• Title/Summary/Keyword: Acetyl-1-carnitine

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HPLC Determination and Pharmacokinetics of Endogenous Acetyl-L-Carnitine (ALC) in Human Volunteers Orally Administered a Single Dose of ALC

  • Kwon, Oh-Seung;Chung, Youn-Bok
    • Archives of Pharmacal Research
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    • v.27 no.6
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    • pp.676-681
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    • 2004
  • Acetyl-L-camitine (ALC), a naturally occurring endogenous compound, has been shown to improve the cognitive performance of patients with senile dementia Alzheimer's type, and to be involved in cholinergic neurotransmission. Because ALC is an endogenous compound, valida-tion of the analytical methods of ALC in the biological fluids is very important and difficult. This study was presented validation and correction for plasma ALC concentrations and pharmacok-inetics after oral administration of ALC to human volunteers. ALC concentrations in human plasma were corrected by subtracting the concentration of blank plasma from each sample. Precision and accuracy (bias %) for uncorrected ALC concentrations were below 2.6 and 6.5% for intra-days, and 4.0 and 9.4% for inter-days, respectively. Precision and accuracy (bias %)for corrected ALC concentrations were below 10.9 and 6.0% for intra-days, and 10.5 and 16.9% for inter-days, respectively. Quantitation limit was $0.1{\;}\mu\textrm{g}/mL$. After oral administration of a 500 mg ALC tablet to 8 healthy volunteers, the principle pharmacokinetic parameters were 4.2 h of the half-life$ (t_{1/2},{\beta})$, the area under the curve $(AUC_{0{\rightarrow}8){\;}of{\;}9.88{\;}\mu\textrm{g}{\cdot}h/mL$, and 3.1 h of the time ($T_{max}$) to reach $C_{max}$. This study first describes the pharmacokinetic study after oral admin-istration of a single dose of ALC in human volunteers.

Ameliorative effects of black ginseng on nonalcoholic fatty liver disease in free fatty acid-induced HepG2 cells and high-fat/high-fructose diet-fed mice

  • Park, Miey;Yoo, Jeong-Hyun;Lee, You-Suk;Park, Eun-Jung;Lee, Hae-Jeung
    • Journal of Ginseng Research
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    • v.44 no.2
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    • pp.350-361
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    • 2020
  • Background: Black ginseng (BG) is a type of Korean ginseng prepared by steaming and drying raw ginseng to improve the saponin content. This study examined the effects of BG on nonalcoholic fatty liver disease (NAFLD) in HepG2 cells and diet-induced obese mice. Methods: HepG2 cells were treated with free fatty acids to induce lipid accumulation before supplementation with BG. NAFLD-induced mice were fed different doses (0.5%, 1%, and 2%) of BG for 8 weeks. Results: BG significantly reduced lipid accumulation and expression of lipogenic genes, peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding protein alpha, sterol regulatory element-binding protein-1c, and fatty acid synthase in HepG2 cells, and the livers of mice fed a 45% high-fat diet with 10% fructose in the drinking water (HFHF diet). BG supplementation caused a significant reduction in levels of aspartate aminotransferase and alanine aminotransferase, while antioxidant enzymes activities were significantly increased in 45% high-fat diet with 10% fructose in the drinking water diet-fed mice. Expression of proliferator-activated receptor alpha and carnitine palmitoyltransferase I were upregulated at the transcription and translation levels in both HepG2 cells and diet-induced obese mice. Furthermore, BG-induced phosphorylation of AMP-activated protein kinase and acetyl CoA carboxylase in both models, suggesting its role in AMP-activated protein kinase activation and the acetyl CoA carboxylase signaling pathway. Conclusion: Our results indicate that BG may be a potential therapeutic agent for the prevention of NAFLD.

