• Journal of Ginseng Research
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• v.45 no.1
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• pp.22-31
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• 2021

Atherosclerosis (AS) is a leading cause of cardiovascular diseases (CVDs) and it results in a high rate of death worldwide, with an increased prevalence with age despite advances in lifestyle management and drug therapy. Atherosclerosis is a chronic progressive inflammatory process, and it mainly presents with lipid accumulation, foam cell proliferation, inflammatory response, atherosclerotic plaque formation and rupture, thrombosis, and vascular calcification. Therefore, there is a great need for reliable therapeutic drugs or remedies to cure or alleviate atherosclerosis and reduce the societal burden. Ginsenosides are natural steroid glycosides and triterpene saponins obtained mainly from the plant ginseng. Several recent studies have reported that ginsenosides have a variety of pharmacological activities against several diseases including inflammation, cancer and cardiovascular diseases. This review focuses on describing the different pharmacological functions and underlying mechanisms of various active ginsenosides (Rb1,-Rd, -F, -Rg1, -Rg2, and -Rg3, and compound K) for atherosclerosis, which could provide useful insights for developing novel and effective anti-cardiovascular drugs.

• Korean Journal of Pharmacognosy
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• v.53 no.2
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• pp.64-69
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• 2022

When blood vessels are damaged, a rapid hemostatic response should occur in order to lower blood loss and keep normal circulation, and platelet activation and aggregation are essential. Nevertheless, abnormal or excessive platelet aggregation can be a reason of cardiovascular diseases including thrombosis, atherosclerosis, and stroke. Therefore, the screening for a substance which can regulate platelet activation and suppress aggregation reaction is very important for treatment and prevention of cardiovascular diseases. Artemether is a methyl ether derivative of artemisinin, which is isolated from the antimalarial plant Artemisia annua, but research on platelet aggregation or its mechanisms is still insufficient. This study identified the effects of artemether on U46619-induced human platelet aggregation and their granule secretion (ATP and serotonin release). In addition, the effects of artemether on the phosphorylation of PI3K/Akt or MAPK, which are related to signal transduction in platelet aggregation, were studied. As the results, artemether significantly lowered PI3K/Akt and MAPK phosphorylation, which inhibited platelet aggregation through granule secretion (ATP and serotonin release) dose-dependently. Therefore, we suggest that artemether is an antiplatelet substance that regulates PI3K/Akt and MAPK pathway and is of value as a therapeutic and preventive agent for platelet-derived cardiovascular diseases.

• Journal of Applied Biological Chemistry
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• v.65 no.4
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• pp.463-469
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• 2022

Cudrania tricuspidata (C. tricuspidata), a medicinal plant widely employed throughout Asia in ethnomedicine, has various bioactive properties, including antidiabetic, antiobesity, antitumor, and anti-inflammatory activities. In addition, the C. tricuspidata root extract reportedly inhibits platelet aggregation. Therefore, we focused on the active substances present in the C. tricuspidata extract. Sanggenon N (SN) is a flavonoid found in the root bark of C. tricuspidata. In the present study, we examined the inhibitory effects of SN on platelet aggregation, phosphoproteins, thromboxane A₂ generation, and integrin αIIbβ3 activity. SN inhibited collagen-induced human platelet aggregation in a dose-dependent manner without cytotoxicity. Furthermore, SN suppressed Ca²⁺ mobilization and influx through associated signaling molecules, such as inositol 1, 4, 5-triphosphate receptor I (Ser¹⁷⁵⁶), and extracellular signal-regulated kinase. In addition, SN inhibited thromboxane A₂ generation and associated signaling molecules, including cytosolic phospholipase A₂ and mitogen-activated protein kinase p38. Finally, SN could inhibit integrin (αIIb/β₃) activity by regulating vasodilator-stimulated phosphoprotein and Akt. Collectively, SN possesses potent antiplatelet effects and is a potential therapeutic drug candidate to prevent platelet-related thrombosis and cardiovascular disease.

