• Proceedings of the Ginseng society Conference
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• 1993.09a
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• pp.40-48
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• 1993

Intravenous administration of saponin extracted from the root of Panax ginseng lowered the blood pressure dose-dependently (10-200 mg/kg, B.W) in anesthetized rats. Therefore, experiments were designed to study the hypothesis that the lowering of blood pressure is associated with the release of endothelium-derived relaxing factor and the accumulation of guanosine 3, 5-cyclic monophosphate (cGMP). Rings of thoracic aorta with and without endothelium were suspended for the measurement of isometric tension in organ chamber and the tissue content of cGMP was measured by radioimmunoassay. All experiments were performed in the presence of $indomethacin(10^{-5}M).$ Ginseng saponin $(10^{-5}-3{\times}10^{-6}g/ml)$ relaxed contractions induced by phenylephrine $10^{-6}M)$ in the aorta with endothelium but not in that without endothelium. Treatment of aortic rings with $N^G$ monomethyl-L-arginine (L-NMMA, $10^{-4}M$ for 30 min), a competitive inhibitor of nitric oxide synthase, and methylene blue $(MB,\;3{\times}10^{-7}M$ for 30 min). an inhibitor of soluble guanylate cyclase, diminished the relaxation induced by Ginseng saponin. Ginseng saponin $10^{-4}g/ml$ for 2 min) increased the accumulation of cGMP in rings with endothelium. L-NMMA and MB inhibited the accumulation of cGMP induced by Ginseng saponin. These data suggest that vascular relaxations induced by Ginseng saponin are mediated by release of endothelium-derived relaxing factor and the accumulation of cGMP. The effect of Ginseng saponin on endothelial function in hypercholesterolemic rabbits was examined. In hypercholesterolemic rabbits fed with $2\%$ cholesterol for 8 weeks, relaxation of aortic rings to acetylcholine was impaired. The impaired relaxations of aortic rings in hypercholesterolemic rabbits were improved by dietary supplementation of Ginseng saponin, probably because of an improved release of endothelium - derived relaxing factor.

• Bulletin of the Korean Chemical Society
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• v.31 no.11
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• pp.3327-3332
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• 2010

We investigated the effects of newly synthesized 4-[(butylsulfinyl)methyl]-1,2-benzenediol (SMBD) on the prevention of atherosclerosis in hypercholesterolemic rabbits. SMBD exhibited stronger inhibition of $Cu^{2+}$-induced low-density lipoprotein oxidation than that of ascorbic acid or simvastatin. Three-month-old rabbits were fed an atherogenic diet containing 0.5% cholesterol and 10% coconut oil, while other two groups were given an atherogenic diet with intravenous injection of either simvastatin or SMBD (0.33 mg/kg/day) for 4 weeks. The concentrations of plasma cholesterol and thiobarbituric acid reactive substances were significantly decreased in SMBD groups, compared to the control group. Also, aortic lipid level in the SMBD group significantly lower than that in the control group. Furthermore, compared with the control group, the SMBD group significantly inhibited the increase of aortic intimal thickness by 36% via reducing of aortic reactive oxygen species and cyclooxygenase-2 protein levels. We conclude that raised antioxidant effect of SMBD results in significant prevention against hypercholesterolemia.

• YAKHAK HOEJI
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• v.44 no.1
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• pp.71-79
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• 2000

Curcumin, the yellow pigment in turmeric, curry and mustard, has anti-inflammatory and anti-carcinogenic activities. In this study; we investigated the hypocholesterolemic and anti-atherogenic effect of curcumin in rabbits. Hypercholesterolemia was induced by feeding high cholesterol diet to male rabbits for 30 days, and the animals were then fed high cholesterol diet containing 0.1% (w/w) or 0.5% (w/w) curcumin for additional 30 days. Supplementation of 0.l% curcumin tended to lower serum total cholesterol and low density lipoprotein (LDL)-cholesterol levels and inhibit serum lipid peroxidation. In the 0.5% curcumin-supplemented group, serum total cholesterol was significantly lowered by 11.7%, LDL-cholesterol by 12.8% and lipid peroxidation by 47.9% compared to the control group. Hepatic cholesterol and triglyceride contents were also significantly lowered by 50.6% and 37.4%, respectively compared to the control group. Lipid staining of the arteries isolated from the curcumin-treated rabbits showed that curcumin significantly decreased formation of fatty streaks and atheromatous plaques on the intima of the arteries. These results demonstrated that curcumin lowered serum cholesterol concentration, hepatic cholesterol and triglyceride contents, and accumulation of cholesterol in the artery These cholesterol lowering effects of curcumin, together with its anti-oxidative and anti-inflammatory activities, may play some important roles in preventing atherosclerosis.

