• The Korean Journal of Physiology and Pharmacology
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• 제17권4호
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• pp.283-289
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• 2013

This study was designed to evaluate the protective effect of Korean red ginseng (KRG) against ischemia/reperfusion (I/R) injury in isolated guinea pig heart. KRG has been shown to possess various ginsenosides, which are the major components of Panax ginseng. These components are known naturally occurring compounds with beneficial effects and free radical scavenging activity. The heart was induced to ischemia for 60 min, followed by 120 min reperfusion. The hearts were randomly allocated into five groups (n=8 for each group): normal control (N/C), KRG control, I/R control, 250 mg/kg KRG group and 500 mg/kg KRG group. KRG significantly increased hemodynamics parameters such as aortic flow, coronary flow and cardiac output. Moreover, KRG significantly increased left ventricular systolic pressure (LVSP), the maximal rate of contraction (+dP/$dt_{max}$) and maximal rate of relaxation (-dP/$dt_{max}$). Also, treatment of KRG ameliorated electrocardiographic index such as the QRS, QT and RR intervals. Moreover, KRG significantly suppressed the lactate dehydrogenase, creatine kinase-MB fraction and cardiac troponin I and ameliorated the oxidative stress markers such as malondialdehyde and glutathione. KRG was standardized through ultra performance liquid chromatograph analysis for its major ginsenosides. Taken together, KRG has been shown to prevent cardiac injury by normalizing the biochemical and oxidative stress.

• BMB Reports
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• 제43권11호
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• pp.756-760
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• 2010

Recent studies have reported that delayed-rectifier Kv channels regulate apoptosis in the nervous system. Herein, we investigated changes in the expression of the delayed-rectifier Kv channels Kv1.2, Kv2.1, and Kv3.1 after acute spinal cord injury (SCI) in rats. We performed RT-PCR analysis and found an increase in the level of Kv2.1 mRNA after SCI but no significant changes in the levels of Kv1.2 and Kv3.1 mRNA. Western blot analysis revealed that Kv2.1 protein levels rapidly decreased and then dramatically increased from 1 day, whereas Kv3.1b protein levels gradually and sharply decreased at 5 days. Kv1.2 protein levels did not change significantly. In addition, Kv2.1 clusters were disrupted in the plasma membranes of motor neurons after SCI. Interestingly, the expressional changes and translocation of Kv2.1 were consistent with the apoptotic changes on day 1. Therefore, these results suggest that Kv2.1 channels probably contribute to neuronal cell responses to SCI.

• 대한약침학회지
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• 제21권3호
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• pp.159-167
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• 2018

Objectives: Myocardial reperfusion is the only logical cure for ischemic heart disease. However, ischemic-reperfusion (I/R) injury is one of the underlying factors facilitating and accelerating the apoptosis in the myocardium. This study set to investigate the impact of Teucrium polium (TP) hydro-alcoholic extract on I/R induced apoptosis in the isolated rat heart. Methods: Isolated rat hearts were classified into six groups. The control samples were subjected to 80 min of perfusion with Krebs-Henseleit bicarbonate (KHB) buffer; in control-ischemia group, after primary perfusion (20 min) the hearts were exposed to global ischemia (20 min) and reperfusion (40 min). Pretreated groups were perfused with $500{\mu}M$ of vitamin C and various TP concentrations (0.5, 1, 2 mg/ml) for 20 min, and then the hearts were exposed to ischemia and reperfusion for 20 min and 40 min, respectively. Cardiodynamic parameters including rate pressure product (RPP), heart rate (HR), the maximum up/down rate of left ventricular pressure (${\pm}dp/dt$), left ventricular developed pressure (LVDP), and coronary artery flow (CF) were achieved from Lab Chart software data. The Bax and BCl-2 gene expressions were measured in heart samples. Results: Hearts treated with TP extract and vit C represented a meaningful improvement in cardiac contractile function and CF. The overexpression of Bcl-2, downregulation of Bax, and improvement of apoptotic index (Bax/Bcl-2) were observed in pretreated TP extract and vit C hearts. Conclusion: The TP extract was found to ameliorate the cardiac function in the reperfused myocardium. Also, it can hinder apoptotic pathways causing cardioprotection.

