Planta Med 2007; 73(5): 433-438
DOI: 10.1055/s-2007-967182
Original Paper
Pharmacology
© Georg Thieme Verlag KG Stuttgart · New York

Prevention of Early Liver Injury by Breviscapine in Streptozotocin-Induced Diabetic Rats

Yong-Gui Wu1 , Ling-Ling Xia2 , Hui Lin1 , Dian Zhou1 , Hao Qian1 , Shan-Tan Lin3
  • 1Department of Nephrology, The First Affiliated Hospital, Anhui Medical University, Hefei, P. R. China
  • 2Department of Infectious Diseases, The First Affiliated Hospital, Anhui Medical University, Hefei, P. R. China
  • 3Department of Nephropathy, Huashan Hospital, FuDan University, Shanghai, P. R. China
Further Information

Publication History

Received: July 23, 2005 Revised: March 7, 2007

Accepted: March 13, 2007

Publication Date:
19 April 2007 (online)

Abstract

The aim of this study was to investigate the protective effect of breviscapine extracted from the Chinese herb Erigeron breviscapus on liver injury in diabetic rats induced by streptozotocin. Treatment with breviscapine significantly reduced liver weight, liver lipid level, fatty liver and liver fibrosis score in diabetic rats. Treatment with breviscapine also significantly decreased lipid peroxidation malondiadehyde levels and increased the activities of antioxidative enzymes such as superoxide dismutase, catalase and glutathione peroxidase in diabetic liver. Immunohistochemical observations revealed that macrophage (ED-1-positive cells) infiltration in diabetic liver was inhibited by treatment with breviscapine. Western blot analysis showed that the expression of transforming growth factor-β1 in diabetic liver was lowered by breviscapine treatment. In conclusion, our results indicate that breviscapine has potential as a treatment for diabetic liver injury through attenuating liver lipid accumulation and oxidative stress.

