Angiogenic Effects of Korea Red Ginseng Water Extract in the In Vitro and In Vivo Models

홍삼수용성추출물이 혈관신생에 미치는 영향

  • Rho, Euy-Joon (Department of Oriental Medical Prescription, College of Oriental Medicine, Wonkwang University) ;
  • Ryu, Seong-Hun (Department of Oriental Medical Prescription, College of Oriental Medicine, Wonkwang University) ;
  • Kim, Gyu-Min (Department of Oriental Medical Prescription, College of Oriental Medicine, Wonkwang University) ;
  • Lee, Sang-Hyun (Department of Oriental Medical Prescription, College of Oriental Medicine, Wonkwang University) ;
  • Yun, Young-Gab (Department of Oriental Medical Prescription, College of Oriental Medicine, Wonkwang University)
  • 노의준 (원광대학교 한의과대학 방제학교실) ;
  • 유승훈 (원광대학교 한의과대학 방제학교실) ;
  • 김규민 (원광대학교 한의과대학 방제학교실) ;
  • 이상현 (원광대학교 한의과대학 방제학교실) ;
  • 윤용갑 (원광대학교 한의과대학 방제학교실)
  • Published : 2009.04.25

Abstract

Angiogenesis is important for promoting cardiovascular disease, wound healing, and tissue regeneration. We here investigated the pharmacological effects of Korea red ginseng water extract (KRGE) on angiogenesis and its underlying signal mechanism. This study showed that KRGE increased in vitro proliferation, migration, and tube formation of human umbilical endothelial cells, as well as stimulated in vivo angiogenesis. KRGE-induced angiogenesis was accompanied by phosphorylation of ERK1/2, Akt, and endothelial nitric oxide synthase (eNOS) as well as an increase in NO production. Inhibition of PI3K activity by wortmannin completely inhibited KRGE-induced angiogenesis and phosphorylation of Akt, ERK1/2, and eNOS, indicating that PI3K/Akt activation is an upstream event of KRGE-mediated angiogenic pathway. The MEK inhibitor PD98059 completely blocked KRGE-induced angiogenesis and ERK phosphorylation without affecting Akt and eNOS activation. However, the eNOS inhibitor NMA effectively inhibited tube formation, but partially blocked proliferation and migration as well as ERK phosphorylation without altering Akt and eNOS activation, revealing that eNOS/NO pathway is in part involved in ERK1/2 activation. This study first demonstrated the critical involvement of both ERK1/2 and eNOS activation in KRGE-induced angiogenesis, which lie on downstream of PI3K/Akt. Thus, these results indicate that KRGE requires activation of both the PI3K/Akt-dependent ERK1/2 and eNOS signal pathways and their cross-talk for its full angiogenic activity.

Keywords

References

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