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Cyanidin-3-glucoside Inhibits ATP-induced Intracellular Free $Ca^{2+}$ Concentration, ROS Formation and Mitochondrial Depolarization in PC12 Cells

  • Perveen, Shazia;Yang, Ji Seon;Ha, Tae Joung;Yoon, Shin Hee
    • The Korean Journal of Physiology and Pharmacology
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    • v.18 no.4
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    • pp.297-305
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    • 2014
  • Flavonoids have an ability to suppress various ion channels. We determined whether one of flavonoids, cyanidin-3-glucoside, affects adenosine 5'-triphosphate (ATP)-induced calcium signaling using digital imaging methods for intracellular free $Ca^{2+}$ concentration ([$Ca^{2+}$]i), reactive oxygen species (ROS) and mitochondrial membrane potential in PC12 cells. Treatment with ATP ($100{\mu}M$) for 90 sec induced [$Ca^{2+}$]i increases in PC12 cells. Pretreatment with cyanidin-3-glucoside ($1{\mu}g/ml$ to $100{\mu}g/ml$) for 30 min inhibited the ATP-induced [$Ca^{2+}$]i increases in a concentration-dependent manner ($IC_{50}=15.3{\mu}g/ml$). Pretreatment with cyanidin-3-glucoside ($15{\mu}g/ml$) for 30 min significantly inhibited the ATP-induced [$Ca^{2+}$]i responses following removal of extracellular $Ca^{2+}$ or depletion of intracellular [$Ca^{2+}$]i stores. Cyanidin-3-glucoside also significantly inhibited the relatively specific P2X2 receptor agonist 2-MeSATP-induced [$Ca^{2+}$]i responses. Cyanidin-3-glucoside significantly inhibited the thapsigargin or ATP-induced store-operated calcium entry. Cyanidin-3-glucoside significantly inhibited the ATP-induced [$Ca^{2+}$]i responses in the presence of nimodipine and ${\omega}$-conotoxin. Cyanidin-3-glucoside also significantly inhibited KCl (50 mM)-induced [$Ca^{2+}$]i increases. Cyanidin-3-glucoside significantly inhibited ATP-induced mitochondrial depolarization. The intracellular $Ca^{2+}$ chelator BAPTA-AM or the mitochondrial $Ca^{2+}$ uniporter inhibitor RU360 blocked the ATP-induced mitochondrial depolarization in the presence of cyanidin-3-glucoside. Cyanidin-3-glucoside blocked ATP-induced formation of ROS. BAPTA-AM further decreased the formation of ROS in the presence of cyanidin-3-glucoside. All these results suggest that cyanidin-3-glucoside inhibits ATP-induced calcium signaling in PC12 cells by inhibiting multiple pathways which are the influx of extracellular $Ca^{2+}$ through the nimodipine and ${\omega}$-conotoxin-sensitive and -insensitive pathways and the release of $Ca^{2+}$ from intracellular stores. In addition, cyanidin-3-glucoside inhibits ATP-induced formation of ROS by inhibiting $Ca^{2+}$-induced mitochondrial depolarization.

Pharmacokinetics of Paclitaxel in Rabbits with Carbon Tetrachloride-Induced Hepatic Failure

