• Journal of Applied Biological Chemistry
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• v.66
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• pp.171-178
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• 2023

Morus alba, a popular medicinal plant belonging to the family Moraceae, has long been used commonly in traditional medicine and has various physiological activities, including antidiabetic, anti-microbial, diuretic, anti-oxidant, and anti-cancer activities. Morusinol was isolated from the root bark of M. alba; however, its biological effects have not yet been reported. Therefore, we examined the inhibitory effects of morusinol on human platelet aggregation, Ca²⁺ mobilization, and αIIb/β₃ activity. Our data showed that collagen-induced human platelet aggregation was inhibited by morusinol without cytotoxicity. In this study, we examined whether morusinol inhibits platelet aggregation through the regulation of integrin αIIb/β₃ and its associated signaling molecules. We observed that morusinol inhibited αIIb/β₃ activation by regulating vasodilator-stimulated phosphoprotein, phosphatidylinositol-3 kinase, Akt (protein kinase B), and glycogen synthase kinase-3α/β. These results show that morusinol inhibited fibronectin adhesion, fibrinogen binding, and clot retraction. Taken together, morusinol shows strong antiplatelet and anti-clot retraction effects and is a potential therapeutic drug candidate to prevent platelet-related thrombosis and cardiovascular disease.

• Applied Chemistry for Engineering
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• v.33 no.5
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• pp.545-550
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• 2022

As a result of the rapid entry into an aging society and westernized eating habits, the number of heart disease patients caused by angina pectoris, myocardial infarction, and high blood pressure has increased by more than 100,000 over five years. Heart disease has consistently ranked second in the cause of death in Korea over the past eight years, and medical expenses consumed annually reach 6 trillion won. While various treatments are being proposed for more patients, drug-coated balloon catheters have been developed and gradually commercialized to solve the disadvantages of stent implantation such as restenosis and increased risk of bleeding due to long-term double antiplatelet medication. In Korea, it began to use a drug-coated balloon catheter with the first release of it called "SeQuent Please^Ⓡ (Bibrown Korea)" in 2010. Its demand increased gradually as insurance benefits were applied in 2012. Drug-coated balloon angioplasty is increasing in use not only in Korea but also around the world, especially in the Asia-Pacific region, including Japan. Until now, the demand for domestic products is increasing, and if the efficiency in vivo and clinical trials is proven in the future, it is expected to be an effective procedure compared to high-risk stent implantation.

• Korean Journal of Clinical Pharmacy
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• v.15 no.2
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• pp.105-117
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• 2005

Following intracoronary stenting, antiplatelet therapy lead to greater protection from thrombotic complication. A few data are available about the effect of clopidogrel versus cilostazol, an antiplatelet commonly used after intracoronary stenting. To evaluate the efficacy and safety of clopidogrel plus aspirin compared with those of cilostazol plus aspirin in coronary stenting and to evaluate the efficacy of clopidogrel loading dose prior to coronary stealing in clopidogrel group. Data were retrospectively collected from medical charts of patients who had undergone coronary stenting and received either clopidogrel with or without loading 300 mg followed by 75 mg/d (n=58), or 200 mg/d cilostazol(n=72) for 1 year, between January 2000 and May 2002. All patients in both groups received aspirin 200 mg/d throughout the study. The primary endpoints at 7, 30, 180 and 365 days after stealing were the composite of death, Myocardial Infarction, stroke, angina, and revascularization in the intent to treat population and restenosis at follow up angiography. The secondary endpoints were the incidence of bleeding complications at 7, 30, and 365 days, and durg adverse effects at 365 days after stenting. At 180 and 365 days after stenting, the combined primary endpoints were significantly reduced in clopidogrel plus aspirin group (relative risk 0.39; 95% CI 0.17 to 0.92; p=0.021, RR 0.43; 95% CI 0.22 to 0.84; p=0.0085, respectively). However, the combined primary endpoints were not significantly different between the two groups at 7 and 30 days (p:1.00, p=0.79, respectively). Angiographic restenosis rate was 14.3% in clopidogrel plus aspirin uoup and 32.1% in cilostazol plus aspirin group (p=0.19). 300mg of clopidogrel loading dose did not significantly reduce the combined primary endpoints at 30 days after stenting (RR 0.14; 95% CI 0.01 to 2.65; p=0.23). The rate of bleeding complications and drug adverse effects were not different between the two groups. In patients undergoing intracoronary stenting, clopidogrel plus aspirin therapy is more beneficial than cilostazol plus aspirin in reducing major adverse cardiac events with similar rate of bleeding complication. A loading dose of clopidogrel did not lead to a statistically significant reduction in major adverse cardiac events.

