• Journal of Microbiology and Biotechnology
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• v.14 no.6
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• pp.1318-1323
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• 2004

This study describes the purification and characterization of a novel antihypertensive angiotensin 1­converting enzyme (ACE) inhibitory peptide from Saccharomyces cerevisiae. Maximal production of the ACE inhibitor from Saccharomyces cerevisiae was obtained from 24 h of cultivation at $30^{\circ}C$ and its ACE inhibitory activity was increased by about 1.5 times after treatment of the cell-free extract with pepsin. After the purification of ACE inhibitory peptides with ultrafiltration, Sephadex G-25 column chromatography, and reverse-phase HPLC, an active fraction with an $IC_{50}$ of 0.07 mg and $3.5\%$ yield was obtained. The purified peptide was a novel decapeptide, showing very low similarity to other ACE inhibitory peptide sequences, and its amino acid sequence was Tyr-Asp-Gly-Gly-Val-Phe-Arg-Val-Tyr-Thr. The purified inhibitor competitively inhibited ACE and also showed a clear antihypertensive effect in spontaneously hypertensive rats (SHR) at a dosage of 1 mg/kg body weight.

• Journal of Microbiology and Biotechnology
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• v.16 no.5
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• pp.757-763
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• 2006

Angiotensin I-converting enzyme (ACE) inhibitors have generally been very useful to remedy or prevent hypertension. This study describes the extraction and characterization of an ACE inhibitor from the fruiting body of Pholiota adiposa ASI 24012, which can be used as an antihypertensive drug. The maximal ACE inhibitory activity $(IC_{50};0.25mg)$ was obtained when the fruiting body of Pholiota adiposa ASI 24012 was extracted with distilled water at $30^{\circ}C$ for 12 h. After the purification of ACE inhibitor with ultrafiltration, Sephadex G-25 column chromatography, and reverse-phase HPLC, an active fraction with an $IC_{50}$ of 0.044 mg was obtained. The purified ACE inhibitory peptide was a novel pentapeptide, showing very little similarity to other ACE inhibitory peptide sequences. The molecular mass of the purified ACE inhibitor was estimated to be 414 daltons with a sequence of Gly-Glu-Gly-Gly-Pro, and showed a clear antihypertensive effect on spontaneously hypertensive rats (SHR) at a dosage of 1 mg/kg.

• Asian-Australasian Journal of Animal Sciences
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• v.16 no.9
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• pp.1369-1373
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• 2003

ACE (Angiotensin-I converting enzyme) inhibitory peptides derived from foods are thought to suppress high blood pressure by inhibiting ACE. We tried to make efficient production of the ACE inhibitory hydrolysate from egg albumen. A hydrolysate digested by neutrase presented the highest ACE inhibitory activity ($IC_50\;value=256.35{\mu}g/ml$) and the proper proteolysis was occurred by 1.0% enzyme addition and 4 h incubation at $47^{\circ}C$. Antihypertensive effect of neutrase hydrolysate was investigated in spontaneously hypertensive rats (SHR, n=5). Systolic blood pressure (SBP) was decrease by 6.88% (-14.14 mmHg, p<0.05) at 3 h after oral administration of 300 mg/kg body weight, and by 13.33% (-27.72 mmHg, p<0.05) by emulsified hydrolysate. These results showed that it is very effective to utilize egg albumen as a protein source for the production of ACE inhibitory peptides. However, further studies are required to investigate the methods to increase recovery yield and the isolation of active peptide is necessary for determining its sequence responsible for ACE inhibitory activity.

• Korean Journal of Pharmacognosy
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• v.36 no.1 s.140
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• pp.17-20
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• 2005

We previously reported that the exogenous administration of cumambrin A, a sesquiterpene lactone from the dried flowers of Chrysanthemum boreale Makino has a pharmacological effect on normalization of blood pressure in the spontaneously hypertensive rats (SHR). In the present study, we further investigated the effect of cumambrin A on the relaxation of phenylephrine-induced precontracted rat aortic artery rings. The potency of cumambrin A was than compared to verapamil, a well known $Ca^{2+}-channel$ blocker. The results demonstrate that the isolated rat aortic arteries are relaxed to basal tension at a concentration of $5{\times}10^{-5}\;M$ cumambrin A treatment. The results also show that the phenylephrine-induced contraction is inhibited by a pretreatment of cumambrin A. Co-treatment of cumambrin A and verapamil showed a strong synergetic effect on the relaxation of rat aortic artery rings. Thus, these data demonstrate that cumambrin A is a potent relaxant of rat aortic smooth muscle and suggest that cumambrin A modulates intracellular or extracellular $Ca^{2+}$ mobilization.

