铁皮石斛对缺血再灌注诱导的心律失常的保护作用

为研究甘氨酸（Glycine,Gly）对肝脏IGF-1表达和分泌的影响,本文一方面采用不同浓度Gly离体处理HepG2肝细胞,另一方面采用小鼠尾静脉注射1.0 g/kg Gly和等摩尔Ala,0.5 h和1 h后采集血液、肝脏和肌肉样品。研究采用定量PCR检测了IGF-1以及IGFBPs基因表达水平的影响,同时运用Western blot法分析了肝细胞和肝脏生长激素受体通路（JAK2/STAT5）与肌肉IGF-I受体通路（ERK/Akt/mTOR）的变化。研究结果发现,不同浓度的Gly能剂量依赖性提高HepG2细胞IGF-1的蛋白和mRNA表达水平;1.0 g/kg Gly能显著提高小鼠血清中的IGF-1和白蛋白含量,且极显著提高肝脏IGF-1和IGFBP-3 mRNA水平,下调IGFBP-1 mRNA水平。细胞和活体试验均表明,Gly能够有效激活肝细胞和肝脏JAK2/STAT5信号通路,同时提高腓肠肌IGF-I受体信号通路磷酸化水平。这些研究说明甘氨酸可能直接提高肝脏生长激素受体信号通路敏感性,从而促进IGF-1的表达和分泌。研究结果为深入揭示甘氨酸的分子营养学功能和作用机制提供了实验依据。     

Comparative effects of safflower oil and perilla oil on serum and hepatic lipid levels, fatty acid compositions of serum and hepatic phospholipids, and hepatic mRNA expressions of 3-hydroxy-3-methylglutaryl CoA reductase, LDL receptor, and cholesterol 7alpha-hydroxylase in young and adult rats

Male Wistar rats, 4 and 33 weeks of age, were fed the diets containing safflower oil (SO-diet, 77.3% linoleic acid) or perilla oil (PO-diet, 58.4% -linolenic acid) for 7 days. Serum total cholesterol was lower on the PO-diet in both ages. On the other hand, hepatic cholesterol and phospholipids were significantly higher in the PO group than in the SO group of the adult rats. The PO group showed significantly lower 20:4 n-6 but higher 18:2 n-6 in hepatic phosphatidylcholine compared with the SO group in both ages. Hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase mRNA was significantly lower on the PO-diet than on the SO-diet irrespective of age. The present results show that -linolenic acid has a higher hypocholesterolemic ability than linoleic acid in rats irrespective of age and these fatty acids behaved differently in affecting hepatic mRNA expressions of HMG-CoA reductase, LDL receptor, and cholesterol 7-hydroxylase.     

平卧菊三七对小鼠血糖及血脂的影响

高血糖和高血脂已严重威胁人类健康,本研究探讨平卧菊三七（GPM）对小鼠血糖和血脂的影响,并通过分子生物学手段阐明其作用机制。将40只昆明小鼠随机分成4组,即对照组、2%、4%和8% GPM,喂养小鼠12周,称量小鼠体重和脏器,测定血中的生化指标和肝脏及粪中脂类含量,用qRT-PCR及蛋白印迹等方法分析肝脏mRNA和蛋白表达的变化。结果显示GPM对小鼠体重增加和脏器重量没有明显变化。4%以上GPM与对照组相比显著降低血中的甘油三酯（TG）、总胆固醇、低密度脂蛋白的胆固醇和血糖及肝脏中TG的浓度。而粪中的TG却明显增加。8% GPM明显抑制羟甲基戊二酰CoA还原酶（HMGCR）的活力和mRNA及蛋白表达水平,而Glut4的mRNA和蛋白表达明显增加。以上结果表明GPM通过调节HMGCR和Glut4的mRNA及蛋白表达,和抑制肠道对TG吸收,达到降糖降脂作用。     

Bioefficacy of EPA–DHA from lipids recovered from fish processing wastes through biotechnological approaches

