• Korean Journal of Plant Resources
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• v.32 no.4
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• pp.282-289
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• 2019

Gastritis is an inflammatory disease involving the stomach and is caused by several factors, including stress, non-steroidal anti-inflammatory drugs such as aspirin, liquor, and Helicobacter pylori. In Korea, Leonurus japonicus Houttuyn (LJW) has been used as traditional medicine for vaginal bleeding, hematuria, and bruise. Previous studies have reported that LJW exhibited hepatoprotective, cardioprotective, and anti-hyperlipidemic effect. However, the effect of the water extract of LJW on gastritis was not elucidated. Thus, we evaluated the anti-gastric effect and genotoxicity of LJW. LJW effectively prevented the degeneration of surface mucous cells and glandular epithelial cells and vascular congestion induced by HCl/EtOH. Micronucleus assay indicated that the rate of micronucleated polychromatic erythrocytes/polychromatic erythrocytes was not significantly different compared that of the control. Further experiments are required to determine the role of LJW in the gastric injury process such as cyclooxygenase signaling pathway and the secretion of mucus in the stomach.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.5
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• pp.335-345
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• 2022

Pyroptosis is an inflammatory form of programmed cell death that is linked with invading intracellular pathogens. Cardiac pyroptosis has a significant role in coronary microembolization (CME), thus causing myocardial injury. Tanshinone IIA (Tan IIA) has powerful cardioprotective effects. Hence, this study aimed to identify the effect of Tan IIA on CME and its underlying mechanism. Forty Sprague-Dawley (SD) rats were randomly grouped into sham, CME, CME + low-dose Tan IIA, and CME + high-dose Tan IIA groups. Except for the sham group, polyethylene microspheres (42 ㎛) were injected to establish the CME model. The Tan-L and Tan-H groups received intraperitoneal Tan IIA for 7 days before CME. After CME, cardiac function, myocardial histopathology, and serum myocardial injury markers were assessed. The expression of pyroptosis-associated molecules and TLR4/MyD88/NF-κB/NLRP3 cascade was evaluated by qRT-PCR, Western blotting, ELISA, and IHC. Relative to the sham group, CME group's cardiac functions were significantly reduced, with a high level of serum myocardial injury markers, and microinfarct area. Also, the levels of caspase-1 p20, GSDMD-N, IL-18, IL-1β, TLR4, MyD88, p-NF-κB p65, NLRP3, and ASC expression were increased. Relative to the CME group, the Tan-H and Tan-L groups had considerably improved cardiac functions, with a considerably low level of serum myocardial injury markers and microinfarct area. Tan IIA can reduce the levels of pyroptosis-associated mRNA and protein, which may be caused by inhibiting TLR4/MyD88/NF-κB/NLRP3 cascade. In conclusion, Tanshinone IIA can suppress cardiomyocyte pyroptosis probably through modulating the TLR4/MyD88/NF-κB/NLRP3 cascade, lowering cardiac dysfunction, and myocardial damage.

• Herbal Formula Science
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• v.31 no.3
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• pp.157-169
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• 2023

Gracilaria Verrucosa (GV), a seaweed used in traditional Korean medicine, was studied for its effects on MI-induced heart failure in rats. MI is caused by a blocked coronary artery, leading to severe cardiac dysfunction. The study used a rat model to assess cardiac changes over time and evaluate the impact of GV on heart failure. Ischemia was induced through LAD ligation surgery, and the extent of ischemic area was measured as a prognostic factor. GV extract administration significantly improved cardiac morphology and reduced cardiac weight compared to the MI group. GV treatment also improved cardiac function, as evidenced by positive effects on chamber dilation during MI-induced heart failure. Parameters such as ejection fraction (EF) and fractional shortening (FS) were measured. The MI group showed decreased EF and FS compared to the sham group, while these parameters improved in the GV group. GV treatment also reduced levels of LDH, CPK, and CK-MB in the serum, indicating reduced myocardial damage. Histological analysis revealed that GV treatment attenuated cardiac hypertrophy and fibrosis, with reduced collagen deposition in the myocardium. Immunohistochemistry analysis showed suppressed expression of TGF-β1 and collagen 1, involved in fibrosis. In conclusion, GV showed potential in improving cardiac function in a rat model of MI-induced heart failure. It alleviated myocardial damage, attenuated cardiac hypertrophy and fibrosis, and suppressed fibrotic markers. Further studies are needed to explore its clinical efficacy and underlying mechanisms in cardiac diseases beyond animal models.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.2
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• pp.143-155
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• 2023

