• Korean Journal of Clinical Pharmacy
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• v.15 no.1
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• pp.41-45
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• 2005

심바스타틴은 cholesterol 생합성 과정에서 속도 조절 효소인 HMG-CoA reductase의 강력한 상경적 길항약으로서 고지혈증 치료에 널리 쓰이는 약물이다. 심바스타틴 제제인 MSD 사의 조코 20 mg정을 대조약으로 하여 시험약인 유영 제약의 엘바스타 20mg정의 생물학적 동등성 평가를 하기 위해 22명의 건강한 지원자를 모집하였다. 지원자를 두 군으로 나누어 2정씩 투여하였고 $2{\times}2$ 교차시험을 실시하였다. 심바스타틴의 혈장 중의 농도를 정량하기 위하여 발리데이션된 LC/MS/MS를 사용하였다. 채혈 시간은 투약 전 및 투약 후 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 시간에 걸쳐 총 12시점에 걸쳐 시행하였다. 생물학적 동등성을 판정하기 위한 파라미터로 12시간까지의 혈장 중 농도곡선 하 면적 ($AUC_{12hr}$)과 최고 혈중 농도($C_{max}$)를 사용하였다. 12시간 까지의 혈중 농도 곡선 하 면적의 기하 평균은 $17.30ng{\cdot}ml/hr$(시험약)과 $17.35ng{\cdot}ml/hr$(대조약)으로 나타났다. 최고 혈중 농도의 경우 각 각 5.08 ng/ml(시험약)과 5.20 ng/ml(대조약)으로 관찰 되었다. $AUC_{12hr}$의 경우 로그변환한 평균치 차의 $90{\%}$ 신뢰구간이 log0.8510 - log1.1694이었고, $C_{max}$의 경우 log0.8176 - log1.1649로 계산되어 두 항목 모두 log0.8-log1.25이어야 한다는 식품의약품 안전청과 FDA의 기준을 모두 만족시켰다. 이상의 결과를 종합하면 시험약 엘바스타 정 20mg은 대조약 조코정 20 mg에 대하여 생물학적 동등한 것으로 판정되었다.트리머 전기비저항 탐사를 수행하였다. 이를 통해 하저에 케이블을 설치하는 방식에 비해 매우 신속하고 경제적으로 하저에 분포하는 이상대의 분포범위와 발달방향을 규명할 수 있었다.대에 대해 가장 효과적이다. 모델과 현장 적용 결과들을 통해 GRM SSM 방법을 이용하여 불규칙한 굴절면을 가진 지층들에 대해 좀 더 신뢰할 수 있는 정밀한 탄성파 속도를 산출할 수 있음을 보여주고 있다.별한 주의를 기울여야 한다.EX>$\alpha/\beta$=10인 경우 $62.0\~121.9\;Gy_{10}$ (중앙값: $93.0\;Gy_{10}$)의 분포를, ${\alpha/\beta}=3$인 경우 $93.6\~187.3\;Gy_3$ (중앙값=$137.6\;Gy_3$ )의 분포를 보였다. MD-BED $Gy_3$는 직장합병증 발생과의 관계는 통계적으로 유의하였고, 방광합병증과는 유의하지 않았다. 직장합병증과의 연관성은 MD-BED $Gy_3$보다 개별 환자의 직장전벽 총 선량 BED값인 R-BED $Gy_3$가 훨씬 더 높았다. 요도카테터 풍선의 후방지점이 대변하는 방광의 총 선량 BED값인 V-BED $Gy_3$도 방광합병증과 경향성 테스트에서 통계적 유의성을 보였다. 하지만, 어떠한 방사선선량도 골반제어율과 의미 있는 상관관계를 보이지 않았다. 본 기관에서 주치의의 선호도에 따라 강내근접치료가 외부방사선치료의 중간에 시행되는 형태인 샌드위치기법과 외부방사선치료 후반부에 시행되는 순차적 기법으로 구분하였을 때, 두 방식간 치료성적 및 합병증의 차이는 없었다. 총 치료기간에 대한 분석에서는 치료기간이 길어질수록 재발 위험이 커지는 경향을 보였으나, 나이 및 병기, 종양의 크기, MD-BED $Gy_{10}$

• Korean Journal of Food Science and Technology
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• v.40 no.6
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• pp.691-695
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• 2008

