• Title/Summary/Keyword: $S_N1$ mechanism

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Endothelium Dependent Vasorelaxant Action of ChungGongGo Extract on Arterial Contraction in Rabbit (청공고(淸空膏)의 내피세포 의존성 혈관이완효과)

  • Oh, Chul;Kim, Ho-Hyun;Ko, Heung
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.22 no.3
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    • pp.666-671
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    • 2008
  • This study was undertaken to define the effect of ChungGongGo extract on norepinephrine-induced arterial contraction in rabbit. In order to investigate the effect of ChungGongGo extract on rabbit's contracted vascular ring detached from common carotid artery, vascular ring with intact or damaged endothelium was used for the experiment using organ bath. To analyze the mechanism of ChungGongGo extract-induced relaxation, ChungGongGo extract was infused into contracted vascular ring which had been pretreated by $N{\omega}$-nitro-L-arginine(L-NNA), Methylene blue(MB), and $Ca^{2+}$ was infused into contracted vascular ring induced by NE or KCl after treatment of ChungGongGo in $Ca^{2+}$-free solution. The results were as follows: ChungGongGo extract had an effective relaxation to the contracted vascular ring by NE in 1.0mg/ml and 0mg/ml level. ChungGongGo extract had an effective relaxation to the intact endothelium vascular ring, but when endothelium was removed, vascular ring did not relax. ChungGongGo extract-induced relaxation was inhibited by the pretreatment of L-NNA and MB. Pretreatment of ChungGongGo extract inhibit the contraction by influx of extra-$Ca^{2+}$ in contracted vascular ring induced by NE in $Ca^{2+}$-free solution. As mentioned above, we suggest that ChungGongGo relaxes vascular ring through suppress influx of extra-cellular $Ca^{2+}$ by the action of nitric oxide from endothelium.

Involvement of nitric oxide-induced NADPH oxidase in adventitious root growth and antioxidant defense in Panax ginseng

  • Tewari, Rajesh Kumar;Kim, Soohyun;Hahn, Eun-Joo;Paek, Kee-Yoeup
    • Plant Biotechnology Reports
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    • v.2 no.2
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    • pp.113-122
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    • 2008
  • Nitric oxide (NO) affects the growth and development of plants and also affects plant responses to various stresses. Because NO induces root differentiation, we examined whether or not it is involved in increased ROS generation. Treatments with sodium nitroprusside (SNP), an NO donor, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO), a specific NO scavenger, and $N{\omega}-nitro-{\text\tiny{L}}-arginine$ methyl ester hydrochloride (${\text\tiny{L}}-NAME$), an NO synthase (NOS) inhibitor, revealed that NO is involved in the adventitious root growth of mountain ginseng. Supply of an NO donor, SNP, activates NADPH oxidase activity, resulting in increased generation of $O_2{^{{\cdot}-}}$, which subsequently induces growth of adventitious roots. Moreover, treatment with diphenyliodonium chloride (DPI), an NADPH oxidase inhibitor, individually or with SNP, inhibited root growth, NADPH oxidase activity, and $O_2{^{{\cdot}-}}$ anion generation. Supply of the NO donor, SNP, did not induce any notable isoforms of enzymes; it did, however, increase the activity of pre-existing bands of NADPH oxidase, superoxide dismutase, catalase, peroxidase, ascorbate peroxidase, and glutathione reductase. Enhanced activity of antioxidant enzymes induced by SNP supply seems to be responsible for a low level of $H_2O_2$ in the adventitious roots of mountain ginseng. It was therefore concluded that NO-induced generation of $O_2{^{{\cdot}-}}$ by NADPH oxidase seems to have a role in adventitious root growth of mountain ginseng. The possible mechanism of NO involvement in $O_2{^{{\cdot}-}}$ generation through NADPH oxidase and subsequent root growth is discussed.

A Study on the Hypotensive Action of Methanol Extract of Plantaginis Seed in the Rabbit (차전자 메탄올 엑기스의 혈압강하작용에 관한 연구)

