• Title/Summary/Keyword: Atherosclerosis

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Screening for Human ACAT-1 and ACAT-2 Inhibitory Activity of Edible Plant Extracts (식물추출물의 Human-ACAT 저해활성 검색)

  • Lee, Dae-Young;Jeong, Tae-Sook;Lyu, Ha-Na;Bang, Myun-Ho;Hong, Yoon-Hee;Lee, Youn-Hyung;Baek, Nam-In
    • Korean Journal of Medicinal Crop Science
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    • v.16 no.5
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    • pp.341-348
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    • 2008
  • Cholesterol acyltransferase (ACAT) catalyzes the acylation of cholesterol to cholesteryl ester with long chain fatty acids and ACAT inhibition is a useful strategy for treating hypercholesterolemia or atherosclerosis. Inhibitory effects on ACAT of the MeOH extracts prepared from 163 edible plants were evaluated. 15 species out of 163 species exhibited higher than 50% of inhibition on the hACAT-1 and 9 species exhibited higher than 50% of inhibition on the hACAT-2 activity at their concentration of $100\;{\mu}g/mL$.

Anti-sclerotic Effect of Cinnamomi Ramulus Via Suppression of MMP-9 Activity and Migration of TNF-$\alpha$-induced HASMC (인간대동맥평활근의 유주능 및 기질금속단백분해효소의 억제를 통한 계지의 항동맥경화능)

  • Kim, Jai-Eun;Lee, Chang-Sup;Choi, Sung-Kyu;Choi, Dall-Yeong
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.23 no.5
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    • pp.974-979
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    • 2009
  • Proliferation of vascular smooth muscle cell(VSMC) is one of the key features in onset of atherosclerosis and restenosis after vascular surgery such as stent implant. Atherosclerotic plaques are usually composed of collagen, elatsin and smooth muscle cells. Release of matrix metalloproteinases(MMPs) is considered to have correlation with development of atherosclerotic plaques. Based on the hypothesis that MMP inhibition would be helpful in the treatment of atherosclerosis, we investigated inhibition of MMP activity and migration of TNF-$\alpha$-induced human aortic smooth muscle cell(HASMC) by Cinnamomi Ramulus(CC). The result from gelatin zymography showed that CC inhibited MMP-9 activity in a dose-dependent manner. In addition, CC considerably inhibited the migration of HASMC induced by TNF-$\alpha$, while it showed little cytotoxic effect on HASMC. These results suggest that CC can be a potential anti-atherosclerotic agent through inhibition of MMP-9 activity and SMC migration.

Laminar Flow Inhibits ER Stress-Induced Endothelial Apoptosis through PI3K/Akt-Dependent Signaling Pathway

  • Kim, Suji;Woo, Chang-Hoon
    • Molecules and Cells
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    • v.41 no.11
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    • pp.964-970
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    • 2018
  • Atherosclerosis preferentially involves in prone area of low and disturbed blood flow while steady and high levels of laminar blood flow are relatively protected from atherosclerosis. Disturbed flow induces endoplasmic reticulum (ER) stress and the unfolded protein response (UPR). ER stress is caused under stress that disturbs the processing and folding of proteins resulting in the accumulation of misfolded proteins in the ER and activation of the UPR. Prolonged or severe UPR leads to activate apoptotic signaling. Recent studies have indicated that disturbed flow significantly up-regulated $p-ATF6{\alpha}$, $p-IRE1{\alpha}$, and its target spliced XBP-1. However, the role of laminar flow in ER stress-mediated endothelial apoptosis has not been reported yet. The present study thus investigated the role of laminar flow in ER stress-dependent endothelial cell death. The results demonstrated that laminar flow protects ER stress-induced cleavage forms of PARP-1 and caspase-3. Also, laminar flow inhibits ER stress-induced $p-eIF2{\alpha}$, ATF4, CHOP, spliced XBP-1, ATF6 and JNK pathway; these effects are abrogated by pharmacological inhibition of PI3K with wortmannin. Finally, nitric oxide affects thapsigargin-induced cell death in response to laminar flow but not UPR. Taken together, these findings indicate that laminar flow inhibits UPR and ER stress-induced endothelial cell death via PI3K/Akt pathway.

