Ginsenoside Rg3 inhibits phenylephrine-induced vascular contraction through induction of nitric oxide synthase.
Ginsenoside Rg3 (Rg3) isolated from Panax ginseng relaxes vessels and exerts a cytoprotective effect. In view of the fact that nitric oxide (NO) is involved in vascular hyporeactivity and immunostimulation, the effects of total ginsenosides (GS) and Rg3 on the vascular responses and the expression of inducible nitric oxide synthase (iNOS) were investigated. Vasocontraction of endothelium-denuded aortic ring was induced by phenylephrine with or without GS or Rg3. The expression of iNOS was assessed by Western blot and RT-PCR analyses. NF-kappaB activation was monitored by gel shift, immunoblot and immunocytochemical analyses. Incubation of the endothelium-denuded aortic ring with GS or Rg3 inhibited phenylephrine-induced vasocontraction, which was abrogated by NOS inhibition. GS or Rg3 increased NO production in aortic rings, but Rb1, Rc, Re and Rg1 had no effect. Aortic rings obtained from rats treated with GS or Rg3 responded to phenylnephrine to a lesser extent, while producing NO to a larger extent, than those from control animals. GS or Rg3 induced iNOS in vascular smooth muscle. Rg3 induced iNOS with increase in NO production in Raw264.7 cells. Rg3 increased NF-kappaB DNA binding, whose band was supershifted with anti-p65 and anti-p50 antibodies, and elicited p65 nuclear translocation, which was accompanied by phosphorylation and degradation of I-kappaBalpha. PKC regulated iNOS induction by Rg3. In conclusion, Rg3 relaxes vessels as a consequence of NO production, to which iNOS induction contributes, and iNOS induction by Rg3 accompanied NF-kappaB activation, which involves phosphorylation and degradation of I-kappaBalpha and nuclear translocation of p65.
Kim
Nak Doo
ND
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Sillim-dong, Kwanak-gu, Seoul 151-742, South Korea. ndk@snu.ac.kr
Kim
Eun Mi
EM
Kang
Keon Wook
KW
Cho
Min Kyung
MK
Choi
So Yeon
SY
Kim
Sang Geon
SG
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000293:injuries / Q000378:metabolism; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000293:injuries; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D036145:Ginsenosides / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D020672:I-kappa B Proteins / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D005894:Panax / Q000737:chemistry; D010656:Phenylephrine / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D051996:Transcription Factor RelA
D036145:Ginsenosides; D020672:I-kappa B Proteins; D016328:NF-kappa B; D051996:Transcription Factor RelA; D010656:Phenylephrine; C097367:ginsenoside Rg3; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase