• 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.

• Proceedings of the Korean Society of Applied Pharmacology
• /
• 1993.04a
• /
• pp.83-83
• /
• 1993

생체내 기능조절에 중요한 역할을 하는 prostaglandins(PGs)는 신경계 세포, 순환기계세포, 거삭세포, 섬유아세포 및 암세포 등 여러 부위에 널리 분포되어 있다. 본 연구에서는 PGs생체내 전구체인 arachidonic acid와 구조유사체인 eicosapentaenoic acid(EPA) 및 docosahexaenoic acid(DHA)에 의한 순환기계효과를 TXA$_2$ 생합성과 관련하여 규명하고져 하였다. 또한 여러 가지 면역요법 중 암세포 살해능이 있는 lymphokine activated killer(LAK) 세포의 생성력과 생체내 면역세포 중 암세포의 일차적인 방어작용을 하는 것으로 알려진 natural killer(NK) 세포의 활성도를 PGs생성과 연관시켜 검토하므로써 암환자에 저하되어 있을 면역기구와 PGs와의 상관관계를 규명하고자 하였다.

• Journal of Applied Biological Chemistry
• /
• v.64 no.3
• /
• pp.317-322
• /
• 2021

Among the different cardiovascular disorders (CVDs), the activation of platelets is a necessary step. Based on this knowledge, therapeutic treatments for CVDs that target the disruption of platelet activation are proving to be worthwhile. One such substance, a bioactive 6,7-dihydroxy derived from coumarin, is 6,7-Dihydroxy-2H-1-benzopyran-2-one (esculetin). This compound has demonstrated several pharmacological effects on CVDS as well as various other disorders including diabetes, obesity, and renal failure. In various reports, esculetin and its effect has been explored in experimental mouse models, human platelet activation, esculetin-inhibited collagen, and washed human platelets exhibiting aggregation via arachidonic acid. Yet, esculetin affected aggregation with agonists like U46619 or thrombin in no way. This study investigated esculetin and how it affected human platelet aggregation activated through U46619. Ultimately, we confirmed that esculetin had an effect on the aggregation of human platelets when induced from U46619 and clarified the mechanism. Esculetin interacts with the downregulation of both phosphoinositide 3-kinase/Akt and mitogen-activated protein kinases, important phosphoproteins that are involved in activating platelets and their signaling process. The effects of esculetin reduced TXA₂ production, phospholipase A₂ activation, and platelet secretion of intracellular granules (ATP/serotonin), ultimately causing inhibition of overall platelet aggregation. These results clearly define the effect of esculetin in inhibiting platelet activity and thrombus formation in humans.

• Journal of Nutrition and Health
• /
• v.30 no.6
• /
• pp.639-647
• /
• 1997

The effect of excess L-ascorbic acid(AsA) in blood, liver lipid levels and peroxidation status were investigate . Ten Sprague-Dawley male rats weighing 150-200g were fed 300mg AsA/100g body weight/day, mixed into ground chow diet, for 4 weeks. And another set of then rats were fed only chow diet as the control. Average body weight gain was slightly lowered by AsA feeding without food intake change. The AsA group showed higher AsA levels in plasma and liver than the control group. In addition, the AsA group showed a higher plasma TBARS value. Liver TBARS seemed to be elevated in the AsA, but not significantly. The hemolysis of red cells tended to increase with excess AsA, accompanied by a raised GSH-Px activity and lowered total GSH levels. Plasma HDL-Chol level was increased while the levels of total Chol, LDL-plus VLDL-Chol , and triglyceride were unchanged . Atherogenic index decreased. Hepatic TG levels were also decreased, but the total amount of Chol increased slightly . Platelet TXA$_2$ production was inhibited by excess AsA feeding. Above results indicafe that oral feeding of excess AsA may be beneficial in reducing the risk of atherosclerosis ; however such practice may be detrimental for tissue lipid peroxidation and weight gain.

