Download PDF
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)

Also available at
    Permissions and Reprints

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.

Key words

scutellarin - atherosclerosis - hypercholesterolemia - vasorelaxation - nitric oxide - cholesterol

References

  • 1 Prasad K, Kalra J. Oxygen free radicals and hypercholesterolemic atherosclerosis: effect of vitamin E.  Am Heart J. 1993;  125 958-973
    CrossrefPubMedGoogle Scholar
  • 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
    Google Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 6 Rosenson R S. Pluripotential mechanisms of cardioprotection with HMG‐CoA reductase inhibitor therapy.  Am J Cardiovasc Drugs. 2001;  1 411-420
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 10 Ruan Z P, Yu W D. Experimental study on anti-inflammation influence of scutellarin.  J Changzhi Med Coll. 2004;  18 88-89
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 15 McCord E L, Goenka S. Development of thyroid follicular adenoma on simvastatin therapy.  Tenn Med. 2000;  93 210-212
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 17 Kannel W B. Range of serum cholesterol values in the population developing coronary artery disease.  Am J Cardiol. 1995;  76 69C-77C
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 27 Förstermann U, Münzel T. Endothelial nitric oxide synthase in vascular disease: from marvel to menace.  Circulation. 2006;  113 1708-1714
    CrossrefPubMedGoogle Scholar
  • 28 Chatterjee A, Catravas J D. Endothelial nitric oxide (NO) and its pathophysiologic regulation.  Vascul Pharmacol. 2008;  49 134-140
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar

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