Vascular smooth muscle dysfunction and remodeling induced by ginsenoside Rg3, a bioactive component of Ginseng

Toxicological Sciences

Volumn 117, Issue 2, 2010, Pages 505-514

  Lee, Jin Young ^a   Lim, Kyung Min ^a   Kim, Sun Young ^a   Bae, Ok Nam ^a   Noh, Ji Yoon ^a   Chung, Seung Min ^a   Kim, Keunyoung ^a   Shin, Yoo Sun ^a   Lee, Moo Yeol ^b   Chung, Jin Ho ^a  

^a Seoul National University   (South Korea)

^b Chonnam National University   (South Korea)

Author keywords

Extracellular Ca2+ influx; Ginsenoside Rg3; Smooth muscle dysfunction

Indexed keywords

1,4 DIHYDRO 2,6 DIMETHYL 5 NITRO 4 [2 (TRIFLUOROMETHYL)PHENYL] 3 PYRIDINECARBOXYLIC ACID METHYL ESTER; CALCIUM CHANNEL L TYPE; CALCIUM ION; GINSENOSIDE RG 3;

AORTA; ARTICLE; BLOOD PRESSURE REGULATION; CALCIUM CELL LEVEL; CALCIUM TRANSPORT; CARDIOTOXICITY; GINSENG; IN VITRO STUDY; IN VIVO STUDY; NONHUMAN; RAT; SMOOTH MUSCLE CONTRACTILITY; THORACIC AORTA; VASCULAR SMOOTH MUSCLE;

ANIMALS; AORTA, THORACIC; APOPTOSIS; BLOOD PRESSURE; CALCIUM; CALCIUM CHANNELS, L-TYPE; CALCIUM SIGNALING; CYTOSOL; GINSENOSIDES; MALE; MUSCLE, SMOOTH, VASCULAR; ORGAN CULTURE TECHNIQUES; PANAX; PLANT EXTRACTS; RATS; RATS, SPRAGUE-DAWLEY; VASOCONSTRICTION;

ANIMALIA; PANAX GINSENG; RATTUS;

EID: 77956900953     PISSN: 10966080     EISSN: 10960929     Source Type: Journal    
DOI: 10.1093/toxsci/kfq201     Document Type: Article

References (54)