The effect of fish oil recovered from fish visceral waste (FVW-FO) on serum and liver lipids, activity of HMG-CoA reductase in liver microsomes and EPA + DHA incorporation in liver, heart and brain were evaluated. Rats were fed different concentrations of FVW-FO providing 1.25%, 2.50%, 5.0% EPA + DHA recovered by either fermentation or enzymatic hydrolysis for 8 weeks. Feeding FVW-FO reduce triacylglycerols (5.96–20.3%), total cholesterol (7.9–21.5%) and LDL (7.39–21.7%) cholesterol levels in serum compared to group fed on a control diet (groundnut oil). The activity of HMG-CoA reductase was reduced (p < 0.05) in the FVW-FO fed groups compared to the control. EPA + DHA level in serum, liver, brain and heart increased with increments in dietary EPA + DHA. Results show the hypolipidemic property of FVW-FO and reduced HMG-CoA reductase activity which is proportional to the incorporation of EPA + DHA. Recovery of FVW-FO will address the increasing demand for fish oil and reduce pollution problems.     

In vitro hypoglycaemic and hypolipidemic potential of white tea polyphenols

The leaves at different processing stages of a single tea cultivar in order to obtain white (WT), green (GT) and black tea (BT) samples, were analysed. The capacities of tea polyphenolics to influence the glucose and lipid metabolism in HepG2 cell lines were evaluated. WT appeared the most active in reducing the glucose and cholesterol uptake (+17.7% and +32.4% in the glucose and cholesterol cell medium concentration, respectively). Incubation with WT enhanced LDL receptor binding activity by 40% (+20% for GT and +0% for BT) and led to an increase in HDL cell medium concentration of 33.3% (+20% for GT and +0% for BT). Finally, WT revealed the best inhibition capacity against lipase activity, and triglyceride levels in the cell medium increased by 400% (+382.6% for GT and +191.3% for BT). The present study intended to contribute to the little knowledge about the potential health benefits of white tea in individuals affected by metabolic syndrome.     

山茶油对游离脂肪酸诱导的HepG2细胞脂质代谢的影响

目的:探究山茶油对游离脂肪酸诱导的HepG2细胞脂质代谢的影响。方法:首先,利用CCK8法测定不同浓度山茶油对HepG2细胞活性的影响以选定适宜浓度进行后续实验。其次,采用不同浓度山茶油对HepG2细胞进行24 h干预,再使用0.5 mmol/L游离脂肪酸处理24 h诱导建立脂肪肝细胞模型。然后,通过油红O染色法判断各组间的脂滴生成情况,并参照相关试剂盒测定各干预下细胞内脂质水平的变化情况。最后,通过qRT-PCR法测定细胞内脂质代谢相关基因的表达,以探讨山茶油调节脂质代谢的作用及其可能的机制。结果:与正常对照组相比,造模干预组细胞内的甘油三酯(TG)和低密度脂蛋白胆固醇(LDL-C)含量显著升高(P<0.05),高密度脂蛋白胆固醇(HDL-C)含量显著降低(P<0.05);与造模干预组相比,茶油预处理显著逆转了游离脂肪酸诱导细胞内TG、HDL-C和LDL-C含量的变化(P<0.05)。qRT-PCR结果表明,与造模干预组相比,山茶油预处理显著降低了游离脂肪酸诱导的HepG2细胞内脂肪酸转运酶(CD36)、固醇调节元件结合蛋白-1c(SREBP-1c)、脂肪酸合成酶(...     

