Planta Med 2011; 77(16): 1769-1773
DOI: 10.1055/s-0030-1271135
Biological and Pharmacological Activity
Original Papers
© Georg Thieme Verlag KG Stuttgart · New York

Astilbin Attenuates Hyperuricemia and Ameliorates Nephropathy in Fructose-Induced Hyperuricemic Rats

Lvyi Chen1 , Zhou Lan2 , Yongqiang Zhou1 , Fei Li1 , Xin Zhang1 , Chunfeng Zhang1 , Zhonglin Yang1 , Ping Li1
  • 1Key Laboratory of Modern Chinese Medicines, China Pharmaceutical University, Ministry of Education, Nanjing, P. R. China
  • 2Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing, P. R. China
Further Information

Publication History

received Nov. 20, 2010 revised March 22, 2011

accepted April 26, 2011

Publication Date:
25 May 2011 (online)

Abstract

Astilbin is a flavonoid compound isolated from the rhizome of Smilax china L. The effects and possible mechanisms of astilbin on hyperuricemia and nephropathy rats were elucidated in this study. Different dosages of astilbin (1.25, 2.5, and 5.0 mg/kg) were administered to 10 % fructose-induced hyperuricemic rats. The results demonstrated that astilbin significantly decreased the serum uric acid (Sur) level by increasing the urinary uric acid (Uur) level and fractional excretion of urate (FEUA) but not inhibiting the xanthine oxidase (XOD) activity. In addition, kidney function parameters such as serum creatinine (Scr) and blood urea nitrogen (BUN) were recovered in astilbin-treated hyperuricemic rats. Further investigation indicated that astilbin prevented the renal damage against the expression of transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF) and also exerted a renal protective role by inhibiting formation of monosodium urate (MSU) and production of prostaglandin E2 (PGE2) and interleukin-1 (IL-1). These findings provide potent evidence for astilbin as a safe and promising lead compound in the development of a disease-modifying drug to prevent hyperuricemia and nephropathy.