1. 2+-dependent regulation of vascular tone. J. Anesth. 21, 220-231.
2. Ang-Lee, M. K., Moss, J., and Yuan, C. S. (2001). Herbal medicines and perioperative care. JAMA 286, 208-216.
3. Ardanaz, N., and Pagano, P. J. (2006). Hydrogen peroxide as a paracrine vascular mediator: regulation and signaling leading to dysfunction. Exp. Biol. Med. 231, 237-251.
4. Bae, O. N., Lim, E. K., Lim, K. M., Noh, J. Y., Chung, S. M., Lee, M. Y., Yun, Y. P., Kwon, S. C., Lee, J. H., Nah, S. Y., et al. (2008a). Vascular smooth muscle dysfunction induced by monomethylarsonous acid (MMA III): a contributing factor to arsenic-associated cardiovascular diseases. Environ. Res. 108, 300-308.
5. Bae, O. N., Lim, K. M., Han, J. Y., Jung, B. I., Lee, J. Y., Noh, J. Y., Chung, S. M., Lee, M. Y., and Chung, J. H. (2008b). U-shaped dose response in vasomotor tone: a mixed result of heterogenic response of multiple cells to xenobiotics. Toxicol. Sci. 103, 181-190.
6. Bai, C. X., Takahashi, K., Masumiya, H., Sawanobori, T., and Furukawa, T. (2004). Nitric oxide-dependent modulation of the delayed rectifier K+ current and the L-type Ca2+ current by ginsenoside Re, an ingredient of Panax ginseng, in guinea-pig cardiomyocytes. Br.J.Pharmacol.142, 567-575.
7. Bkaily, G., Jacques, D., and Pothier, P. (1999). Use of confocal microscopy to investigate cell structure and function. Methods Enzymol. 307, 119-135.
8. Bohr, D. F., Dominiczak, A. F., and Webb, R. C. (1991). Pathophysiology of the vasculature in hypertension. Hypertension 18, III69-III75.
9. Buettner, C., Phillips, R. S., Davis, R. B., Gardiner, P., and Mittleman, M. A. (2007). Use of dietary supplements among United States adults with coronary artery disease and atherosclerotic risks. Am. J. Cardiol. 99, 661-666.
10. 2+ entry mechanisms of vascular contraction. Hypertension 42, 818-824.
11. 2+ channel subtypes in bovine chromaffin cells. J. Ethnopharmacol. 74, 75-81.
12. Coon, J. T., and Ernst, E. (2002). Panax ginseng: a systematic review of adverse effects and drug interactions. Drug Saf. 25, 323-344.
13. Crijns, F. R., Wolffenbuttel, B. H., De Mey, J. G., and Struijker Boudier, H. A. (1999). Mechanical properties of mesenteric arteries in diabetic rats: consequences of outward remodeling. Am. J. Physiol. 276, H1672-H1677.
14. De Mey, J. G., Schiffers, P. M., Hilgers, R. H., and Sanders, M. M. (2005). Toward functional genomics of flow-induced outward remodeling of resistance arteries. Am. J. Physiol. Heart Circ. Physiol. 288, H1022-H1027.
15. Engel, R. R., and Smith, A. H. (1994). Arsenic in drinking water and mortality from vascular disease: an ecologic analysis in 30 counties in the United States. Arch. Environ. Health 49, 418-427.
16. Ernst, E. (2002). The risk-benefit profile of commonly used herbal therapies: Ginkgo, St John's Wort, Ginseng, Echinacea, Saw Palmetto, and Kava. Ann. Intern. Med. 136, 42-53.
17. Ernst, E. (2007). 'First, do no harm' with complementary and alternative medicine. Trends Pharmacol. Sci. 28, 48-50.
18. Fusi, F., Marazova, K., Pessina, F., Gorelli, B., Valoti, M., Frosini, M., and Sgaragli, G. (2000). On the mechanisms of the antispasmodic action of some hindered phenols in rat aorta rings. Eur. J. Pharmacol. 394, 109-115.
19. Haijiang, Z., Yongjiang, W., and Yiyu, C. (2003). Analysis of 'SHENMAI' injection by HPLC/MS/MS. J. Pharm. Biomed. Anal. 31, 175-183.
20. Harmon, K. J., Couper, L. L., and Lindner, V. (2000). Strain-dependent vascular remodeling phenotypes in inbred mice. Am. J. Pathol. 156, 1741-1748.
21. Jeong, S. M., Lee, J. H., Kim, J. H., Lee, B. H., Yoon, I. S., Kim, D. H., Rhim, H., Kim, Y., and Nah, S. Y. (2004). Stereospecificity of ginsenoside Rg3 action on ion channels. Mol. Cells 18, 383-389.
22. Kerns, W., Schwartz, L., Blanchard, K., Burchiel, S., Essayan, D., Fung, E., Johnson, R., Lawton, M., Louden, C., MacGregor, J., et al. (2005). Drug-induced vascular injury-a quest for biomarkers. Toxicol. Appl. Pharmacol. 203, 62-87.
23. Khalil, R. A. (2005). Sex hormones as potential modulators of vascular function in hypertension. Hypertension 46, 249-254.
24. Kim, J. H., Lee, J. H., Jeong, S. M., Lee, B. H., Yoon, I. S., Lee, J. H., Choi, S. H., Kim, D. H., Park, T. K., Kim, B. K., et al. (2006). Stereospecific effects of ginsenoside Rg3 epimers on swine coronary artery contractions. Biol. Pharm. Bull. 29, 365-370.
25. Kim, N. D., Kang, S. Y., Park, J. H., and Schini-Kerth, V. B. (1999). Ginsenoside Rg3 mediates endothelium-dependent relaxation in response to ginsenosides in rat aorta: role of K+ channels. Eur. J. Pharmacol. 367, 41-49.
26. Kim, N. D., Kim, E. M., Kang, K. W., Cho, M. K., Choi, S. Y., and Kim, S. G. (2003). Ginsenoside Rg3 inhibits phenylephrine-induced vascular contraction through induction of nitric oxide synthase. Br. J. Pharmacol. 140, 661-670.
27. Larsen, B. T., Gutterman, D. D., and Hatoum, O. A. (2006). Emerging role of epoxyeicosatrienoic acids in coronary vascular function. Eur. J. Clin. Invest. 36, 293-300.
