Effects of ginseng saponins isolated from Red Ginseng roots on burn wound healing in mice.
1. We recently demonstrated that ginsenoside Rb1 (C54H92O23, molecular weight 1108) isolated from ginseng, when intravenously infused into rats with permanent middle cerebral artery occlusion, reduced cerebral infarct volume and ameliorated place navigation disability of the animals, through an anti-apoptotic action and possibly promotion of vascular regeneration. To investigate the ginsenoside Rb1-mediated vascular regeneration in vivo in a more easily accessible experimental systems, we made a burn wound on the backs of mice and topically applied either Vaseline (vehicle) alone or Vaseline containing low doses of ginsenoside Rb1 to the wound. 2. Surprisingly, we found that ginsenoside Rb1 at low concentrations (100 pg g(-1), 1 pg g(-1) and 10 fg g(-1) ointment) exhibited the strongest burn wound-healing action. Furthermore, ginsenoside Rb1 (100 fg-1 ng per wound) increased neovascularization in the surrounding tissue and production of vascular endothelial growth factor (VEGF) and interleukin (IL)-1beta from the burn wound, compared to those mice with burn wounds treated with vehicle alone. 3. In human keratinocyte cultures (HaCaT cells), ginsenoside Rb1 (100 fg ml(-1) to 1 ng ml(-1)) enhanced VEGF production induced by IL-1beta and expression of hypoxia-inducible factor (HIF)-1alpha. 4. These findings suggest that the promotion of burn wound healing by ginsenoside Rb1 might be due to the promotion of angiogenesis during skin wound repair via the stimulation of VEGF production, through the increase of HIF-1alpha expression in keratinocytes, and due to the elevation of IL-1beta resulting from the macrophage accumulation in the burn wound.
Kimura
Yoshiyuki
Y
Division of Biochemical Pharmacology, Department of Fundamental Medical Science, Ehime University School of Medicine, Shitsukawa, Toon City, Ehime 791-0295, Japan. yokim@m.ehime-u.ac.jp
Sumiyoshi
Maho
M
Kawahira
Kazuhiro
K
Sakanaka
Masahiro
M
D000818:Animals; D002056:Burns / Q000188:drug therapy*; D002460:Cell Line; D036145:Ginsenosides / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000032:analysis; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018919:Neovascularization, Physiologic / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000096:biosynthesis; D014945:Wound Healing / Q000187:drug effects*
D036145:Ginsenosides; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007375:Interleukin-1; D019394:Ki-67 Antigen; D042461:Vascular Endothelial Growth Factor A; C442759:ginsenoside Rb1