Age-Associated Increasing of MCP-1 in Adults

  • Im, Jee-Aee;Kim, Sang-Hwan
    • Biomedical Science Letters
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    • v.13 no.3
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    • pp.183-187
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    • 2007
  • Monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) playa key role in development of atherosclerosis. To take into account the atherogenic properties of MCP-1 and IL-8 and its influence on insulin resistance, we examined circulating levels of MCP-1 and IL-8 in adults. We recruited 292 subjects (84 males and 208 females) aged between 29 and 79 years. MCP-1 and IL-8 levels were measured by enzyme-linked immunosorbent assay. Age, total cholesterol, HDL-cholesterol, and LDL-cholesterol levels were significantly higher in female subjects (P<0.01, respectively), but diastolic blood pressure (BP) was significantly lower in female subjects compared to male subjects. MCP-1 and IL-8 levels were tended to increase with age, the highest in their seventies. MCP-1 (P=0.05) and IL-8 (P<0.01) levels were higher in males than in females. MCP-1 was positively correlated with age (r=0.17, P<0.05), IL-8 (r=0.26, P<0.01), fasting insulin (r=0.30, P<0.01), and HOMA-IR (r=0.29, P<0.01). In linear regression analysis, age was found to be independent factor associated with MCP-1 adjusted by age, BMI, fasting glucose, triglyceride, and systolic BP. In conclusion, age was found to be independent factor associated with MCP-1. It is possible that an increase of MCP-1 in adults with age may be risk to atherosclerosis and diabetic properties.

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Screening of Anti-atherogenic Substances from Insect Resources (곤충자원으로부터 항동맥경화 활성물질 탐색)

  • Park, Doo-Sang;Yoon, Mi-Ae;Xu, Ming-Zhe;Yu, Ha-Na;Kim, Ju-Ryoung;Jeong, Tae-Sook;Park, Ho-Yong
    • Korean Journal of Pharmacognosy
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    • v.35 no.3 s.138
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    • pp.233-238
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    • 2004
  • Lipoprotein-associated phospholipase $A_2\;(Lp-PLA_2)$ is a potential biomarker of coronary heart disease and plays an important proinflammatory role in the progression of atherosclerosis. Also acyl-CoA: cholesterol acyltransferase (ACAT) and oxidized low-density lipoprotein (LDL) playa key role in atherosclerosis, respectively. And so, the inhibitory activities of the methanol extracts of 42 insect resources were examined on $Lp-PLA_2$, ACAT, and LDL oxidation for screening of anti-atherogenic substances. Among them, the methanol extracts of Eurydema rugosa significantly inhibited all of upper three activities. Several kinds of tested insects having high inhibitory effect with the methanol extracts were extracted with n-hexane, ethyl acetate, and acetone, and their inhibitory activities were tested.

Arginase II Inhibitory Activity from Crude Drugs

  • Lim, Chae-Jin;Hung, Tran Manh;Ryoo, Sung-Woo;Lee, Jeong-Hyung;Min, Byung-Sun;Bae, Ki-Hwan
    • Natural Product Sciences
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    • v.17 no.2
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    • pp.113-116
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    • 2011
  • Arginase competitively inhibits nitric oxide synthase (NOS) via use of the common substrate L-arginine. Arginase II has recently reported as a novel therapeutic target for the treatment of cardiovascular diseases such as atherosclerosis. In our experiment, the EtOH extracts of four-hundreds extracts drugs were investigated for the arginase inhibitory activity. Among them, four extracts exhibited over 50% inhibition of arginase II activity compared to control at a concentration of 150${\mu}g/ml$. In particular, the seed of Arctium lappa, gum-resin of Boswellia carterii, aerial part of Artemisia apiacea and rhizome of Cyperus rotundus inhibited arginase II activity, with $IC_{50}$ values of 118.4, 135.4, 123.9 and 86.7${\mu}g/ml$, respectively. In addition, four plant extracts showed less than 20% inhibition of arginase I activity at 150${\mu}g/ml$. These plants might be the potential candidate materials in the development of the novel atherosclerosis drug.

Human Acyl-CoA: Cholesterol Acyltransferase Inhibitory Effect of Flavonoids from Roots of Glycine max (L.) Merr

  • Lee, Jin-Hwan;Seo, Woo-Duck;Jeong, Seong-Hun;Jeong, Tae-Sook;Lee, Woo-Song;Park, Ki-Hun
    • Journal of Applied Biological Chemistry
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    • v.49 no.2
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    • pp.57-61
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    • 2006
  • Isoflavones 1-3 and pterocarpans 4-8 were isolated from methanol extract of roots of Glycine max. In inhibitory effect against human acyl-CoA:cholesterol acytransferase (ACAT)-1 and ACAT-2, glyceollin I 5 showed potent hACAT-1 ($IC_{50}=299.0{\mu}M$) and hACAT-2 ($IC_{50}=82.7{\mu}M$) inhibitory activities.