28. 2+ channel subtypes. Mol. Cells 21, 52-62.
29. Lee, J. Y., Bae, O. N., Chung, S. M., Lee, M. Y., and Chung, J. H. (2001). Menadione induces endothelial dysfunction mediated by oxidative stress and arylation. Chem. Biol. Interact. 137, 169-183.
30. 2+ sensor. Proc. Natl. Acad. Sci. U.S.A. 103, 13232-13237.
31. Lyle, A. N., and Griendling, K. K. (2006). Modulation of vascular smooth muscle signaling by reactive oxygen species. Physiology (Bethesda) 21, 269-280.
32. McAllister, I. L., Douglas, J. P., Constable, I. J., and Yu, D. Y. (1998). Laser-induced chorioretinal venous anastomosis for nonischemic central retinal vein occlusion: evaluation of the complications and their risk factors. Am. J. Ophthalmol. 126, 219-229.
33. Mohri, M., Koyanagi, M., Egashira, K., Tagawa, H., Ichiki, T., Shimokawa, H., and Takeshita, A. (1998). Angina pectoris caused by coronary microvascular spasm. Lancet 351, 1165-1169.
34. Morano, I. (2003). Tuning smooth muscle contraction by molecular motors. J. Mol. Med. 81, 481-487.
35. Nader, T., Rothenberg, S., Averbach, R., Charles, B., Fields, J. Z., and Schneider, R. H. (2000). Improvements in chronic diseases with a comprehensive natural medicine approach: a review and case series. Behav. Med. 26, 34-46.
36. Navarro-Antolin, J., Levitsky, K. L., Calderon, E., Ordonez, A., and Lopez-Barneo, J. (2005). Decreased expression of maxi-K+ channel beta1-subunit and altered vasoregulation in hypoxia. Circulation 112, 1309-1315.
37. Nobe, K., Miyatake, M., Nobe, H., Sakai, Y., Takashima, J., and Momose, K. (2004). Novel diacylglycerol kinase inhibitor selectively suppressed an U46619-induced enhancement of mouse portal vein contraction under high glucose conditions. Br. J. Pharmacol. 143, 166-178.
38. Parekh, A. B., and Putney, J. W., Jr. (2005). Store-operated calcium channels. Physiol. Rev. 85, 757-810.
39. Partridge, C. R., Williams, E. S., Barhoumi, R., Tadesse, M. G., Johnson, C. D., Lu, K. P., Meininger, G. A., Wilson, E., and Ramos, K. S. (2005). Novel genomic targets in oxidant-induced vascular injury. J. Mol. Cell Cardiol. 38, 983-996.
40. Pharand, C., Ackman, M. L., Jackevicius, C. A., Paradiso-Hardy, F. L., and Pearson, G. J. (2003). Use of OTC and herbal products in patients with cardiovascular disease. Ann. Pharmacother. 37, 899-904.
41. Sanders, K. M. (2001). Invited review: mechanisms of calcium handling in smooth muscles. J. Appl. Physiol. 91, 1438-1449.
42. Schepke, M., Heller, J., Paschke, S., Thomas, J., Wolff, M., Neef, M., Malago, M., Molderings, G. J., Spengler, U., and Sauerbruch, T. (2001). Contractile hyporesponsiveness of hepatic arteries in humans with cirrhosis: evidence for a receptor-specific mechanism. Hepatology 34, 884-888.
43. Scott, G. I., Colligan, P. B., Ren, B. H., and Ren, J. (2001). Ginsenosides Rb1 and Re decrease cardiac contraction in adult rat ventricular myocytes: role of nitric oxide. Br. J. Pharmacol. 134, 1159-1165.
44. Shan, J. J., Li, B., Taniguchi, N., and Pang, P. K. (1996). Inhibition of membrane L-type calcium channel activity and intracellular calcium concentration by 24R, 25-dihydroxyvitamin D3 in vascular smooth muscle. Steroids 61, 657-663.
45. Shukla, N., Freeman, N., Gadsdon, P., Angelini, G. D., and Jeremy, J. Y. (2001). Thapsigargin inhibits angiogenesis in the rat isolated aorta: studies on the role of intracellular calcium pools. Cardiovasc. Res. 49, 681-689.
46. Siegel, R. K. (1979). Ginseng abuse syndrome. Problems with the panacea. JAMA 241, 1614-1615.
47. Siegel, R. K. (1980). Ginseng and high blood pressure. JAMA 243, 32.
48. 2+ level and contraction on exposure of rat aorta to lysophosphatidylcholine. Eur. J. Pharmacol. 378, 177-186.
49. Taggart, M. J., and Wray, S. (1998). Hypoxia and smooth muscle function: key regulatory events during metabolic stress. J. Physiol. 509(Pt 2), 315-325.
50. 2+ channels modulate expression of smooth muscle differentiation marker genes via a rho kinase/myocardin/SRF-dependent mechanism. Circ. Res. 95, 406-414.
51. Ward, M. R., Pasterkamp, G., Yeung, A. C., and Borst, C. (2000). Arterial remodeling. Mechanisms and clinical implications. Circulation 102, 1186-1191.
52. Xie, H. T., Wang, G. J., Sun, J. G., Tucker, I., Zhao, X. C., Xie, Y. Y., Li, H., Jiang, X. L., Wang, R., Xu, M. J., et al. (2005). High performance liquid chromatographic-mass spectrometric determination of ginsenoside Rg3 and its metabolites in rat plasma using solid-phase extraction for pharmacokinetic studies. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 818, 167-173.
53. Yeh, G. Y., Davis, R. B., and Phillips, R. S. (2006). Use of complementary therapies in patients with cardiovascular disease. Am. J. Cardiol. 98, 673-680.
54. Yoshida, T., Yamauchi, H., and Fan Sun, G. (2004). Chronic health effects in people exposed to arsenic via the drinking water: dose-response relationships in review. Toxicol. Appl. Pharmacol. 198, 243-252.