Planta Med 2009; 75(11): 1203-1208
DOI: 10.1055/s-0029-1185539
Pharmacology
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Suppression of Diet-Induced Hypercholesterolemia by Scutellarin in Rats

Qing Li1 , 2 , Jian-Hong Wu2 , De-Jian Guo2 , Huan-Le Cheng2 , Shi-Lin Chen1 , 2 , Shun-Wan Chan2 , 3
  • 1Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, P. R. China
  • 2State Key Laboratory of Chinese Medicine and Molecular Pharmacology, Shenzhen, P. R. China
  • 3Open Laboratory of Chirotechnology, Department of Applied Biology and Chemical Technology, The Hong Kong , Polytechnic University, Hong Kong SAR, P. R. China
Further Information

Publication History

received Nov. 10, 2008 revised February 18, 2009

accepted February 25, 2009

Publication Date:
06 April 2009 (online)

Abstract

Hypercholesterolemia is a major risk factor for the development and progression of cardiovascular diseases including atherosclerosis. A major active ingredient, scutellarin, from the plant Erigeron breviscapus was investigated for its hypocholesterolemic and atheroscleroprotective effects (30 and 100 mg/kg/day, p. o.). The serum lipid profile (total cholesterol, triglycerides, high density lipoprotein cholesterol and low density lipoprotein cholesterol) was monitored and aortic functions in Sprague-Dawley rats fed with normal diet, atherogenic diet or atherogenic diet plus oral administration of either scutellarin or simvastatin (a positive control) were tested. It was found that scutellarin markedly attenuated the increased serum total cholesterol induced by atherogenic diet. It caused a significant reduction in the atherogenic index. In addition, scutellarin administration could significantly enhance acetylcholine-induced nitrate/nitrite production, increase the gene expression of endothelial nitric oxide synthase and improve acetylcholine-induced endothelium-dependent vasorelaxation in rat isolated aortas. These data revealed that scutellarin could reduce the atherogenic properties of dietary cholesterol in rats. However, whether scutellarin's atheroscleroprotective potential targets endothelial function directly or indirectly on its antioxidative activity remains to be determined.