• Biomedical Science Letters
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• v.29 no.3
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• pp.184-189
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• 2023

Normal activation of platelets and their aggregation are crucial during hemostasis process. It appears excessive or abnormal aggregation of platelets may bring about cardiovascular diseases like stroke, atherosclerosis, and thrombosis. For this reason, finding a substance that can regulate platelet aggregation or suppress aggregation will aid in the prevention and treatment of cardiovascular diseases. Artemisinin, a compound derived from Artemisia or Scopolia plants, has shown potential in various areas such as anticancer and Alzheimer's disease research. However, the specific role and mechanisms by which artemisinin influences platelet activation and thrombus formation are not yet fully understood. This study investigated the effects of artemisinin on platelet activation and thrombus formation. This study examined the effect of artemisinin on regulation of U46619-induced platelet aggregation, granule secretion. In addition, the effects of artemisinin on phosphorylation of PI3K/Akt and MAPK pathway involved in platelet aggregation was studied. As a result, artemisinin significantly downregulated of PI3K/Akt and MAPK pathway. In addition, artemisinin significantly reduced granule secretion, and platelet aggregation was inhibited by artemisinin. Therefore, we suggest that artemisinin is an anti-platelet substance that regulates PI3K/Akt and MAPK pathway and is valuable as a therapeutic and preventive agent for platelet-derived cardiovascular disease.

• Korean Journal of Clinical Laboratory Science
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• v.51 no.1
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• pp.34-41
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• 2019

Platelet aggregation is essential for the formation of a hemostatic plug in the case of blood vessel damage. On the other hand, excessive platelet aggregation may cause cardiovascular disorders, such as thrombosis, atherosclerosis, and myocardial infarction. Scopoletin, which found in the root of plants in the genus Scopolia or Artemisia, has anti-coagulation and anti-malaria effects. This study examined the effects of scopoletin on human platelet aggregation induced by collagen. Scopoletin had anti-platelet effects via the down-regulation of thromboxane $A_2$ ($TXA_2$) production and intracellular $Ca^{2+}$ mobilization ($[Ca^{2+}]_i$), which are aggregation-inducing molecules produced in activated platelets. On the other hand, scopoletin increased both the cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) levels, which are known as intracellular $Ca^{2+}$-antagonists and aggregation-inhibiting molecules. In particular, scopoletin increased the potently cAMP level more than cGMP, which led to suppressed fibrinogen binding to ${\alpha}IIb/{\beta}_3$ in collagen-induced human platelet aggregation. In addition, scopoletin inhibited collagen-elevated adenosine triphosphate (ATP) release in a dose-dependent manner. The results suggest that aggregation amplification through granule secretion is inhibited by scopoletin. Therefore, scopoletin has potent anti-platelet effects and may have potential for the prevention of platelet-derived vascular diseases.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.122-127
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• 2023

Cardiovascular disease (CVD) is increasingly increasing as the main cause of death worldwide, and activation of platelet in vascular damage is one of the important causes of CVD. In recent, there is a growing interest in anti-thrombotic materials through platelet suppression, and efforts are being made to reduce side effects by using natural bioactive compounds. Known as one of the Flavonoids, hydroxygenkwanin (HGK) is a purified substance in Daphne Genkwa, which is known to have antibacterial, anti-inflammatory and anti-cancer effects, and has been reported to serve as an inhibitor of tissue factor that prevents thrombosis, but its anti-platelet effects and the action mechanisms is not known. In this study, we confirmed that the effects of HGK on the collagen-induced human platelets activation. HGK suppressed phosphorylation of PI3K/AKT and mitogen-activated protein kinases during platelet signaling, and reduced granule secretion in platelets such as ATP and serotonin. In addition, HGK inhibited the phosphorylation of cPLA₂ and strongly undermined the production of TXA₂, which is a powerful aggregation amplifier. As a result, the platelet aggregation derived by Collagen, a cohesive induced substance, was strongly suppressed by HGK to an IC₅₀ of 86.36 µM. Therefore, HGK might be worth the antithrombotic substance that inhibits the activation and aggregation of human platelets that occur through blood vessel damage.

• Journal of Life Science
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• v.27 no.2
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• pp.247-266
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• 2017

