• Journal of Nutrition and Health
• /
• v.26 no.7
• /
• pp.829-838
• /
• 1993

This study was designed to compare the effect of different dietary fats on the incidence of colorectal tumor, the level of plasma thromboxane B2(TXB2) and fatty acid profiles of platelet and colonic mucosal lipids in N - methyl - N - nitro - N - nitrosoguanidine(MNNG) - treated rats. Male Sprague Dawley rats, at 8 weeks old, were divided into 2 groups and infused intrarectally with saline(control group) or with 2mg MNNG(carcinogen-treated group) twice a week for 3 weeks. Each group was again divided into 4 groups and fed one of four diets(BT, CO, PO, FO) containing dietary fat at 9%(w/w) level for 37 weeks, Dietary fats were beef tallow(7.2%)+corn oil(1.8%) for BT, corn oil(9.0%) for CO, perilla oil(9.0%) for PO, fish oil (6.5%)+corn oil (2.5%) for FO diets. MNNG-treated rats had colonic tumor, while no tumors(adenocarcinoma and adenoma) than others. Tumor sizes in BT-MNNG rats ranged from 2mm papillary form to 15mm of polypoid. However, the size of tumors in PO-MNNG or FO-MNNG rats could not be measured by gross examination. BT-MNNG and CO-MNNG groups were higher in the level of plasma TXB2 and the ratio of c20 : 4/c20 :5 platelet. PO-MNNG groups were lower in the ratio of c20 : 4/c20 : 5(p<0.05) in fatty acid of colonic mucosal lipids suggesting that perilla oil and fish oil could reduce the level of PGE2 and TXB2 by modifying its precursor content and restrain tumor promotion in colon. Effect of perilla oil rich in $\alpha$-linolenic acid on colon carcinogenesis was similar to that of fish oil and thus perilla oil could have a protective effect against colon cancer possibly by inhibiting the production of arachidonic acid metabolite.

• Journal of Nutrition and Health
• /
• v.24 no.2
• /
• pp.97-103
• /
• 1991

The increase in alcohol consumption level has been noticed in Korea recently. Alcohol appreciably inhibits cell mediated immunity and this may contribute to the high prevalence of serious infection such as pulmonary tuberculosis among alcoholic subjects. The present study was undertaken to examine the effect of ethanol on the cyclooxygenase metabolites of human monocyte in vitro. Monocytes were activated with 800 units of gamma interferon(IFN-${\gamma}$) for 3 days following apply of Ficool-hypaque density gradient and gelatin coated flasks for separation of monocytes. Ethanol with addition of 100mM, 300mM and 600 mM for 30 minutes to 106 monocytes with/without previous IFN-${\gamma}$ treatment caused a dose dependent decrease in the production of thromboxane B2, 6-keto-PGE1$\alpha$ and PGE2 by radioimmunoassay at 6 hours after ethanol treatment. Quite different from the findings after 6 hours there was dose dependent increase in three prostaglandins without IFN-${\gamma}$ treatment after 24 hours of incubation. With previous treatment of IFN-${\gamma}$ reduced productions of three prostaglandins at 24 hours than control is spite of ethanol stimjulation. These findings show that IFN-${\gamma}$ can inhibit alcohol induced derangement of arachidonic acid metabolism of monocytes.

• Korean Journal of Veterinary Research
• /
• v.56 no.2
• /
• pp.67-74
• /
• 2016