Fermented Kochujang Supplement Shows Anti-obesity Effects by Controlling Lipid Metabolism in C57BL/6J Mice Fed High Fat Diet

  • Koo, Bon-Sun;Seong, So-Hui;Kown, Dae-Young;Sohn, Hee-Sook;Cha, Youn-Soo
    • Food Science and Biotechnology
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    • v.17 no.2
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    • pp.336-342
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    • 2008
  • The aim of the present study was to assess the anti-obesity effects of fermented kochujang supplement in C57BL/6J mice. Thirty mice were divided into 3 groups; normal diet control group (ND), high fat diet control group (HD), and high fat diet plus kochujang supplemented group (HDK). Results were as follows: 1. Fennented kochujang supplement in high fat diet decreased body weight and epidydimal and back fat weight compared to non-supplement in HD group. 2. Lipid content and blood glucose level were lower in HDK group than HD group. 3. Fermented kochujang supplement increased mRNA level of lipolytic genes such as acyl-CoA synthetase (ACS), carnitine palmitoyltransferase-1 (CPT-1), and uncoupling proteins-1 (UCP-1) expression, whereas decreased mRNA level of adipogenic genes such as acetyl CoA carboxylase (ACC) expression. These findings suggest that fermented kochujang supplement in high fat diet normalized body weight, epididymal and back fat weight, lipid content, and blood glucose levels through controlling lipid metabolism and provides basic information on the control of obesity.

Hepatoprotective Effects of Gardenia jasminoides Ellis Extract in Nonalcoholic Fatty Liver Disease Induced by a High Fat Diet in C57BL/6 Mice

  • Nam, Mi-Kyung;Choi, Hye-Ran;Cho, Jin-Sook;Cho, Soo-Min;Lee, Young-Ik
    • Natural Product Sciences
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    • v.20 no.1
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    • pp.65-70
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    • 2014
  • This study was carried out to investigate the potential effects of Gardenia jasminoides (GJ) extracts, on hepatic steatosis and lipid metabolism in mice fed with high-fat diet (HFD). GJ extracts (100 mg/kg, ${\times}10$ weeks) fed mice showed reduced body weight, adipose tissue weight, reduced aminotransferase level in plasma and hepatic lipid (triglyceride, total cholesterol) content. These effects were accompanied by decreased expression of lipogenic genes, sterol regulatory element binding protein-1c (SREBP-1c), liver X receptor (LXR), fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), cluster of differentiation 36 (CD36), lipoprotein lipase (LPL) and decreased lipogenic enzyme FAS and HMG-CoAR enzyme activities while elevating carnitine palmitoyltrasferase-1 (CPT) activity. Based on these results, we speculated that the inhibitory effect on hepatic steatosis of GJ extract containing geniposide is the result of suppression of lipid synthesis in mice fed with HFD, suggesting that GJ extract may be beneficial in preventing hepatic steatosis.

Effects of Oenanthe javanica, Coicis lachryma-jobi L. var., and Plantaginis asiatica L. Water Extracts on Activities of Key Enzymes on Lipid Metabolism (미나리 줄기(Oenanthe javanica), 율무(Coicis lachryma-jobi L. var.), 차전자(Plantaginis asiatica L.) 물 추출물이 지질대사)

  • Lee, Hyeon-Ju;Chung, Mi-Ja;Kim, Dae-Jung;Choe, Myeon
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.38 no.11
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    • pp.1516-1521
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    • 2009
  • This study was carried out to estimate beneficial effects of medicinal plant [Oenanthe javanica (MNR), Coicis lachryma-jobi L. var. (YM), Plantaginis asiatica L. (CJJ)] water extracts on activities of key enzymes such as lipoprotein lipase (LPL), acyl-CoA synthetase (ACS) and carnitine acetyltransferase (CAT) on lipid metabolism. LPL and ACS were extracted from the epididymal adipose tissue and liver of Zucker lean rats (lean) and Zucker fatty rats (fa/fa). MNR or YM water extract treatment significantly reduced the activity of lean and fa/fa LPL. When 10000 ppm of MNR, YM, and CJJ water extracts were tested, they decreased fa/fa LPL activity by 32.5%, 30.1% and 22.8%, respectively. The lean ACS activity was significantly higher in YM water extract treatment compared to the control and the MNR water extract treatment significantly increased the activity of fa/fa ACS, compared to the activity in the control (p<0.05). MNR water extract activated fa/fa ACS activity by 12-fold compared with control at 10000 ppm concentration. CAT activity was significantly higher in 10000 ppm and 20000 ppm CJJ water extract treatment than in the control. Thus, the MNR, YM and CJJ water extracts may have beneficial effects due to activities of enzymes related with fat metabolism in obese humans.

