• Preventive Nutrition and Food Science
• /
• 제12권3호
• /
• pp.141-147
• /
• 2007

Cordycepin (3'-deoxyadenosine), which comes from Cordyceps militaris, the Chinese medicinal fungal genus Cordyceps, is used in the treatment of various diseases such as cancer and chronic inflammation. We recently reported that cordycepin has a novel antiplatelet effect through the down regulation of $[Ca^{2+}]_{i}$ and the elevation of cGMP/cAMP production. In this study, we further investigated the effect of cordycepin on collagen-induced platelet aggregation in the presence of cGMP-dependent protein kinase (PKG)- or cAMP-dependent protein kinase (PKA)-inhibitor. PKG inhibitor Rp-8-pCPT-cGMPS potentiated the collagen-induced platelet aggregation, but PKA inhibitor Rp-8-Br-cAMPS did not. However, both Rp-8-pCPT-cGMPS and Rp-8-Br-cAMPS reduced inhibition by cordycepin of collagen-induced platelet aggregation. Moreover, cordycepin inhibited $Ca^{2+}-dependent$ phosphorylation of both 47 kDa- and 20 kDa-protein in the presence of both PKG inhibitor and PKA inhibitor. Taken altogether, these results suggest that the inhibitory effect of cordycepin on collagen-induced platelet aggregation is associated with cGMP/PKG- and cAMP/PKA-pathways, and thus cordycepin may be an efficacious intervention against platelet aggregation-mediated thrombotic disease.

• 대한약학회:학술대회논문집
• /
• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
• /
• pp.108.2-108.2
• /
• 2003

Kaempferol, a flavonol compound, has been reported as the anti-oxidant and anti-angiogenic agent and it has been found to inhibit cell growth in vitro. Abnormal proliferation of vascular smooth muscle cells (VSMCs) plays an important role in development of atherosclerosis. In this study, we examined the anti-proliferative effect and its mechanism on rat aortic VSMCs treated by kaempferol. kaempferol significantly inhibited the platelet-derived growth factor (PDGF)-BB-induced proliferation of rat aortic VSMCs in concentration-dependent manner by cell count and ［$^3$H］-thymidine incorporation assay. (omitted)

• 대한한방부인과학회지
• /
• 제19권3호
• /
• pp.151-173
• /
• 2006

Purpose : This study was performed to evaluate anti-thrombotic and anti-inflammatory effects of BokbangHongdeungPaejangSan water extract (BHPS). Methods : BHPS was investigated using cultured cells and a murine models. As for the parameters of inflammation, levels of several inflammatory cytokines and chemical mediators which are known to be related to inflammation were determined in mouse lung fibroblast cells (mLFC) and RAW 264.7 cells. Results : In experiment of anti-thrombotic effect, BHPS inhibited the platelet aggregation induced by ADP and epinephrine, and inhibited pulmonary embolism induced by collagen and epinephrine. BHPS increased Platelet number and fibrinogen amount, and shortened PT and APTT in thrombus model induced by dextran. In experiment of anti-inflammatory effect, BHPS inhibited IL-1${\beta}$, IL-6, TNF-${\alpha}$, COX-2 and NOS-II mRNA expression in a concentration-dependent manner in RAW 264.7 cell line, and inhibited significantly NO production at 50, 100 ${\mu}g/ml$, and also inhibited ROS production in a concentration-dependent manner. BHPS inhibited IL-1${\beta}$, IL-6 and TNF-${\alpha}$ production significantly in serum of acute inflammation-induced Balb/c mice, and decreased IL-1${\beta}$, IL-6 and TNF-${\alpha}$ production in spleen tissue, but increased IL-1${\beta}$, IL-6 and TNF-${\alpha}$ production in liver tissue. BHPS increased survival rate at the 3th day in ICR mice with lethal endotoxemia induced by LPS. Conclusion : These results suggest that BHPS can be used for treating diverse female diseases caused by thrombosis and inflammation such as endometriosis, pelvic pain, cervicitis, pelvic inflammatory disease and pelvic tuberculosis and so forth.