References

  • 1 Prasad K, Kalra J. Oxygen free radicals and hypercholesterolemic atherosclerosis: effect of vitamin E.  Am Heart J. 1993;  125 958-973
  • 2 Farmer J A, Gotto A M. Dyslipidemia and other risk factors for coronary artery disease. Braunwald E Heart disease. Philadelphia; Saunders 1997: 1126-1160
  • 3 Yan L P, Chan S W, Chan A SC, Chen S L, Ma X J, Xu H X. Puerarin decreases serum total cholesterol and enhances thoracic aorta endothelial nitric oxide synthase expression in diet-induced hypercholesterolemic rats.  Life Sci. 2006;  79 324-330
  • 4 Böger R H, Bode-Böger S M, Frölich J C. The L-arginine-nitric oxide pathway: role in atherosclerosis and therapeutic implications.  Atherosclerosis. 1996;  127 1-11
  • 5 Kuchan M J, Frangos J A. Role of calcium and calmodulin in flow-induced nitric oxide production in endothelial cells.  Am J Physiol. 1994;  266 C628-C636
  • 6 Rosenson R S. Pluripotential mechanisms of cardioprotection with HMG‐CoA reductase inhibitor therapy.  Am J Cardiovasc Drugs. 2001;  1 411-420
  • 7 Zhu B H, Guan Y Y, He H, Lin M J. Erigeron breviscapus prevents defective endothelium-dependent relaxation in diabetic rat aorta.  Life Sci. 1999;  65 1553-1559
  • 8 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 1113-1117
  • 9 Wang L X, Zeng J P, Huang Z F, Liu Z P, Wei X B, Wang Z Y, An J, Zhang X M. Antioxidant effect of scutellarin on PC12 cell injury induced by hydrogen peroxide in culture.  Chin J Biochem Pharm. 2005;  26 347-349
  • 10 Ruan Z P, Yu W D. Experimental study on anti-inflammation influence of scutellarin.  J Changzhi Med Coll. 2004;  18 88-89
  • 11 Liu H, Yang X L, Tang R, Liu J, Xu H B. Effect of scutellarin on nitric oxide production in early stages of neuron damage induced by hydrogen peroxide.  Pharmacol Res. 2005;  51 205-210
  • 12 Pan Z, Feng T, Shan L, Cai B, Chu W, Niu H, Lu Y, Yang B. Scutellarin-induced endothelium-independent relaxation in rat aorta.  Phytother Res. 2008;  22 1428-1433
  • 13 Lin L L, Liu A J, Liu J G, Yu X H, Qin L P, Su D F. Protective effects of scutellarin and breviscapine on brain and heart ischemia in rats.  J Cardiovasc Pharmacol. 2007;  50 327-332
  • 14 Hu X M, Zhou M M, Hu X M, Zeng F D. Neuroprotective effects of scutellarin on rat neuronal damage induced by cerebral ischemia/reperfusion.  Acta Pharmacol Sin. 2005;  26 1454-1459
  • 15 McCord E L, Goenka S. Development of thyroid follicular adenoma on simvastatin therapy.  Tenn Med. 2000;  93 210-212
  • 16 Chen W, Suruga K, Nishimura N, Gouda T, Lam V N, Yokogoshi H. Comparative regulation of major enzymes in the bile acid biosynthesis pathway by cholesterol, cholate and taurine in mice and rats.  Life Sci. 2005;  77 746-757
  • 17 Kannel W B. Range of serum cholesterol values in the population developing coronary artery disease.  Am J Cardiol. 1995;  76 69C-77C
  • 18 Sorensen K E, Celermajer D S, Georgakopoulos D, Hatcher G, Betteridge D J, Deanfield J E. Impairment of endothelium-dependent dilation is an early event in children with familiar hypercholesterolemia and is related to the lipoprotein levels.  J Clin Invest. 1994;  93 50-55
  • 19 Hu M Y, Li Y L, Jiang C H, Liu Z Q, Qu S L, Huang Y M. Comparison of lycopene and fluvastatin effects on atherosclerosis induced by a high-fat diet in rabbits.  Nutrition. 2008;  24 1030-1038
  • 20 Baylis C, Vallance P. Measurement of nitrite and nitrate levels in plasma and urine – what does this measure tell us about the activity of the endogenous nitric oxide system?.  Curr Opin Nephrol Hypertens. 1998;  7 59-62
  • 21 Kleinbongard P, Dejam A, Lauer T, Rassaf T, Schindler A, Picker O, Scheeren T, Gödecke A, Schrader J, Schulz R, Heusch G, Schaub G A, Bryan N S, Feelisch M, Kelm M. Plasma nitrite reflects constitutive nitric oxide synthase activity in mammals.  Free Radic Biol Med. 2003;  35 790-796
  • 22 Pritchard Jr K A, Groszek L, Smalley D M, Sessa W C, Wu M, Villalon P, Wolin M S, Stemerman M B. Native low-density lipoprotein increases endothelial cell nitric oxide synthase generation of superoxide anion.  Circ Res. 1995;  77 510-518
  • 23 Gilgun-Sherki Y, Rosenbaum Z, Melamed E, Offen D. Antioxidant therapy in acute central nervous system injury: current state.  Pharmacol Rev. 2002;  54 271-284
  • 24 Jin L, Caldwell R B, Li-Masters T, Caldwell R W. Homocysteine induces endothelial dysfunction via inhibition of arginine transport.  J Physiol Pharmacol. 2007;  58 191-206
  • 25 Chan S W, Li S, Kwok C Y, Benzie I FF, Szeto Y T, Guo D J, He X P, Yu P HF. Antioxidant activity of Chinese medicinal herbs.  Pharm Biol. 2008;  46 587-595
  • 26 Liu H, Yang X, Zhou L, Xu H. Study on reactive oxygen species scavenging effects of scutellarin.  Zhong Yao Cai. 2002;  25 491-493
  • 27 Förstermann U, Münzel T. Endothelial nitric oxide synthase in vascular disease: from marvel to menace.  Circulation. 2006;  113 1708-1714
  • 28 Chatterjee A, Catravas J D. Endothelial nitric oxide (NO) and its pathophysiologic regulation.  Vascul Pharmacol. 2008;  49 134-140
  • 29 Stroes E, Hijmering M, van Zandvoort M, Wever R, Rabelink T J, van Faassen E E. Origin of superoxide production by endothelial nitric oxide synthase.  FEBS Lett. 1998;  438 161-164

Dr. Shun-Wan Chan

Department of Applied Biology and Chemical Technology
Open Laboratory of Chirotechnology
The Hong Kong Polytechnic University

Hong Kong SAR

People's Republic of China

Phone: + 85 2 34 00 87 18

Fax: + 85 2 23 64 99 32

Email: bcswchan@polyu.edu.hk

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