• Nutrition Research and Practice
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• v.4 no.2
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• pp.114-120
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• 2010

The effects of grape seeds extract and grape peels extract prepared from grape pomace on the activity of antioxidant enzymes, degree of lipid peroxidation in serum and liver tissue were investigated in rabbits fed on high cholesterol diet. New Zealand white rabbits were divided as follows ; 1) NOR (normal group); 2) CHOL (cholesterol group); 3) GSH (cholesterol + grape seed extract group); 4) GPE (cholesterol + grape peel extract); 5) GSP (cholesterol + grape seed powder); 6) GPP (cholesterol + grape peel powder); 7) GE (cholesterol + grape seed and peel extract); 8) GP (cholesterol + grape seed and peel powder). Eight groups of rabbits were studied for 8 weeks. At the end of the experimental period, rabbits were sacrificed and the liver tissue were removed. Then, GSH, GPx, GST, CAT and MDA in the liver were measured. In liver tissues, total glutathione contents (GSH), glutathione peroxidase (GPx) and catalase (CAT) activity, which was significantly higher by grape seed extract supplementation. The level of malondialdehyde (MDA) was lower in the serum of rabbits fed grape seed extract or grape peel powder plus cholesterol than in the serum of rabbits fed cholesterol alone. It is therefore likely that grape seed extract prepared from grape pomace functioned as antioxidants in vivo, negating the effects of the oxidative stress induced by 1% cholesterol diet. The grape seed extract was found effective in converting the oxidized glutathione into reduced glutathione, and in removing $H_2O_2$ that is created by oxidative stress. The grape peel powder was found to have small influence on reduced glutathione content, CAT and GPX activity, but it increased GST activity in liver tissues, resulting in promoting the combination of lipid peroxide and glutathione (GSH), and further, lowering the formation of lipid peroxide in the serum. Therefore, grape pomace (grape seed extract and grape peel powder) supplementation is considered to activate the antioxidant enzyme system and prevent damage with hypercholesterolemia.

• Biomolecules & Therapeutics
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• v.19 no.4
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• pp.472-476
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• 2011

Hypercholesterolemia indirectly increases the risk of arterial and venous thrombosis by enhancing the ability of platelets to aggregate. Yacon (Smallanthus sonchifolius) is composed of fructooligosaccharides, proteins, minerals and phenolic compounds, and has potential benefits for the management of diabetes. This study investigated whether the consumption of yacon in the diet inhibits platelet aggregation under hypercholesterolemic conditions. Male New Zealand white rabbits were fed one of five dietary interventions: a normal control diet, 0.5% cholesterol diet, 0.5% cholesterol diet+a low dose of yacon (0.5 g/kg body weight given orally each day), 0.5% cholesterol diet+a high dose of yacon (2.5 g/kg body weight given orally each day), or a 0.5% cholesterol diet+lovastatin (2 mg/kg body weight given orally each day). After 8 weeks, blood was collected to measure the amount of collagen- and thrombin-induced platelets present. Yacon inhibited the platelet aggregation induced by low doses of agonists (0.5 ${\mu}g/mL$ collagen and 0.02 units/ml thrombin) in a concentration-dependent manner. In addition, yacon concentration-dependently inhibited collagen-induced arachidonic acid liberation. Moreover, n-hexane, chloroform and ethyl acetate fractions showed a marked and selective inhibition of the platelet aggregation induced by collagen, again in a dose-dependent manner. These fractions, especially that of chloroform, significantly suppressed platelet aggregation. The results of this study demonstrate that when yacon is added to a cholesterol-enriched diet, cholesterol-induced platelet aggregation returns to control levels. This may also be beneficial in preventing atherosclerosis and reducing risk factors for coronary artery disease and stroke.

• Biomedical Science Letters
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• v.11 no.3
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• pp.383-388
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• 2005

This study reports that the effect of Mori radicis cortex, Mulberry root-bark, on the lipid peroxidation products formation in the liver, blood serum and atherosclerosis of hypercholesterolemia rabbits fed Mulberry root-bark for eight weeks. The rabbits were permitted a fixed quantity to extract of Mulberry root-bark mixed hypercholesterol fodder. The lipid peroxidation products, malondialdehyde (MDA) was significantly diminished. Total cholesterol in serum worthily decreased. Also, triglyceride and high density lipoproteins (HDLs) increased after feeding Mori radicis cortex. Besides, thicky atheromatous plaque on the wall of aorta of rabbits fed on hypercholesterol diet were markedly attenuated by Mulberry root-bark extract. These results support and substantiate the extract of Mulberry root-bark as protection against lipid peroxidation in the liver, blood serum and atherosclerosis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.2
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• pp.380-388
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• 2002

