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Horm Metab Res 2006; 38(2): 82-88
DOI: 10.1055/s-2006-925118
Original Basic
© Georg Thieme Verlag KG Stuttgart · New York

Suppression of Transforming Growth Factor-β1 Gene Expression by Danggui Buxue Tang, a Traditional Chinese Herbal Preparation, in Retarding the Progress of Renal Damage in Streptozotocin-induced Diabetic Rats

Y.  W.  Zhang1 , D.  Xie1 , B.  Xia1 , R.  T.  Zhen1 , I.-M.  Liu2 , J.-T.  Cheng3
  • 1Department of Chinese with western medicine, Zhongnan Hospitial, Wuhan University, Wuhan, China
  • 2Department of Pharmacy, Tajen University, Yen-Pou, Pingtung Shien, Taiwan
  • 3Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan City, Taiwan
Further Information

Publication History

Received 17 May 2005

Accepted after revision 7 November 2005

Publication Date:
08 March 2006 (online)

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Abstract

Danggui buxue tang (DBT), a preparation containing Angelica sinensis (danggui) and Astragalus membranaceus (huangqi) at a ratio of 1 : 5, is used widely in China for stimulating red blood cell production and enhancing cardiovascular function. The present study was undertaken to characterize the effects of this preparation on diabetic nephropathy using streptozotocin-diabetic rats as a model. Streptozotocin-dependent alterations in renal weight/body weight ratio, urinary albumin and β2-microglobulin concentrations, urinary albumin excretion rate, and creatinine clearance were ameliorated after eight weeks of treatment with either DBT or the angiotensin-converting enzyme inhibitor, benazepril. DBT, but not benazepril, partially attenuated the increases in blood glucose, triglycerides and cholesterol in STZ-diabetic rats. Additionally, the increased expression of transforming growth factor-β1 mRNA in the renal cortex due to streptozotocin-induced diabetes was modestly attenuated by these treatments. However, eight weeks of treatment with DBT failed to modify the concentration of angiotensin II in plasma or kidney, indicating that the ability of the preparation to retard the progression of kidney disease was not attributable to inhibition of the renin-angiotensin system. We propose that DBT alleviates renal alterations in diabetes and slows the progression of diabetic nephropathy by suppressing transforming growth factor-β1 mRNA expression. The preparation may therefore be useful as an adjuvant therapy for controlling diabetes and its complications.

Key words

Angelica sinensis - angiotensin II - astragalus membranaceus - benazepril - danggui buxue tang - nephropathy - type 1 diabetes