The objective of this study was to evaluate the effects of glycoprotein isolated from Morus indica L. (MIL) on plasma cholesterol levels and on the activities of hepatic detoxicant enzymes in ICR mice. MIL glycoprotein evidenced good scavenging activities against lipid peroxyl radicals. When the mice were treated with Triton WR-1339, the levels of total cholesterol (TC) and low-density lipoprotein (LDL)-cholesterol in plasma increased significantly by 53.9 and 47.5 mg/dL, respectively, as compared to the controls. However, when pretreated with MIL glycoprotein $(100{\mu}g/mL)$, ICR mice showed marked reductions to 55.4 and 47.0 mg/dL, as compared to Triton WR-1339 treatment alone. Interestingly, high density lipoprotein cholesterol levels were unchanged. These results indicate that the MIL glycoprotein is capable of scavenging lipidperoxyl radicals, lowering plasma lipid levels, and increasing the activities of detoxicant enzymes in the mouse liver.

• Journal of Nutrition and Health
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• v.39 no.2
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• pp.91-99
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• 2006

This study was conducted to investigate the effects of mulberry fruit, mulberry leaves and silkworm powder with different mixing ratios on hepatic antioxidative system and lipid metabolism in streptozotocin-induced diabetic rats. Sprague-Dawley male rats weighing $100{\pm}10g$ were induced diabetic by 50 mg/kg bw streptozotocin and randomly assigned to following experimental groups; normal diet group (DM), 0.3% and 0.6% mulberry fruit diet groups (F and 2F), 0.3% mulberry leaves diet group (M), 0.3% silkworm powder diet group (S), 0.15% mulberry fruit+0.15% mulberry leaves diet group (FM), 0.15% mulberry fruit+0.15% silkworm powder diet group (FS), 0.1 % mulberry fruit+0.1 % mulberry leaves+0.1% silkworm powder diet group (FMS). The experimental diets were fed for 4 weeks. Hepatic SOD activity was not changed significantly by any of single or combined supplementations of mulberry fruit, leaves and silkworm powder but GSH-px and catalase activities were increased by the groups supplemented with two or three of the test ingredients (FM, FS, FMS) as compared with the DM group. Hepatic TBARS value was not reduced significantly by any of the supplementations but lipofuscin contents were significantly reduced in the FM, FS and FMS groups as compared with the DM group. Hepatic mitochondria and microsomal carbonyl values were reduced by the single and combined supplementations of the test ingredients. Hepatic HMG-CoA reductase activities were increased in the all supplementation groups as compared with the DM group. Hepatic total lipid and triglyceride contents were increased but cholesterol contents reduced in the supplemented groups. The effects on the enzyme activities, peroxide or its products and lipid contents were most remarkable in the FMS group. In conclusion, mulberry fruit, mulberry leaves and silkworm powder have the favorable effects on antioxidative system and lipid metabolism in the diabetic liver and the mulberry fruit, leaves and silkworm powder with equal ratio exert the synergistic effect expectedly to prevent diabetic complications.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.4
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• pp.498-506
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• 2014

The objective of this study was to investigate the beneficial effects of mulberry extract (MBE) on blood flow improvement. The $SC_{50}$ value for the DPPH radical scavenging activity of MBE was $89.36{\pm}5.46{\mu}g/mL$. Analysis of the cellular toxicity of MBE on RAW 264.7 and HepG2 cells showed no toxicity under a concentration of 2,500 ${\mu}g/mL$. We found that MBE inhibited the enzyme activity of cyclooxygenase (COX)-2 as well as oxidation of human LDL. Western blotting analysis showed that MBE inhibited protein expression of COX-2 and 5-lipoxygenase in RAW 264.7 cells. In addition, MBE inhibited protein expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in human umbilical vein endothelial cells. Furthermore, MBE reduced the serum levels of total cholesterol and C-reactive protein in a concentration-dependent manner. These results both in vitro and in vivo suggest that MBE can be employed for the improvement of blood flow.

