• Title/Summary/Keyword: anti-atherosclerosis

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Peroxynitrite Scavenging Mechanism of Zingiberis Rhizoma (생강(生薑)의 Peroxynitrite 제거 기전)

  • Shin Sang-Guk;Jeong Ji-Cheon
    • The Journal of Internal Korean Medicine
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    • v.24 no.1
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    • pp.75-83
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    • 2003
  • Objectives : Peroxynitrite($ONOO^-$), formed from the reaction of $O2^-$ and NO, is a cytotoxic species that can oxidize several cellular components such as proteins, lipids and DNA. It has been involved in the aging process and age-related diseases such as Alzheimer's disease, rheumatoid arthritis, cancer and atherosclerosis. The aim of this study was to investigate scavenging activities of $ONOO^-$ and its precursors, NO and $O_{2^-}$ and its scavenging mechanism of Zingiberis Rhizoma (ZR). Methods : To investigate scavenging activities of $ONOO^-,\;NO,\;O_{2^-}$ and its scavenging mechanism, we used fluorescent probes like DCFDA, DAF-2 and DHR 123. The $ONOO^-$ scavenging activity on ZR was assayed by measuring oxidized dihydrorhodamine 123 (DHR 123) by fluorometry. The scavenging efficacy was expressed as IC50, showing the concentration of each sample that is required to cause 50% inhibition of DHR 123 oxidation. In a separate study, the protective effect of ZR on $ONOO^-$-induced nitration of bovine serum albumin was investigated through immuno-assay with a monoclonal anti-nitryrosine antibody, and a horseradish peroxidase-conjugated anti-mouse secondary antibody from sheep. Results : ZR markedly scavenged authentic $ONOO^-,\;O_{2^-}$ and NO. It also inhibited $ONOO^-$ induced by $O_{2^-}$ and NO which are derived from SIN-1. The data demonstrated that ZR led to decreased $ONOO^-$ mediated nitration of tyrosine through electron donation. It also inhibited the nitration of bovine serum albumin induced by $ONOO^-$ in a dose-dependent manner. Furtheremore, it blocked LPS-induced ROS and RNS generation. Conclusions : These results suggest that ZR can be developed as an effective $ONOO^-$ scavenger for the prevention of aging process and age-related diseases.

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Anti-platelet Effects of Isoscopoletin through Regulation of PI3K/Akt and MAPK on Collagen-induced Human Platelets (콜라겐-유도의 사람 혈소판에서 PI3K/Akt 및 MAPK 조절을 통한 Isoscopoletin의 항혈소판 효과)

  • Lee, Dong-Ha
    • Korean Journal of Pharmacognosy
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    • v.51 no.3
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    • pp.151-157
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    • 2020
  • When blood vessels are damaged, a rapid hemostatic reaction occurs to minimize blood loss and maintain normal circulation. Platelet activation and aggregation is essential in this process. However, excessive platelet aggregation or abnormal platelet aggregation may be the cause of cardiovascular disease, such as thrombosis, stroke and atherosclerosis. Therefore, it is important to prevent and treat cardiovascular disease by finding substances that can regulate platelet activation and suppress aggregation reactions. Isoscopoletin, which is mainly found in the roots of plants Artemisia or Scopolia, has been reported to have potential pharmacological effects on anticancer and Alzheimer's disease, but its role and mechanisms for platelet aggregation and thrombus formation are unknown. This study confirmed the effect of isoscopoletin on major regulation of collageninduced human platelet aggregation, TXA2 production and intracellular granular secretion (ATP and serotonin release). In addition, the effects of isoscopoletin on phosphorylation of phosphorylated proteins PI3K/Akt and MAPK involved in signal transduction in platelet aggregation was studied. As a result, isoscopoletin significantly inhibited the phosphorylation of PI3K/Akt and MAPK, significantly inhibiting platelet aggregation through TXA2 production and intracellular granular secretion (ATP and serotonin release). Therefore, we suggest that isoscopoletin is an anti-platelet substance that regulates phosphorylation of phosphorus proteins such as PI3K/Akt and MAPK and is valuable as a preventive and therapeutic agent for platelet-derived cardiovascular disease.

