Planta Med 2009; 75(13): 1400-1404
DOI: 10.1055/s-0029-1185745
Pharmacology
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Echinacoside Elicits Endothelium-Dependent Relaxation in Rat Aortic Rings via an NO-cGMP Pathway

Wen-Jun He1 , 2 , Tai-Hui Fang2 , Xu Ma1 , Ke Zhang1 , Zhi-Zhong Ma1 , Peng-Fei Tu1
  • 1State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing, P. R. China
  • 2Department of Pharmacology, Nanjing University of Traditional Chinese Medicine, Nanjing, P. R. China
Further Information

Publication History

received February 23, 2009 revised April 22, 2009

accepted April 26, 2009

Publication Date:
25 May 2009 (online)

Abstract

The aim of this study was to identify and elucidate the vasorelaxant activity of echinacoside, a phenylethanoid glycoside isolated from the medicinal herb Cistanche tubulosa, and its possible underlying mechanism on isolated rat thoracic aortic rings pre-contracted with phenylephrine (PE, 1 µM) and KCl (60 mM). Echinacoside (30–300 µM) exhibited an acute relaxation in endothelium-intact rings in a concentration-dependent manner, while this relaxation was significantly inhibited in endothelium-denuded condition and in the presence of the endothelial nitric oxide synthase (eNOS) inhibitor, Nw -nitro-L-arginine methyl ester (L‐NNA, 100 µM), an unselective soluble guanylate cyclase blocker, methylene blue (10 µM), the selective sGC inhibitor 1H-[1, 2, 4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 1 µM); in addition, atropine (1 µM), a selective muscarinic receptor antagonist, partially affected the relaxation. However, the cyclooxygenase inhibitor indomethacin (5 µM) had no influence on the action. Echinacoside enhanced the cyclic guanosine monophosphate (cGMP) production in aortic rings contracted with PE. These results indicate for the first time that echinacoside mediates the endothelium-dependent vasodilator action in rat thoracic aortic rings through nitric oxide (NO)-cGMP pathway.