• Journal of Nutrition and Health
• /
• 제36권2호
• /
• pp.101-108
• /
• 2003

Antiplatelet aggregation, anticoagulant and lipid-lowering drugs are clinically widely used for secondary preventive purpose in the cardiovascular patients, but there is no primary preventive agents to prevent these diseases. With the aim of developing effective primary agents for cardiovascular diseases, we tried to formulate an optimized mixture of natural plants extract containing Theae sinensis, Camelliae sinensis, Vitis vinifera, Gingko folium and curcuminoids from Curcuma longa and to evaluate its anti-thrombotic and anti-hypercholesterolemic effects in vivo. The inhibitory effect of curcuminoids on vascular smooth muscle cell proliferation and migration were also investigated in vitro. in the animal experiments treated with hyperlipidemic diet, oral treatment of curcuminoids and natural plants extracts mixture (100 mg/kg) into male Sprague Dawley rats for 7 week simultaneously inhibited platelet aggregation as well as improved lipid profile in the blood. Compared to control group, both of curcuminoids-treated and mixture-treated groups revealed significantly decrease of total cholesterol (24.4%, 28.6%), free cholesterol (25.1%, 24.0%), cholesterol ester (14.6%, 29.0%), LDL-cholesterol (27.0%, 32.0%) and triglyceride (15.0%, 31.0%), respectively. However, both groups showed increase of HDL-cholesterol (46.6% and 51.5%) . In particular, atherogenic index of curcuminoids and mixture treatment group was significantly decreased to 47.0% and 56.0%, respectively. Furthermore, oral treatment of curcuminoids and mixture significantly inhibited collagen-induced platelet aggregation (21.1% and 29.1%, respectively), compared to control group. The anti-thrombotic values of mixture was almost similar to that of aspirin treatment (100 mg/kg) group. These results suggest that the oral treatment of curcuminoids-based natural plant extract mixture improved cardiovascular conditions in hyperlipidemic rats.

• BMB Reports
• /
• 제40권5호
• /
• 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.

• 동의생리병리학회지
• /
• 제20권4호
• /
• pp.957-965
• /
• 2006

This study was peformed to evaluate antithrombotic activities and anti-inflammatory effects of Kami-BoyangHwanoh-Tang(KBHT). The major findings were summarized as follows. In experiment of anti-thrombotic effect; KBHT inhibited human platelet aggregation induced by ADP and epinephrine as compared with the control group and inhibited pulmonary embolism induced by collagen and epinephrine (inhibitory rate is 50 %). KBHT increased platelet number significantly and also KBHT shortened PT and APTT significantly as compared with the control group in thrombus model induced by dextran. In experiment of anti-inflammatory effect; KBHT inhibited $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, COX-2 and NOS-II mRNA expression as compared with the control group in a concentration-dependent degree, and inhibited NO production significantly at 50, $100\;{\mu}g/^{ml}$, and also inhibited ROS production in a concentration-dependent degree as compared with the control group in RAW 264.7 cell line. KBHT inhibited $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ production significantly in serum of acute inflammation-induced mice, and decreased $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ production in spleen tissue, and also decreased IL-6 and $TNF-{\alpha}$ production in liver tissue, but increased $IL-1{\beta}$ production in liver tissue of acute inflammation-induced mice. KBHT increased survival rate at 3rd day in mice with lethal endotoxemia induced by LPS. These results suggest that KBHT can be useful in treating diverse female diseases caused by thrombosis and inflammation such as endometrosis, myoma, pelvic congestion, chronic cervicitis, chronic pelvic inflammatory disease and so on.

• 대한한의학회지
• /
• 제30권2호
• /
• pp.88-103
• /
• 2009

Objectives: There is currently increased interest in the identification of natural antioxidant compounds derived from various plants. Peony Root (PR) is used worldwide for the treatment of many types of cardiovascular disease including atherosclerosis and hypertension. It has been used in Korean traditional medicine for the treatment of glycosuria, hypertension and cancer. However, to date, no studies concerning the antioxidant properties of PR have been conducted. Therefore, this study was conducted to evaluate the in vitro scavenging activity, inhibitory effect of LDL oxidation of pro-oxidant reactive species and anti-thrombosis effect in response to treatment with PR using various screening methods including biological and non-biological oxidants. Methods: In this study, the antioxidant activity of extract from PR was studied with in vitro methods by measuring the antioxidant activity by TEAC, measuring the scavenging effects on reactive oxygen species (ROS) [superoxide anion, hydroxyl radical] and on reactive nitrogen species (RNS) [nitric oxide and peroxynitrite] as well as measuring the inhibitory effect on $Cu^{2+}$-induced human LDL oxidation and the inhibitory effect on collagen-induced platelet aggregation. Results: The PR extracts were found to have a potent scavenging activity of oxidative stress [DPPH, superoxide anion, hydroxyl radical, nitric oxide and peroxynitrite, etc.] as well as an inhibitory effect on LDL oxidation and on platelet aggregation. Conclusions: The PR extracts have anti-oxidative and anti-atherosclerotic effects in vitro system, which can be used for developing pharmaceutical drugs against oxidative stress and atherosclerosis.

