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.
Key words
Breviscapine - diabetes - liver - oxidative stress - macrophage - transforming growth
factor-β1
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