Percutaneous coronary intervention and acute coronary syndrome are both closely tied to the frequently occurring complication of coronary microembolization (CME). Resveratrol (RES) has been shown to have a substantial cardioprotective influence in a variety of cardiac diseases, though its function and potential mechanistic involvement in CME are still unclear. The forty Sprague-Dawley rats were divided into four groups randomly: CME, CME + RES (25 mg/kg), CME + RES (50 mg/kg), and sham (10 rats per group). The CME model was developed. Echocardiography, levels of myocardial injury markers in the serum, and histopathology of the myocardium were used to assess the function of the cardiac muscle. For the detection of the signaling of TLR4/MyD88/NF-κB along with the expression of pyroptosis-related molecules, ELISA, qRT-PCR, immunofluorescence, and Western blotting were used, among other techniques. The findings revealed that myocardial injury and pyroptosis occurred in the myocardium following CME, with a decreased function of cardiac, increased levels of serum myocardial injury markers, increased area of microinfarct, as well as a rise in the expression levels of pyroptosis-related molecules. In addition to this, pretreatment with resveratrol reduced the severity of myocardial injury after CME by improving cardiac dysfunction, decreasing serum myocardial injury markers, decreasing microinfarct area, and decreasing cardiomyocyte pyroptosis, primarily by blocking the signaling of TLR4/MyD88/NF-κB and also reducing the NLRP3 inflammasome activation. Resveratrol may be able to alleviate CME-induced myocardial pyroptosis and cardiac dysfunction by impeding the activation of NLRP3 inflammasome and the signaling pathway of TLR4/MyD88/NF-κB.

• BMB Reports
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• v.56 no.12
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• pp.663-668
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• 2023

C-reactive protein (CRP) is an inflammatory marker and risk factor for atherosclerosis and cardiovascular diseases. However, the mechanism through which CRP induces myocardial damage remains unclear. This study aimed to determine how CRP damages cardiomyocytes via the change of mitochondrial dynamics and whether survivin, an anti-apoptotic protein, exerts a cardioprotective effect in this process. We treated H9c2 cardiomyocytes with CRP and found increased intracellular ROS production and shortened mitochondrial length. CRP treatment phosphorylated ERK1/2 and promoted increased expression, phosphorylation, and translocation of DRP1, a mitochondrial fission-related protein, from the cytoplasm to the mitochondria. The expression of mitophagy proteins PINK1 and PARK2 was also increased by CRP. YAP, a transcriptional regulator of PINK1 and PARK2, was also increased by CRP. Knockdown of YAP prevented CRP-induced increases in DRP1, PINK1, and PARK2. Furthermore, CRP-induced changes in the expression of DRP1 and increases in YAP, PINK1, and PARK2 were inhibited by ERK1/2 inhibition, suggesting that ERK1/2 signaling is involved in CRP-induced mitochondrial fission. We treated H9c2 cardiomyocytes with a recombinant TAT-survivin protein before CRP treatment, which reduced CRP-induced ROS accumulation and reduced mitochondrial fission. CRP-induced activation of ERK1/2 and increases in the expression and activity of YAP and its downstream mitochondrial proteins were inhibited by TAT-survivin. This study shows that mitochondrial fission occurs during CRP-induced cardiomyocyte damage and that the ERK1/2-YAP axis is involved in this process, and identifies that survivin alters these mechanisms to prevent CRP-induced mitochondrial damage.

• The Korean Journal of Pharmacology
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• v.30 no.3
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• pp.321-330
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• 1994

The protective effect of 'ischemic preconditioning (PC)' on ischemia-reperfusion injury of heart has been reported in various animal species, but without known mechanisms in detail. In an attempt to investigate the cardioprotective mechanism of PC, we examined the effects of PC on the myocardial oxidative injuries and the oxygen free radical production in the ischemia-reperfusion model of isolated Langendorff preparations of rat hearts. PC was performed with three episodes of 5 min ischemia and 5 min reperfusion before the induction of prolonged ischemia (30 min)-reperfusion(20 min). PC prevented the depression of cardiac function (left ventricular pressure x heart rate) observed in the ischemic-reperfused heart, and reduced the release of lactate dehydrogenase during the reperfusion period. On electron microscopic pictures, myocardial ultrastructures were relatively well preserved in PC hearts as compared with non-PC ischemic-reperfused hearts. In PC hearts, lipid peroxidation of myocardial tissue as estimated from malondialdehyde production was markedly reduced. PC did not affect the activity of xanthine oxidase which is a major source of oxygen radicals in the ischemic rat hearts, but the myocardial content of hypoxanthine (a substrate for xanthine oxidase) was much lower in PC hearts. It is suggested from these results that PC brings about significant myocardial protection in ischemic-reperfused heart and this effect may be related to the suppression of oxygen free radical reactions.