• 약학회지
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• 제41권6호
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• pp.829-836
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• 1997

Studies on the effect of quinones on cardiac function has been conducted with normal hearts. But not with injured hearts, I.e. ischemia/reperfusion-injured heart. Quinone compounds are known to produce oxygen free radicals during metabolism, and for this reason, quinones are implicated in the aggravation of ischemia/reperfusion injury or cardioprotection, as in the case of ischemic preconditioning depending on the experimental conditions. The present study was carried out to examine the effect of 2-chloro-3-(4-cyanophenylamino)-1.4-naphthoquinone (NQ-Y15) on cardiac function of ischemic/reperfused and normal rat hearts. In isolated perfused hearts, various functional parameters such as left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure (EDP) and maximum positive and negative dP/dt ($[\pm}dP/dt_{max}$), time to contracture, heart rate (HR) and coronary flow rate (CFR) were measured before and 30 min after dosing and following 25 min ischemia/30min reperfusion. NQ-Y15 increased LVDP, +dP/$d_{max}$and -dP/$dt_{min}$ by 18%. 30%, and 40%, respectively. There were no significant changes in other haemodynamic parameters. After ischemia/reperfusion injury, pretreatment with NQ-Y15 induced a significant decrease in LVDP and $[\pm}dP/dt_{max}$, but an increase in EDP. LDH-release was not significantly increased. These results suggested that NQ-Y15 may augment the ventricular contractility but it makes hearts more vulnerable to ischemia/reperfusion injury.

• The Korean Journal of Pain
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• 제21권3호
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• pp.187-196
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• 2008

Background: Upregulation of one type of the pro-inflammatory chemokine (CCL2) and its receptor (CCR2) following peripheral nerve injury contributes to the induction of neuropathic pain. Here, we examined whether another type of chemokine (CCL3) is involved in neuropathic pain. Methods: We measured changes in mechanical and thermal sensitivity in the hind paws of naïve rats or rats with an L5 spinal nerve ligation (SNL) after intra-plantar injection of CCL3 or met-RANTES, an antagonist of the CCL3 receptor, CCR1. We also measured CCL3 levels in the sciatic nerve and the hind paw skin as well as CCR1 expression in dorsal root ganglion (DRG) cells from the lumbar spinal segments. Results: Intra-plantar injection of CCL3 into the hind paw of naive rats mimicked L5 SNL-produced hyperalgesia. Intra-plantar injection of met-RANTES into the hind paw of rats with L5 SNL attenuated hyperalgesia. L5 SNL increased CCL3 levels in the sciatic nerve and the hind paw skin on the affected side. The number of CCR1-positive DRG cells in the lumbar segments was not changed following L5 SNL. Conclusions: Partial peripheral nerve injury increases local CCL3 levels along the degenerating axons during Wallerian degeneration. This CCL3 binds to its receptor, CCR1, located on adjacent uninjured afferents, presumably nociceptors, to induce hyperalgesia in the neuropathic pain state.

• The Korean Journal of Physiology and Pharmacology
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• 제20권3호
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• pp.315-324
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• 2016

Human cardiac fibroblasts (HCFs) have various voltage-dependent $K^+$ channels (VDKCs) that can induce apoptosis. Hydrogen peroxide ($H_2O_2$) modulates VDKCs and induces oxidative stress, which is the main contributor to cardiac injury and cardiac remodeling. We investigated whether $H_2O_2$ could modulate VDKCs in HCFs and induce cell injury through this process. In whole-cell mode patch-clamp recordings, application of $H_2O_2$ stimulated $Ca^{2+}-activated$ $K^+$ ($K_{Ca}$) currents but not delayed rectifier $K^+$ or transient outward $K^+$ currents, all of which are VDKCs. $H_2O_2-stimulated$ $K_{Ca}$ currents were blocked by iberiotoxin (IbTX, a large conductance $K_{Ca}$ blocker). The $H_2O_2-stimulating$ effect on large-conductance $K_{Ca}$ ($BK_{Ca}$) currents was also blocked by KT5823 (a protein kinase G inhibitor) and 1 H-[1, 2, 4] oxadiazolo-[4, 3-a] quinoxalin-1-one (ODQ, a soluble guanylate cyclase inhibitor). In addition, 8-bromo-cyclic guanosine 3', 5'-monophosphate (8-Br-cGMP) stimulated $BK_{Ca}$ currents. In contrast, KT5720 and H-89 (protein kinase A inhibitors) did not block the $H_2O_2-stimulating$ effect on $BK_{Ca}$ currents. Using RT-PCR and western blot analysis, three subtypes of $K_{Ca}$ channels were detected in HCFs: $BK_{Ca}$ channels, small-conductance $K_{Ca}$ ($SK_{Ca}$) channels, and intermediate-conductance $K_{Ca}$ ($IK_{Ca}$) channels. In the annexin V/propidium iodide assay, apoptotic changes in HCFs increased in response to $H_2O_2$, but IbTX decreased $H_2O_2$-induced apoptosis. These data suggest that among the VDKCs of HCFs, $H_2O_2$ only enhances $BK_{Ca}$ currents through the protein kinase G pathway but not the protein kinase A pathway, and is involved in cell injury through $BK_{Ca}$ channels.