Tomato extract has been shown to exert antiplatelet activity in vitro and to change platelet function ex vivo, but with limitations. In this study, antiplatelet activity of water soluble tomato concentrate (Fruitflow I) and dry water soluble tomato concentrate (Fruitflow II) was investigated using rat platelets. Aggregation was induced by collagen and adenosine diphosphate and granule-secretion, $[Ca^{2+}]_i$, thromboxane B2, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) levels were examined. The activation of integrin ${\alpha}_{IIb}{\beta}_3$ and phosphorylation of signaling molecules, including mitogen-activated protein kinase (MAPK) and PI3K/Akt, were investigated by flow cytometry and immunoblotting, respectively. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) were examined. Moreover, in vivo thrombus weight was tested by an arteriovenous shunt model. Fruitflow I and Fruitflow II significantly inhibited agonist induced platelet aggregation, adenosine triphosphate and serotonin release, $[Ca^{2+}]_i$, and thromboxane B2 concentration, while having no effect on cAMP and cGMP levels. Integrin ${\alpha}_{IIb}{\beta}_3$ activation was also significantly decreased. Moreover, both concentrates reduced phosphorylation of MAPK pathway factors such as ERK, JNK, P38, and PI3K/Akt. In vivo thrombus formation was also inhibited. Taken together, these concentrates have the potential for ethnomedicinal applications to prevent cardiovascular ailments and can be used as functional foods.

• Journal of Ginseng Research
• /
• v.46 no.5
• /
• pp.683-689
• /
• 2022

Background: Since ginsenosides exert an anti-thrombotic activity, blood flow-improving effects of DK-MGAR101, an extract of mountain ginseng adventitious roots (MGAR) containing various ginsenosides, were investigated in comparison with an extract of Korean Red Ginseng (ERG). Methods: In Sprague-Dawley rats orally administered with DK-MGAR101 or ERG, oxidative carotid arterial thrombosis was induced with FeCl₃ (35%), and their blood flow and occlusion time were measured. To elucidate underlying mechanisms, the cytoprotective activities on rat aortic endothelial cells (RAOECs) exposed to hydrogen peroxide (H₂O₂) were confirmed. In addition, the inhibitory activities of DK-MGAR101 and ERG on agonist-induced platelet aggregation, thromboxane B₂ production, and ATP granule release from stimulated platelets as well as blood coagulation were analyzed. Results: DK-MGAR101 containing high concentrations of Rb1, Rg1, Rg3, Rg5, and Rk1 ginsenosides (55.07 mg/g) was more effective than ERG (ginsenosides 8.45 mg/g) in protecting RAOECs against H₂O₂ cytotoxicity. DK-MGAR101 was superior to ERG not only in suppressing platelet aggregation, thromboxane B₂ production, and granule release, but also in delaying blood coagulation, FeCl₃-induced arterial occlusion, and thrombus formation. Conclusions: The results indicate that DK-MGAR101 prevents blood vessel occlusion by suppressing platelet aggregation, thrombosis, and blood coagulation, in addition to endothelial cell injury.

• Journal of Microbiology and Biotechnology
• /
• v.32 no.9
• /
• pp.1126-1133
• /
• 2022

This study investigated the contribution of lipoxygenase (LOX) inhibitors, nordihydroguaiaretic acid (NDGA), tetra-O-methyl nordihydroguaiaretic acid (M₄N) and zileuton (ZIL), and thromboxane A2 (TXA₂) inhibitor 4,5-diphenylimidazole (DPI) in the proliferation of Brucella abortus infection. None of the compounds affected the uptake of Brucella into the macrophages. We determined the effect of neutralizing leukotriene B4 (LTB4) receptor and showed that the uptake of the bacteria was inhibited at 30 min post-infection. M₄N treatment attenuated intracellular survival of Brucella at 2 h post-incubation but it was not observed in the succeeding time points. DPI treatment showed reduced survival of Brucella at 24 h post-incubation while blocking LTB4 receptor was observed to have a lower intracellular growth at 48 h post-incubation suggesting different action of the inhibitors in the course of the survival of Brucella within the cells. Reduced proliferation of the bacteria in the spleens of mice was observed in animals treated with ZIL or DPI. Increased serum cytokine level of TNF-α and MCP-1 was observed in mice treated with M₄N or ZIL while a lower IFN-γ level in ZIL-treated mice and a higher IL-12 serum level in DPI-treated mice were observed at 7 d post-infection. At 14 d post-infection, ZIL-treated mice displayed reduced serum level of IL-12 and IL-10. Overall, inhibition of 5-LOX or TXA₂ or a combination therapy promises a potential alternative therapy against B. abortus infection. Furthermore, strong ligands for LTB4 receptor could also be a good candidate for the control of Brucella infection.