  • Choi, Jun-Shik
    • Archives of Pharmacal Research
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    • v.25 no.6
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    • pp.973-977
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    • 2002
  • The pharmacokinetic of paclitaxel (1 mg/kg, i.v.) was investigated in rabbits with carbon tetrachloride-induced hepatic failure. The area under the plasma concentration-time curve (AUC) of paclitaxel was significantly (p<0.01) increased in severe carbon tetrachloride-induced hepatic failure rabbits ($1364.54{\pm}382.07$ ng/ml$\cdot$hr) compared to that of normal rabbits ($567.52{\pm}141.88$ ng/ml$\cdot$hr), but not significantly in moderate carbon tetrachloride-induced hepatic failure rabbits ($803.1{\pm}208.81$ ng/ml$\cdot$hr). The volume of distribution (Vd) (6.25$\pm$1.56 L) and the elimination rate constant($\beta$) ($0.09{\pm}0.025{\;}hr^{-1}$) of paclitaxel in severe carbon tetrachloride-induced hepatic failure rabbits were significantly (p<0.05) decreased compared to those of normal rabbits ($11.65<{\pm}2.91$L, $0.12{\pm}0.030{\;}hr^{-1}$), but not significantly in moderate carbon tetrachloride-induced hepatic failure rabbits ($9.46{\pm}2.37$ L, $0.10{\pm}0.026{\;}hr^{-1}$). Total body clearance ($CL_t$) of paclitaxel in severe carbon tetrachloride-induced hepatic failure rabbits ($0.733{\pm}0.183$ L/hr/kg) was significantly (p<0.01) decreased compared to that of normal rabbits ($1.762{\pm}0.440$ L/hr/kg), but not significantly in moderate carbon tetrachloride-induced hepatic failure rabbits ($1.245{\pm}0.311$ L/hr/kg). The half-life(t1/2) of paclitaxel in severe carbon tetrachloride-induced hepatic failure rabbits ($7.71{\pm}2.16$ hr) was significantly (p<0.05) increased compared to that of normal rabbits ($5.75{\pm}1.44$hr), but not significantly in moderate carbon tetrachloride-induced hepatic failure rabbits ($6.77{\pm}1.76$hr). This results could be due to inhibition of paclitaxel metabolism in liver disorder rabbits since paclitaxel is essentially metabolized in liver. The findings suggest that the dosage regimen of paclitaxel should be adjusted when the drug would be administered in patients with liver disorder in a clinical situation.

Change of Various Characteristics between Spawning and Non-spawning Season in Diploid and Induced Triploid Far Eastern Catfish, Silurus asotus

  • Lim, Sun Young;Gil, Hyun Woo;Park, In-Seok
    • Development and Reproduction
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    • v.21 no.3
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    • pp.275-286
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    • 2017
  • The purpose of this study is to investigate the differences fatty acids and hormonal parameters in the spawning and non-spawning season between the diploid and induced triploid Far Eastern catfish, Silurus asotus. The measured triploids were produced by cold shock for 50 min at $4^{\circ}C$ in May 2014, the spawning season of diploid was in May, and the non-spawning season was designated in January. Estradiol and testosterone and gonadosomatic index of diploid were higher than those of induced triploid in spawning season (P<0.05), and those of diploid in spawning season were higher than non-spawning season. On the other hand, thyroid stimulating hormone and thyroxine of induced triploid were higher than those of diploid in spawning season (P<0.05). Erythrocyte count of diploid was higher than that of induced triploid in spawning season and non-spawning seasons. Mean corpuscular volume and mean corpuscular hemoglobin of induced triploid were higher than those of diploid in both seasons (P<0.05). Percentages of total saturated fatty acids and n-3 polyunsaturated fatty acids of induced triploid were higher than those of diploid in spawning season, but those of diploid were higher in non-spawning season (P<0.05). Percentages of total mono unsaturated fatty acids and total n-6 polyunsaturated fatty acids of diploid were higher than those of induced triploids in spawning season, while those of induced triploid in non-spawning season were higher (P<0.05). Therefore, induced triploids in the spawning season tend to concentrate on growth and lipid-synthesization, whereas, diploids concentrate on reproduction and gonadal maturation rather than on growth. In non-spawning season, growth and lipid-synthesization were not significantly different between diploid and induced triploid.

The Effects of Far-Infrared on Rheumatoid Arthritis Induced Rats (원적외선 전신조사가 류마티스 관절염 유발 흰쥐에 미치는 영향)