  • 고석태;임동윤
    • YAKHAK HOEJI
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    • v.22 no.3
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    • pp.163-174
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    • 1978
  • Plantaginis seed has been applied in Chinese medicine a as well as in folk remedy. It was advocated that Plantaginis S Semeη exerts good therapeutic effects as anti-inflammatory, antitussive, obstipant and diuretic agent in some cases of alimentary, respiratory a and renal disorders. This study was carried out in order to r re-evaluate the pharmacological action, especially the hypotensive a action of Plantaginis Semen and to elucidate the mechanism of its a action, making use of Plantaginis Semen methanol extract (PME), because its basic pharmacological action, i. e., hypotensive action is n not clear. 1) PME, when administered into intravenous route, elicited the h hypotensive response dependent on the dose of PME given to the rabbit anesthetized with urethane. 2) This hypotensive response of P PME was inhibited by atropine and potentiated by physostigmine, but not influ$\varepsilon$need by vagotomization. 3) Depressor effect of PME was blocked by chlorisondamine, phentolamine, and bethanicline, while not altered by cyproheptadine, diphenhydramine and propran¬olol. 4) The secondary pressor response after blocking the depressor e effect of PME by chlorisondamine was produced, but this pressor response was deminished by atropine. 5) PME augmented the pressor e effect of norepinephrine and angiotensin, on the other hand, reduced b blood pressure elevated by carotid occlusion reflex. 6) These observa¬t tions suggest that PME may induce the hypotensive response via dual mechanisms of parasympathomimetic and sympatholytic action, that the positions of this action are cholinergic peripheral site and sympathetic ganglia respectively, and that PME may possess the pressor activity caused by stimulation of "atropine-sensitive site" which seems to existsin the sympathetic ganglia.

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A New Functional Model of Catechol Dioxygenases: Properties and Reactivity of [Fe(BLPA)DBC]$BPh_4$

  • Lim, Ji H.;Lee, Ho J.;이강봉;Jang, Ho G.
    • Bulletin of the Korean Chemical Society
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    • v.18 no.11
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    • pp.1166-1172
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    • 1997
  • [FeⅢ(BLPA)DBC]BPh4, a new functional model for the catechol dioxygenases, has been synthesized, where BLPA is bis((6-methyl-2-pyridyl)methyl)(2-pyridylmethyl)amine and DBC is 3,5-di-tert-butylcatecholate dianion. The BLPA complex has a structural feature that iron center has a six-coordinate geometry with N4O2 donor set. It exhibits EPR signals at g=5.5 and 8.0 which are typical values for the high-spin FeⅢ (S=5/2) complex with axial symmetry. The BLPA complex reacts with O2 within a few hours to afford intradiol cleavage (75%) and extradiol cleavage (15%) products which is very unique result of all [Fe(L)DBC] complexes studied. The iron-catecholate interaction of BLPA complex is significantly stronger, resulting in the enhanced covalency of the metal-catecholate bonds and low energy catecholate to FeⅢ charge transfer bands at 583 and 962 nm in CH3CN. The enhanced covalency is also reflected by the isotropic shifts exhibited by the DBC protons, which indicate increased semiquinone character. The greater semiquinone character in the BLPA complex correlates well with its high reactivity towards O2. Kinetic studies of the reaction of the BLPA complex with 1 atm O2 in CH3OH and CH2Cl2 under pseudo-first order conditions show that the BLPA complex reacts with O2 much slower than the TPA complex, where TPA is tris(2-pyridylmethyl)amine. It is presumably due to the steric effect of the methyl substituent on the pyridine ring. Nevertheless, both the high specificity and the fast kinetics can be rationalized on the basis of its low energy catecholate to FeⅢ charge transfer bands and large isotropic NMR shifts for the BLPA protons. These results provide insight into the nature of the oxygenation mechanism of the catechol dioxygenases.

Does Strategy of Downward Stepping Stair Due to Load of Additional Weight Affect Lower Limb's Kinetic Mechanism?

  • Ryew, Checheong;Yoo, Taeseok;Hyun, Seunghyun
    • International journal of advanced smart convergence
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    • v.9 no.4
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    • pp.26-33
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    • 2020
  • This study measured the downward stepping movement relative to weight change (no load, and 10%, 20%, 30% of body weight respectively of adult male (n=10) from standardized stair (rise of 0.3 m, tread of 0.29 m, width of 1 m). The 3-dimensional cinematography and ground reaction force were also utilized for analysis of leg stiffness: Peak vertical force, change in stance phase leg length, Torque of whole body, kinematic variables. The strategy heightened the leg stiffness and standardized vertical ground reaction force relative to the added weights (p<.01). Torque showed rather larger rotational force in case of no load, but less in 10% of body weight (p<.05). Similarly angle of hip joint showed most extended in no-load, but most flexed in 10% of body weight (p<.05). Inclined angle of body trunk showed largest range in posterior direction in no-load, but in vertical line nearly relative to added weights (p<.001). Thus the result of the study proved that downward stepping strategy altered from height of 30 cm, regardless of added weight, did not affect velocity and length of lower leg. But added weight contributed to more vertical impulse force and increase of rigidity of whole body than forward rotational torque under condition of altered stepping strategy. In future study, the experimental on effect of weight change and alteration of downward stepping strategy using ankle joint may provide helpful information for development of enhanced program of prevention and rehabilitation on motor performance and injury.