• Journal of Life Science
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• v.29 no.12
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• pp.1337-1344
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• 2019

Osteoporosis is characterized by a reduction in bone mass and typically manifests as an increase in fractures. Because this disease is common in elderly populations and lifespans are rapidly increasing, the incidence of osteoporosis has also grown. Most drugs currently used for osteoporosis treatment target osteoclasts in the bone tissue to prevent absorption. However, these medications also cause certain side effects and, furthermore, cannot increase bone mass. Thus, in order to control osteoporosis, regenerative medicine that utilizes adult stem cells and osteoblasts has been extensively studied. Statins, also known as 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, are cholesterol-lowering drugs that have been widely prescribed for cardiovascular diseases. Interestingly, recent studies have reported the beneficial effects of various statins on bone formation via the activation of osteoblasts. Thus, the current study investigated the effects of seven statin-family drugs on osteoblast activity during osteogenic differentiation using adult stem cells from human periosteal tissue. Specifically, statin effects on alkaline phosphatase activity, an early marker of bone cell differentiation, and on calcium deposit, a late marker of bone cell differentiation, were assessed. The results demonstrate that some statins (for example, pitavastatin and pravastatin) have a weak but positive effect on bone formation, and the findings therefore suggest that statin treatments can be a novel modulator for osteogenic differentiation and regenerative medicine using periosteal stem cells.

• Journal of the East Asian Society of Dietary Life
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• v.20 no.1
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• pp.20-29
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• 2010

Naringin has antioxidant and antihyperlipidemic properties, however, phenolic compounds including naringin are unstable in the presence of light, heat and oxygen. Beta-cyclodextrin ($\beta$-CD) is a cyclic heptamer composed of seven glucose units that enhances the stability and solubility of molecules through the formation of inclusion complexes. This study was conducted out to compare the effects of CD-naringin (CD-N) inclusion complexes with naringin on lipid metabolism in high fat-fed animals. Male C57BL/6 mice were fed either CD-N (0.048%, w/w) or naringin (N, 0.02%, w/w) in a 20% high-fat (HFC, 15% lard, 5% corn oil, w/w) diet for 10 weeks. Orlistat (Xenical, 0.01%, w/w) was used as a positive control (PC). There were no differences in body weight, food intake, liver and heart weights, plasma triglyceride(TG), leptin, adiponectin, resistin, IL-$1{\beta}$ and IL-6 concentrations, and hepatic $\beta$-oxidation, carnitine palmitoyl transferase(CPT), glucose-6-phosphate dehydrogenase (G6PD) and malic enzyme activities between the HFC and CD-N groups or between the HFC and N groups. However, both CD-naringin and naringin supplementation les to a significant reduction in the epididymal and perirenal white adipose tissue weights, plasma free fatty acid, insulin and blood glucose concentrations, hepatic cholesterol and TG contents and hepatic fatty acid synthase (FAS), phosphatidate phosphohydrolase (PAP) and HMG-CoA reductase activities compared to the HFC group. The plasma HDL-cholesterol concentration was significantly higher in CD-N and N groups than in HF and PC groups. These results indicate that both CD-naringin and naringin supplementation effectively improved plasma and hepatic lipid metabolism without differences between CD-N and naringin groups.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.9
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• pp.1215-1226
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• 2011

The objective of this study was to investigate the anti-obesity and lipid-lowering effects of extracts of persimmon leaf (PWE), buckwheat leaf (BWE), and chinese matrimony vine leaf (LWE) in rats fed a high-fat diet (HFD). Male Sprague-Dawley rats (n=40) were divided into four groups: HFD (35% fat, w/w), HFD (38.5% fat, w/w) supplemented with PWE (10%, w/w), BWE (10%, w/w), and LWE (10%, w/w) groups. The epididymal, perirenal, and interscapular white adipose tissue (WAT) weights as well as plasma leptin level were lowest in the LWE group. Supplementation with PWE and BWE also tended to lower the perirenal and retroperitonal WAT weights compared to the HFD control group, and there was a significant decrease in plasma leptin concentration. Furthermore, plasma triglyceride concentration, hepatic cholesterol content, and hepatic lipid droplet accumulation were significantly lower in the PWE, BWE, and LWE groups than in the HFD group. BWE supplementation markedly lowered plasma total cholesterol concentration, although there were no significant differences in plasma HDL-cholesterol concentration and ratio of HDL-cholesterol/total cholesterol among the groups. Hepatic HMG-CoA reductase activity was significantly higher in the PWE and LWE groups than in the HFD group, and hepatic ACAT was not changed by extract supplementation. However, supplementation with PWE, BWE, and LWE significantly increased fecal acidic sterol content in rats fed a HFD. These results suggest that supplementation with PWE, BWE, and LWE may be an effective anti-obesity strategy by lowering body fat weight and improving plasma and hepatic lipid profiles in HFD-fed rats.