• Journal of radiological science and technology
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• v.37 no.2
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• pp.109-116
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• 2014

Many studies have suggested that in the era of Drug-Eluting Stents(DES) are one of the causes of In-Stent Restenosis(ISR) of Stent Fracture(SF). The present study sought to evaluate clinical characteristics of patients with stent fracture after successful DES implantation. The 4,701 patients were selected for analysis who underwent a follow-up coronary angiography irrespective of ischemic symptoms. The overall incidence of SF was 32 patients(male:female=19:13, Av. age $62.44{\pm}9.8$year, 0.68%). Fractures of Sirolimus-Eluting Stents(SES), Paclitaxel-Eluting Stents(PES), Biolimus A9-Eluting Stents(BES), Everolimus-Eluting Etents(EES), Endothelial Progenitor Cell Capture Stent(EPC) and Zotarolimus-Eluting Stents(ZES) are accounted for 19(59.4%), 9(28.1%), 2(6.3%), 1(3.1%), 1(3.1%) and 0(0%) respectively. SF developed in the left Anterior Dscending(LAD) artery in 16 patients(50%) and in complex(type B2, C) lesions in 25 patients(69.4%). Ten patients were treated with heterogenous DES, the rest being treated with either homogenous DES(3 patients), plain old balloon angioplasty(3 patients), or conservative medical treatment(17 patients). None of the patients with SF suffered from cardiac death during a follow-up period of $32.9{\pm}12.4$ months. The overall rate of DES fracture over up to 3.7 years of follow-up was 0.68% with higher incidence in SES than in PES. SF frequently occurred in the LAD artery and in complex lesions. Of the patients with SF, coronary intervention was performed only when the binary restenosis lesion was significant. During the follow-up, patients with SF have continued on combination antiplatelet therapy. There is a very low rate of major adverse cardiac events(post-detection of SF), especially cardiac death associated with SF.

• Translational and Clinical Pharmacology
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• v.26 no.4
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• pp.160-165
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• 2018

Indobufen ($Ibustrin^{(R)}$), a reversible inhibitor of platelet aggregation, exists in two enantiomeric forms in 1:1 ratio. Here, we characterized the anti-platelet effect of S- and R-indobufen using response surface modeling using $NONMEM^{(R)}$ and predicted the therapeutic doses exerting the maximal efficacy of each enantioselective S- and R-indobufen formulation. S- and R-indobufen were added individually or together to 24 plasma samples from drug-naïve healthy subjects, generating 892 samples containing randomly selected concentrations of the drugs of 0-128 mg/L. Collagen-induced platelet aggregation in platelet-rich plasma was determined using a Chrono-log Lumi-Aggregometer. Inhibitory sigmoid $I_{max}$ model adequately described the anti-platelet effect. The S-form was more potent, whereas the R-form showed less inter-individual variation. No significant interaction was observed between the two enantiomers. The anti-platelet effect of multiple treatments with 200 mg indobufen twice daily doses was predicted in the simulation study, and the effect of S- or R-indobufen alone at various doses was predicted to define optimal dosing regimen for each enantiomer. Simulation study predicted that 200 mg twice daily administration of S-indobufen alone will produce more treatment effect than S-and R-mixture formulation. S-indobufen produced treatment effect at lower concentration than R-indobufen. However, inter-individual variation of the pharmacodynamic response was smaller in R-indobufen. The present study suggests the optimal doses of R-and S-enantioselective indobufen formulations in terms of treatment efficacy for patients with thromboembolic problems. The proposed methodology in this study can be applied to the develop novel enantio-selective drugs more efficiently.