无斑鹞鲼蛋白质对大鼠胆固醇代谢的影响

目的：探讨无斑鹞鲼蛋白（Aetobatus flagelum protein,AFP）对高胆固醇模型大鼠胆固醇代谢的影响,并对其可能的作用机制加以研究。方法：5 周龄雄性Sprague-Dawley（SD）大鼠,适应性饲养1 周后,按体质量随机分为酪蛋白对照组、5% AFP组、10% AFP组,分别给予高胆固醇饲料及分别添加5%和10% AFP的高胆固醇饲料。28 d后测定大鼠血清总胆固醇（total cholesterol,TC）、高密度脂蛋白胆固醇（high density lipoprotein cholesterol,HDL-C）水平,肝脏TC、游离胆固醇水平,粪便中胆汁酸和中性固醇含量以及肝脏3-羟基-3-甲基戊二酸单酰辅酶A（3-hydroxy-3-methyl glutaryl coenzyme A reductase,HMG-CoA）、胆固醇酰基转移酶2（acyl coenzyme Acholesterolacyltransferase 2,ACAT2）、胆固醇7α-羟化酶1（cholesterol 7α-hydroxylase 1,CYP7A1）的mRNA表达量。结果：与酪蛋白对照组相比,无斑鹞鲼蛋白可显著降低大鼠血清和肝脏中的TC含量（P＜0.05）,明显增加血清HDL-C含量（P＜0.05）,极显著降低大鼠动脉粥样硬化指数（P＜0.01）。此外,无斑鹞鲼蛋白可明显增加大鼠粪便中胆汁酸和中性固醇的排出量（P＜0.05）,并可降低大鼠肝脏中ACAT2 mRNA的表达量（P＜0.05）,增加CYP7A1 mRNA的表达量（P＜0.05）,而对HMG-CoA mRNA的作用不显著。结论：无斑鹞鲼蛋白可明显降低大鼠血清和肝脏中的TC含量,降低大鼠血清动脉粥样硬化指数,其作用机制主要与增加肝脏内胆固醇的分解代谢以及促进粪便中性固醇和胆汁酸的排出有关。     

Antiobese and hypocholesterolaemic effects of an Adenophora triphylla extract in HepG2 cells and high fat diet-induced obese mice

The ethyl acetate extract from Adenophora triphylla root (ATea) had strong antioxidant effect. We hypothesised that a high fat (HF) diet might induce oxidative stress and so, dietary antioxidant may have beneficial effects on hypercholesterolaemia, but the underlying mechanisms involved are not fully understood. To test this hypothesis, C57BL/6 mice were fed with HF diet for 9 weeks. In the last 4 weeks, the HF diet was supplemented with 0, 25 or 75 mg/kg ATea. ATea decreased body weight gain and both ATea doses significantly reduced the plasma and hepatic cholesterol levels of the obese mice. Analysis of the hepatic expression of proteins known to play important roles in cholesterol metabolism indicated that ATea significantly enhanced low density lipoprotein receptor (LDL receptor) and cholesterol 7α-hydroxylase (CYP7A1) expression but inhibited the 3-hydroxy-3-methylglutaryl–CoA reductase (HMG–CoA reductase) expression in HepG2 cells and mice. No mutagenic activity was observed at high doses of ATea.     

Taurine alleviates dyslipidemia and liver damage induced by a high-fat/cholesterol-dietary habit

Eight male hamsters per group were assigned randomly to one of the following diets: chow diet (Control); high-fat/cholesterol diet (HFCD); HFCD supplemented with 1% Tau (HFCD/1% Tau); HFCD supplemented with 2% Tau (HFCD/2% Tau). Tau supplementation improved (P < 0.05) serum lipids and cholesterol profile in the high-fat/cholesterol-dietary hamsters. Although hepatic cholesterol/triacylglycerol in the high-fat/cholesterol-dietary hamsters were not (P > 0.05) changed by Tau supplementation, faecal cholesterol and bile acid outputs were increased (P < 0.05). Two percent Tau supplementation unregulated (P < 0.05) HMG-CoA reductase and cholesterol 7-α hydroxylase (CYP7A1) expressions in the high-fat/cholesterol-dietary hamsters. Besides, Tau supplementation also increased (P < 0.05) LDL receptor mRNA expressions in high-fat/cholesterol-dietary hamsters. Tau supplementation also reduced serum GPT and GOT values and C-reactive protein (CRP) levels in the high-fat/cholesterol-dietary hamsters. Results clearly indicated that Tau could alleviate blood lipids and hepatic damage induced by a high-fat/cholesterol-dietary diet.     