Choline and basic amine drugs efflux from brain to blood across the blood-brain barrier

  • Lee, Na-Young;Kang, Young-Sook
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2003.11a
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    • pp.107-107
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    • 2003
  • The purpose of this study is to examine that the efflux transport system for choline from brain to blood is present at the blood-brain barrier (BBB) using brain efflux index (BEI) method. [$^3$H]Choline was microinjected into parietal cortex area 2 (Par2) region of rat brain, and was eliminated from the brain with an apparent elimination half life of 45 min. The BBB efflux clearance of [$^3$H]choline was 0.12 $m\ell$/min/g brain, which was calculated from the efflux rate constant (1.5${\times}$10$\^$-2/ min$\^$-1/) and the distribution volume in the brain slice (8.1 $m\ell$/g brain). This process was saturable and significantly inhibited by various organic cationic compounds including hemicholinium-3, tetraethylammonium chloride (TEA) and verapamil, by antioxidant, ${\alpha}$-phenyl-n-tert-butyl nitrone (PBN), and by Alzheimer's disease therapeutics, such as acetyl $\ell$-carnitine and tacrine. In conclusion, this finding is the first direct in vivo evidence that choline is transported from brain to the blood across the BBB via a carrier-mediated efflux transport process.

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Dietary Niacin Supplementation Suppressed Hepatic Lipid Accumulation in Rabbits

  • Liu, Lei;Li, Chunyan;Fu, Chunyan;Li, Fuchang
    • Asian-Australasian Journal of Animal Sciences
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    • v.29 no.12
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    • pp.1748-1755
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    • 2016
  • An experiment was conducted to investigate the effect of niacin supplementation on hepatic lipid metabolism in rabbits. Rex Rabbits (90 d, n = 32) were allocated to two equal treatment groups: Fed basal diet (control) or fed basal diet with additional 200 mg/kg niacin supplementation (niacin). The results show that niacin significantly increased the levels of plasma adiponectin, hepatic apoprotein B and hepatic leptin receptors mRNA (p<0.05), but significantly decreased the hepatic fatty acid synthase activity and adiponectin receptor 2, insulin receptor and acetyl-CoA carboxylase mRNA levels (p<0.05). Plasma insulin had a decreasing tendency in the niacin treatment group compared with control (p = 0.067). Plasma very low density lipoproteins, leptin levels and the hepatic adiponectin receptor 1 and carnitine palmitoyl transferase 1 genes expression were not significantly altered with niacin addition to the diet (p>0.05). However, niacin treatment significantly inhibited the hepatocytes lipid accumulation compared with the control group (p<0.05). In conclusion, niacin treatment can decrease hepatic fatty acids synthesis, but does not alter fatty acids oxidation and triacylglycerol export. And this whole process attenuates lipid accumulation in liver. Besides, the hormones of insulin, leptin and adiponectin are associated with the regulation of niacin in hepatic lipid metabolism in rabbits.

A Case of Statin-Induced Interstitial Pneumonitis due to Rosuvastatin

  • Kim, Se Yong;Kim, Se Jin;Yoon, Doran;Hong, Seung Wook;Park, Sehhoon;Ock, Chan-Young
    • Tuberculosis and Respiratory Diseases
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    • v.78 no.3
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    • pp.281-285
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    • 2015
  • Statins lower the hyperlipidemia and reduce the incidence of cardiovascular events and related mortality. A 60-year-old man who was diagnosed with a transient ischemic attack was started on acetyl-L-carnitine, cilostazol, and rosuvastatin. After rosuvastatin treatment for 4 weeks, the patient presented with sudden onset fever, cough, and dyspnea. His symptoms were aggravated despite empirical antibiotic treatment. All infectious pathogens were excluded based on results of culture and polymerase chain reaction of the bronchoscopic wash specimens. Chest radiography showed diffuse ground-glass opacities in both lungs, along with several subpleural ground-glass opacity nodules; and a foamy alveolar macrophage appearance was confirmed on bronchoalveolar lavage. We suspected rosuvastatin-induced lung injury, discontinued rosuvastatin and initiated prednisolone 1 mg/kg tapered over 2weeks. After initiating steroid therapy, his symptoms and radiologic findings significantly improved. We suggest that clinicians should be aware of the potential for rosuvastatin-induced lung injury.