Effects of KanghwalSokdantang(KS) on LDL Oxidation in Macrophage Cell (대식세포의 oxLDL 생성에 미치는 강활속단탕의 영향)

  • Ko Seong-Gyu;Jeong Yong-Su;Sun Seung-Ho
    • The Journal of Internal Korean Medicine
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    • v.24 no.2
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    • pp.203-212
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    • 2003
  • Objective : As a link in chain of research to confirm the oriental medical prescription which has the anti-atherosclerosis effects, this research evaluated the effects on the macrophage-related factors by using KanghwalSokdantang(KS). Methods : In order to perform this research, we have evaluated the effects on the oxLDL formation from the macrophages, the nitric oxide formation, and the oxidation of macrophages. Thus, with this evaluation, we have investigated the applicapability on the artherosclerosis. Results : KanghwalSokdantang has showed a noticeable reduction of protein oxidation in the process of oxLDL formation, has remarkably restrained phospholipid peroxidation, an index to estimated the phospholipid oxidation and reduction that are formed in the process of macrophage's oxLDL formation, and has increased the nitrite concentration noticeably in the LDL-dealing macrophages. By increasing the survival rate of macrophages, KanghwalSokdantang has restrained the cellular damages. KanghwalSokdantang is ineffective on the LDH outflow from damaged cells. $1{\mu}g/ml$ KanghwalSokdantang sample has increased acid phosphatase activity remarkably. Conclusion : KanghwalSokdantang has the possibility to be used in the prevention and treatment of atherosclerosis, which is formed by the oxLDL formation of macrophages.

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The Inhibiton Effects of Hypercholesterolemia and Platelet in Fermented and Non-Fermented Preparation of Garlic

  • Kim, Hyun-Kyoung
    • International Journal of Internet, Broadcasting and Communication
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    • v.11 no.4
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    • pp.1-10
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    • 2019
  • This Dietary cholesterol augments lipid profile and primes production and activation of platelets, leading to development of atherosclerosis which produce several detrimental effects on cardiovascular health. Ethnomedicine and Mediterranean diet are natural sources and cost effective modes against several ailments including cardiovascular diseases while fermented foods have gained interest due to their increased nutrient profile, enhanced bioavailability and efficacy. Garlic has been known to reduce cholesterol and inhibit platelet activation. We examined whether fermented garlic ameliorates effects of hypercholesterolemia and platelet functions in rats. Methodology: Male SD rats were fed with hypercholesterolemia diet and treated with spirulina, fermented and non-fermented preparations of garlic for one month. Platelet aggregation and granule secretion were assessed to evaluate platelet activation. Liver and kidney weights, lipid and enzymatic profile of serum and whole blood analysis was performed. Expressions of SREBP, ACAT-2 and HMG-CoA were assessed using RT-PCR while liver and adipose tissues were analyzed for histological changes. Both fermented and non-fermented garlic inhibited platelet aggregation and granule secretion while fermented garlic showed greater inhibitor tendency. Fermented garlic significantly reduced liver weight and triglycerides concentrations than non-fermented garlic. Similarly, fermented garlic greatly abrogated the detrimental effects of steatosis on liver and adipose tissues. Fermented garlic significantly improved lipid profile and modulated platelet functions, thereby inhibiting atherosclerosis and platelet related cardiovascular disorders.

The Model for Evaluation on Blood Flow of Functional Food in Human Intervention Study (인체에서 식품의 혈행 개선 효능 평가 모델)

  • Lim, Yeni;Kwon, Oran;Kim, Ji Yeon
    • Journal of Lipid and Atherosclerosis
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    • v.7 no.2
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    • pp.88-97
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    • 2018
  • The prevalence of atherothrombotic disease continues to rise, presenting an increasing number of challenges to modern society and creating interest in functional foods. Platelet activation, adhesion, and aggregation at vascular endothelial disruption sites are key events in atherothrombotic disease. Physiological challenges such as hyperlipidemia, obesity, and cigarette smoking are associated with vascular changes underlying platelet aggregation and inflammatory processes. However, it is difficult to determine the beneficial response of functional foods in healthy subjects. To address this problem, challenge models and high-risk models related to smokers, obesity, and dyslipidemia are proposed as sensitive measures to evaluate the effects of functional foods in healthy subjects. In this review, we construct a model to evaluate the effects of functional food such as natural products on blood flow based on a human intervention study.