Advertisement

Vascular effects of Siberian ginseng (Eleutherococcus senticosus): endothelium-dependent NO- and EDHF-mediated relaxation depending on vessel size

  • Chiu-Yin Kwan
  • Wen-Bo Zhang
  • Si-Mui Sim
  • Takeshi Deyama
  • Sansei Nishibe
Original Article

Abstract

Siberian ginseng (SG) has been widely and historically consumed as a health food product for the improvement of self well-being, but whether vascular relaxation may contribute to such a therapeutic health effect has not been studied. We therefore investigated the vasorelaxant effect of the aqueous extract of the roots of SG (Eleutherococcus senticosus Maxim) using several in vitro vascular rings prepared from dog carotid artery, rat aorta and rat mesenteric artery. SG extract (0.04–0.8 mg/ml) caused concentration-dependent relaxation in dog carotid arterial rings pre-contracted with 100 μM phenylephrine (PE), and the relaxation was primarily endothelium-dependent. Treatment with 100 μM L-NOARG (a nitric oxide synthase inhibitor) either prevented or totally reverted SG-induced relaxation, suggesting that the endothelium-dependent relaxation was mediated by NO. Similar endothelium-dependent vascular relaxant responses were also obtained with rat aortic and mesenteric arterial rings, except that it occurred over a relatively higher concentration range of SG (0.5–2.0 mg/ml). When tested in the presence of 300 μM L-NAME, the vasorelaxant effect of SG was inhibited totally in rat aorta but only partially in rat mesenteric artery. The relaxation to SG that was insensitive to L-NAME in rat mesenteric arterial rings was eliminated when the rings (both proximal and distal ends) were pre-treated with a combination of 300 μM L-NAME and 15 mM KCl indicating the involvement of endothelium-derived hyperpolarizing factor (EDHF). This vasorelaxant response of the SG extract was inhibited partially by atropine (1 μM), completely by TEA (5 mM), but not by indomethacin (1 μM) or propranolol (10 μM). SG up to 2 mg/ml had no effect on KCl-induced contraction in any of the vascular rings studied. When compared with carbachol-induced (CCh) relaxation, SG resembles CCh in that the sensitivity to L-NAME inhibition is dependent on vascular size, i.e. aorta >proximal end of mesenteric artery >distal end of mesenteric artery. However, SG exhibited different potencies to relaxation while CCh showed similar potency (EC50 of about 0.2 μM) in all three vascular segments. In conclusion, we have demonstrated that the vascular effect of SG is endothelium-dependent and mediated by NO and/or EDHF depending on the vessel size. Other vasorelaxation pathways, such as inhibition of K+-channels and activation of muscarinic receptors, may also be involved.

Keywords

Siberian ginseng Eleuthero Vascular relaxation Nitric oxide Endothelium-derived hyperpolarizing factor 

Notes

Acknowledgements

This work was supported by a seeding grant from McMaster University. S.M.S. is on sabbatical leave from the Department of Pharmacology, University of Malaya, Kuala Lumpur, Malaysia. We acknowledge the excellent technical assistance of Ms. J. Miller, who was supported by a summer research fellowship award from the Institute of Aboriginal People’s Health, CIHR, Canada.