Effect of Aloe on Learming and Memory lmpaiments in Dementia Animal Model SAMP8 (치매동물모델 SAMP8에 있어서 기억. 학습장해에 미치는 알로에의 영향 III. SAMP8의 신경전달물질 및 그 대사산물에 미치는 알로에의 투여효과)

  • Choi, Jin-Ho;Kim, Dong-Woo;Kim, Jae-il;Han, Sang-Seop;Shim, Chang-Sub
    • Journal of Life Science
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    • v.6 no.2
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    • pp.142-148
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    • 1996
  • Aloe(Aloe arborescens M$_{ILL}$) has been used as a home medicine for the past several thousand in the world, and has been studied on anti-bacterial and anti-fungal activities, hypotension, atherosclerosis, myocardiac infartion, apoplexy, diabetes as a chronic digenerative disease, tumors, gastrointestinal tract, liver and pancreas' diseases, and genitourinary tract etc. SAMP8 as a learing and memory impairment animal model were fed basic and/or experimental diets with 1.0% freezing dried(FD)-aloe for 8 months. The passive avoidance tests such as acqusition trial and retention test were significantly higher in aloe group than in control group. Grading score of senescence resulted in a marked decreases in aloe group compared with control group. Acetylcholinesterase(AChE) activity was remarkably increased in aloe group compared with control group. Neurotransmitters such as dopamine(DA) and serotonin(5-HT) almost did not change by the feeding of aloe-added diet, but their metabolites such as homovanillic acid(HVA) and 5-hydroxy-indole acetic acid(5-HIAA) in aloe group were significantly increased compared with control group. Therefore, the ratios of HVA/DA and 5-HIAA/5-HT as a ratio of metabolite on neurotransmitter were significantly increased by the feeding of aloe-added diet. These results suggest that aloe vara may be activated acetylcholinesterase, the metabolite of neurotransmitter, and ratios of metabolite on neurotransmitter, resulting ina greater prevention of learning and memory impairments such as Alzheimertype dementia.

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Protopanaxadiol modulates LPS-induced inflammatory activity in murine macrophage RAW264.7 cells

  • Lee, Whi-Min;Kim, Sung-Dae;Kim, Kil-Soo;Song, Yong-Bum;Kwak, Yi-Seong;Cho, Jae-Youl;Park, Hwa-Jin;Oh, Jae-Wook;Rhee, Man-Hee
    • Journal of Ginseng Research
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    • v.30 no.4
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    • pp.181-187
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    • 2006
  • Protopanaxadiol (PPD) is a mixture of protopanaxadiol type saponins with a dammarane skeleton, from Korean red ginseng (Panax ginseng C.A. Meyer; Araliaceae). Korean ginseng is well-known herb to treat almost all kinds of diseases in Oriental medicine. This herb was particularly prescribed for treatment various inflammatory diseases, including rheumatoid arthritis, atherosclerosis, and diabetes mellitus, for centuries. To understand the efficacy of ginseng against inflammatory diseases, we aimed to show anti-inflammatory activities of the PPD in murine macrophage cell line, RAW264.7 cells using nitric oxide (NO) production assay and the expressions of pro-inflammatory cytokines, such as tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), interleukin-$1{\beta}$ (IL-$1{\beta}$), and IL-6, and monocyte chemotactic protein-1 (MCP-1). We found that PPD saponin significantly blocked LPS ($1{\mu}g/ml$)-induced NO production in a dose-dependent manner. In addition, PPD abrogated the expressions of LPS-induced pro-inflammatory cytokines, such as IL-$1{\beta}$ and MCP-1. Moreover, cyclooxygenase (COX)-2, a critical enzyme to produce prostaglandin E2 (PGE2), was significantly inhibited by PPD in LPS-activated RAW264.7 cells. Taken together, these results suggested that anti-inflammatory efficacy of Korean red ginseng on inflammatory diseases is, at least, due to the NO inhibitory activity and the inhibition of the expressional level of inflammatory cytokines and/or mediators.

Anti-apoptotic effects of autophagy via ROS regulation in microtubule-targeted and PDGF-stimulated vascular smooth muscle cells