  • Kim Gye Yeop;Cho Kyoung Oh;Kim Myung Hee;Cheong Hyun Woo
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.18 no.5
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    • pp.1301-1308
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    • 2004
  • The purpose of this study was to observe the effects of far-infrared on rheumatoid arthritis induced rats by type ⅡI collagen with the change of arthritis index, hind paw volume, TNF-α and histopathologic findings. Thirty-six Sprauge-Dawley rats which were divided into four group. Group Ⅰ : Normal group, Group Ⅱ : Collagen-Induced Arthritis group, Group Ⅲ : Far-Infrared 25㎝ radiation group, Group Ⅳ : Far-Infrared 35㎝ radiation group. The results of this study were as follows: In arthritis index, far-infrared radiation group(Ⅲ, Ⅳ) are more decreased than collagen-induced arthritis group(Ⅱ). Group Ⅲ and Ⅳ showed the most significant effect at 14 day(p<0.05). In hind paw, far-infrared 25㎝ radiation group(Ⅲ) significantly decreased more than only collagen-induced arthritis group on day 14(p<0.05). Far-infrared 35㎝ radiation group(Ⅳ) significantly decreased more than collagen-induced arthritis group on day 3, 7 and 14(p<0.05). In the ELISA study of TNF-α concentration, collagen-induced arthritis group significantly increased in the concentration more than normal group. Far-infrared radiation group(Ⅲ, Ⅳ) decreased in TNF-α concentration more than collagen-induced arthritis group(Ⅱ) on day 14. In histopathologic findings, collagen-induced arthritis(Ⅱ) and far-infrared 25㎝ radiation group(Ⅲ) increased in synovial membrane thickness on 3 day. Far-infrared 35 em radiation group(Ⅳ) decreased in the concentration more than collagen-induced arthritis group on day 14. The above results suggest that far-infrared radiation effectively reduced in rheumatoid arthritis. It would be considered that far-infrared has an effects on relieving rheumatoid arthritis.

Analysis on the Induced Lightning Shielding Effect According to the Neutral Wire Installation Structure of a 22.9kV Distribution Line (22.9kV 배전선로 중성선 설치 구조에 따른 유도뢰 차폐효과 분석)

  • Kim, Jeom-Sik;Kim, Do-Young;Park, Yong-Beom
    • The Transactions of the Korean Institute of Electrical Engineers P
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    • v.59 no.2
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    • pp.191-196
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    • 2010
  • The electricity distribution system in Korea is adopting a multi-grounding system. Protection of this distribution system against lightning is performed by installing overhead ground wires over the high voltage wires, and connecting the overhead ground wires to the ground every 200 m. The ground resistance in this system is limited not to exceed $50\Omega$ and overhead ground wire and neutral wire are multiple parallel lines. Although overhead ground wire and neutral wire are installed in different locations on the same pole, this circuit configuration has duplicated functions of providing a return path for unbalanced currents and protecting the distribution system against induced lightning. Therefore, the purpose of this study is to analyze the induced lightning shielding effect according to the neutral wire installation structure of a 22.9kV distribution line in order to present a new 22.9kV distribution line structure model and characteristics. This study calculated induced lightning voltage by performing numerical analysis when an overhead ground wire is present in the multi-grounding type 22.9kV distribution line structure, and calculated the induced lightning shielding effect based on this calculated induced lightning voltage. In addition, this study proposed and analyzed an improved distribution line model allowing the use of both overhead wire and neutral wire to be installed in the current distribution lines. The result of MATLAB simulation using the conditions applied by Yokoyama showed almost no difference between the induced lightning voltage developed in the current line and that developed in the proposed line. This signifies that shielding the induced lightning voltage through overhead wire makes no difference between current and proposed distribution line structures. That is, this study found that the ground resistance of the overhead wire had an effect on the induced lightning voltage, and that the induced lightning shielding effect of overhead wire is small.

Effects of Oral Administration of Herb-combined Remedy of Diabetes Mellitus on Blood Glucose Levels and Anti-oxidative Enzymatic System in Streptozotocin-induced Diabetic Rats (한약복합처방의 경구투여가 Streptozotocin에 의해 유발된 당뇨병 백서의 혈당과 항산화효소계에 미치는 영향)