• 대한약리학회:학술대회논문집
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• 대한약리학회 2006년도 The 6th Congress of the Federation of Asian and Oceanian Physiological Societies
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• pp.73-73
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• 2006

• The Korean Journal of Physiology and Pharmacology
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• 제22권2호
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• pp.145-153
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• 2018

The subgranular zone (SGZ) of hippocampal dentate gyrus (HDG) is a primary site of adult neurogenesis. Toll-like receptors (TLRs), are involved in neural system development of Drosophila and innate immune response of mammals. TLR2 is expressed abundantly in neurogenic niches such as adult mammalian hippocampus. It regulates adult hippocampal neurogenesis. However, the role of TLR2 in adult neurogenesis is not well studied in global or focal cerebral ischemia. Therefore, this study aimed to investigate the role of TLR2 in adult neurogenesis after photochemically induced cerebral ischemia. At 7 days after photothrombotic ischemic injury, the number of bromodeoxyuridine (BrdU)-positive cells was increased in both TLR2 knock-out (KO) mice and wild-type (WT) mice. However, the increment rate of BrdU-positive cells was lower in TLR2 KO mice compared to that in WT mice. The number of doublecortin (DCX) and neuronal nuclei (NeuN)-positive cells in HDG was decreased after photothrombotic ischemia in TLR2 KO mice compared to that in WT mice. The survival rate of cells in HDG was decreased in TLR2 KO mice compared to that in WT mice. In contrast, the number of cleaved-caspase 3 (apoptotic marker) and the number of GFAP (glia marker)/BrdU double-positive cells in TLR2 KO mice were higher than that in WT mice. These results suggest that TLR2 can promote adult neurogenesis from neural stem cell of hippocampal dentate gyrus through increasing proliferation, differentiation, and survival from neural stem cells after ischemic injury of the brain.

• Biomolecules & Therapeutics
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• 제6권4호
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• pp.358-363
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• 1998

Intravenous lipid emulsion is used extensively as a major component of parenteral nutrition for patients in the surgical intensive care unit. Abnormal cardiovascular function related to lipid infusion has been reported although conflicting results exist. In the present study, we investigated the effects of intravenous emulsions of long-chain triglyceride (LCT) and medium-chain triglyceride (MCT) on myocardial ischemia/ reperfusion injury and on platelet aggregation in rat. There was no difference between LCT and MCT considering the effects on left ventricular developed pressure (LVDP) and coronary flow rate (CFR) before and after ischemia/reperfusion in isolated rat heart. On the other hand, a difference was found between LCT and MCT with regard to their effects on heart rate (HR) and end diastolic pressure (EDP) after ischemia/reperfusion. After ischemia/reperfusion, HR was significantly (P<0.05) reduced and EDP significantly (P<0.05) inc.eased by LCT (18$\pm$2.0% and 42.8$\pm$8.9%, respectively), but not by MCT Ex vivo platelet aggregation induced by collagen was reduced by LCT infusion, but not by MCT These findings suggest that MCT may have slightly more favorable effect than LCT on the myocardial function after ischemia/reperfusion in rat.

• Journal of Ginseng Research
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• 제28권1호
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• pp.18-26
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• 2004

The effect of Panax ginseng administration in muscle inflammatory process induced after eccentric exercise, that causes myofibrillar disruption, was studied. Changes in lipid peroxidation, inflammation, glycogen levels in muscle and release of myocellular proteins to blood were measured. The analyses were performed immediately after eccentric exercise and over week since this period are necessary for the muscle damage-repair cycle. The ginseng extract (100 mg kg$^{-1}$ ) was orally administered to rats for three months, before the eccentric exercise performance. The results showed the protective role of ginseng against skeletal muscle damage. This effect could be associated with their membrane stabilising capacity since creatine kinase (CK) activity was significantly decreased 96 h post-exercise from 523$\pm$70 to 381$\pm$53 and 120 h post-exercise from 443$\pm$85 to 327$\pm$75 in treated animals. $\beta$-glucuronidase activity, as indicator of inflammation, showed a significant reduction of about 15-25% in soleus, vastus and triceps in these post-exercise times. The lipid peroxidation, measured by malondyaldehyde levels, was significantly decreased in the 24 h post-exercise period in soleus and vastus intermedius muscles and on the recovery period. Finally ginseng administration reduced significantly the decrease of the glycogen levels immediately after exercise and when the regenerative process took place (72-168 h post exercise). Collectively, the results have showed that ginseng did not inhibit the vital inflammatory response process associated with the muscle damage-repair cycle but presumably ameliorate the injury.