  • Park, Hyun-Soo;Han, Joo-Hui;Jung, Sang-Hyuk;Lee, Do-Hyung;Heo, Kyung-Sun;Myung, Chang-Seon
    • The Korean Journal of Physiology and Pharmacology
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    • v.22 no.3
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    • pp.349-360
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    • 2018
  • Autophagy has been studied as a therapeutic strategy for cardiovascular diseases. However, insufficient studies have been reported concerning the influence of vascular smooth muscle cells (VSMCs) through autophagy regulation. The aim of the present study was to determine the effects of VSMCs on the regulation of autophagy under in vitro conditions similar to vascular status of the equipped micro-tubule target agent-eluting stent and increased release of platelet-derived growth factor-BB (PDGF-BB). Cell viability and proliferation were measured using MTT and cell counting assays. Immunofluorescence using an $anti-{\alpha}-tubulin$ antibody was performed to determine microtubule dynamic formation. Cell apoptosis was measured by cleavage of caspase-3 using western blot analysis, and by nuclear fragmentation using a fluorescence assay. Autophagy activity was assessed by microtubule-associated protein light chain 3-II (LC-II) using western blot analysis. Levels of intracellular reactive oxygen species (ROS) were measured using $H_2DCFDA$. The proliferation and viability of VSMCs were inhibited by microtubule regulation. Additionally, microtubule-regulated and PDGF-BB-stimulated VSMCs increased the cleavage of caspase-3 more than only the microtubule-regulated condition, similar to that of LC3-II, implying autophagy. Inhibitory autophagy of microtubule-regulated and PDGF-BB-stimulated VSMCs resulted in low viability. However, enhancement of autophagy maintained survival through the reduction of ROS. These results suggest that the apoptosis of conditioned VSMCs is decreased by the blocking generation of ROS via the promotion of autophagy, and proliferation is also inhibited. Thus, promoting autophagy as a therapeutic target for vascular restenosis and atherosclerosis may be a good strategy.

Study of Developmet of External Medicine Based on the Result of Prior Study and Folk Remedy Using Scolopendra subspinipes mutilans as a Single Medicine in Korea and China (한국과 중국에서의 오공을 단방으로 사용한 민간요법과 선행연구결과를 기반으로 한 외치 한약제제 개발에 대한 고찰)

  • Kim, Sin Seo;Kim, Myung Dong
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.29 no.3
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    • pp.203-217
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    • 2015
  • Scolpendra subspinipes (centipede) is pungent in flavor, activates the channels to stop pain, and, removes toxins and resolves masses. So it has been used as a folk remedy. We researched folk remedies which used centipede as a single medicine and results of its prior clinical and experimental study, and figured out that centipedes are effective on ulcerative disease, herpes zoster, clavus, insect bite, inflammatory disease, furunculus, pain disease by external therapy, and oral administration is effective on anti-cancer such as hepatoma and uterine cancer, cerebrovascular disease, inhibition of atherosclerosis, sedation of central nervous system, antipyretic action, and anti-inflammation, and centipede Herb-Acupuncture is effective on inflammatory disease and pain disease. Centipede preparation materials for external therapy were sesame oil, perilla oil, vinegar, salt, and, burnt alum. Fumigation of centipede treated paronychia, pertussis, and hemorrhoids. For the external therapy, the way of centipede powder mixing with other materials has been used. It is needed that we use dusted powder to make skin absorb its ingredients more easily, and we study intensely minor ingredients to make centipede components absorbed more effectively and do pharmacological action. Also, fumigation, a kind of another external therapy, is considered to be effective treatment of upper respiratory infection like pertussis, so it needs an in-depth study on centipede fumigation.

Anti-inflammatory Effect of Bodusan (보두산(寶豆散) 메탄올 추출물의 항염증 효과)

  • Kim, Pan-Joon;Yun, Hyun-Jeong;Heo, Sook-Kyoung;Kim, Kyoung-Ae;Kim, Dong-Wan;Kim, Jae-Eun;Park, Sun-Dong
    • The Korea Journal of Herbology
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    • v.24 no.2
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    • pp.49-56
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    • 2009
  • Objectives : Inflammation is important event in the development of vascular diseases including hypertension, atherosclerosis, and restenosis. Bodusan (BDS) was a traditional Korean herbal medicine and widely used in treatment of gastrointestinal complaint and stomach ulcer. The aim of this study was to determine whether BDS and its components inhibit production of nitrite, PGE2 and proinflammatory cytokines in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. Methods : Cytotoxic activity of BDS and its components on RAW 264.7 cells was using 5-(3caroboxymcrophages. eth-oxyphenyj)-2H-tetra-zolium inner salt (MTS) assay. The nitric oxide (NO) production was measured by Griess reagent system. And proinflammatory cytokines were measured by ELISA kit. The levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression were detected by western blot. Results : Our results indicated that BDS and its components significantly inhibited the LPS-induced NO and PGE2 production. Moreover. BDS and its components inhibited iNOS and COX-2 expression accompanied by an attenuation of TNF-${\alpha}$, IL-11${\beta}$, IL-6 and MCP-1 formation in macrophages. Conclusions: These results indicate that BDS and its components have potential as an anti-inflammatory agent.