CCR5-mediated Recruitment of NK Cells to the Kidney Is a Critical Step for Host Defense to Systemic Candida albicans Infection

  • Nu Z. N. Nguyen;Vuvi G. Tran;Saerom Lee;Minji Kim;Sang W. Kang;Juyang Kim;Hye J. Kim;Jong S. Lee;Hong R. Cho;Byungsuk Kwon
    • IMMUNE NETWORK
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    • v.20 no.6
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    • pp.49.1-49.15
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    • 2020
  • C-C chemokine receptor type 5 (CCR5) regulates the trafficking of various immune cells to sites of infection. In this study, we showed that expression of CCR5 and its ligands was rapidly increased in the kidney after systemic Candida albicans infection, and infected CCR5-/- mice exhibited increased mortality and morbidity, indicating that CCR5 contributes to an effective defense mechanism against systemic C. albicans infection. The susceptibility of CCR5-/- mice to C. albicans infection was due to impaired fungal clearance, which in turn resulted in exacerbated renal inflammation and damage. CCR5-mediated recruitment of NK cells to the kidney in response to C. albicans infection was necessary for the anti-microbial activity of neutrophils, the main fungicidal effector cells. Mechanistically, C. albicans induced expression of IL-23 by CD11c+ dendritic cells (DCs). IL-23 in turn augmented the fungicidal activity of neutrophils through GM-CSF production by NK cells. As GM-CSF potentiated production of IL-23 in response to C. albicans, a positive feedback loop formed between NK cells and DCs seemed to function as an amplification point for host defense. Taken together, our results suggest that CCR5-mediated recruitment of NK cells to the site of fungal infection is an important step that underlies innate resistance to systemic C. albicans infection.

Dasatinib Inhibits Lyn and Fyn Src-Family Kinases in Mast Cells to Suppress Type I Hypersensitivity in Mice

  • Lee, Dajeong;Park, Young Hwan;Lee, Ji Eon;Kim, Hyuk Soon;Min, Keun Young;Jo, Min Geun;Kim, Hyung Sik;Choi, Wahn Soo;Kim, Young Mi
    • Biomolecules & Therapeutics
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    • v.28 no.5
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    • pp.456-464
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    • 2020
  • Mast cells (MCs) are systemically distributed and secrete several allergic mediators such as histamine and leukotrienes to cause type I hypersensitivity. Dasatinib is a type of anti-cancer agent and it has also been reported to inhibit human basophils. However, dasatinib has not been reported for its inhibitory effects on MCs or type I hypersensitivity in mice. In this study, we examined the inhibitory effect of dasatinib on MCs and MC-mediated allergic response in vitro and in vivo. In vitro, dasatinib inhibited the degranulation of MCs by antigen stimulation in a dose-dependent manner (IC50, ~34 nM for RBL-2H3 cells; ~52 nM for BMMCs) without any cytotoxicity. It also suppressed the secretion of inflammatory cytokines IL-4 and TNF-α by antigen stimulation. Furthermore, dasatinib inhibited MC-mediated passive cutaneous anaphylaxis (PCA) in mice (ED50, ~29 mg/kg). Notably, dasatinib significantly suppressed the degranulation of MCs in the ear tissue. As the mechanism of its effect, dasatinib inhibited the activation of Syk and Syk-mediated downstream signaling proteins, LAT, PLCγ1, and three typical MAP kinases (Erk1/2, JNK, and p38), which are essential for the activation of MCs. Interestingly, in vitro tyrosine kinase assay, dasatinib directly inhibited the activities of Lyn and Fyn, the upstream tyrosine kinases of Syk in MCs. Taken together, dasatinib suppresses MCs and PCA in vitro and in vivo through the inhibition of Lyn and Fyn Src-family kinases. Therefore, we suggest the possibility of repositioning the anti-cancer drug dasatinib as a treatment for various MC-mediated type I hypersensitive diseases.

Study of a Recurring Anticyclonic Eddy off Wonsan Coast in Northern Korea Using Satellite Tracking Drifter, Satellite Ocean Color and Sea Surface Temperature Imagery (위성원격탐사를 이용한 동해 원산연안의 재발생 와동류 연구)