Supporting Information

References

  • 1 Wortmann R L. Gout and hyperuricemia.  Curr Opin Rheumatol. 2002;  14 281-286
  • 2 Martinon F, Petrilli V, Mayor A, Tardivel A, Tschopp J. Gout-associated uric acid crystals activate the NALP3 inflammasome.  Nature. 2006;  440 237-241
  • 3 Kang D H, Nakagawa T. Uric acid and chronic renal disease: possible implication of hyperuricemia on progression of renal disease.  Semin Nephrol. 2005;  25 43-49
  • 4 Zhou X Y, Matavelli L, Frohlich E D. Uric acid: its relationship to renal hemodynamics and the renal renin-angiotensin system.  Curr Hypertens Rep. 2006;  8 120-124
  • 5 Horiuchi H, Ota M, Nishimura S, Kaneko H, Kasahara Y, Ohta T, Komoriya K. Allopurinol induces renal toxicity by impairing pyrimidine metabolism in mice.  Life Sci. 2000;  66 2051-2070
  • 6 State Administration of Traditional Chinese Medicine of People's Republic of China .Zhong-hua-ben-cao. Shanghai: Shanghai Science and Technology Publisher; 1999: 157-160
  • 7 Chen Y, Wang Q, Li B, Li L, Pan L N, Huang Y. Study on identification and quality for Smilax china L. of compound gout granules.  Asia-Pacific Tradit Med. 2008;  4 237-239
  • 8 Butterweck V, Jürgenliemk G, Nahrstedt A, Winterhoff H. Flavonoids from Hypericum perforatum show antidepressant activity in the forced swimming test.  Planta Med. 2000;  66 3-6
  • 9 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
  • 10 Cai Y, Chen T, Xu Q. Astilbin suppresses collagen-induced arthritis via the dysfunction of lymphocytes.  Inflamm Res. 2003;  52 334-340
  • 11 Li G S, Jiang W L, Yue X D, Qu G W, Tian J W, Wu J, Fu F H. Effect of astilbin on experimental diabetic nephropathy in vivo and in vitro.  Planta Med. 2009;  75 1470-1475
  • 12 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 56-59
  • 13 Perez-Ruiz F, Calabozo M, Garcia Erauskin G, Ruibal A, Herrero-Beites A M. Renal underexcretion of uric acid is present in patients with apparent high urinary uric acid output.  Arthritis Care Res. 2002;  47 610-613
  • 14 Mo S F, Zhou F, Lv Y Z, Hu Q H, Zhang D M, Kong L D. Hypouricemic action of selected flavonoids in mice: structure–activity relationships.  Biol Pharm Bull. 2007;  30 1551-1556
  • 15 Nakagawa T, Hu H, Zharikov S, Tuttle K R, Short R A, Glushakova O, Ouyang X, Feig D I, Block E R, Herrera-Acosta J, Patel J M, Johnson R J. A causal role for uric acid in fructose-induced metabolic syndrome.  Am J Physiol Renal Physiol. 2006;  290 F625-F631
  • 16 Hallfrisch J. Metabolic effects of dietary fructose.  FASEB J. 1990;  4 2652-2660
  • 17 Fields M, Lewis C G, Lure M D. Allopurinol, an inhibitor of xanthine oxidase, reduces uric acid levels and modifies the signs associated with copper deficiency in rats fed fructose.  Free Radic Biol Med. 1996;  20 595-600
  • 18 Shimada M, Johnson R J, May Jr. W S, Lingegowda V, Sood P, Nakagawa T, Van Q C, Dass B, Ejaz A A. A novel role for uric acid in acute kidney injury associated with tumour lysis syndrome.  Nephrol Dial Transplant. 2009;  24 2960-2964
  • 19 Chen C J, Shi Y, Hearn A, Fitzgerald K, Golenbock D, Reed G, Akira S, Rock K L. MyD88-dependent IL-1 receptor signaling is essential for gouty inflammation stimulated by monosodium urate crystals.  J Clin Invest. 2006;  116 2262-2271
  • 20 Guan Z, Buckman S Y, Miller B W, Springer L D, Morrison A R. Interleukin-1beta-induced cyclooxygenase-2 expression requires activation of both c-Jun NH2-terminal kinase and p 38 MAPK signal pathways in rat renal mesangial cells.  J Biol Chem. 1998;  273 28670-28676
  • 21 Narumiya S, Sugimoto Y, Ushikubi F. Prostanoid receptors: structures, properties, and functions.  Physiol Rev. 1999;  79 1193-1226
  • 22 Qi W E, Chen X M, Poronnik P, Pollock C A. Transforming growth factor-β/connective tissue growth factor axis in the kidney.  Int J Biochem Cell Biol. 2008;  40 9-13
  • 23 Gupta S, Clarkson M R, Duggan J, Brady H R. Connective tissue growth factor: potential role in glomerulosclerosis and tubulointerstitial fibrosis.  Kidney Int. 2000;  58 1389-1399
  • 24 Okada H, Kikuta T, Kobayashi T, Inoue T, Kanno Y, Takigawa M, Sugaya T, Kopp J B, Suzuki H. Connective tissue growth factor expressed in tubular epithelium plays a pivotal role in renal fibrogenesis.  J Am Soc Nephrol. 2005;  16 133-143
  • 25 Hu Q H, Wang C, Li J M, Zhang D M, Kong L D. Allopurinol, rutin and quercetin attenuate hyperuricemia and renal dysfunction in rats induced by fructose intake: renal organic ion transporter involvement.  Am J Physiol Renal Physiol. 2009;  297 1080-1091

Chunfeng Zhang

Key Laboratory of Modern Chinese Medicines
China Pharmaceutical University

No. 24 Tongjia Lane

Nanjing City 210009

P. R. China

Phone: +86 25 83 27 14 26

Fax: +86 25 83 27 14 26

Email: zhangchunfeng67@163.com

Zhonglin Yang

Key Laboratory of Modern Chinese Medicines
China Pharmaceutical University

No. 24 Tongjia Lane

Nanjing City 210009

P. R. China

Phone: +86 25 83 27 14 26

Fax: +86 25 83 27 14 26

Email: zlyang1950@yahoo.cn

>