小麦低聚肽对HepG2细胞胆固醇代谢的影响

目的:在对小麦低聚肽的基础理化成分和分子量分布进行分析的基础上,观察不同浓度的小麦低聚肽对人肝癌细胞株HepG2胆固醇代谢的影响。方法:将培养的HepG2细胞随机分为5组:对照组、2、4、6、8g/L小麦低聚肽实验组。经小麦低聚肽作用24h后,进行反转录-聚合酶链反应（RT-PCR）,定量分析低密度脂蛋白受体（LDLR）和3-羟基-3-甲基戊二酸单酰辅酶A还原酶（HMGCR）mRNA的表达。结果:与对照组相比,经小麦低聚肽作用后,各实验组HepG2细胞LDLR mRNA表达明显增加（p<0.05或p<0.01）,其中6g/L小麦低聚肽组的LDLR mRNA表达增加最多;HMGCR mRNA表达均降低,2、4、6g/L小麦低聚肽组的HMGCR mRNA表达极显著降低（均为p<0.01）,其中2g/L小麦低聚肽组的HMGCR mRNA表达降低最多。结论:不同浓度的小麦低聚肽均能升高HepG2细胞内LDLR mRNA水平和降低HMGCR mRNA水平,从而起到降低胆固醇的作用,为其开发利用提供了一定的实验依据和理论基础。      

Vanillin rich fraction regulates LDLR and HMGCR gene expression in HepG2 cells

Vanillin and its analogs have been exploited for their various health benefits. This work aimed to investigate the antioxidant properties and regulatory effects of vanillin rich fraction (VRF) extracted from vanilla pods using the supercritical fluid extraction (SFE) and commercial vanillin on low density lipoprotein receptor (LDLR) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) gene expression in HepG2 cells. The vanillin content in the VRF was 2.6% (w/w) obtained at a temperature of 80 °C and a pressure of 600 bar. The VRF exhibited better antioxidant activity compared to the vanillin in DPPH and BCB tests. LDLR mRNA level was increased significantly by 2, 3 and 1.3 fold in the VRF treated cells at 100, 200 and vanillin treated cells at 100, respectively, compared with untreated cells. On the other hand, the HMGCR mRNA level was decreased significantly by 14, 58 and 13% respectively, in the VRF treated cells at 100, 200 and V treated cells at 100, respectively, compared with untreated cells. The VRF showed potential antioxidant activity and regulated genes involved in cholesterol metabolism including LDLR and HMGCR in dose-dependent manner.     

Korean red ginseng attenuates hepatic lipid accumulation via AMPK activation in human hepatoma cells

In this study, we examined Korean red ginseng (KRG) extract affects on the lipid metabolism in HepG2 cells. Increase in AMP-activated protein kinase (AMPK) phosphorylation was observed when the cells were treated with KRG. Activation of AMPK was also demonstrated by measuring the phosphorylation of acetyl-CoA caboxylase (ACC), a substrate of AMPK. KRG down-regulated gene expressions of sterol regulatory element binding protein 1c (SREBP1c) and its target proteins, such as fatty acid synthase (FAS) and stearoyl-CoA desaturase (SCD1) in time- and dose-dependent fashions. In contrast, gene expressions of peroxisome proliferator-activated receptor α (PPARα) and CD36 were increased. These effects were reversed in the presence of compound C, an AMPK inhibitor. However, there were no differences in gene expressions of SREBP2, 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, and low-density-lipoprotein receptor (LDLR). Taken together, KRG induced supression of SREBP1c and activation of PPARα via AMPK and these effects seem to be one of anti-hyperlipidemic mechanism of KRG in HepG2 cells.     

