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Planta Med 2009; 75(14): 1470-1475
DOI: 10.1055/s-0029-1185802
Pharmacology
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Effect of Astilbin on Experimental Diabetic Nephropathy in vivo and in vitro

Gui-Sheng Li1 [*] , Wang-Lin Jiang1 , 2 [*] , Xi-Dian Yue2 , Gui-Wu Qu2 , Jing-Wei Tian1 , Juan Wu2 , Feng-Hua Fu1
  • 1School of Pharmacy, Yantai University, Yantai, P. R. China
  • 2Shandong Engineering Research Center for Natural Drug, Yantai, P. R. China
Further Information

Publication History

received March 2, 2009 revised May 7, 2009

accepted May 17, 2009

Publication Date:
16 June 2009 (online)

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Abstract

Astilbin, a flavonoid compound, was isolated from the rhizome of Smilax glabra Roxb. This study was conducted to investigate the efficacy of astilbin on experimental diabetic nephropathy (DN) in vivo and in vitro and its possible mechanisms. Astilbin was added in high glucose stimulated HK-2 cells, streptozotocin-induced experimental DN, randomized to receive intragastric (i. g.) astilbin to observe its anti-renal lesion effect. Results showed that astilbin inhibited high glucose stimulated HK-2 cell production of transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF) in vitro, especially CTGF; analogic results was also found in vivo. I. g. of astilbin 2.5 mg/kg or 5 mg/kg significantly ameliorated renal function, reduced kidney index, while it increased body weight and survival time in animals. In addition there was no significant difference in blood glucose level between the STZ-treated group and the astilbin groups. Furthermore, astilbin ameliorated the pathological progress of renal morphology. Astilbin can exert an early renal protective role to DN, inhibit production of TGF-β1 and especially of CTGF. We suggest that astilbin inhibition of CTGF may be a potential target in DN therapy. This work provides the first evidence for astilbin as a new candidate of DN therapeutic medicine.

Key words

astilbin (3‐0‐alpha‐1‐rhamnosyl‐(2R,3R)‐dihydroquercetin) - transforming growth factor‐β1 - connective tissue growth factor - diabetic nephropathy