• Biomolecules & Therapeutics
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• v.5 no.4
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• pp.390-401
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• 1997

In order to investigate the pharmacological properties of New Woohwangchungsimwon Liquid (NCL), effects of Woohwangchungsimwon Liquid (CL) and NCL were compared. In isolated rat aorta, NCL and CL showed the relaxation of blood vessels in maximum contractile response to phenylephrine (10$^{-6}$ M) without regard to intact endothelium or denuded rings of the rat aorta. Furthermore, the presences of the inhibitor of NO synthase and guanylate cyclase did not affect the relaxation of NCL and CL. NCL and CL inhibited the vascular contractions induced by acetylcholine, prostaglandin endoperoxide or peroxide in a dose-dependent manner. In conscious spontaneously hypertensive rats (SHRs), NCL and CL significantly decreased heart rate. NCL and CL, at high doses, had a negative inotropic effect that was a decrease of LVDP and (-dp/dt)/(+dp/dt) in the isolated perfused rat hearts, and also decreased the contractile force and heart rate in the isolated rat right atria. In excised guinea-pig papillary muscle, NCL and CL had no effects on parameters of action potential at low doses, whereas inhibited the cardiac contractility at high doses. These results suggested that NCL and CL have weak cardiovascular effects with relaxation of blood vessels and decrease of heart rate, and that this effect is no significant differences between two preparations.

• Journal of Ginseng Research
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• v.32 no.2
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• pp.89-98
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• 2008

There are increasing evidences in the literatures on the potential role of ginsenosides in treating cardiovascular diseases. In this article, current information about ginsenosides-mediated vascular relaxation are reviewed. From the published studies using isolated organs, cell culture systems and animal models, ginsenosides are shown to relax blood vessels and improve blood flow through diverse mechanisms, including nitric oxide release by activating eNOS phosphorylation via PI3K/Akt and/or ERK1/2 pathways in endothelial cells, induction of inducible nitric oxide synthase through activation of NF-${\kappa}$B, reducing the intracelluar Ca$^{2+}$ levels by activating Ca$^{2+}$-activated K$^{+}$ channels in vascular smooth muscle cells and reducing platelet aggregation by decreasing thromboxane A$_2$ formation and intracelluar Ca$^{2+}$in platelets. In addition, the relevant clinical trials regarding the effects of ginsenosides on the cardiovascular disease are summarized, particulary focusing on managing hypertension and improving thrombotic disorders. Finally, antagonistic effects of ginsenosides on the prostaglandin H$_2$ receptor and scavenging effects on the generation of oxygen-derived free radicals in spontaneously hypertensive rats (SHR) are discussed.

• YAKHAK HOEJI
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• v.56 no.5
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• pp.309-313
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• 2012

Antiobesity, hypotriglyceridemic and antihypertensive activities of isoflavone-free peptide mixture (black soybean peptide, BSP) were reported in our previous experiments. In the present study, angiotensin converting enzyme inhibitory (ACEi) activity was decreased in the aorta tissues of spontaneously hypertensive rats (SHRs) treated with BSP (1% in drink water) for 4 weeks, but not in serum. BSP administration significantly decreased ACE activity by 17.5% (from $33.2{\pm}4.5$ to $27.4{\pm}1.96$ mUnit/mg, p=0.0013) in aorta tissue hydrolysate. BSP treatment also decreased significantly mean blood pressure (BP) (from $213.0{\pm}16.96$ to $184.0{\pm}6.53$ mmHg, p<0.0001) as expected. These results indicate that BSP has antihypertensive activity as well as ACEi activity.

• Biomolecules & Therapeutics
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• v.7 no.1
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• pp.66-78
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• 1999