• Natural Product Sciences
• /
• 제5권1호
• /
• pp.54-59
• /
• 1999

Both ethanol and water extracts of unossified velvet antler were found to exhibit a significant immuno-stimulating activity as measured by carbon clearance test in mice, a remarkable anti-fatigue effect in weight-loaded forced swimming performance in mice, a significant anti-stress effect on immobilization in rats. The antler extracts also showed a weak but significant anti-thrombotic activity. These findings are indicative of adaptogenic properties of antlers and their normalizing effects during stressful condition.

• 동의생리병리학회지
• /
• 제22권6호
• /
• pp.1509-1517
• /
• 2008

The flowers and buds of Lonicera Flower (LF), are used in Korean herbal medicine for latent-heat-clearing, antipyretic, detoxicant and anti-inflammatory ailments. This plant is used worldwide for the treatment of many types of inflammatory disease including respiratory infections, diabetes mellitus, rheumatoid arthritis and play an important role in immune reaction. These pharmaceutical effects of LF looks like to be related to its antioxidant capacity and phytochemicals containing in LF. In this study, the antioxidant activity of extract from LF was studied in vitro methods by measuring the antioxidant activity by TEAC, measuring the scavenging effects on reactive oxygen species (ROS) [superoxide anion, hydroxyl radical] and on reactive nitrogen species (RNS) [nitric oxide and peroxynitrite] as well as measuring the inhibitory effect on $Cu^{2+}$ induced human LDL oxidation and the inhibitory effect on collagen induced platelet aggregation. The LF extracts were found to have a potent scavenging activity, as well as an inhibitory effect on LDL oxidation and on platelet aggregation. In conclusion, the LF extracts have anti-oxidative and anti-atherosclerotic effects in vitro system, which can be used for developing pharmaceutical drug against oxidative stress and atherosclerosis.

• Journal of Ginseng Research
• /
• 제41권4호
• /
• pp.548-555
• /
• 2017

Background: Korean Red Ginseng has been used for several decades to treat many diseases, enhancing both immunity and physical strength. Previous studies have documented the therapeutic effects of ginseng, including its anticancer, antiaging, and anti-inflammatory activities. These activities are mediated by ginsenosides present in the ginseng plant. Ginsenoside Rg3, an effective compound from red ginseng, has been shown to have antiplatelet activity in addition to its anticancer and anti-inflammatory activities. Platelets are important for both primary hemostasis and the repair of the vessels after injury; however, they also play a crucial role in the development of acute coronary diseases. We prepared ginsenoside Rg3-enriched red ginseng extract (Rg3-RGE) to examine its role in platelet physiology. Methods: To examine the effect of Rg3-RGE on platelet activation in vitro, platelet aggregation, granule secretion, intracellular calcium ($[Ca^{2+}]_i$) mobilization, flow cytometry, and immunoblot analysis were carried out using rat platelets. To examine the effect of Rg3-RGE on platelet activation in vivo, a collagen plus epinephrine-induced acute pulmonary thromboembolism mouse model was used. Results: We found that Rg3-RGE significantly inhibited collagen-induced platelet aggregation and $[Ca^{2+}]_i$ mobilization in a dose-dependent manner in addition to reducing ATP release from collagen-stimulated platelets. Furthermore, using immunoblot analysis, we found that Rg3-RGE markedly suppressed mitogen-activated protein kinase phosphorylation (i.e., extracellular stimuli-responsive kinase, Jun N-terminal kinase, p38) as well as the PI3K (phosphatidylinositol 3 kinase)/Akt pathway. Moreover, Rg3-RGE effectively reduced collagen plus epinephrine-induced mortality in mice. Conclusion: These data suggest that ginsenoside Rg3-RGE could be potentially be used as an antiplatelet therapeutic agent against platelet-mediated cardiovascular disorders.