  • Lee, Eun-Bang;Cho, Myung-Rae;Kim, Jae-Hong;Ryu, Chung-Ryeol
    • Journal of Acupuncture Research
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    • v.25 no.1
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    • pp.57-72
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    • 2008
  • Objectives : The Herb-combined Remedy(HCR) for diabetes mellitus is known as an anti-hyperglycaemic agent. But its exact mechanisms are unclear. The present study was carried out to investigate its anti-hyperglycaemic and anti-oxidative effects in STZ-induced diabetic rats. Methods : Experimental diabetes was induced by injection of STZ(80mg/kg) to ratsvia the peritoneum. The experimental animals were divided into 4 groups : normal group, control group(STZ-induced diabetic rats with no treatment), HCR group(STZ-induced diabetic rats with HCR treatment), MF group(STZ-induced diabetic rats with Metformin treatment). The effects of HCR on STZ-induced diabetes was observed by measuring fasting blood glucose, changes of body weight, food uptake, and water uptake glucose levels in the normal state decline rates in blood glucose levels DPPH free-radical scavenging activity superoxide dismutase in RBC lysate catalase activity in RBC lysate and glutathione reductase activity in RBC lysate. Results : Treatment with HCR regulated blood glucose levels. Treatment with HCR also prevented weight loss in STZ-induced diabetic rats. In addition, oral glucose tolerance decreased following treatment with HCR. Direct anti-oxidative effects on DPPH free-radical scavenging were not observed, but treatment with HCR elevated SOD levels in blood cell lysates from STZ-induced diabetic rats. In addition, the HCR-treatment group showed an elevated tendency to glutathione reductase activity. Conclusions : These results demonstrate that HCR has anti-hyperglycaemic and anti-oxidative effects in STZ-induced diabetic rats.

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Inhibitory Effects of Extracts from Traditional Herbal Drugs on 5-Hydroxytryptophan-Induced Diarrhea in Mice (생쥐에서 5-Hydroxytryptophan에 의한 설사에 대한 각종 전통 생약 추출물의 억제 효과)

  • Yoo, Jae-Sun;Jung, Jun-Sub;Lee, Tae-Hee;Son, Kun-Ho;Suh, Hong-Won;Song, Dong-Keun;Kim, Yung-Hi
    • Korean Journal of Pharmacognosy
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    • v.26 no.4
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    • pp.355-359
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    • 1995
  • To find serotonin(5-hydroxytryptamine, 5-HT)-antagonizing activities in traditional herbal drugs, crude extracts from 66 kinds of traditional herbal drugs were randomly screened for inhibitory effects on 5-hydroxytryptophan(HTP)-induced diarrhea in mice. Intraperitoneal injection of 5-HTP(2.5 mg/kg) induced diarrhea in 92% of mice, when observed from 10 to 15 min after injection. Crude extracts(2 g/kg) from 66 kinds of traditional herbal drugs were orally pretreated for 1 h before 5-HTP injection. Of the 66 herbal drugs screened, Ephedrae Herba(麻黃), Cimicifugae Rhizoma(升麻), Anisi stellati Fructus(八角茴香), Aurantii Fructus(枳實), Polygalae Radix(遠志) showed the most potent inhibiting activities against 5-HTP(2.5 mg/kg)-induced diarrhea in mice. There are at least 3 possible mechanisms that would be responsible for the inhibitory effect of crude extracts on 5-HTP-induced diarrhea; 1) crude extract-induced inhibition of the activity of aromatic aminoacid decarboxylase catalyzing the conversion of 5-HTP to 5-HT, 2) crude extract-induced blockade of 5-HT receptor(s) in the gastrointestinal tract responsible for 5-HTP-induced diarrhea, 3) crude extract-induced inhibition of gastrointestinal activity, irrespective of 5-HT system. The exact mechanisms and molecules, responsible for the inhibitory effect of crude extracts on 5-HTP-induced diarrhea remain to be clarified.

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Ameliorative Effect of Schisandra chinensis and Ribes fasciculatum Extracts on Hydrogen Peroxide-Induced Neuronal Cell Death in Neuroblastic PC12 Cells and the Scopolamine-Induced Cognitive Impairment in a Rat Model (오미자칠해목 추출물의 과산화수소로 유발된 PC12뇌세포 사멸과 스코폴라민으로 유발된 렛드 동물모델에 대한 개선 효과)

