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

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

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Ginseng, one of most well-known herbal medicines, is widely and indiscreetly used among the patients with cardiovascular disorders, raising concern over abuse of this medicine and unwanted effects. In this study, we investigated the effects of ginsenoside Rg3 (Rg3), an active ingredient of ginseng, on vascular contractility and structural integrity to explore its potential vascular toxicity. In isolated rat aorta, Rg3 suppressed the normal agonist-induced contractile response. This suppression persisted even after a rigorous washout. In the endothelium-denuded aortic ring, impairment of vascular contractility by Rg3 was retained, suggesting that vascular smooth muscle was affected. In primary vascular smooth muscle cells, Rg3 abolished agonist-induced Ca2+ increase, indicating that Ca2+ regulation was disrupted. Rg3 suppressed the contraction induced by Bay K8644, an L-type Ca2+ channel activator, whereas store-operated Ca2+ channel or intracellular Ca2+ store-mediated contraction was not affected, suggesting that the L-type Ca2+ channel was selectively impaired by Rg3. These in vitro results were further confirmed in vivo where Rg3 treatment significantly attenuated the agonist-induced pressor response. More importantly, 4-week repeated treatment with Rg3 in normal animals induced eutrophic outward remodeling in the thoracic aorta, that is, it brought about an increased luminal area without changes in the wall area. These results suggest that Rg3 can induce the vascular smooth muscle dysfunction by disturbing Ca2+ influx from the L-type Ca2+ channel, ultimately leading to impaired vascular contractility and structural remodeling.

Original languageEnglish
Pages (from-to)505-514
Number of pages10
JournalToxicological Sciences
Volume117
Issue number2
DOIs
StatePublished - 19 Jul 2010

Keywords

  • Extracellular Ca influx
  • Ginsenoside Rg3
  • Smooth muscle dysfunction

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