The inhibitory effects of the traditional herbal medicine Hwao-tang on the progression of the atherosclerotic lesions were studied using the spontaneous familial hypercholesterolemia (FH) model, Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbits. Hwao-tang is activate blood circulation, vital energy and regulate menstruation, etc. Nowadays, Hwao-tang is mainly used for the treatment of inflammation, hyperlipemia and arteriosclerosis. However, pharmacological mechanisms of Hwao-tang on lipid metabolism and atherosclerosis formation are poorly understood. We have investigated the pharmacological effects of Hwao-tang on hypercholesterolemia and atherosclerosis using a spontaneous experimental model. In conclusion, the protection of extracts of HOT and its herbs on the ischemic infarction induced artificially might be related to their inhibitory effects on DIC, platelet coagulation and thrombic action. These suggest that Hwao-tang has inhibitory effects on the development of atheromatous plaque formation in spontaneous FH model rabbits. It is possible that the anti oxidative effects of Hwao-tang on LDL led to the beneficial effects observed in this study.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.1
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• pp.181-185
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• 2002

The thrombosis is the category of blood stasis. Blood stasis is a pathologicial state resulting from the reverse or impeded flow of blood in the body or the stagnation of blood flow in local parts as well as abnormal blood outside of the vessles which remains in the body and fails to disperse. Hwao-tang has been reported to have a hypolipidemic effect in patients with hypercholesterolemia, and in highcholesterol-induced experimental models. The present paper reports the effects of HOT on atherosclerosis using a spontaneous experimental model, Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbits. We have also investigated the pharmacological effect of extracts obtained from HOT on collagen-and ADP-induced blood platelet aggregation, thrombin-induced conversion of fibrinogen and fibrinolysis in in vitro experiments. In conclusion, the protection of extracts of Korean herbs' HOT on the ischemic infarction induced artificially might be involved to their inhibition of thrombotic action.

• Journal of Chest Surgery
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• v.41 no.6
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• pp.687-694
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• 2008

Background: Although aortic valve sclerosis causes no significant hemodynamic alterations, it is associated with an increased risk of cardiovascular death and myocardial infarction. However, the role of ${\beta}_3$ integrin in aortic valve sclerosis remains unclear. Material and Method: Twenty male New Zealand rabbits were divided into two groups. Group 1 rabbits (n=10) received a normal chow diet, while group 2 (n=10) rabbits received a diet containing 1% cholesterol for 12 weeks. After the rabbits were euthanized, their aortic valves and ascending aortas were excised for analysis. Result: Total serum cholesterol ($2,148.3{\pm}1,012.5\;mg/dL$ versus $53.7{\pm}31.8\;mg/dL$, p<0.05), triglyceride ($240.4{\pm}218.3\;mg/dL$ versus $31.6{\pm}6.4\;mg/dL$, p<0.05), and low density lipoprotein (LDL)-cholesterol($2,065.3{\pm}960.9\;mg/dL$ versus $29.1{\pm}30.9\;mg/dL$, p<0.05) levels were significantly higher in the cholesterol diet group compared with the normal diet group. Myofibroblasts and macrophages were more highly expressed in the aortic valve leaflets of rabbits in the cholesterol diet group than of those in the normal diet group. A real-time polymerase chain reaction revealed decreased ${\beta}_3$ integrin mRNA levels in the hypercholesterolemic aortic valves and aortas. Conclusion: The present study shows that hypercholesterolemia induces aortic valve sclerosis. These findings suggest that alterations in ${\beta}_3$ integrin may playa role in the development of aortic valve sclerosis.

• BMB Reports
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• v.35 no.2
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• pp.172-177
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• 2002

We previously reported that cholesteryl ester transfer protein (CETP) inhibitory peptides (designated $P_{28}$ and $P_{10})$ have anti-atherogenic effects in hypercholesterolemic rabbits (Biochim. Biophys. Acta (1998) 1391, 133-144). To further investigate those effects, we studied rabbit plasma that was collected after 30 h of a $P_{28}$ or $P_{10}$ injection. We found that there is a strong correlation between the in vivo CETP inhibition effects and alterations of lipoprotein particle size distribution in rabbit plasma, as determined on an agarose gel electrophoresis and gel filtration column chromatography. In vivo effects of the peptide were observed again in C57BL/6 mice that expressed simian CETP. The $P_{28}$ or $P_{10}$ peptide ($7\;{\mu}g/g$ of body weight) that was dissolved in saline was injected subcutaneously into the mice. The $P_{28}$ injection caused the partial inhibition of plasma CETP activity up to 50%, decreasing the total plasma cholesterol concentration by 30%, and increasing the ratio of HD/total-cholesterol concentration by 150% in the CETP-transgenic (tg) mice. The CETP inhibition by the $P_{28}$ or $P_{10}$ made alterations that modulated the size re-distribution of the lipoproteins in the blood stream. Particle size of the very low (VLDL) and low density lipoproteins (LDL) from the peptide-injected group was highly decreased compared to the saline-injected group (determined on the gel filtration column chromatography). In contrast, The HDL particle size of the $P_{28}$-injected group increased compared to the control group (saline-injected). The expression level of the CETP mRNA of the $P_{28}$-injected CETP-tg mouse appeared lower than the saline-injected CETP-tg mouse. These results suggest that the injection of the CETP inhibitory peptide could affect the CETP expression level in the liver by influencing lipoprotein metabolism.