• Biomolecules & Therapeutics
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• v.22 no.2
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• pp.100-105
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• 2014

Apigenin, a natural flavonoid found in a variety of vegetables and fruits, has been shown to possess many biological functions. The present study was undertaken to investigate the influence of apigenin on vascular smooth muscle contractility and to determine the mechanism involved. Denuded aortic rings from male rats were used and isometric contractions were recorded and combined with molecular experiments. Apigenin significantly relaxed fluoride-, thromboxane $A_2$ mimetic- or phorbol ester-induced vascular contraction, which suggests that apigenin could be an anti-hypertensive that reduces agonist-induced vascular contraction regardless of endothelial nitric oxide synthesis. Furthermore, apigenin significantly inhibited fluoride-induced increases in pMYPT1 levels and phorbol ester-induced increases in pERK1/2 levels, which suggests the mechanism involving the inhibition of Rho-kinase and MEK activity and the subsequent phosphorylation of MYPT1 and ERK1/2. This study provides evidence regarding the mechanism underlying the relaxation effect of apigenin on agonist-induced vascular contraction regardless of endothelial function.

• 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 Nutrition and Health
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• v.26 no.5
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• pp.513-523
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• 1993

In this experiment, we investigated the hypolipidemic and antithrombotic effects of rats fed diets with different common oils in Korea for different feeding periods(4 weeks or 12 weeks), using Korean sesame oil, perilla oil, rice bran oil and mixed oil. W-3/w-6 ratio of each group was 0.001, 1.44, 0.03 and 0.112, respectively. P/S ratio of each group was 9.64, 10.49, 5.58 and 1.68, respectively. The result were as follows: 1) According to the age, body fat accumulation was increased. 2) Perilla oil(w-3 rich) decreased total lipid, triglyceride and total cholesterol, and increased HDL/total cholesterol ratio. 3) With regard to the compositono of platelet fatty acids, Perilla oil increased w-3/w-6 ratio of the platelet. Perilla oil lengthened bleeding time and decreased MDA(MalonDAdehyde) formation which determined in place of Thromboxane A2(TXA2) in platelet. This result can suggest that linoleic acid of perrilla oil seem to supress the conversion of linoleic acid to arachidonic acid(AA 20:4, w-6) and eicosapentaenoic acid(EPA, 20:5, w-3) trannnsformed from linolenic acid to suppress the conversion of arachidonic acid to TXA2. Since TXA2 is platelet-aggregating and vasoconstricting agent, the reduction of TXA2 tgeneration by platelet with increased linolenic acid intakes shows prologed bleeding time. In conclusion, w-3 rich perilla oil has strong hypolipidemic and antithrombotic effects by changing fatty acid profiles of the platelet.

• Proceedings of the Ginseng society Conference
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• 1993.09a
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• pp.94-101
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• 1993

Lipophilic fraction(LF) from Panax ginseng C.A. Meyer inhibited the aggregation of human platelets induced by th rombin(0.1u/$m{\ell}$). LF and Molsidomine(vasodilator) induced the stimulation of cGMP - elevation and 50KD - Phosphorylation. and then the inhibition of 20KD - Phosphorylation in human platelets activated by thrombin. LF also inhibited the $Ca^{2-}-influx$ into platelets. When rat(SD : male) was fed with LF, the level of cGMP was increased in rat platelets stimulated by collagen and thrombin. On the other hand. verapamil, $Ca^{2-}-antagonist$ increased cAMP level ;n platelet stimulated by thrombin. but LF does not affected. However LF potently inhibited the thromboxane $A_2(TXA_2)$ production. The results suggest that the inhibitory effects of LF are mediated by regulation the phosphorylatior. of 50KD via cGMP-elevation and depend upon the decrease of $TXA_2$ level.

• Journal of Ginseng Research
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• v.35 no.4
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• pp.442-448
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• 2011

We previously reported that in vitro anti-platelet activity of tissue-cultured mountain ginseng (TCMG) ethanol extracts show improved efficacy when compared with commercial ginseng products such as Korean red ginseng and Panax ginseng. However, information on the anti-platelet activity of the ethyl acetate fraction from TCMG adventitious roots is limited. Therefore, in this study, we further investigated the effects of an ethyl acetate extract of TCMG (EA-TCMG) adventitious roots on in vitro antiplatelet activity in whole human blood and its effect on peripheral blood flow in mice. We found that EA-TCMG inhibited platelet aggregation with $IC_{50}$ values of 271, 180, and 147 ${\mu}g$/mL induced by collagen, adenosine-5'-diphosphate, and arachidonic acid, respectively. Among the three agonists used, thromboxane $A_2$ formation induced by arachidonic acid was markedly suppressed. Furthermore, EA-TCMG improved the peripheral circulatory disturbance by improving vascular blood flow. In conclusion, these results suggest that ethyl acetate extracts from TCMG adventitious roots might inhibit vascular platelet aggregation and thrombus formation.

