• Journal of Korean Neurosurgical Society
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• 제55권3호
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• pp.125-130
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• 2014

Objective : This study was conducted to elucidate neuroprotective effect of carnosine in early stage of stroke. Methods : Early stage of rodent stroke model and neuroblastoma chemical hypoxia model was established by middle cerebral artery occlusion and antimycin A. Neuroprotective effect of carnosine was investigated with 100, 250, and 500 mg of carnosine treatment. And antioxidant expression was analyzed by enzyme linked immunosorbent assay (ELISA) and western blot in brain and blood. Results : Intraperitoneal injection of 500 mg carnosine induced significant decrease of infarct volume and expansion of penumbra (p<0.05). The expression of superoxide dismutase (SOD) showed significant increase than in saline group in blood and brain (p<0.05). In the analysis of chemical hypoxia, carnosine induced increase of neuronal cell viability and decrease of reactive oxygen species (ROS) production. Conclusion : Carnosine has neuroprotective property which was related to antioxidant capacity in early stage of stroke. And, the oxidative stress should be considered one of major factor in early ischemic stroke.

• 동의생리병리학회지
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• 제21권1호
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• pp.117-125
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• 2007

Neuronal ischemia is a pathological process caused by a lack of oxygen (anoxia) and glucose (hypoglycemia), resulting in neuronal death. It is believed that apoptosis is one of the mechanisms involved in ischemic cell death. Neuronal apoptosis is a process characterized by nuclear DNA fragmentation, changes of plasma membrane organization. To elucidate the mechanism of neuronal death following ischemic insult and to develop neuroprotective effects of Daebowonjeon(DBWJ) against ischemic damage, in vitro models are used. In vitro models of cell death have been devloped with pheochromocytoma (PC12) cell, which have become widely used as neuronal models of oxidative stress, trophic factor, serum deprivation and chemical hypoxia. Using a special ischemic device and PC12 cultures, we investigated an in vitro model of ischemia based on combined Oxygen and Glucose Deprivation (OGD) insult, followed by reoxygenation, mimicking the pathological conditions of ischemia. In this study, Daebowonjeon rescued PC12 cells from Oxygen-Glucose Deprivation (OGD)-induced cell death in a dose-dependent manner The nuclear staining of PC12 cells clearly showed that DBWJ attenuated nuclear condensation and fragmentation which represent typical neuronal apoptotic characteristics. DBWJ also prevents the LDH release and induction of Hypoxia Inducing Factor (HIF)-1 by OGD-exposed PC12 cells. Furthermore, DBWJ reduced the activation of polyADP-ribose polymerase (PARP) by OGO-exposed PC12 cells. These results suggest that apoptosis is an important characteristic of OGD-induced neuronal death and that oriental medicine, such as DBWJ, may prevent PC12 cell from OG D-induced neuronal death by inhibiting the apoptotic process.

• 약학회지
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• 제44권6호
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• pp.558-565
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• 2000

SK-1080 is one of the newly developed orally active nonpeptide angiotensinII $AT_1-receptor$ antagonist that selectively acts at $AT_1$ receptor with high affinity. The cardiac effect on ischemia/reperfusion injury of SK-1080 was compared with those of losartan, a prototype of this class, in isolated rat hearts. Isolated perfused rat heart was pretreated with drug for 10 min and then subjected to global ischemia for 30 min followed by reperfusion with- or without drug for 30 min. The possible additive effect of SK-1080 on the platelet aggregation and coagulation in human blood was also studied. We investigated whether SK-1080 effects the platelet aggregation induced by ADP, a platelet agonist partially dependent on $thromboxaneA_2$. The clotting times in the prothrombin time (PT) and activated partial thromboplastin time (APTT) were also examined in human plasma in vitro as coagulation screening test. SK-1080 improved reperfusion function (LVDP, left ventricular developed pressure; PRP, rate-pressure product) in a dose-dependent manner. SK-1080 reduced ADP-induced platelet aggregation compared with vehicle but less than losartan, and did not affect clotting times.

• 대한본초학회지
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• 제28권2호
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• pp.45-53
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• 2013

Objectives : The purpose of the study is to determine the neuroprotective effects of the water and 80% EtOH extract of some herbal medicine plant on ischemia reperfusion-induced cell death in SK-N-SH human brain neuronal cells. Methods : SK-N-SH cells were treated with 3mM sodium azide and 10 mM 2-deoxy-D-glucose for 45 min, ptior to the addition of different concentrations of herbal medicine plant extract (0, 10, 25, 50, 100, 250, 500, 1000 ${\mu}g/ml$) for 2 hr and then reperfused with growth medium, incubated for 24 h. Cell viability was determined by WST-1 assay, and ATP/ADP levels were measured by ADP/ATP ratio assay kit. Results : Herbal medicine plant extract significantly inhibited decreasing the cell viability in ischemia-induced SK-N-SH cells. Also increased the ratio of ADP/ATP in ischemia-induced neuronal cells. Conclusions : Our results suggest that herbal medicine plant extract has a neuroprotective property via increasing the energy levels in neuronal cells, suggesting that extract may has a therapeutic potential in the treatment of ischemic brain injury. The exact component and mechanism remains for the future study.