In order to investigate the pharmacological properties of New Wonbang Woohwangchungsimwon Liquid (NSCL), effects of Wonbang Woohwangchungsimwon Liquid (SCL) and NSCL were compared. In isolated rat aorta, NSCL and SCL showed the relaxation of blood vessels in maximum contractile response to phenylephrine (10$^{-6}$ M) regardless to intact endothelium or denuded rings of the rat aorta. Furthermore, the presences of the inhibitor of NO synthase and guanylate cyclase did not affect the relaxing effect of NSCL and SCL. NSCL and SCL inhibited the vascular contractions induced by acetylcholine, prostaglandin endoperoxide or peroxide in a dose-dependent manner. In conscious spontaneously hypertensive rats (SHRs), NSCL and SCL significantly decreased heart rate. NSCL and SCL, at high doses, had a negative inotropic effect that was a decrease of left ventricular developed pressure and (-dp/dt)/(+dp/dt) in the isolated perfused rat hearts, and also decreased the contractile force and heart rate in the isolated rat right atria. In excised guinea-pig papillary muscle, NSCL and SCL had no effects on parameters of action potential such as resting membrane potential, action potential amplitude, APD$_{90}$ and V$_{max}$ at low doses, whereas inhibited the cardiac contractility at high doses. These results suggested that NSCL and SCL have weak cardiovascular effects with relaxation of blood vessels and decrease of heart rate, and that this effect is no significant differences between cardiovascular effects of two preparations.s.

• Korean Journal of Food Science and Technology
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• v.26 no.3
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• pp.213-220
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• 1994

Gastrodia (G) Rhizoma has been used clinically as an oriental herbal medicine with sedative, anticonvulsive, and depressor effects. The present study tested effects of G. Rhizoma extracts on the coronary circulation and myocardial oxygen consumption in perfused rat hearts. Sprague Dawley rats (SD) and spontaneously hypertensive rats (SHR) were employed as experimental animals and nonworking Langendorff heart perfusion technique introduced for heart experiments. G. Rhizoma extracts were prepared from grinding G. Rhizoma into powder, extracting in water and 50% ethanol for 4 or 16 hr and diluting with Krebs-Henseleit bicarbonate perfusion buffer to be 70%. Hearts were perfused with bicarbonate buffer oxygenated with 95% $O_{2}:$ 5% $CO_{2}$ at constant coronary perfusion pressure of $90cmH_{2}O$. The diluted extracts were infused into coronary arteries in a concentration of $1{\sim}5\;{\mu}M$ for $7{\sim}8 min. While in SD water- or ethanol-extracts of G. Rhizoma extracted for 16 hr increased coronary perfusate flow (CPF) and decreased coronary vascular resistance (CVR), ethanol-extracts in SHR produced coronary vasoconstriction associated with enhanced CVR. G. Rhizoma extracts-induced increase in CPF reduced myocardial oxygen extraction, and thus myocardial oxygen consumption ($MVO_{2}$) remained at that observed prior to infusion of extracts. In SD and SHR 16 hr-water-extracts markedly altered coronary venous effluent pH and $Pco_{2}$ and evoked metabolic acidosis, which could be a coronary vasodilator mechanism decreasing CVR. In this study, the extracts decreasing CVR in SD and SHR did not augment the lactate production. Therefore, although the effects of the extracts on cardiac function and coronary circulation depended on solvents and duration for extraction, the 16hr-water-extracts, at least, exhibited coronary vasodilation in SD and SHR. Conversely, ethanol-extracts constricted coronary arteries in SHR. G. Rhizoma extracts-induced vasodilation might be due to the metabolic acidosis rather than due to the increased lactate production. The results indicate that G. Rhizoma extracts obtained from proper extracting procedures can be used as a safe and clinically applicable herbal medicine in the cardiovascular diseases such as coronary artery disease and hypertension for vasodilatory and antihypertensive actions.

• Journal of Acupuncture Research
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• v.22 no.2
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• pp.13-18
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• 2005

This study was undertaken to investigate the effects of electroacupuncture(EA) on Choksamni(ST36), a well-known acupuncture site, on nicotinamide adenine dinucleotide phosphate-diaphorase(NADPH-d), neuropeptide Y(NPY) and vasoactive intestinal peptide(VIP) in the cerebral cortex of spontaneously hypertensive rats(SHR). EA on Choksamni was applied using 2Hz electrical biphasic pulses of 10min, 3 times a week for a total of 10 sessions. Thereafter we evaluated changes in NADPH-d-positive neurons histochemically and changes in NPY and VIP-positive neurons immunohistochemically. The optical density of NADPH-d-positive neurons in the Choksamni group was significantly lower in all areas of the cerebral cortex than in the control group. However, the optical density of NPY-positive neurons in the Choksamni group was similar to that of the controls in most areas of the cerebral cortex, with the exception of the primary motor and visual cortices. The optical density of VIP-positive neurons in the Choksamni group was significantly decreased as compared to the control group in most areas of the cerebral cortex, with the exception of the cingulate cortex. The present results demonstrated that EA on Choksamni changes the activity of the NO system, and that stimulation at the same level, causes selective changes within the peptidergic system in the cerebral cortex of SHR.