References

  • 1 Stone B G, Van Thiel D H. Diabetes mellitus and the liver.  Semin Liver Dis. 1985;  1 8-28.
  • 2 Keefe E, Adesman P, Stenze P. Steatosis and cirrhosis in an obese diabetic.  Dig Dis Sci. 1987;  32 441-5.
  • 3 West I C. Radicals and oxidative stress in diabetes.  Diabet Med. 2000;  17 171-80.
  • 4 Baydas G, Canatan H, Turkoglu A. Comparative analysis of the protective effects of melatonin and vitamin E on streptozotocin-induced diabetes mellitus.  J Pineal Res. 2002;  32 225-30.
  • 5 de Cavanagh E MV, Inserra F, Toblli J, Stella I, Fraga C G, Ferder L. Enalapril attenuates oxidative stress in diabetic rats.  Hypertension. 2001;  38 130-36.
  • 6 Zhang R W, Zhang Y L, Wang J S, Lin Y Y, Shang B. Isolation and identification of flavoroids from shortscape fleabane (Erigeron breviscapus).  Chin Trad Herb Drugs. 1988;  19 99-201 [in Chinese].
  • 7 Chen X X, He B, Chen Y Y. Mechanisms of inhibitory effects of breviscapine on lipid peroxidation in rat brain mitochondria.  J Chin Pharm Sci. 1998;  7 209-13 [in Chinese].
  • 8 Ali A, Gan L, Liu Q, Liu H, Xu H B. Antioxidant effect of scutellarin and its antagonistic action on the liver toxicity of Se in rats.  Chin Pharmacol Bull. 2003;  19 113-5 [in Chinese].
  • 9 Shuai J, Dong W W. Experimental research of PKC inhibitor, erigeron breviscapus on the ischemic/reperfusion brain injury.  Chin Pharmacol Bull. 1998;  14 75-7 [in Chinese].
  • 10 He W, Liu Y M, Chen H, Zeng F D. Effect of breviscapine on brain edema and neutrophil infiltration induced by focal cerebral ischemia and reperfusion in rats.  Chin J Pharmacol Toxicol. 2004;  18 161-5 [in Chinese].
  • 11 Zhang Z, Sun M, Wang H, Le J. Protective effect of erigeron injections on hepatotoxicity induced by intestinal ischemia-reperfusion in mice.  J Hyg Res. 2001;  30 1-3 [in Chinese].
  • 12 Yang X F, He W, Lu W H, Zeng F D. Effects of scutellarin on liver function after brain ischemia/reperfusion in rats.  Acta Pharmacol Sin. 2003;  24 1118-24.
  • 13 Folch J, Lees M, Slone Stanley G H. A simple method for the isolaton and purification of total lipids from animal tissues.  J Biol Chem. 1957;  226 497-509.
  • 14 Foster L B, Dunn R T. Stable reagents for determination of serum triglycerides by a colorimetric Hantzsch condensation method.  Clin Chem. 1973;  19 338-40.
  • 15 Parekh A C, Jung R T. Cholesterol determination with ferric acetateuranyl acetate and sulphuric acid-ferrous sulphate reagents.  Anal Chem. 1970;  42 1423-7.
  • 16 Morrison W R, Smith L M. Preparations of fatty acid methyl esters and dimethyl acetals from lipids with boron fluoride methanol.  J Lipid Res. 1964;  5 600-7.
  • 17 Toblli J E, Ferder L, Stella I, Angerosa M, Inserra F. Enalapril prevents fatty liver in nephritic rats.  J Nephrol. 2002;  15 358-67.
  • 18 Bradford M M. A rapid and sensitive method of the quantification of microgram quantities of protein utilizing the principle of protein dye binding.  Anal Biochem. 1976;  72 248-54.
  • 19 Busaranogla M, Acbay O, Sonsuz A. A controlled trial of gemfibrozil in the treatment of patients with nonalcoholic steatohepatitis.  J Hepatol. 1999;  31 384.
  • 20 Liu H, Yang X L, Wang Y, Tang X Q, Jiang D Y, Xu H B. Protective effects of scutellarin on superoxide-induced oxidative stress in rat cortical synaptosomes.  Acta Pharmacol Sin. 2003;  24 1113-7.
  • 21 Hensley K, Kobinson K A, Gabbita S P, Salsman S, Floyd R A. Reactive oxygen species, cell signaling, and cell injury.  Free Radic Biol Med. 2002;  28 1456-62.
  • 22 Poli G, Parola M. Oxidative damage and fibrogenesis.  Free Radic Biol Med. 1997;  22 287-305.
  • 23 Dooley S, Delvoux B, Lahme B, Mangasser-Stephan K, Gressner A M. Modulation of transforming growth factor β response and signaling during transdifferentiation of rat hepatic stellate cells to myofibroblasts.  Hepatology. 2000;  31 1094-106.
  • 24 Bedossa P, Paradis V. Transforming growth factor-beta (TGF-beta): a key-role in liver fibrogenesis.  J Hepatol. 1995;  22 37-42.
  • 25 Olaso E, Friedman S L. Molecular regulation of hepatic fibrogenesis.  J Hepatol. 1998;  29 836-47.
  • 26 Bissell D M, Roulot D, George J. Transforming growth factor β and the liver.  Hepatology. 2001;  34 859-67.
  • 27 Starkel P, Sempoux C, Leclercq I, Herin M, Deby C, Desager J P. et al . Oxidative stress, KLF6 and transforming growth factor-β up-regulation differentiate non-alcoholic steatohepatitis progressing to fibrosis from uncomplicated steatosis in rats.  J Hepatol. 2003;  39 538-46.
  • 28 Parola M, Muraca R, Dianzani I, Barrera G, Leonarduzzi G, Bendinelli P. et al . Vitamin E dietary supplementation inhibits transforming growth factor β1 gene expression in the rat liver.  FEBS Lett. 1992;  308 267-70.

Prof. Dr. Yong-Gui Wu

Department of Nephrology

The First Affiliated Hospital

Anhui Medical University

Hefei 230032

People's Republic of China

Phone: +86 551 292 2450

Fax: +86 551 363 3742

Email: wygxll@ah163.com

>