• Biomedical Science Letters
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• v.20 no.2
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• pp.70-76
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• 2014

In this study, we investigated the effect of DMSO, a highly dipolar organic liquid, in collagen ($5{\mu}g/ml$)-stimulated platelet aggregation. DMSO inhibited platelet aggregation at 0.5% by inhibiting production of thromboxane $A_2$ ($TXA_2$) which was associated with blocking cyclooxygenase (COX)-1 activity and $TXA_2$ synthase. In addition, DMSO significantly increased the formation of cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP) and cyclic guanosine monophosphate (cGMP) from guanosine triphosphate (GTP). On the other hand, DMSO (0.1~0.5% concentration) did not affect the LDH release which indicates the cytotoxicity. Based on these results, DMSO has anti-platelet effect by regulation of several platelet signaling pathways, therefore we suggest that DMSO could be a novel strategy on many thrombotic disorders.

• Journal of Nutrition and Health
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• v.33 no.2
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• pp.134-140
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• 2000

This study was performed to investigate the effects of n-3 fatty acids on renal function in male Sprague-Dawley rats of different ages 5-, 15- and 19-months old. The rats were fed a 20%(w/w) lipid diet containing 10% fish oil, compared with control animals fed a 20% lipid diet without fish oil for 4 weeks. The results were as follows: kidney weights were significantly higher in fish oil-fed rats compared to control rats. Plasma levels of total lipid, total cholesterol, and triglyceride markedly increased, with aging and LDL-cholesterol showing a significantly lower level in fish oil-fed rats than control rats. The urinary protein and glomerular filtration rate (GFR) increased with aging. GFR was higher in fish oil-fed rats. However, urinary protein was the same in the two groups. Renal medulla thromboxane B$_2$(TXB$_2$)tended to be lower in fish oil-fed 19-month-old rats. Urinary TXB$_2$and PGE$_2$were found to be higher proteinuria. Light microscopic examination showed interstitial inflammation, tubular atrophy, interstitial fibrosis and glomerular mesangium increase. Although glomerular sclerosis increased with aging, fish oil in the diet had no effect on histological changes. In conclusion, plasma lipid, urinary protein excretion and renal histological change showed a significant increase with aging. The reduction of TXB$_2$in the medulla and increase of GFR caused by fish oil indicated n-3 fatty acid could affect renal function in line with the hypolipidemic effect.

• Korean Journal of Pharmacognosy
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• v.18 no.1
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• pp.5-13
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• 1987

Male rats were fed diets containing perilla oil, sardine oil or corn oil for 15 weeks in order to investigate their antithrombotic effects. Rats given perilla oil and sardine oil diets showed significantly longer bleeding time, and lower level of malondialdehyde generation during thrombin-induced aggregation of platelets than rats given corn oil. With regard to the composition of platelet fatty acid, the ratio of eicosapentaenoic acid(EPA) $(20:5{\omega}3)$ to arachidonic acid $(20:4{\omega}6)$ of perilla oil, sardine oil and corn oil treated rats were 0.54, 0.96 and 0.01, respectively, suggesting that linolenic acid $(18:3{\omega}3)$ of perilla oil was metabolized to EPA which is known to have antithrombotic activity.

• Biomolecules & Therapeutics
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• v.24 no.1
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• pp.57-61
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• 2016

Fisetin, a natural flavonoid found in a variety of vegetables and fruits, has been shown to possess many biological functions. The present study was undertaken to investigate the influence of fisetin on vascular smooth muscle contractility and to determine the mechanism involved. Denuded aortic rings from male rats were used and isometric contractions were recorded and combined with molecular experiments. Fisetin significantly relaxed fluoride-, thromboxane $A_2$- or phorbol ester-induced vascular contraction suggesting as a possible anti-hypertensive on the agonist-induced vascular contraction regardless of endothelial nitric oxide synthesis. Furthermore, fisetin significantly inhibited fluoride-induced increases in pMYPT1 levels and phorbol ester-induced increases in pERK1/2 levels suggesting the mechanism involving the inhibition of Rho-kinase activity and the subsequent phosphorylation of MYPT1 and MEK activity and the subsequent phosphorylation of ERK1/2. This study provides evidence regarding the mechanism underlying the relaxation effect of fisetin on agonist-induced vascular contraction regardless of endothelial function.

• Journal of Applied Biological Chemistry
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• v.62 no.4
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• pp.425-431
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• 2019

Platelet activation is essential for hemostatic process on blood vessel damage. However, excessive platelet activation can cause some cardiovascular diseases including atherosclerosis, thrombosis, and myocardial infarction. Scoparone is commonly encountered in the roots of genus Artemisia or Scopolia, and has been studied for its potential pharmacological properties including immunosuppression and vasorelaxation, but antiplatelet effects of scoparone have not been reported yet. We investigated the effect of scoparone on human platelet activation prompted by an analogue of thromboxane A₂, U46619. As the results, scoparone dose-dependently increased cyclic adenosine monophosphate (cAMP) levels as well as cyclic guanosine monophosphate (cGMP) levels, both being aggregation-inhibiting molecules. In addition, scoparone strongly phosphorylated inositol 1, 4, 5-triphosphate receptor (IP3R) and vasodilator-stimulated phosphoprotein (VASP), substrates of cAMP dependent kinase and cGMP dependent kinase. Phosphorylation of IP₃R by scoparone resulted in inhibition of Ca²⁺ mobilization in calcium channels in a dense tubular system, and phosphorylation of VASP by scoparone led to an inability of fibrinogen being able to bind to αIIb/β3. Finally, scoparone inhibited thrombin-induced fibrin clotting, thereby reducing thrombus formation. Therefore, we suggest that scoparone has a strong antiplatelet effect and is highly probable to prevent platelet-derived vascular disease.