References

  • 1 Tu P F, Wang B, Deyama T, Zhang Z G, Lou Z C. Analysis of phenylethanoid glycosides of Herba Cistamchis by RP-HPLC.  Acta Pharm Sin. 1997;  32 294
  • 2 Chinese Pharmacopoeia Committee Editing .Chinese Pharmacopoeia, Part I, 2005 edition. Beijing; Chemical and Industrial Publisher 2005: 90
  • 3 Speroni E, Govoni P S, Guizzardi S, Renzulli C, Guerra M C. Anti-inflammatory and cicatrizing activity of Echinacea pallida Nutt. root extract.  J Ethnopharmacol. 2002;  79 265-272
  • 4 Tian X F, Pu X P. Phenylethanoid glycosides from Cistanche salsa inhibit apoptosis induced by 1-methyl-4-phenylpyridium ion in neurons.  J Ethnopharmacol. 2005;  97 59-63
  • 5 Deng M, Zhao J Y, Tu P F, Jiang Y, Li Z B, Wang Y H. Echinacoside rescues the SHSY5Y neuronal cells from TNF-α induced apoptosis.  Eur J Pharmacol. 2004;  505 11-18
  • 6 Pellati F, Benvenuti S, Magro L, Melegari M, Soragni F. Analysis of phenolic compounds and radical scavenging activity of Echinacea spp.  J Pharm Biomed Anal. 2004;  35 289-301
  • 7 Xiong Q B, Tezuka Y, Kaneko T, Li H, Tran L Q, Hase K, Namba T. Inhibition of nitric oxide by phenylethanoids in activated macrophages.  Eur J Pharmacol. 2000;  400 137-144
  • 8 Heilmann J, Calis I, Kirmizibekmez H, Schuhly W, Harput S, Sticher O. Radical scavenger activity of phenylethanoid glycosides in FMLP stimulated human polymorphonuclear leukocytes: structure–activity relationships.  Planta Med. 2000;  66 746-748
  • 9 Geng X C, Song L W, Pu X P, Tu P F. Neuroprotective effects of phenylethanoid glycosides from Cistanches salsa against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic toxicity in C57 mice.  Biol Pharm Bull. 2004;  27 797-801
  • 10 Chen H, Jing F C, Li C L, Tu P F, Zheng Q S, Wang Z H. Echinacoside prevents the striatal extracellular levels of monoamine neurotransmitters from diminution in 6-hydroxydopamine lesion rats.  J Ethnopharmacol. 2007;  114 285-289
  • 11 Costantino I. Neurovascular regulation in the normal brain and in Alzheimer's disease.  Nat Rev. 2004;  5 347-360
  • 12 Gao C, Wang C S, Wu G Z, Tu P F. Effect of Cistanche glycosides on learning and memory impairment in vascular dementia rat.  Chin Tradit Herb Drugs. 2005;  36 1852-1855
  • 13 Yoshikawa M, Matsuda H, Morikawa T, Xie H H, Nakamura S, Muraoka O. Phenylethanoid oligoglycosides and acylated oligosugars with vasorelaxant activity from Cistanche tubulosa.  Bioorg Med Chem. 2006;  14 7468-7475
  • 14 Furchgott R F, Zawadzki J V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine.  Nature. 1980;  288 373-376
  • 15 Jaffe E A, Ann N Y. Physiologic functions of normal endothelial cells.  Acad Sci. 1985;  454 279-291
  • 16 Beny J L, Brunet P C. Neither nitric oxide nor nitroglycerin accounts for all the characteristics of endothelially mediated vasodilatation of pig coronary arteries.  Blood Vessels. 1988;  25 308-311
  • 17 Palmer R M, Ashton D S, Moncada S. Vascular endothelial cells synthesize nitric oxide from L-arginine.  Nature. 1988;  333 664-666
  • 18 Luscher T F. The endothelium in hypertemsion: bystander, target or mediator?.  J Hypertens. 1994;  12 S105-S106
  • 19 Vanhoutte P M, Boulanger C M. Endothilium-dependent responses in hypertension.  Hypertens Res. 1995;  18 87-89
  • 20 Jiang F, Drummond G R, Dusting G J. Suppression of oxidative stress in the endothelium and vascular wall.  Endothelium. 2004;  11 79-88
  • 21 Jia C Q, Shi H M, Wu X M, Li Y Z, Chen J J, Tu P F. Determination of echinacoside in rat serum by reversed-phase high-performance liquid chromatography with ultraviolet detection and its application to pharmacokinetics and bioavailability.  J Chromatogr B. 2006;  844 308-313
  • 22 Furchgott R F, Cherry P D, Zawadzki J V, Jothianandan D. Endothelial cells as mediators of vasodilation of arteries.  J Cardiovasc Pharmacol. 1984;  6 S336-S343
  • 23 Tirapelli C R, Ambrosio S R, da Costa F B, Coutinho S T, de Oliveira D C, de Oliveir A M. Analysis of the mechanisms underlying the vasorelaxant action of kaurenoic acid in the isolated rat aorta.  Eur J Pharmacol. 2004;  492 233-241
  • 24 Rubanyi G M. The role of endothelium in cardiovascular homeostasis and diseases.  J Cardiovasc Pharmacol. 1993;  22 S1-S14
  • 25 Moncada S, Higgs A. The L-arginine-nitric oxide pathway.  N Engl J Med. 1993;  329 2002-2012
  • 26 Sato K, Ozaki H, Karaki H. Changes in cytosolic calcium level in vascular smooth muscle strip measured simultaneously with contraction using fluorescent calcium indicator fura 2.  J Pharmacol Exp Ther. 1988;  246 294-300
  • 27 Furchgott R F, Vanhoutte P M. Endothelium-derived relaxing and contracting factors.  FASEB J. 1989;  3 2007-2018
  • 28 Satake N, Kiyoto S, Shibata S, Gandhi V, Jones D J, Morikawa M. Possible mechanisms of inhibition with atropine against noradrenaline-induced contraction in the rabbit aorta.  Br J Pharmacol. 1992;  107 553-558
  • 29 Kobayashi T, Tahara Y, Matsumoto M. Roles of thromboxane A (2) and prostacyclin in the development of atherosclerosis in apoE deficient mice.  J Clin Invest. 2004;  114 784-794

Prof. Dr. Peng-Fei Tu

State Key Laboratory of Natural and Biomimetic Drugs
School of Pharmaceutical Sciences
Peking University Health Science Center

No. 38 Hua Yuan Rd.

Beijing 100091

People's Republic of China

Phone: + 86 10 82 80 27 50

Fax: + 86 10 82 80 27 50

Email: pengfeitu@vip.163.com

    >