• Archives of Pharmacal Research
• /
• v.21 no.6
• /
• pp.774-778
• /
• 1998

Brazilin [7,11b-dihydrobenz[b]indeno[1,2-d]pyran-3,6a,9,10(6H)-tetrol] inhibited thrombin-, collagen- and ADP-induced aggregation of washed rat platelets. T hrombin- and collagen-induced ATP release were also inhibited by brazilin in a concentration-dependent manner. Brazilin inhibited the formation of platelet thromboxane $A_2$ caused by thrombin, whereas it had no effect on the prostaglandin $D_2$ formation. Brazilin inhibited $^3H$-arachidonic acid liberation from membrane phospholipids of thrombin-stimulated platelets. Brazilin inhibited the rise of intracellular free calcium caused by thrombin. These results indicate that the inhibition of phospholipase ($PLA_2$) activity and [$[Ca^{2+}]_1$ elevation might be at least a part of antiplatelet mechanism of brazilin.

• The Korean Journal of Physiology and Pharmacology
• /
• v.2 no.6
• /
• pp.779-786
• /
• 1998

A reversed-phase high-performance liquid chromatogrphy (RP-HPLC) has been developed to analyze the metabolites of arachidonic acid based on the specificities of ultraviolet absorption of these various metabolites and is sensitive to the nanogram level. This procedure makes it possible to extract complex mixtures of eicosanoids efficiently with a single step and to analyze them simultaneously by RP-HPLC from biological samples using octadesylsilyl silica extraction column and $PGB_2$ as an internal standard. The cyclooxygenase products {prostaglandin $(PG)D_2,\;PGE_1,\;PGE_2,\;PGF_{1{\alpha}},\;PGF{2{\alpha}},\;6-keto-PGF_{1{\alpha}},$ and thromboxane $B_2(TXB_2)}$ and lipid peroxidation product, isoprostanes, of arachidonic acid were monitored by one isocratic HPLC system at 195 nm wavelength. The lipoxygenase products ${leukotriene(LT)B_4,\;LTC_4,\;LTD_4,$ and 5-hydroxyeicosatetraenoic acid (5-HETE), 12-HETE, 15-HETE} were measured by another isocratic HPLC system at 280 nm for LTs and 235 nm for HETEs. This method provides a simple and reliable way to extract and assess quantitatively the final arachidonic acid metabolites.

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

• BMB Reports
• /
• v.40 no.5
• /
• pp.678-683
• /
• 2007

Extracts from the leaves of the Ginkgo biloba are becoming increasingly popular as a treatment that is claimed to reduce atherosclerosis, coronary artery disease, and thrombosis. In this study, the effect of ginkgolide B (GB) from Ginkgo biloba leaves in collagen (10 ${\mu}g/ml$)-stimulated platelet aggregation was investigated. It has been known that human platelets release matrix metallo-proteinase-9 (MMP-9), and that it significantly inhibited platelet aggregation stimulated by collagen. Zymographic analysis confirmed that pro-MMP-9 (92-kDa) was activated by GB to form an MMP-9 (86-kDa) on gelatinolytic activities. And then, activated MMP-9 by GB dose-dependently inhibited platelet aggregation, intracellular $Ca^{2+}$ mobilization, and thromboxane $A_2$ ($TXA_2$) formation in collagen-stimulated platelets. Activated MMP-9 by GB directly affects down-regulations of cyclooxygenase-1 (COX-1) or $TXA_2$ synthase in a cell free system. In addition, activated MMP-9 significantly increased the formation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), which have the anti-platelet function in resting and collagen-stimulated platelets. Therefore, we suggest that activated MMP-9 by GB may increase the intracellular cAMP and cGMP production, inhibit the intracellular $Ca^{2+}$ mobilization and $TXA_2$ production, thereby leading to inhibition of platelet aggregation. These results strongly indicate that activated MMP-9 is a potent inhibitor of collagen-stimulated platelet aggregation. It may act a crucial role as a negative regulator during platelet activation.

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