Modulation of lipid metabolism by polyphenol‐rich grape skin extract improves liver steatosis and adiposity in high fat fed mice

This study investigated the influence of polyphenol‐rich grape skin extract (GSE) on adiposity and hepatic steatosis in mice fed a high fat diet (HFD) and its underlying mechanisms based on adipose and hepatic lipid metabolism. C57BL/6J mice were fed a normal diet or a HFD (20% fat, w/w) with or without GSE (0.15%, w/w) for 10 weeks. The supplementation of GSE significantly lowered body weight, fat weight, plasma free fatty acid level, and hepatic lipid accumulation compared to the HFD group. Plasma leptin level was significantly lower, while the plasma adiponectin level was higher in the GSE group than in the HFD group. GSE supplementation significantly suppressed the activities of lipogenic enzymes in both adipose and liver tissues, which was concomitant with β‐oxidation activation. Furthermore, GSE reversed the HFD‐induced changes of the expression of genes involved in lipogenesis and β‐oxidation in the liver. These findings suggest that GSE may protect against diet‐induced adiposity and hepatic steatosis by regulating mRNA expression and/or activities of enzymes that regulate lipogenesis and fatty acid oxidation in the adipose tissue and liver.     

黑木耳多肽对棕榈酸诱导的脂肪肝细胞的降脂作用

目的:探究黑木耳多肽(Auricularia auricula polypeptides,AAP)对由棕榈酸(palmitic acid,PA)诱导的HepG2细胞脂肪肝模型的降脂作用.方法:本实验通过比较HepG2细胞内甘油三酯(triglyceride,TG)积累水平,筛选出分子质量低于3 kDa的多肽(AAP-3...     

Lipid-lowering and LDL-oxidation inhibitory effects of aqueous extract of freshwater clam (Corbicula fluminea)--using tilapia as an animal model

A previous study has demonstrated that tilapia able to exhibit hyperlipidemia and hypercholesterolemia is a good model for the evaluation of beneficial effects of nutraceuticals. In this study, tilapia were used to evaluate the in vitro and in vivo effects of a hot water extract (FC-HW) of freshwater clam (Corbicula fluminea). FC-HW prolonged the lag phase of Cu(2+)-induced human and tilapia LDL oxidation. The prolongation of the lag phase was concentration-dependent in human (r(2)= 0.94) and tilapia LDL (r(2)= 0.98). The antioxidative potential of FC-HW was 0.33% (on a weight basis) of Trolox, a positive control. Male tilapia (n= 24) were randomly divided into 2 groups and separately fed for 60 d with an isocaloric also isoprotein diet containing 2% (w/w) FC-HW or a control diet. Body length and body mass were significantly higher in fish fed FC-HW than those of the control group (P < 0.05). Total triacylglycerol, cholesterol, and LDL-C in plasma of the FC-HW group were significantly lower (-89.9%, -61.8%, and -54.5%, respectively), while plasma total antioxidant capacity of the FC-HW group was higher and the lag phase in Cu(2+)-induced LDL oxidation was longer than those of the control group (P < 0.05). FC-HW demonstrated hypolipidemia and hypocholesterolemia effects and inhibited human LDL oxidation in vitro and tilapia LDL both in vitro and ex vivo, indicative that FC-HW can be a potential nutraceutical to reduce the risk factors of atherosclerosis.     

Chestnut (Castanea crenata) inner shell extract inhibits development of hepatic steatosis in C57BL/6 mice fed a high-fat diet

The effects of chestnut inner shell extract (CISE) on hepatic steatosis and lipid metabolism in mice fed high-fat diet (HFD) were evaluated. Hepatic triacylglycerol and plasma lipid levels decreased significantly in CISE-administered mice compared to control group. Relative mRNA expression levels for lipogenic genes SREBP-1c, FAS, ACCs, ACAT, and HMG-CoA were significantly decreased in CISE-administered mice (P < 0.05). CISE suppressed FAS and HMG-CoA reductase activity and increased CPT activity. To determine the active compound of CISE, the fractionation of CISE have conducted and resulted in the isolation of scoparone and scopoletin, as main compounds contained in CISE. Based on these results, we speculate that the inhibitory effect on hepatic steatosis of CISE containing scoparone and scopoletin may be the result of suppression of lipid synthesis and the acceleration of fatty acid oxidation in mice fed HFD, suggesting that CISE may be beneficial in preventing hepatic steatosis.     

