [doi:10.1097/01.ju.0000138473.38447.f0]

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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. [doi:10.1152/ajprenal.00139.2003]

    Article  PubMed  CAS  Google Scholar 

  • Ng, T.B., 2006. Pharmacological activity of sanchi ginseng (Panax notoginseng). J. Pharm. Pharmacol., 58(8): 1007–1019. [doi:10.1211/jpp.58.8.0001]

    Article  PubMed  CAS  Google Scholar 

  • 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. [doi:10.1093/nar/30.9.e36]

    Article  PubMed  Google Scholar 

  • Strutz, F., Müller, G.A., 2006. Renal fibrosis and the origin of the renal fibroblast. Nephrol. Dial. Transplant., 21(12): 3368–3370. [doi:10.1093/ndt/gfl199]

    Article  PubMed  Google Scholar 

  • 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).

    PubMed  CAS  Google Scholar 

  • 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).

    CAS  Google Scholar 

  • Wang, W., Koka, V., Lan, H.Y., 2005. Transforming growth factor-beta and Smad signalling in kidney diseases. Nephrology, 10(1):48–56. [doi:10.1111/j.1440-1797.2005.00334.x]

    Article  PubMed  Google Scholar 

  • 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. [doi:10.1016/j.jconrel.2007.04.005]

    Article  CAS  Google Scholar 

  • 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).

    PubMed  CAS  Google Scholar 

  • 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. [doi:10.1172/JCI16219]

    PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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. [doi:10.1093/ndt/gfl017]

    Article  PubMed  CAS  Google Scholar 

  • 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. [doi:10.1002/jcb.20799]

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jun-ming Fan.

Additional information

The two authors contributed equally to this work

Project (No. 30170437) supported by the National Natural Science Foundation of China

Rights and permissions

Reprints and permissions

About this article

Cite this article

Xie, Xs., Yang, M., Liu, Hc. et al. Influence of ginsenoside Rg1, a panaxatriol saponin from Panax notoginseng, on renal fibrosis in rats with unilateral ureteral obstruction. J. Zhejiang Univ. Sci. B 9, 885–894 (2008). https://doi.org/10.1631/jzus.B0820024

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1631/jzus.B0820024

Key words

CLC number

Navigation