Cordyceps is a traditional Chinese medicinal herb well-known in China, Korea and Japan since B.C. 2,000. The original entomopathogenic fungus, Cordyceps sinensis belonging to the genus Cordyceps could not be found inside Korean peninsula due to the absence of the host insect for the corresponding entomogenous fungus. The development of artificial production methods of Korean type Cordyceps using the silkworm Bombyx mori as in vivo culture medium for the the entomopathogenic fungus Paecilomyces tenuipes is the first, and wonderful occasion in the research history of insect industry of this global world. The aim of this article is to review the historical research background, mass-production methods, and pharmacological effects of the silkworm-dongchunghacho (Paecilomyces tenuipes) which is a newly developed Korean medicinal insect-borne mushroom, and another non-insect-borne medicinal mushroom (Cordyceps militaris and Cordyceps pruinosa). Their biological actions include anti-tumor, immunostimulating, anti-fatigue, anti-stress, anti-oxidant, anti-aging, anti-diabetic, anti-inflammatory, anti-thrombosis, hypolipidaemic and insecticidal effects. The bioactive principles are protein-bound polysaccharides (hexose, hexosamin), cordycepin, D-manitol, acidic polysaccharide etc. Protein-bound polysaccharides and n-butanol fractions were demonstrated to show a significant anti-tumor activities but did not show a cytotoxicities. D-mannitol exhibited a significant prolongation of the life span in tumor bearing mice. Ergosterol did not show an efficient anti-tumor activity, but showed a significant phagocytosis enhancing activity. Anti-tumor activity of silkworm-dongchunghacho might be attributed to immuno-stimulating activities rather than cytotoxic effects [164]. Also this review comprises the breeding of Dongchunghacho varieties, optimization of culture conditions, improvement of learning and memory by Dongchunghacho, application of them as foods and chemical constituents.

• Tuberculosis and Respiratory Diseases
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• v.47 no.1
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• pp.103-110
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• 1999

A thromboembolic event in patients later given a diagnosis of cancer is the result rather than the cause of the cancer. The risk of hidden cancer is significantly higher for patients with recurrent idiopathic thromboembolism compared to those with secondary deep vein thrombosis. Microemboli from hepatic or adrenal metastases and large-sized emboli from the great veins invaded by the tumor are the sources of tumor embolization The intraarterial tumor emboli less likely invade the arterial wall. Thrombus formation and organization may be capable of destroying tumor cells within pulmorlary blood vessels. Therefore, all tumor emboli are not true metastases. The treatment of deep vein thrombosis and pulmonary embolism in patients with cancer consists of anticoagulation with heparin and warfarin, venacaval filters, appropriate anti-neoplastic agents, and surgical methods(embolectomy, thromboendarterectomy). However, considerable literatures suggest that oral anticoagulant such as warfarin is ineffective in the treatment of those. We report a case of primary unknown squamous cell carcinoma incidentally found in the thrombus after pulmonary embolectomy.

• Journal of Life Science
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• v.20 no.6
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• pp.914-921
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• 2010

In this study, we carried out a series of experiments to know whether melatonin, an anti-oxidative and immunosuppressive agent, played an important role in endothelial cells. It was revealed that melatonin had little or no effect on endothelial proliferation, cell death or migration. Additionally, melatonin had no effect on adhesion of THP-1 leukocytes to bovine aortic endothelial cells (BAECs) and THP-1 homotypic cell aggregation. In contrast, it was shown that melatonin diminished the basal level of nitric oxide by PP2A-mediated dephosphorylation of endothelial nitric oxide synthase (eNOS), leading to enhanced detachment of BAEC from the extracellular matrix. Collectively, melatonin in high doses decreases the NO production via regulations of PP2A and eNOS activities, inducing detachment of endothelial cells, a possible initial step for thrombosis.

• Archives of Pharmacal Research
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• v.29 no.10
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• pp.898-903
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• 2006

The antiplatelet and antithrombotic activities of Korean Red Ginseng (KRG) were examined on rat carotid artery thrombosis in vivo, and platelet aggregation in vitro and ex vivo. Administration of KRG to rats not only prevented carotid artery thrombosis in vivo in a dose-dependent manner, but also significantly inhibited ADP- and collagen-induced platelet aggregation ex vivo, while failed to prolong coagulation times such as activated partial thromboplastin time (APTT) and prothrombin time (PT), indicating the antithrombotic effect of KRG might be due to its anti platelet aggregation rather than anticoagulation effect. In line with the above observations, KRG inhibited U46619-, arachidonic acid-, collagen- and thrombin-induced rabbit platelet aggregation in vitro in a concentration-dependent manner, with $IC_{50}$ values of $620{\pm}12$, $823{\pm}22$, $722{\pm}21$ and $650{\pm}14\;{\mu}g/mL$, respectively. Accordingly, KRG also inhibited various agonists-induced platelet serotonin secretions as it suppressed platelet aggregation. These results suggest that KRG has a potent antithrombotic effect in vivo, which may be due to antiplatelet rather than anticoagulation activity, and KRG intake may be beneficial to the individuals with high risks of thrombotic and cardiovascular diseases.