Effect of the monascus pigment threonine derivative on regulation of the cholesterol level in mice

Different amino acid derivatives were synthesized during cultivation of a Monascus species. Derivatives exhibiting an inhibitory activity against HMG-CoA reductase were screened by in vitro tests. The threonine derivative had a high inhibitory activity of 38% while four other derivatives showed a greater than 23% activity. The orange monascus pigment showed a high activity of 36%. In vivo tests using female C57BL/6 mice were performed with the threonine derivative and orange pigment. Changes in the cholesterol and lipid levels in mice due to addition of the pigments were investigated. The total cholesterol (TC) level of mouse serum was reduced by 8–9% with the threonine derivative and by 16% with orange pigment. Supplementation with the threonine derivative and orange pigment decreased the LDL cholesterol level by 18–26% and increased the HDL cholesterol level by 1–9%. The atherogenic index (AI) value was reduced by 23–27% with pigment supplementation. The anti-atherosclerosis effect of monascus pigments can be induced by control of the lipid content in the serum rather than in the liver of mice.     

刺梨果酒改善2型糖尿病大鼠糖脂代谢紊乱的研究

为探究刺梨果酒对2型糖尿病大鼠糖脂代谢紊乱的影响及可能机制。采用高脂高糖膳食联合腹腔注射链佐霉素（Streptozocin,STZ）建立2型糖尿病大鼠模型,将造模成功的大鼠分为刺梨果酒高（8 mL/kg）、中（4 mL/kg）、低（2 mL/kg）剂量组和模型组,并设空白对照组,给药期间每2周测一次空腹血糖,实验时间28 d。实验结束后测量血清和肝脏中高密度脂蛋白胆固醇（High-density lipoprotein cholesterol,HDL-C）、果糖胺（fructosamine,FMN）、甘油三酯（Triglyceride,TG）、低密度脂蛋白胆固醇（Low-density lipoprotein cholesterol,LDL-C）、总胆固醇（Total cholesterol,TC）、肝糖原等含量;采用实时灾光定量PCR（real time polymerase chain reaction,RT-PCR）测定肝脏中腺苷酸活化蛋白激酶（AMP-activated protein kinase α,AMPK）、乙酰辅酶A羧化酶（Acetyl-CoA carboxylases alpha,ACACA）、β-羟-β-甲戊二酸单酰辅酶A还原酶（3-hydroxy-3-methylglutaryl coenzyme A reductase,HMG-CoA）、脂肪酸合成酶（fatty acid synthetase,FASN）、和葡萄糖转运载体2（Glucose Transporter 2,GLUT2）、胆固醇7α-羟化酶（Cholesterol 7α-hydroxylase,CYP7A1）等mRNA相对表达量。结果表明,与模型组相比,刺梨果酒可减缓2型糖尿病大鼠体重减轻和多饮、多食的症状;高、中剂量刺梨果酒降低实验大鼠空腹血糖和果糖胺的效果显著（P<0.05）;各剂量组均有降低实验大鼠血清和肝脏TC、TG、LDL-C的含量和升高HDL-C含量的作用,其中高、中剂量效果显著（P<0.05）;低、中、高刺梨果酒均可显著（P<0.05）上调AMPK、GLUT2和ACACA mRNA表达量,低、中、高刺梨果酒均可上调FASN mRNA表达量,其中高、中剂量组上调FASN mRNA表达量显著（P<0.05）;中、高剂量刺梨果酒可显著（P<0.05）下调G6Pase、PEPCK、HMG-COA和CYP7A1 mRNA表达量。结论:刺梨果酒改善2型糖尿病大鼠糖脂代谢紊乱的机制可能与通过抑制内源性胆固醇、增加脂肪的从头合成及提高葡萄糖跨膜转速率有关。