References

  • 1 Ziyadeh F N, Sharma K. Overview: combating diabetic nephropathy.  J Am Soc Nephrol. 2003;  14 1355-1357
    CrossrefPubMedSearch in Google Scholar
  • 2 Abdel W N, Mason R M. Connective tissue growth factor and renal diseases: some answers, more questions.  Curr Opin Nephrol Hypertens. 2004;  13 53-58
    PubMedSearch in Google Scholar
  • 3 Van Nieuwenhoven F A, Jensen L J, Flyvbjerg A, Goldschmeding R. Imbalance of growth factor signalling in diabetic kidney disease: is connective tissue growth factor (CTGF, CCN2) the perfect intervention point?.  Nephrol Dial Transplant. 2005;  20 6-10
    PubMedSearch in Google Scholar
  • 4 Zhou G, Li C, Cai L. Advanced glycation end-products induce connective tissue growth factor-mediated renal fibrosis predominantly through transforming growth factor beta-independent pathway.  Am J Pathol. 2004;  165 2033-2043
    CrossrefPubMedSearch in Google Scholar
  • 5 Kobayashi T, Okada H, Inoue T, Kanno Y, Suzuki H. Tubular expression of connective tissue growth factor correlates with interstitial fibrosis in type 2 diabetic nephropathy.  Nephrol Dial Transplant. 2006;  21 548-549
    PubMedSearch in Google Scholar
  • 6 Goldschmeding R, Aten J, Ito Y, Blom I, Rabelink T, Weening J J. Connective tissue growth factor: just another factor in renal fibrosis?.  Nephrol Dial Transplant. 2000;  15 296-299
    CrossrefPubMedSearch in Google Scholar
  • 7 Boor P, Sebeková K, Ostendorf T, Floege J. Treatment targets in renal fibrosis.  Nephrol Dial Transplant. 2007;  22 3391-3407
    CrossrefPubMedSearch in Google Scholar
  • 8 Haraguchi H, Mochida Y, Sakai S, Masuda H, Tamura Y, Mizutani K, Tanaka O, Chou W H. Protection against oxidative damage by dihydroflavonols in Engelhardtia chrysolepis.  Biosci Biotechnol Biochem. 1996;  60 945-948
    PubMedSearch in Google Scholar
  • 9 Igarashi K, Uchida Y, Murakami N, Mizutani K, Masuda H. Effect of astilbin in tea processed from leaves of Engelhardtia chrysolepis on the serum and liver lipid concentrations and on the erythrocyte and liver antioxidative enzyme activities of rats.  Biosci Biotechnol Biochem. 1996;  60 513-515
    PubMedSearch in Google Scholar
  • 10 Wang J, Zhao Y, Xu Q. Astilbin prevents concanavalin A-induced liver injury by reducing TNF-α production and T lymphocytes adhesion.  J Pharm Pharmacol. 2004;  56 495-502
    CrossrefPubMedSearch in Google Scholar
  • 11 Xu Q, Wu F, Cao J, Chen T, Jiang J, Saiki I, Koda A. Astilbin selectively induces dysfunction of liver-infiltrating cells: novel protection from liver damage.  Eur J Pharmacol. 1999;  377 93-100
    CrossrefPubMedSearch in Google Scholar
  • 12 Yan R, Xu Q. Astilbin selectively facilitates the apoptosis of interleukin-2-dependent phytohemagglutinin-activated Jurkat cells.  Pharmacol Res. 2001;  44 135-139
    CrossrefPubMedSearch in Google Scholar
  • 13 Cai Y, Chen T, Xu Q. Astilbin suppresses collagen-induced arthritis via the dysfunction of lymphocytes.  Inflamm Res. 2003;  52 334-340
    CrossrefPubMedSearch in Google Scholar
  • 14 Fei M J, Wu X F, Xu Q. Astilbin inhibits contact hypersensitivity via negative cytokine regulation distinct form cyclosporin A.  J Allergy Clin Immunol. 2005;  116 1350-1356
    CrossrefPubMedSearch in Google Scholar
  • 15 Chen T, Li J, Cao J, Xu Q, Komatsu K, Namba T. A new flavanone isolated from Rhizoma Smilacis glabrae and the structural requirements of its derivatives for preventing immunological hepatocyte damage.  Planta Med. 1999;  65 559-563
    PubMedSearch in Google Scholar
  • 16 Panchapakesan U, Sumual S, Pollock C A, Chen X. PPARgamma agonists exert antifibrotic effects in renal tubular cells exposed to high glucose.  Am J Physiol Renal Physiol. 2005;  289 1153-1158
    CrossrefPubMedSearch in Google Scholar
  • 17 Thulesen J, Poulsen S S, Jørgensen P E, Nexø E. Adrenergic blockade in diabetic and uninephrectomized rats: effects on renal size and on renal and urinary contents of epidermal growth factor.  Nephron. 1999;  81 172-182
    CrossrefPubMedSearch in Google Scholar
  • 18 Remuzzi G, Bertani T. Pathophysiology of progressive nephropathies.  N Engl J Med. 1998;  339 1448-1456
    CrossrefPubMedSearch in Google Scholar
  • 19 Mauer S M. Structural-functional correlations of DN.  Kidney Int. 1994;  45 612-622
    PubMedSearch in Google Scholar
  • 20 Wolf G, Ziyadeh F N. Molecular mechanisms of diabetic renal hypertrophy.  Kidney Int. 1999;  56 393-405
    CrossrefPubMedSearch in Google Scholar
  • 21 Paueksakon P, Revelo M P, Ma L J, Marcantoni C, Fogo A B. Microangiopathic injury and augmented PAI‐1 in human diabetic nephropathy.  Kidney Int. 2002;  61 2142-2148
    CrossrefPubMedSearch in Google Scholar
  • 22 Lee H B, Ha H. Plasminogen activator inhibitor-1 and diabetic nephropathy.  Nephrology. 2005;  10 S11-S13
    CrossrefPubMedSearch in Google Scholar
  • 23 Bottinger E P, Letterio J J, Roberts A B. Biology of TGF-β1 in knockout and transgenic mouse models.  Kidney Int. 1997;  51 1355-1360
    CrossrefPubMedSearch in Google Scholar
  • 24 Schull M M, Ormsby I, Kier A B. Targeted disruption of the mouse TGF-β1 gene results in multifocal inflammatory disease.  Nature. 1992;  359 693-699
    CrossrefPubMedSearch in Google Scholar
  • 25 Rossing P. Promotion, prediction and prevention of progression of nephropathy in type 1 diabetes mellitus.  Diabet Med. 1998;  15 900-919
    CrossrefPubMedSearch in Google Scholar
  • 26 Lewis E J, Hunsicker L G, Bain R P, Rohde R D. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group.  N Engl J Med. 1993;  329 1456-1462
    CrossrefPubMedSearch in Google Scholar

1 These authors contributed equally to this project and should be considered co-first authors.

Prof. Feng-Hua Fu

School of Pharmacy
Yantai University

32# Qingquan Road

Laishan District

Yantai 264005

P. R. China

Phone: + 86 53 52 10 32 22

Fax: + 86 53 56 70 60 60

Email: Fenghua@luye-pharm.com

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