• 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.4
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• pp.242-248
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• 2023

Platelets are activated at the sites of vascular injury by a number of molecules, including adenosine diphosphate, collagen and thrombin. The full platelet aggregation is absolutely essential for the normal hemostasis. Glycyrrhiza glabra is a well-known medicinal herb that grows in various parts of the world and is known to have various effects such as antioxidant, anti-inflammatory, anti-atherogenic, anti-osteoporotic and skin-whitening. However, the platelet inhibitory effect of Glycyrrhiza glabra extract (GGE) has not been identified. In this study, we investigated if GGE inhibited platelet aggregation. We observed that GGE inhibited collagen-induced platelet aggregation, Ca²⁺ mobilization, and thromboxane A2 generation. In addition, GGE suppressed phosphorylation of phosphatidylinositol-3 kinase (PI3K), Akt and elevated phosphorylation of inositol 1,4,5-trisphosphate receptor (IP3R), vasodilator stimulated phosphoprotein (VASP). Taken together, GGE showed strong antiplatelet effects and may be used to block platelet-mediated cardiovascular diseases.

• Journal of Yeungnam Medical Science
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• v.40 no.4
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• pp.328-334
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• 2023

An aging population and changes in dietary habits have increased the incidence of diabetes, resulting in complications such as diabetic foot ulcers (DFUs). DFUs can lead to serious disabilities, substantial reductions in patient quality of life, and high financial costs for society. By understanding the etiology and pathophysiology of DFUs, their occurrence can be prevented and managed more effectively. The pathophysiology of DFUs involves metabolic dysfunction, diabetic immunopathy, diabetic neuropathy, and angiopathy. The processes by which hyperglycemia causes peripheral nerve damage are related to adenosine triphosphate deficiency, the polyol pathway, oxidative stress, protein kinase C activity, and proinflammatory processes. In the context of hyperglycemia, the suppression of endothelial nitric oxide production leads to microcirculation atherosclerosis, heightened inflammation, and abnormal intimal growth. Diabetic neuropathy involves sensory, motor, and autonomic neuropathies. The interaction between these neuropathies forms a callus that leads to subcutaneous hemorrhage and skin ulcers. Hyperglycemia causes peripheral vascular changes that result in endothelial cell dysfunction and decreased vasodilator secretion, leading to ischemia. The interplay among these four preceding pathophysiological factors fosters the development and progression of infections in individuals with diabetes. Charcot neuroarthropathy is a chronic and progressive degenerative arthropathy characterized by heightened blood flow, increased calcium dissolution, and repeated minor trauma to insensate joints. Directly and comprehensively addressing the pathogenesis of DFUs could pave the way for the development of innovative treatment approaches with the potential to avoid the most serious complications, including major amputations.

• 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.

• Neonatal Medicine
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• v.18 no.2
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• pp.365-369
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• 2011

Tetralogy of Fallot (TOF) assumes its' most severe form when accompanied by pulmonary atresia (PA). Preserving the patent ductus arteriosus to maintain pulmonary blood flow is life-saving for patients with this congenital heart disease. Milrinone, a selective phosphodiesterase III inhibitor, is a potent vasodilator. Here, we report the successful use of milrinone for a newborn infant with TOF and PA for keeping the ductus arteriosus open and thereby maintaining pulmonary circulation. Milrinone is a useful drug because of its inotropic, lusitropic, and pulmonary vasodilating effects, in addition to its ability to keep the ductus arteriosus open and its relatively mild side-effects. Case series and comparative studies will be needed in the future to verify the effectiveness of this drug.

• Journal of Life Science
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• v.9 no.2
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• pp.201-206
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• 1999

Nitric oxide(NO) is a potent and selective pulmonary artery vasodilator. Erythropoietin(EPO) is produced in the kidney in response to reduced oxygen availability. In this study, blood samples were collected for determination of NO and EPO concentrations in 18 normal newborns and 16 newborns with respiratory distress syndrome(RDS). Serum was measured by Ding's method for NO concentration and by enzyme-linked immunosorbant assay for EPO concentration. Nitric ion concentration in serum was 14.9$\pm$3.2 $\mu$M in normal control group and 12.8$\pm$3.3 $\mu$M in RDS group. EPO concentration in serum was 16.2$\pm$3.4 mU/ml in normal control group and 21.2$\pm$5.4 mU/ml in RDS group. These results show the decrease of NO and increase of EPO in RDS newborn patients in comparison with normal newborns. Such imbalances may contribute to the development of several clinical symptoms.

• The Journal of Korean Medical History
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• v.23 no.1
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• pp.23-41
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• 2010

Greater yang disease(太陽病) is a syndrome induced by peripheral obstruction. One of them is "wind stroke(中風)" with the obstruction in lymphatic system. The other obstruction appearing on circulatory system is called "cold damage(傷寒)." Kyejitang(桂枝湯) is the formula prescribed for greater yang wind stroke pattern(太陽中風證) which is caused by peripheral lymphatic duct obstruction. Ramulus Cinamoni acts as a vasodilator and Radix Paeoniae relieves the abdominal tension. They make blood move to the internal organ and this can remove the retention of peripheral lymphatic system. Covering the patient with a blanket and getting him/her to have hot and thin rice gruel causes slight Diaphoresis, contributing to relieving the retention of lymphatic system. Disharmony between nutrient and defense(營衛不和) means that pressure becomes different between lymphatic system and vascular system. Kyejitang(桂枝湯) is called releasing muscles formula(解肌劑) because it can resolve such pressure difference. Diaphoresis is not a means to eliminate pathogenic qi(邪氣) from the body. That is the syndrome proving that the body fluid has moved around when disordered fluid distribution is corrected. Therefore, diaphoresis should be induced weakly all the time. If diaphoresis is induced excessively, body fluid will move more than desired and then illness cannot be cured. In Sanghanlun(傷寒論), dispersing drugs aim at addressing the retention in the exterior field, but it actually applies to the entire exterior and interior to make body fluid move. Therefore, diaphoresis does not just act on exterior field, and freeing the stool does not only apply to interior field. Distribution of body fluid changed by pathogenic qi(邪氣) influences the whole body because the human body has a closed circulatory system. Sanghanlun(傷寒論) has included treatments for pathogenic disease. However, its value should not be limited to pathogenic disease. It is because controlling blood flow by sending body fluid to the place a doctor wants is certainly worth using for treatment of non-exogenous disease or chronic illnesses.