References

  • 1 Ning L, Chen C X, Jin R M, Wu Y P, Zhang H G, Sun C L, Song C Q, Hu Z B. Effect of components of dang-gui-bu-xue decoction on hematopenia.  Zhongguo Zhong Yao Za Zhi. 2002;  27 50-53
    PubMedGoogle Scholar
  • 2 Song Z H, Ji Z N, Lo C K, Dong T T, Zhao K J, Li O T, Haines C J, Kung S D, Tsim K W. Chemical and biological assessment of a traditional chinese herbal decoction prepared from Radix Astragali and Radix Angelicae Sinensis: orthogonal array design to optimize the extraction of chemical constituents.  Planta Med. 2004;  70 1222-1227
    Article in Thieme ConnectPubMedGoogle Scholar
  • 3 Hsieh C C, Lin W C, Lee M R, Hsu S L, Liu H S, Kao S T, Hsieh M T. Dang-Gui-Bu-Xai-Tang modulated the immunity of tumor bearing mice.  Immunopharmacol Immunotoxicol. 2003;  25 259-271
    CrossrefPubMedGoogle Scholar
  • 4 Huntley A L, Ernst E. A systematic review of herbal medicinal products for the treatment of menopausal symptoms.  Menopause. 2003;  10 465-476
    PubMedGoogle Scholar
  • 5 Bruno G, Merletti F, Biggeri A, Bargero G, Ferrero S, Pagano G, Cavallo P erin . Progression to overt nephropathy in type 2 diabetes: the Casale Monferrato Study.  Diabetes Care. 2003;  26 2150-2155
    PubMedGoogle Scholar
  • 6 Makino H, Nakamura Y, Wada J. Remission and regression of diabetic nephropathy.  Hypertens Res. 2003;  26 515-519
    CrossrefPubMedGoogle Scholar
  • 7 Cai Q, Li X, Wang H. Astragali and Angelica protect the kidney against ischemia and reperfusion injury and accelerate recovery.  Chin Med J (Engl). 2001;  114 119-123
    PubMedGoogle Scholar
  • 8 Zhang S L, To C, Chen X, Filep J G, Tang S S, Ingelfinger J R, Chan J S. Essential role(s) of the intrarenal renin-angiotensin system in transforming growth factor-beta1 gene expression and induction of hypertrophy of rat kidney proximal tubular cells in high glucose.  J Am Soc Nephrol. 2002;  13 302-312
    PubMedGoogle Scholar
  • 9 Locatelli F, Canaud B, Eckardt K U, Stenvinkel P, Wanner C, Zoccali C. The importance of diabetic nephropathy in current nephrological practice.  Nephrol Dial Transpl. 2003;  18 1716-1725
    CrossrefPubMedGoogle Scholar
  • 10 Dominguez J H, Tang N, Xu W, Evan A P, Siakotos A N, Agarwal R, Walsh J, Deeg M, Pratt J H, March K L, Monnier V M, Weiss M F, Baynes J W, Peterson R. Studies of renal injury III: lipid-induced nephropathy in type II diabetes.  Kidney Int. 2000;  57 92-104
    CrossrefPubMedGoogle Scholar
  • 11 Dahlquist G, Stattin E L, Rudberg S. Urinary albumin excretion rate and glomerular filtration rate in the prediction of diabetic nephropathy; a long-term follow-up study of childhood onset type-1 diabetic patients.  Nephrol Dial Transplant. 2001;  16 1382-1386
    PubMedGoogle Scholar
  • 12 Peng A, Gu Y, Lin S Y. Herbal treatment for renal diseases.  Ann Acad Med Singapore. 2005;  34 44-51
    PubMedGoogle Scholar
  • 13 Schrijvers B F, DeVriese A S, Flyvbjerg A. From hyperglycemia to diabetic kidney disease: the role of metabolic, hemodynamic, intracellular factors and growth factors/cytokines.  Endocr Rev. 2004;  25 971-1010
    CrossrefPubMedGoogle Scholar
  • 14 Schnaper H W, Hayashida T, Hubchak S C, Poncelet A C. TGF-beta signal transduction and mesangial cell fibrogenesis.  Am J Physiol Renal Physiol. 2003;  284 243-252
    PubMedGoogle Scholar
  • 15 Miyazono K. TGF-beta signaling by Smad proteins.  Cytokine Growth Factor Rev. 2000;  11 15-22
    CrossrefPubMedGoogle Scholar
  • 16 Cruzado J M, Lloberas N, Torras J, Riera M, Fillat C, Herrero-Fresneda I, Aran J M, Alperovich G, Vidal A, Grinyo J M. Regression of advanced diabetic nephropathy by hepatocyte growth factor gene therapy in rats.  Diabetes. 2004;  53 1119-1127
    PubMedGoogle Scholar
  • 17 Hong S W, Isono M, Chen S, Iglesias-De La Cruz M C, Han D C, Ziyadeh F N. Increased glomerular and tubular expression of transforming growth factor-beta1, its type II receptor, and activation of the Smad signaling pathway in the db/db mouse.  Am J Pathol. 2001;  158 1653-1663
    PubMedGoogle Scholar
  • 18 Ziyadeh F N. Mediators of diabetic renal disease: the case for TGF-Beta as the major mediator.  J Am Soc Nephrol. 2004;  15 S55-S57
    CrossrefPubMedGoogle Scholar
  • 19 Parving H H, Lehnert H, Brochner-Mortensen J, Gomis R, Andersen S, Arner P. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes.  New Engl J Med. 2001;  345 870-878
    CrossrefPubMedGoogle Scholar
  • 20 Huang X R, Chen W Y, Truong L D. Chymase is upregulated in diabetic nephropathy: implications for an alternative pathway of angiotensin II-mediated diabetic renal and vascular disease.  J Am Soc Nephrol. 2003;  14 1738-1747
    CrossrefPubMedGoogle Scholar
  • 21 Li J H, Huang X R, Zhu H J, Johnson R, Lan H Y. Role of TGF-beta signaling in extracellular matrix production under high glucose conditions.  Kidney Int. 2003;  63 2010-2019
    CrossrefPubMedGoogle Scholar
  • 22 Tian Y C, Fraser D, Attisano L, Phillips A O. TGF-beta1-mediated alterations of renal proximal tubular epithelial cell phenotype.  Am J Physiol Renal Physiol. 2003;  285 130-142
    PubMedGoogle Scholar
  • 23 Monkawa T, Hiromura K, Wolf G, Shankland S J. The hypertrophic effect of transforming growth factor-beta is reduced in the absence of cyclin-dependent kinase-inhibitors p21 and p27.  J Am Soc Nephrol. 2002;  13 1172-1178
    CrossrefPubMedGoogle Scholar
  • 24 Benigni A, Zoja C, Corna D, Zatelli C, Conti S, Campana M, Gagliardini E, Rottoli D, Zanchi C, Abbate M, Ledbetter S, Remuzzi G. Add-on anti-TGF-beta antibody to ACE inhibitor arrests progressive diabetic nephropathy in the rat.  J Am Soc Nephrol. 2003;  14 1816-1824
    CrossrefPubMedGoogle Scholar
  • 25 Ma J, Peng A, Lin S. Mechanisms of the therapeutic effect of astragalus membranaceus on sodium and water retention in experimental heart failure.  Chin Med J. 1998;  111 17-23
    PubMedGoogle Scholar
  • 26 Yu L, Li J Z, Wang H Y. Research on the application of astragali and angelica in treating renal disease and its mechanisms.  Zhongguo Zhong Xi Yi Jie He Za Zhi. 2001;  21 396-399
    PubMedGoogle Scholar
  • 27 Cheng J T. Review: drug therapy in Chinese traditional medicine.  J Clin Pharmacol. 2000;  40 445-450
    CrossrefPubMedGoogle Scholar
  • 28 Huang W H, Song C Q. Research progresses in the chemistry and pharmacology of Angelica sinensis (Oliv.) Diel.  Zhongguo Zhong Yao Za Zhi. 2001;  26 47-151
    PubMedGoogle Scholar

Prof. Juei-Tang Cheng

Department of Pharmacology · College of Medicine · National Cheng Kung University · Tainan City · Taiwan 70101, R.O.C.

Phone: +886 (6) 237-2706

Fax: +886 (6) 238-6548 ·

Email: jtcheng@mail.ncku.edu.tw

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