  • Park, Eun-kuk;Han, Kyung-Hoon;Heo, Jae-Hyeok;Kim, Nam-Ki;Bae, Mun-Hyoung;Seo, Young-Ha;Yong, Yoon-joong;Jeong, Seon-Yong;Choi, Chun-Whan
    • The Korean Journal of Food And Nutrition
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    • v.33 no.3
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    • pp.347-355
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    • 2020
  • Cognitive impairment is considered to be key research topics in the field of neurodegenerative diseases and in understanding of learning and memory. In the present study, we investigated neuroprotective effects of Schisandra chinensis (SC) and Ribes fasciculatum (RF) extracts in hydrogen peroxide-induced neuronal cell death in vitro and scopolamine-induced cognitive impairment in Sprague Dawley® (SD) rat in vivo. Apoptotic cell death in neuroblastic PC12 cell line was induced by hydrogen peroxide for 1 hour at 100 μM. However, mixture of SC and RF treatment prevented peroxide induced PC12 cell death with no neurotoxic effects. For in vivo experiment, the effect of SC and RF extracts on scopolamine-induced cognitive impairment in SD rat was evaluated by spontaneous alternation behavior in Y-Maze test. After 30 min scopolamine injection, the scopolamine-induced rats presented significantly decreased % spontaneous alteration and acetylcholine level, compared to non-induced group. However, treatment of SC+RF extracts rescued the reduced % spontaneous alteration with acetylcholine concentration from hippocampus in scopolamine-induced rats. These results suggested that mixture of SC and RF extract may be a potential natural therapeutic agent for the prevention of cognitive impairment.

Analysis of Analytical Models and Numerical Model for Evaluating Induced Infiltration Rate (유도침투량의 정량화를 위한 해석모형과 수치모형의 분석)

  • Lee, Do-Hun;Lee, Eun-Tae
    • Journal of Korea Water Resources Association
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    • v.32 no.3
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    • pp.301-310
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    • 1999
  • In this paper a numerical model and two analytical models in the hydraulically connected stream-aquifer system were analyzed to compare the induced infiltration rate curves derived from each model. And we also examined the effects of anisotropy of hydraulic conductivity and the direction of the ambient ground water flow on the quantification of the induced infiltration rate. The induced infiltration rate curve determined by models is very simple and useful for estimating the induced infiltration rate since it contains only four physical variables such as the induced infiltration rate, the pumping rate, the distance between the pumping well and the stream, and the ambient ground water flow rate. Under the conditions tested in this paper the induced infiltration rate curves resulted from the Wilson's analytical model and FEWA numerical model were in good agreement, and the anisotropic ratio of hydraulic conductivity was evaluated as a physical factor which influences the behaviour of the induced infiltration rate curve. The methods and results of the paper might Icad to improve the understanding of the induced infiltration phenomenon and can be applied to the planning and disign of pumping well and the optimal determination of the induced infiltration rate and pumping rate for water quality management of the water supply wells.

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Study on Peripheral Mechanism and Opioid Receptors Implicated in Electroacupunture-induced Inbibition of Chronic Pain (만성통증을 억제하는 전침효과의 말초성 기전과 아편양물질수용기에 관한 연구)

  • 신홍기;이서은;박동석
    • The Journal of Korean Medicine
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    • v.24 no.3
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    • pp.108-117
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    • 2003
  • Objective : The central opioid mechanism of acupuncture analgesia has been fairly well documented in acute behavioral experiments, but little electrophysiological study has been performed on the peripheral mechanism and subtypes of opioid receptors responsible for acupuncture-induced antinociception in chronic animal models. In the present electrophysiological experiment, we studied the peripheral mechanism and opioid receptor subtypes which Were implicated in electroacupuncture-induced antinociception in the rat with chronic inflammatory and neurogenic pain. Methods : In the rat with complete Freund's adjuvant-induced inflammation and spinal nerve injury, dorsal horn cell responses to afferent C fiber stimulation were recorded before and after electroacupuncture (EA) stimulation applied to the contralateral Zusanli point for 30 minutes. Also studied Were the effects of specific opioid receptor antagonists and naloxone methiodide, which can not cross the blood-brain barrier, on EA-induced inhibitory action. Results : EA-induced inhibitory action was significantly attenuated by naloxone methiodide, suggesting that EA-induced inhibition was mediated through peripheral mechanism. Pretreatment, but not posttreatment of naltrexone and spinal application significantly blocked EA-induced inhibitory actions. In inflammatory and neurogenic pain models, ${\mu}-$ and ${\delta}-opioid$ receptor antagonists (${\beta}-funaltrexamine$ & naltrindole) significantly reduced EA-induced inhibitory action, but ${\kappa}-opioid$ receptor antagonist had weak inhibitory effect on EA-induced antinociception. Conclusion : These results suggest that 2Hz EA-stimulation induced antinoeiceptive action is mediated through peripheral as well as central mechanism, and mainly through ${\mu}-$ and ${\delta}-opioid$ receptors.

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