Inhibitory Effects of Ginseng Saponins on c-fos mRNA Expression and the Proliferation of Rat Aortic Vascular Smooth Muscle Cells Stimulated by Angiotensin II

  • Choi, Woong;Jung, Jin-Young;Kim, Hun-Sik;Yun, Yeo-Pyo;Park, Jong-Dae;Ahn, Hee-Yul
    • The Korean Journal of Physiology and Pharmacology
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    • v.2 no.2
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    • pp.201-207
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    • 1998
  • To evaluate the possibility that the ginseng saponins could be developed as an anti-arteriosclerotic agent, we examined the inhibitory effects of ginseng saponins (total saponin[TS], panaxatriol[PT], panaxadiol[PD]) on the expression of c-fos mRNA and the proliferation of cultured rat aortic vascular smooth muscle cells (VSMCs) stimulated by angiotensin II (Ang II). TS and PT (1.0 mg/ml) suppressed c-fos mRNA induction in VSMCs stimulated by $10^{-5}$ M Ang II. The order of inhibitory potency was PT>TS. Ginseng saponins ($0.01{\sim}1.0$ mg/ml) inhibited the proliferation of VSMCs stimulated by Ang II in a concentration dependent manner, the inhibitory potency was TS>PT>PD at $0.1{\sim}1.0$ mg/ml. These results suggest that ginseng saponins may suppress Ang II-stimulated proliferation of aortic VSMCs which can be seen in atherosclerosis, hypertension and restenosis.

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The relationship between serum adiponectin and inflammatory cytokines in obese Korean juveniles

  • Byun, Sung Hwan;Kwon, Eun Byul;Kim, Se Young
    • Clinical and Experimental Pediatrics
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    • v.57 no.12
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    • pp.533-537
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    • 2014
  • Purpose: Obesity is related to systemic inflammatory processes causing cardiovascular complications. Intercellular adhesion molecule-1 (ICAM-1), CD40 ligand (CD40L), P-selectin are newly described mediators of inflammation and have a significant effect in atherosclerosis. Adiponectin has shown anti-inflammatory effects in adults. The aim of this study was to evaluate the relationship between adiponectin and inflammatory mediators in children and adolescents. Methods: Fifty children or adolescents, twenty two with a body mass index (BMI) over 95th percentile, and twenty eight with a BMI below 75th percentile were included in the study. Serum soluble ICAM-1 (sICAM-1), P-selectin, CD40L, lipid profiles, aspartate aminotransferase, alanine aminotransferase, glucose and insulin were measured to evaluate associations with adiponectin. Comparison of these variables was performed between the obese and the nonobese group. Results: We found a adiponectin to be significant lower and sICAM-1 significant higher in the obese group compared to the nonobese group, but there were no significant differences in P-selectin and soluble CD40L. Adiponectin was negatively associated with ICAM-1 and P-selectin in the obese group. Conclusion: Negative associations of adiponectin with ICAM-1 and P-selectin in obese children and adolescents suggest that serum adiponectin level may represent the inflammatory status.

Inhibitory Effect of Chlorogenic Acid on Low-Density Lipoprotein Oxidation Induced by Cu ion

  • Jeon, Eun-Raye;Karki, Rajendra;Kim, Dong-Wook
    • Korean Journal of Plant Resources
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    • v.23 no.6
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    • pp.519-525
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    • 2010
  • Chlorogenic acid, formed of an ester of caffeic acid and quinic acid, which is naturally abundant in many plant species, was used as a model O-dihydoxy phenolic compound. In the previous study, we have reported that the isolated constituent from Apocynum venetum leaves has an inhibitory effect on $Cu^{2+}$-induced oxidative modification of low-density lipoprotein (LDL). Among them, chlorogenic acid showed the most potent anti-LDL oxidative activity than other compounds. For the reason, we investigated the inhibitory effect of the chlorogenic acid on $Cu^{2+}$-induced oxidative modification of LDL, monitored a lag time in the conjugated-diene formation and TBARS formation, and measured TNBS free amino acid group, and form cell formation in vitro system. The TBARS- and diene- formation were strongly inhibited by chlorogenic acid ($0{\sim}100\;{\mu}g/ml$) with dose dependent manner. On the other hand, TNBS reactive lysine amino groups on LDL oxidation were protected by chlorogenic acid- treated cell group. Therefore, chlorogenic acid inhibited to cholesterol accumulation in the isolated peritoneal macrophage.