• Journal of Chest Surgery
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• v.36 no.11
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• pp.799-811
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• 2003

Background: The aim of this study is to define the cardioprotective effects (hemodynamic, cytochemical and ultrastructural of the newly developed Histidine-Tryptophan-Ketoglutarate (HTK) cardioplegia compared to DelNido cardioplegia. Material and Method: Seventy-nine isolated rat hearts were divided into three groups on the basis of techniques of cardioplegia infusion. Twenty-eight hearts (Group 1) were flushed with cold DelNido cardioplegia with every 40 minutes for 2 hours. Twenty-seven hearts (Group 2) were flushed with cold HTK cardioplegia for once during the 2 hours. Twenty-four hearts (Group 3) were flushed with cold HTK cardioplegia with every 40 minutes for 2 hours. Heart rate, left ventricular developed pressure (LVDP), changes of + dp/dt max, coronary flow, and rate-pressure product value were measured at pre-ischemic, post-reperfusion 15 minutes, 30 minutes, and 45 minutes for hemodynamic study. Aspartate aminotransferase (AST), lactate dehydrogenase (LD), creatine kinase (CK), CK-MB, troponin-I, myoglobin, and lactate were measured at pre-ischemic and post-reperfusion 45 minutes for cytochemical parameters. Mitochondrial scores were counted in 3 cases from each group for ultrastructural assessment. Result: In hemodynamic study, there were no significant differences among group 1, group 2, and group 3. However, the decrease values of heart rate in group 2 and 3 exhibited significantly lower values than in group 1. In cytochemical study, there were no significant differences among group 1, group 2, and group 3. However, the increase values of lactate in group 2 and 3 exhibited significantly lower values than in group 1. In ultrastructural assessment, the mean myocardial mitochondria scores in group 1, group 2, and group 3 were 2.14$\pm$0.10, 1.52$\pm$0.57, and 2.10$\pm$0.16. Conclusion: HTK solution provides adequate myocardial protection with some advantages over DelNido solution in isolated rat hearts.

• Journal of Chest Surgery
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• v.33 no.7
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• pp.531-540
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• 2000

Baclgrpimd; Recent studies have suggested that the cardioprotective effect of ischemic preconditioning(IP) is closely related to glycogen depletion and attenuation of intracellular acidosis. In the present study, the authors tested this hypothesis by perfusion isolated rabbit hearts with glucose(G) is closely related to glycogen depletion and attenuation of intracellular acidosis. In the present study, the authors tested this hypothesis by perfusion isolated rabbit hearts with glucose(G)-free perfusate. Material and Method; Hearts isolated from New Zealand white rabbits(1.5~2.0 kg body weight) were perfused with Tyrode solution by Langendorff technique. After stabilization of baseline hemodynamics, the hearts were subjected to 45 min global ischemia followed by 120 min reperfusion with IP(IP group, n=13) or without IP(ischemic control group, n=10). IP was induced by single episode of 5 min global ischemia and 10 min reperfusion. In the G-free preconditioned group(n=12), G depletion was induced by perfusionwith G-free Tyrode solution for 5 min and then perfused with G-containing Tyrode solution for 10 min; and 45 min ischemia and 120 min reperfusion. Left ventricular functionincluding developed pressure(LVDP), dP/dt, heart rate, left ventricular end-distolic pressure(LVEDP) and coronary flow (CF) were measured. Myocardial cytosolic and membrane PKC activities were measured by 32P-${\gamma}$-ATP incorporation into PKC-specific peptide and PKC isozymes were analyzed by Western blot with monoclonal antibodies. Infarct size was determined by staining with TTC(tetrazolium salt) and planimetry. Data were analyzed by one-way analysis of variance (ANOVA) and Turkey's post-hoc test. Result ; In comparison with the ischemic control group, IP significantly enhanced functional recovery of the left ventricle; in contrast, functional significantly enhanced functional recovery of the left ventricle; in contrast, functional recovery were not significantly different between the G-free preconditioned and the ischemic control groups. However, the infarct size was significantly reduced by IP or G-free preconditioning(39$\pm$2.7% in the ischemic control, 19$\pm$1.2% in the IP, and 15$\pm$3.9% in the G-free preconditioned, p<0.05). Membrane PKC activities were increased significantly after IP (119%), IP and 45 min ischemia(145%), G-free [recpmdotopmomg (150%), and G-free preconditioning and 45 min ischemia(127%); expression of membrane PKC isozymes, $\alpha$ and $\varepsilon$, tended to be increased after IP or G-free preconditioning. Conclusion; These results suggest that in isolated Langendorff-perfused rabbit heart model, G-free preconditioning (induced by single episode of 5 min G depletion and 10 min repletion) colud not improve post-ischemic contractile dysfunction(after 45-minute global ischemia); however, it has an infarct size-limiting effect.