The effect of fucoxanthin rich power on the lipid metabolism in rats with a high fat diet

  • Ha, Ae Wha;Kim, Woo Kyoung
    • Nutrition Research and Practice
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    • v.7 no.4
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    • pp.287-293
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    • 2013
  • This study determined the effects of fucoxanthin on gene expressions related to lipid metabolism in rats with a high-fat diet. Rats were fed with normal fat diet (NF, 7% fat) group, high fat diet group (HF, 20% fat), and high fat with 0.2% fucoxanthin diet group (HF+Fxn) for 4 weeks. Body weight changes and lipid profiles in plasma, liver, and feces were determined. The mRNA expressions of transcriptional factors such as sterol regulatory element binding protein (SREBP)-1c, Carnitine palmitoyltransferase-1 (CPT1), Cholesterol $7{\alpha}$-hydroxylase1 (CYP7A1) as well as mRNA expression of several lipogenic enzymes were determined. Fucoxanthin supplements significantly increased plasma high density lipoprotein (HDL) concentration (P < 0.05). The hepatic total lipids, total cholesterols, and triglycerides were significantly decreased while the fecal excretions of total lipids, cholesterol, and triglycerides were significantly increased in HF+Fxn group (P < 0.05). The mRNA expression of hepatic Acetyl-CoA carboxylase (ACC), Fatty acid synthase (FAS), and Glucose-6-phosphate dehydrogenase (G6PDH) as well as SREBP-1C were significantly lower in HF+Fxn group compared to the HF group (P < 0.05). The hepatic mRNA expression of Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) and Acyl-CoA cholesterol acyltransferase (ACAT) were significantly low while lecithin-cholesterol acyltransferase (LCAT) was significantly high in the HF+Fxn group (P < 0.05). There was significant increase in mRNA expression of CPT1 and CYP7A1 in the HF+Fxn group, compared to the HF group (P < 0.05). In conclusion, consumption of fucoxanthin is thought to be effective in improving lipid and cholesterol metabolism in rats with a high fat diet.

Effects of Kisspeptin-10 on Lipid Metabolism in Cultured Chicken Hepatocytes

  • Wu, J.;Fu, W.;Huang, Y.;Ni, Y.
    • Asian-Australasian Journal of Animal Sciences
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    • v.25 no.9
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    • pp.1229-1236
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    • 2012
  • Our previous studies showed that kisspeptin-10 (Kp-10) injected in vivo can markedly increase lipid anabolism in liver of quails. In order to investigate the direct effect of Kp-10 on lipid metabolism of hepatocytes in birds, cells were separated from embryos livers and cultured in vitro with 0, 100 and 1,000 nM Kp-10, respectively. The results showed that after 24 h treatment, cells viability was not affected by 100 nM Kp-10, but showed a mild decrease with 1,000 nM Kp-10 compared to the control cells. Based on the results of the cell viability, 100 nM dosage of Kp-10 was selected for the further study and analysis. Compared with control cells, total cholesterol (Tch) contents in 100 nM treated cells were increased by 51.23%, but did not reach statistical significance, while the level of triglyceride (TG), high density of lipoprotein-cholesterol (HDL-C) and low density of lipoprotein-cholesterol (LDL-C) were significantly increased. Real-time PCR results showed that ApoVLDL-II mRNA expression had a tendency to increase, genes including sterol regulatory element-binding protein-1 (SREBP-1), acetyl coenzyme A carboxylase ${\alpha}$ ($ACC{\alpha}$), carnitine palmitoyltransferase 1 (CPT1), 3-hydroxyl-3-methylglutaryl-coenzyme A reductases (HMGCR) and stearyl coenzyme A dehydrogenase-1 (SCD1) mRNA in hepatocytes were significantly down-regulated by 100 nM Kp-10. However, contrary to its gene expression, SREBP-1 protein expression was significantly up-regulated by 100 nM Kp-10. Some of the significant correlations in mRNA expression were found between genes encoding hepatic factors or enzymes involved in lipid metabolism in liver of birds. These results indicate that Kp-10 stimulates lipid synthesis directly in primary cultured hepatocytes of chickens.