• Journal of Nutrition and Health
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• v.51 no.4
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• pp.275-286
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• 2018

Purpose: Our previous study demonstrated that persimmon (Diospyros kaki Thumb.) at different stages of ripening provided different protective effects against high-fat/cholesterol diet (HFD)-induced dyslipidemia in rats. In this study, we compared the metabolites profile and gene expressions related to triglyceride (TG)/cholesterol metabolism in vitro and in vivo after treating with persimmon water extracts (PWE) or tannin-enriched persimmon concentrate (TEP). Methods: Primary and secondary metabolites in test materials were determined by GC-TOF/MS, UHPLC-LTQ-ESI-IT-MS/MS, and UPLC-Q-TOF-MS. The expression of genes related to TG and cholesterol metabolism were determined by RT-PCR both in HepG2 cells stimulated by oleic acid/palmitic acid and in liver tissues obtained from Wistar rats fed with HFD and PWE at 0, 150, 300, and 600 mg/d (experiment I) or TEP at 0, 7, 14, and 28 mg/d (experiment II) by oral gavage for 9 weeks. Results: PLS-DA analysis and heatmap analysis demonstrated significantly differential profiling of metabolites of PWE and TEP according to processing of persimmon powder. In vitro, TEP showed similar hypolipidemic effects as PWE, but significantly enhanced hypocholesterolemic effects compared to PWE in sterol regulatory element-binding protein 2 (SREBP2), HMG-CoA reductase (HMGCR), proprotein convertase subtilisin/kexin type 9 (PCSK9), cholesterol $7{\alpha}-hydroxylase$ (CYP7A1), and low density lipoprotein receptor (LDLR) gene expression. Consistently, TEP and PWE showed similar hypolipidemic capacity in vivo, but significantly enhanced hypocholesterolemic capacity in terms of SREBP2, HMGCR, and bile salt export pump (BSEP) gene expression. Conclusion: These results suggest that column extraction after hot water extraction may be a good strategy to enhance tannins and long-chain fatty acid amides, which might cause stimulation of hypocholesterolemic actions through downregulation of cholesterol biosynthesis gene expression and upregulation of LDL receptor gene expression.

• Korean Journal of Clinical Pharmacy
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• v.16 no.2
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• pp.86-91
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• 2006

There are 3 different hypotheses on how statins may affect bones, through promoting bone formation, inhibiting bone resorption or through anti-inflammatory effect. In the 3 cross-sectional studies above, one showed increase BMD at hip and spine, one showed increase BMD only at mid-forearm and one showed that the risk reduction in fractures is not explained by the changes in BMD however, all 3 studies showed a decrease in risk of fracture associated with statins. In the 2 prospective cohort studies, one showed the use of statins was not associated with BMD at any skeletal site or decreasing the risk of fracture, and the other showed statins except pravastatin decreased in risk of vertebrate fracture but not affecting lumbar spine BMD. All of case-control studies indicated reduction in fracture risk but did not provide any data regarding BMD. 2 of the randomized, controlled studies showed no significant reduction in fracture risk as well as statins' effects on BMD. Finally, one longitudinal study showed statin use reduced fracture risk and increased BMD. Among the conflicting results shown above, even when statin use was shown to increase BMD, it does not seem to account for the reduction in fracture risk. There may be different ways that statins affect bone other than those hypotheses proposed above. Many studies seem to agree that pravastatin does not have any effect on bone. Some studies suggested that the reason statins did not achieve clinically significant increases in BMD in some studies, is due to the low affinity of statins on bone; statins are designed to act in the liver therefore their effective concentration in extrahepatic tissue is low. The limitations to those studies discussed above. Many studies did not account for the change of lifestyle while subjects' were on statins. Increases in weight bearing exercise and changes in diet might affect BMD and thus reduce risk of fractures. Mental alertness and vision acuity might prevent falls from occurring; many statin-users in the studies were young so the risk of fractures from falls would be decreased. Almost all of the studies failed exclude patients with neurological problems. During study periods, many subjects may have been started on drugs for diseases that usually occur with aging which could cause drowsiness and lead to falls. The sample sizes used in some of the trials were small and the duration of treatment and follow up might not have been long enough to see clinically relevant results.