• Journal of Chest Surgery
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• v.37 no.8
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• pp.632-643
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• 2004

Background: The Histidine-Tryptophan-Ketoglutarate (HTK) solution has been shown to provide the excellent myocardial protection as a cardioplegia. The HTK solution has relatively low potassium as an arresting agent of myocardium, and low sodium content, and high. concentration of histidine biological buffer which confer a buffering capacity superior to that of blood.. Since HTK solution has an excellent myocardial protective ability, it is reported to protect myocardium from ischemia for a considerable time (120 minutes) with the single infusion of HTK solution as a cardioplegia. The purpose of this study is to evaluate the cardioprotective effect of HTK solution on myocardium when the ischemia is. exceeding 120 minutes at two different temperature (10 to 12$^{\circ}C$, 22 to 24$^{\circ}C$) using the Langendorff apparatus, Material and Method: Hearts from Sprague-Dawley rat, weighing 300 to 340 g, were perfused with Krebs-Henseleit solution at a perfusion pressure of 100 cm $H_2O$. After the stabilization, the heart rate, left ventricular developed pressure (LVDP), and coronary flow were measured. Single dose of HTK solution was infused into the ascending aorta of isolated rat heart and hearts were preserved at four different conditions. In group 1 (n=10), hearts were preserved at deep hypothermia (10∼12$^{\circ}C$) for 2 hours, in group 2 (n=10), hearts were preserved at moderate hypothermia (22∼24$^{\circ}C$) for 2 hours, in group 3 (n=10), hearts were preserved at deep hypothermia for 3 hours, and in group 4 (n=10), hearts were preserved at moderate hypothermia for 3 hours. After the completion of the preservation, the heart rate, left ventricular developed pressure, and coronary flow were measured at 15 minutes, 30 minutes, and 45 minutes after the initiation of reperfusion to assess the cardiac function. Biopsies were also done and mitochondrial scores were counted in two cases of each group for ultrastructural assessment. Result: The present study showed that the change of heart rate was not different between group 1 and group 2, and group 1 and group 3. The heart rate was significantly decreased at 15 minutes in group 4 compared to that of group 1 (p<0.05 by ANCOVA). The heart rate was recovered at 30 minutes and 45 minutes in group 4 with no significant difference compared to that of group 1. The decrease of LVDP was significant at 15 minutes, 30 minutes and 45 minutes in group 4 compared to that of group 1 (p < 0.001 by ANCOVA). Coronary flow was significantly decreased at 15 minutes, 30 minutes, and 45 minutes in group 4 compared to that of group 1 (p < 0.001 by ANCOVA). In ultrastructural assessment, the mean myocardial mitochondrial scores in group 1, group 2, group 3, and group 4 were 1.02$\pm$0.29, 1.52$\pm$0.26, 1.56$\pm$0.45, 2.22$\pm$0.44 respectively. Conclusion: The HTK solution provided excellent myocardial protection regardless of myocardial temperature for 2 hours. But, when ischemic time exceeded 2 hours, the myocardial hemodynamic function and ultrastructural changes were significantly deteriorated at moderate hypotherma (22∼ 24$^{\circ}C$). This indicates that it is recommended to decrease myocardial temperature when myocardial ischemic time exceeds 2 hours with single infusion of HTK solution as a cardioplegia.