• Journal of Trauma and Injury
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• v.28 no.3
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• pp.104-107
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• 2015

Purpose: Nitric oxide (NO) is a vasodilator and inhaled NO (iNO) is used in acute respiratory distress syndrome (ARDS) to improve alveolocapillary gas exchange. The mechanism to improve oxygenation is likely to redistribute blood flow from unventilated areas to ventilated areas. Though improvement of oxygenation, iNO therapy has not been shown to improve mortality and considered as only rescue therapy in severe hypoxemia. We conducted the study to investigate an efficacy of iNO in trauma patients with severe hypoxemia. Methods: We reviewed the trauma patients who underwent iNO therapy retrospectively from 2010 to 2014. Degree of hypoxemia was represented as $PaO_2/FiO_2$ ratio (PFR) and the severity of patient was represented with sequential organ failure assessment (SOFA) score. Patients were divided into the survivor group and non-survivor group according to the 28-day mortality. Results: A total of 20 patients were enrolled. The mortality of 28-day was 40%. There were no significant differences between survivor and non-survivor group in age, sex, severity of injury, PFR and SOFA score. There was significant difference in initiation time of iNO after injury (p=0.047). Maximum combinations of sensitivity and specificity for timing of iNO therapy were observed using cut-off of 3-day after injury with a sensitivity of 88% and specificity of 75%. Conclusion: Though iNO therapy does not influence the mortality, iNO therapy may decrease the mortality caused by respiratory failure in the early phase of trauma.

• Journal of Chest Surgery
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• v.24 no.5
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• pp.429-437
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• 1991

Beta hydroxytrimethylammonium butyrate[L-carnitine] is highly concentrated in myocardium and it is essential substance for transfer of fatty acids into the mitochondria. We respect that L-carnitine has protective action to myocardium during ischemia. I studied coronary flow and CK - MB isoenzyme of coronary effluent of Langendorff`s isolated rat heart model. As a control group 5 Sprague-Dowley species rat hearts were connected to Langendorff`s isolated rat heart model and perfused for 30 minutes with Kreb-Henseleit buffer solution. After cessation of perfusion for 30 minutes they were reperfused for 30 minutes. In experimental group 10 Sprague-Dowley species rat hearts were perfused with 10mmole /L of L-carnitine contained in Kleb-Henseleit buffer solution. In equilibrium state, coronary flow was 1.7 times greater in experimental group. During reperfusion, both group showed equally decreased flow amount of about 60% of that of equilibrium state. CK-MB isoenzyme level of perfused coronary fluid showed no significant difference in equilibrium state. In reperfusion. CK-MB isoenzyme levels of control group were 17.61$\pm$8. 68U/L at 25 minutes, 23.32$\pm$4.15U /L at 30 minutes; and in experimental group, 13.63$\pm$6. 08U/L at 15 minutes and 13.6$\pm$8.41U /L at 30 minutes respectively. Those values in both states showed significantly lower CK-MB level in experimental group. In conclusion, L-carnitine prevent ischemic myocardial damage during ischemic and reperfusion state of Langendorff`s isolated rat hearts and also I suggest the L-carnitine act potent coronary vasodilator during preischemic and postischemic states of rat hearts.

• Journal of Chest Surgery
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• v.28 no.8
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• pp.742-746
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• 1995

The present study was aimed at investigating possible transmitter mechanisms in the endothelial cell layer in regulating the tone of the vascular smooth muscle. The thoracic aorta was isolated from the anesthetized male white rabbits and its helical strips were prepared. Electrical field stimulation was delivered to platinum wire electrodes positioned parallel to the vessel segment preconstricted with phenylephrine [3.5x10-6 mol/L at a distance of 1.5-2.0 mm. The electrical stimulation [70 V, 5 msec, 0.5-200 Hz caused either relaxation only [34% or a biphasic response [prolonged relaxation following a weak and transient contraction, 66% . The relaxation response was frequency- dependent, and at 200 Hz a complete relaxation was noted. Mechanical rubbing of the endothelial layer abolished or greatly attenuated the relaxation. The relaxation was also markedly attenuated in the presence of NG-nitro- L-arginine methyl ester [10-3mol/L or procaine hydrochloride [3.5x10-4mol/L . Tetrodotoxin,guanethidine, atropine or indomethacin failed to block or enhance the relaxation response to electrical field stimulation. It is concluded that the vascular endothelium in the aorta contains diffusible substances that regulates the function of the smooth muscle layer, in which relaxation is more prominent than contraction. Their release by the electrical stimualtion in vitro may not involve classic neuronal transmitter release mechanisms or metabolism of arachidonic acids by cyclooxygenase. The release of the relaxing agents may require an increase in cytosolic calcium level. The chemical nature of the relaxant may be, to a large extent, nitric oxide.