• Proceedings of the Korean Society of Applied Pharmacology
• /
• 1998.11a
• /
• pp.177-177
• /
• 1998

In the previous report, tetrandrine (TET) and fangchinoline (FAN) showed antithrombotic and antiplatelet aggregation activities. The present study was undertaken to investigate the effects of tetrandrine and fangchinoline on human platelet aggregation, formation of thromboxane B$_2$ and coagulation of platelet poor plasma. TET and FAN inhibited platelet activating factor (PAF) induced human platelet aggregation, but didn't inhibit the specific binding of PAF to its receptor. Meanwhile, TET and FAN also inhibited PAF, thrombin and arachidonic acid induced thromboxane B$_2$ formation in human washed platelets. In addition, neither TET nor FAN showed any anticoagulation activities in the measurement of the activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) using human platelet poor plasma. These results suggest that antithrombotic effects of TET and FAN in mice may be mainly related to the antiplatelet aggregation activities, and the antiplatelet aggregation effects may be related to the intracellular messenger system such as TXA$_2$ formation etc., but not to the binding of PAF to PAF-receptor on the platelet membrane directly.

• Biomolecules & Therapeutics
• /
• v.24 no.6
• /
• pp.659-664
• /
• 2016

Lindera obtusiloba has been used in traditional herbal medicine for the treatment of blood stasis and inflammation. The leaves of Lindera obtusiloba have been reported to exhibit various physiological activities. However, there is little information available on their antiplatelet and antithrombotic activities. Thus, the present study aimed to evaluate the effect of Lindera obtusiloba leaf extract (LLE) on platelet activities, coagulation and thromboembolism. In a platelet aggregation study, LLE significantly inhibited various agonist-induced platelet aggregations in vitro and ex vivo. Furthermore, LLE significantly inhibited collagen-induced thromboxane A2 (TXA2) production in rat platelets. In addition, oral administration of LLE was protective in a mouse model of pulmonary thromboembolism induced by intravenous injection of a mixture of collagen and epinephrine. Interestingly, LLE did not significantly alter prothrombin time (PT) and activated partial thromboplastin time (aPTT). This study indicates that the antithrombotic effects of LLE might be due to its antiplatelet activities rather than anticoagulation. Taken together, these results suggest that LLE may be a candidate preventive and therapeutic agent in cardiovascular diseases associated with platelet hyperactivity.

• The Korean Journal of Pharmacology
• /
• v.20 no.1 s.34
• /
• pp.41-46
• /
• 1984

Cadmium (Cd) was administered by a series of weekly intraperitoneal injections at dose of 2mg/kg in rabbits and rats. The levels of malondialdehyde (MDA) and thromboxane $B^2(TXB_2)$ in platelet-rich plasma from Cd-poisoned animals were significantly higher than those of the control group. Furthermore, the inhibition of 6-keto-prostaglandin $F_{1{\alpha}}$, production in Cd-treated aorta ring was inversely related to the enhancement of platelet aggregation. These results suggest that Cd not only inhibits prostacyclin synthesis in the arterial endothelium, but also stimulates the platelet aggregation by enhancing thromboxane AZ production. These findings are assumed to support the evidence of an effect of Cd toxicity on the vascular wall and platelet function in raising arteriall pressure.

• Proceedings of the Ginseng society Conference
• /
• 1984.09a
• /
• pp.13-19
• /
• 1984