References

  1. Achike FI, Kwan CY (2003) Nitric oxide, human diseases and the herbal products that affect the nitric oxide signaling pathway. Clin Exp Pharmacol Physiol 30:605–615PubMedGoogle Scholar
  2. Baranov AL (1982) Medical uses of ginseng and related plants in the Soviet Union: recent trends in the Soviet literature. J Ethnopharmacol 6:339–353Google Scholar
  3. Busse R, Edwards G, Feletou M, Fleming I, Vanhoutte PM, Weston AH (2002) EDHF: bringing the concepts together. Trends Pharmacol Sci 23:374–380PubMedGoogle Scholar
  4. Deyama T, Nishibe S, Nakazawa Y (2001) Constituents and pharmacological effects of Eucommia and Siberian ginseng. Acta Pharmacol Sin 22:1057–1070PubMedGoogle Scholar
  5. Gillis CN (1997) Ginseng pharmacology: a nitric oxide link? Biochem Pharmacol 54:1–8CrossRefPubMedGoogle Scholar
  6. Guan YY, Kwan CY, Daniel EE (1988) Inhibition of norepinephrine-induced contractile responses of canine mesenteric artery by plant total saponins. Blood Vessels 25:312–315PubMedGoogle Scholar
  7. Hoffman D (1994) The herbalist. In Multimedia CD-Rom (version 2) Hopkins Technology, LLC Hopkins, MNGoogle Scholar
  8. Hu XM (1996) National regulatory authority for Chinese medicinal drugs (Chinese). Ciwujia. In: Zhong Hua Ben Cao (Compendium of Chinese medicinal herbs), vol 1. Shanghai Science and Technology, ShanghaiGoogle Scholar
  9. Kang SY, Schini-Kerth VB, Kim ND (1995) Ginsenosides of the protopanaxatriol group cause endothelium-dependent relaxation in rat aorta. Life Sci 56:1577–1586CrossRefPubMedGoogle Scholar
  10. Kwan CY (1999) The effects of different ginseng extracts on vascular contraction in vitro: evidence for Yin-Yang principle. Acta Phytother 2:73–77Google Scholar
  11. Kwan CY, Zhang WB, Kwan TK, Sakai Y (2003) In vitro relaxation of vascular smooth muscle by atropine: involvement of K+-channels and endothelium. Naunyn-Schmiedebergs Arch Pharmacol 368:1–9Google Scholar
  12. Kwan CY, Zhang WB, Deyama T, Nishibe S (2004) Endothelium-dependent vascular relaxation induced by Eucommia ulmoides Oliv. bark extract is mediated by NO and EDHF in small blood vessels. Naunyn-Schmiedebergs Arch Pharmacol 369:206–211Google Scholar
  13. Nishibe S, Chie FC (1998) The power of Siberian ginseng [in Japanese]. Mainiji Shinbon Sha, TokyoGoogle Scholar
  14. Shen JZ, Zheng XF, Wei EQ, Kwan CY (2003) Green tea catechins evoke a phasic contraction in rat aorta via H2O2-mediated multiple signaling pathways. Clin Exp Pharmacol Physiol 30:88–95CrossRefPubMedGoogle Scholar
  15. Shimokawa H, Yasutake H, Fujii K, Owada MK, Nakaike R, Fukumoto Y, Takayanagi T, Nagao T, Egashira K, Fujishima M, Takeshita A (1996) The importance of the hyperpolarizing mechanism increases as the vessel size decreases in endothelium-dependent relaxation in rat mesenteric circulation. J Cardiovasc Pharmacol 28:703–711PubMedGoogle Scholar
  16. Wilson RK, Kwan TK, Kwan CY, Sorger GJ (2002) Effects of papaya seed extract and benzyl isothiocyanate on vascular contraction. Life Sci 71:497–507CrossRefPubMedGoogle Scholar
  17. Zheng XF, Kwan CY, Daniel EE (1993) Cyclopiazonic acid causes endothelium-dependent relaxation in rat aorta. Acta Pharmacol Sin 14:21–26Google Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Chiu-Yin Kwan
    • 1
  • Wen-Bo Zhang
    • 1
  • Si-Mui Sim
    • 1
  • Takeshi Deyama
    • 2
  • Sansei Nishibe
    • 3
  1. 1.HSC-4N40, Department of Medicine, Faculty of Health SciencesMcMaster UniversityHamiltonCanada
  2. 2.Central Research LaboratoriesYomeishu Seizo Co. Ltd.NaganoJapan
  3. 3.Faculty of Pharmaceutical SciencesHealth Sciences University of HokkaidoHokkaidoJapan

Personalised recommendations