• The Korean Journal of Physiology and Pharmacology
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• 제21권2호
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• pp.145-152
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• 2017

Remote ischemic preconditioning (RIPC) is an intrinsic phenomenon whereby 3~4 consecutive ischemia-reperfusion cycles to a remote tissue (non-cardiac) increases the tolerance of the myocardium to sustained ischemia-reperfusion induced injury. Remote ischemic preconditioning induces the local release of chemical mediators which activate the sensory nerve endings to convey signals to the brain. The latter consequently stimulates the efferent nerve endings innervating the myocardium to induce cardioprotection. Indeed, RIPC-induced cardioprotective effects are reliant on the presence of intact neuronal pathways, which has been confirmed using nerve resection of nerves including femoral nerve, vagus nerve, and sciatic nerve. The involvement of neurogenic signaling has been further substantiated using various pharmacological modulators including hexamethonium and trimetaphan. The present review focuses on the potential involvement of neurogenic pathways in mediating remote ischemic preconditioning-induced cardioprotection.

• Bulletin of the Korean Chemical Society
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• 제30권11호
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• pp.2621-2625
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• 2009

To identify a non-acylguanidine NHE-1 inhibitor, an acylguanidne group was replaced with an imidazole group in the potent NHE-1 inhibitors with furan or benzothiphene core template, found from our previous studies. We synthesized and biologically evaluated 4-heteroaryl-2-amino-5-methylimidazole derivatives. All those imidazole compounds (16-18) represented the potent NHE-1 inhibitory activities, similar to the corresponding acylguanidine compounds.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.286.2-287
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• 2003

The purpose of this paper was to identify the metabolic pathway of a new neuroprotective agent, KR-31543 for ischemia-reperfusion damage in human liver microsomes and characterize cytochrome P450 (CYP) enzymes involved in the in vitro metabolism of KR-31543 generates two metabolites in human liver microsomes : M1, N-(4-chlorophenyl)-N-(2-methyl-2H-tetrazol-5-ylmethyl)amine and M2, hydroxy-KR-31543. (omitted)

• Biomolecules & Therapeutics
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• 제7권2호
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• pp.170-177
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• 1999

PEG-hemoglobin SB1 (SB1), which is a hemoglobin-based oxygen carrier, is intended to use as a safe blood substitute against brain ischemia and stroke. The general pharmacological profiles of SB1 were studied. The doses given were 0, 5, 10, 20 ml/kg and drugs were administered intravenously. The animals used for this study were mouse, rat and guinea pig. SB1 showed no effects on general behavior, motor coordination, spontaneous locomotor activity, hexobarbital sleeping time, anticonvulsant activity, analgesic activity, blood pressure and heart rate, left ventricular peak systolic pressure, left ventricular end diastolic pressure, left ventricular developing pressure, double product, heart rate, coronary flow rate, smooth muscle contraction using guinea pig ileum, gastrointestinal transport, gastric secretion, urinary volume and electrolyte excretion at all doses tested except the decrease of body temperature. These findings demonstrated that SB1 possesses no general pharmacological effects at all doses tested.

• 대한약학회:학술대회논문집
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• 대한약학회 2001년도 Proceedings of International Convention of the Pharmaceutical Society of Korea
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• pp.306.2-307
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• 2001

• 한국임상약학회지
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• 제6권2호
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• pp.32-40
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• 1996

The electrophysiological effects of benzopyran potassium channel openers (PCOs: lemakalim, KR-30450 and KR-30818) on the ischemia/reperfusion-induced arrythmias were investigated. In anesthetized rats, subjected to 45 min occlusion of the left anterior descending coronary artery (LAD) followed by 90 min reperfusion, ventricular arrythmias were identified according to the Lambeth Conventions by lead II ECG. Rats were intravenously given vehicle ($1\%$ DMSO), lemakalim, KR-30450, and KR-30818 alone or in combination with a selective $K_{ATP}$ blocker glibenclamide, 30 min prior to coronary occlusion. Compared to vehicle, lemakalim ($30{\mu}g/kg$ i.v.), the active enantiomer of cromakalim, had a tendancy to increase the duration of ventricular tachycardia (Vl) and ventricular fibrillation (VF), the number of premature ventricular complexes (PVC) and the incidence of VF, especially in the early post-occlusion peroid ($0\~15$ min), while increasing ST-segment elevation. Both KR-30450 ($30{\mu}g/kg$, i.v.) and KR-30818 (30, $100{\mu}g/kg$, i.v.) showed similar proarrhythmic effects to lemakalim (PVC, duration of VT, and incidence of VF) with a tendancy to decrease the duration of VF and ST-segment elevation. Unlike other PCOs, however, glibenclamide (0.3, 1.0 mg/kg) had opposite effects on the induction of arrhythmias (PVC, the duration of VF); it had a tendancy to increase the duration of VT with a slight elevation of ST-segment. It seems likely that glibenclamide (0.3 mg/kg, i.v.), reduced the effects of lemakalim or KR-30450 ($30{\mu}g/kg$, i.v.) on arrhythmias (PVC, VT, VF and ST-segment). These results indicate that, in the coronary occluded rat model of ischemia, lemikuiln and KR-30450 exert a proarrhythmic activity, the effect being considered related to the opening of KATP channel.