In the previous symposium, authors reported about anti-atherogenic action of Panax ginseng, saying that red-ginseng powder increased serum HDL-cholesterol, decreased total cholesterol, TG, NEFA, in addition, decreased platelet adhesiveness. Later, Toyama group including me. reported that ginsenosides esp. $Rb_2$ enhanced HDL and decreased LDL. Also Matsuyama group and Kinki Univ. group reported that ginsenosides $Rg_1,\;Rb_2,$ etc. inhibited platelet aggregation. This paper will be divided into two parts: Experimental and clinical Experimental study; Using a highcholesterol-cholic acid-fed rats, effects of red ginseng extract and several ginsenosides on serum apoprotein-lipoproteins in relation to prostaglandins. Rats received $2\%$ cholesterol 1-1$\%$ cholic acid diet, ginseng extract or ginsenosides 2.5mg/100g/day for 9 days. Red ginseng extract, ginsenosides $Rb_2,\;Rc,\;Rb_1,\;and\;Rg_1,\;esp.\;Rb_2,$ increased HDL, apo-AI, Aii and $PGI_2,$ while they decreased LDL, apo-B and $TXA_2$. Clinical study: Effect of red ginseng powder on hyperlipidemia was observed. Long term administration of red ginseng powder manufactured by Office of Monopoly, Republic of Korea and offered by Japan-Korea Korean Ginseng Co., Kobe, at the dose of 2.7 g/day, was performed in patients with hyperlipidemia up to 4 years. The significant increase in serum HDL-cholesterol and also the significant decrease in total cholesterol, atherogenic index, TG, NEFA and lipoperoxide was observed with 3-48 month administration of red ginseng. Conclusions: Red ginseng and ginsenosides improved hyperlipidemia in rats and in man, with the improvement of blood apoproteins, lipoproteins and prostaglandins in experimental hyperlipidemic animals.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.18 no.6
• /
• pp.1860-1868
• /
• 2004

Geijibokryunghwan has a wide range of therapeutic applications, and some reports have indicated that it has protective activity against atherosclerosis, and more specifically stroke and myocardial infarction. A recent report showed that atherosclerotic plaque volume can be reduced by supplying Geijibokryunghwan extracts for several years. In this study, we used a component of Geijibokryunghwan, which has been used for the prevention of atherosclerosis in Korea for several years, and has proven to be useful in lowering the occurrence of cerebral infarction. In a preliminary study, we found that Geijibokryunghwan potently suppressed platelet aggregation induced by various agonists. In this study, we sought to explore the mechanism by which Geijibokryunghwan inhibits platelet aggregations.

• Journal of Ginseng Research
• /
• v.47 no.6
• /
• pp.706-713
• /
• 2023

Background and objective: The ability to inhibit aggregation has been demonstrated with synthetically derived ginsenoside compounds G-Rp (1, 3, and 4) and ginsenosides naturally found in Panax ginseng 20(S)-Rg3, Rg6, F4, and Ro. Among these compounds, Rk3 (G-Rk3) from Panax ginseng needs to be further explored in order to reveal the mechanisms of action during inhibition. Methodology: Our study focused to investigate the action of G-Rk3 on agonist-stimulated human platelet aggregation, inhibition of platelet signaling molecules such as fibrinogen binding with integrin α_IIbβ₃ using flow cytometry, intracellular calcium mobilization, dense granule secretion, and thromboxane B₂ secretion. In addition, we checked the regulation of phosphorylation on PI3K/MAPK pathway, and thrombin-induced clot retraction was also observed in platelets rich plasma. Key Results: G-Rk3 significantly increased amounts of cyclic adenosine monophosphate (cAMP) and led to significant phosphorylation of cAMP-dependent kinase substrates vasodilator-stimulated phosphoprotein (VASP) and inositol 1,4,5-trisphosphate receptor (IP₃R). In the presence of G-Rk3, dense tubular system Ca²⁺ was inhibited, and platelet activity was lowered by inactivating the integrin αIIb/β₃ and reducing the binding of fibrinogen. Furthermore, the effect of G-Rk3 extended to the inhibition of MAPK and PI3K/Akt phosphorylation resulting in the reduced secretion of intracellular granules and reduced production of TXA₂. Lastly, G-Rk3 inhibited platelet aggregation and thrombus formation via fibrin clot. Conclusions and implications: These results suggest that when dealing with cardiovascular diseases brought upon by faulty aggregation among platelets or through the formation of a thrombus, the G-Rk3 compound can play a role as an effective prophylactic or therapeutic agent.