  • 서영상;장이현;김정희
    • Korean Journal of Remote Sensing
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    • v.16 no.3
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    • pp.211-220
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    • 2000
  • Even though recurring eddies at the terminal end of the East Korean Warm Current have been identified in the thermal infrared imagery from the NOAA/AVHRR sensor and ocean color data from Orbview-2/SeaWiFS sensor, it is difficult to make observation in the field regarding recurring eddies located around the Wonsan coastal area in North Korea. But we could get in situ data related to an eddy from an ARGOS satellite tracking drifter trapped in the eddy on January 4th, 1999. An ARGOS drifter, a NOAA satellite tracked buoy was trapped by the eddy during January 4th.March 18, 1999. The ARGOS drifter rotated 10 times per 72 days on the edge of the eddy located at $39^{\circ}N$, $129^{\circ}E$. The diameter of the eddy was about 100 km. The horizontal rotation velocity of the recurring cold-core anti-cyclonic eddy was 1.53 km/h(42 cm/sec). The sea surface temperatures of the eddy varied from $14.7^{\circ}C$ on January 5, 1999 to $9.6^{\circ}C$ on March 18,1999. To study the mechanism of the recurring eddy. we tried to find out the relationship between the vector of the drifter moving in the eddy and the wind vector in Sokcho and Ulleung Island located near the eddy in southern Korea, and the difference in sea level between Ulleung Island and Mukho. We hope the results of this study would be useful for calibration and validation data of simulation and numerical modeling studies of the recurring eddy.

Effects of Electroacupucture on NMDA Receptor-dependent Spinal ERK MAPK Expression in CFA-induced Pain Model (전침에 의한 CFA유발 통증모델의 NMDA 수용체 의존적 ERK MAPK 발현 변화)

  • Kim, Ha-Neui;Kim, Yu-Ri;Jang, Ji-Yeon;Choi, Yung-Hyun;Lee, Yong-Tae;Choi, Byung-Tae
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.24 no.6
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    • pp.983-988
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    • 2010
  • The present study aims to investigate a possible mechanism of electroacupuncture (EA) in the spinal dorsal horn that may underlie N-methyl-D-aspartate (NMDA) receptor-associated extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) signaling pathways. The hot plate latency of the ipsilateral hindpaw of EA-treated rats was significantly decreased compared with complete Freund's adjuvant (CFA)-injected ones. The expressions of NR1 and NR2B subuint mRNA of NMDA receptor in the whole L4-5 segments are decreased by CFA treatment, but NR2B subunit was significantly recovered by EA treatment. When we detected the expression of ERK, there were no significant difference between normal and CFA-treated rats with EA or NMDA receptor antagonist MK801. But phosphorylated ERK expressions were markedly induced by CFA, but these inductions were significantly modulated by EA treatment. Although hosphorylation of ERK was also arrested by MK801, these inductions of CFA-injected rats was markedly inhibited only by co-treatment with EA and MK801. Phosphorylated cAMP response element-binding protein (CREB), ERK-related transcriptional factor, showed a significant increase in CFA-treated rats and this increase was slightly inhibited by EA and MK801 treatments. But immunoreaction for phosphorylated CREB were significantly increased by CFA treatment in the superficial laminae of the dorsal horn and these inductions were significantly arrested by co-treatment of EA and MK801. Consequently, the hyperalgesia induced by CFA are associated NMDA receptor and EA and MK801 may showed anti-hyperalgesia via same mechanism for inhibition of ERK and CREB phosphorylation in the dorsal horn.

Gardenia jasminoides Exerts Anti-inflammatory Activity via Akt and p38-dependent Heme Oxygenase-1 Upregulation in Microglial Cells (소교세포에서 heme oxygenase-1 발현 유도를 통한 치자(Gardenia jasminoides)의 항염증 효과)

  • Song, Ji Su;Shin, Ji Eun;Kim, Ji-Hee;Kim, YoungHee
    • Journal of Life Science
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    • v.27 no.1
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    • pp.8-14
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    • 2017
  • Died Gardenia jasminoides fruit is used as a dye in the food and clothes industries in Asia. The present study investigated the anti-inflammatory effects of aqueous extract of G. jasminoides fruits (GJ) in BV-2 microglial cells. GJ inhibited lipopolysaccharide-induced nitric oxide (NO) secretion, inducible nitric oxide synthase (iNOS) expression, and reactive oxygen species production, without affecting cell viability. Furthermore, GJ increased the expression of heme oxygenase-1 (HO-1) in a dose-dependent manner. Moreover, the inhibitory effect of GJ on iNOS expression was abrogated by small interfering RNA-mediated knock-down of HO-1. In addition, GJ induced nuclear translocation of nuclear factor E2-related factor 2 (Nrf2), a transcription factor that regulates HO-1 expression. GJ-mediated expression of HO-1 was suppressed by LY294002, a phosphoinositide 3-kinase (PI-3K) inhibitor, and SB203580, a p38 kinase inhibitor, but not by the extracellular signal-regulated kinase (ERK) inhibitor PD98059 or c-Jun N-terminal kinase (JNK) inhibitor SP600125. GJ also enhanced the phosphorylation of Akt and p38. These results suggest that GJ suppresses the production of NO, a pro-inflammatory mediator, by inducing HO-1 expression via PI-3K/Akt/p38 signaling. These findings illustrate a novel molecular mechanism by which extract from G. jasminoides fruits inhibits neuroinflammation.