• Journal of Ginseng Research
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• v.21 no.2
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• pp.125-132
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• 1997

Our previous study showed that in vivo treatment of spontaneously hypertensive rats (SHR) with protopanaxatriol ginsenosides (PPT) reduces the blood pressure and inhibits the con- tractions induced by endothelium-derived contracting factor (prostaglandin endoperoxide ($PGH_2$) and superoxide anion) in aorta isolated from SHR. The aim of the present study is to examine whether PPT improves endothelial functions in the isolated thoracic aorta of SHR in vitro. Treatments of aortic rings with PPT, purified ginsenoside $Rg_1$ ($Rg_1$) or indomethacin normalized endotheliuln-dependent relaxation to acetylcholine, but not with protopanaxadiol ginsenosides (PPD) and purified ginsenoside Rb1 (Rb1). The effects of PPT were dose-dependent. PGH,- and oxygen free radical-inducted contractions in rat aorta without endothelium were inhibited by PPT or $Rg_1$, but not by PPD or $Rb_1$. Contractions induced by PGF2$\alpha$, U-46619, a stable thromboxane A2 agonist or KCI (60 mM) were not inhibited by PPT, $Rg_1$ or $Rb_1$. These findings demonstrate that PPT but not PPD scavenges the oxygen-derived free radicals and/or antagonize the effects of $PGH_2$ in the vascular smooth muscle and may explain the hypotensive effect of ginseng in the SHR.

• Journal of Ginseng Research
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• v.21 no.2
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• pp.119-124
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• 1997

Chronic hypertension is associated with impaired endothelial function such as reduced synthesis/release of endothelium-derived relaxing factor(EDRF, nitric oxide) and increased synthesis/release of endothelium-derived contracting factor(EDCF) including prostaglandin endoperoxide($PGH_2$) , superoxide anion both in animals and in humans. We have previously shown that ginsenosides lower the blood pressure and enhance the release of nitric oxide(NO) from endothelial cells in the rat aorta of the normotensive rats. The aim of the present study is to examine whether in vivo treatment of spontaneously hypertensive rats(SHRs) with protopanaxatriol ginsenosides(PPT) reduces the blood pressure and improves endothelial function in the isolated thoracic aorta of SHR. In addition, the contractile response to $PGH_2$ and superoxide anion in the aorta treated with PPT was assessed. SHRs at the age of 16 weeks were savaged with PPT(30 mg/kg/ day) for 2 weeks and systolic blood pressure was measured by the tail-cuff method. Whereas blood pressure was significantly increased in SHRs by 5.4 mmHg during this period of treatment, treatment of SHRs with PPT blocked the elevation of blood pressure. Endothelium-dependent relaxation to acetylcholine was significantly increased in the PPT-treated animals. $PGH_2$- and oxygen-derived free radical-induced contractions were significantly suppressed in aortic rings without endothelium from PPT-treated SHR. These findings indicate that PPT reduces the blood pressure of SHR, which may be associated with either increase of NO release or by antagonizing superoxide anion and PGH2 in the aortic smooth muscle.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2001.11a
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• pp.94-94
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• 2001

Prostaglandin endoperoxide H synthase (PGHS) catalyzes the committed step in prostaglandins and thromboxane A$_2$-- oxygenation of arachidonic acid to the hydroperoxy endoperoxide PGG$_2$, followed by reduction PGG$_2$to the alcohol PGH$_2$. The two reactions by PGHS -- cyclooxygenase and peroxidase -- occur at distinct but structurally and functionally interconnected sites. The peroxidase reaction occurs at a heme-containing active site located near the protein surface. The cyclooxygenase reaction occurs in a hydrophobic channel in the core of the enzyme. Initially a peroxide reacts with the heme group, yielding Compound I and an alcohol derived from the oxidizing peroxide. Compound I next undergoes an intramolecular reduction by a single electron traveling from Tyr385 along the peptide chain to the proximal heme ligand, His388, and finally to the heme group. Following the binding of arachidonic acid, Tyr385 tyrosyl radical initiates the cyclooxygenase reaction by abstracting the 13-pro(5) hydrogen atom to give an arachidonyl radical, which sequentially reacts with two molecules of oxygen to yield PGG$_2$. In order to characterize PGHS peroxidase active site, we examined various lipid peroxides with purified recombinant ovine PGHS proteins and determined the rate constants. The results have shown that twenty-carbon unsaturated fatty acid hydroperoxides have similar efficiency in peroxidation by PGHS, irrespective of either the location of hydroperoxy group or the number of double bonds. It was also confirmed by the subsequent study with PGHS peroxidase active site mutants.

• Journal of Ginseng Research
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• v.13 no.2
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• pp.202-210
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• 1989

The effects of Ginseng saponins on the in vitro biosynthesis of prostaglandins were examined in order to identify the role of some Ginseng components on the regulation of arachidonic arid metabolism. The productions of prostaglandin $E_2$ (PG$E_2$), $F_2$ (PGF2), thromboxane $B_2$(TX$B_2$) and 6-ketoprostaglandin Fl (6-Keto-PGF1) from [3Hl-arachidonic acid were evaluatpf by radiochromatographic analysis with rabbit kidney microtome, human platelet homogenate and bovine aortic microsome. The amounts of the total prostaglandins produced by cyclooxygenase activity and malondialdehyde from arachidonic acid didn't show significant changes in the presence of Ginseng saponins. Both of panaxadiol and panaxatriol didn't affect the production of PG$E_2$ while the formations of PG$F_2$( and TX$B_2$( were nearkedly reduced and the production of prostacyclin was increased. The formation of TXBE was reduced by ginsenoside $Rb_2$, Rc, and Re, however the production of 6-Keto-PGF1 was increased dose dependently up to 1 mg/ml. Moreover, platelet aggregations induced by arachidonic acid and U46619 (9.11-methanepoxy PG$H_2$), TX$A_2$ mimetics, were also inhibited by three ginsenosides. The effect of G-Re on prostacyclin synthetase was inhibited by tranylcypromine, prostacyclin synthetase inhibitor. These results suggest that Ginseng saponins may not directly act on cyclooxygenase but affect on the divergent pathway from endoperoxide.