Hypolipidemic activity of <Emphasis Type="Italic">Symplocos cochinchinensis</Emphasis> S. Moore leaves in hyperlipidemic rats

The hypolipidemic activity of Symplocos cochinchinensis S. Moore leaves was studied in Triton WR-1339- and high fat diet-induced hyperlipidemic rats. In Triton WR-1339-induced hyperlipidemic rats, the hexane extract (250 and 500 mg/kg) exerted a significant (P < 0.01) lipid-lowering effect compared to ethyl acetate and methanol extracts, as assessed by the reversal of the plasma levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). In high fat diet-fed hyperlipidemic rats, the hexane extract (250 and 500 mg/kg) caused the lowering of lipid levels in the plasma and liver. The hypolipidemic activity of S. cochinchinensis leaves was compared with fenofibrate, a known lipid-lowering drug, in both models.     

Hypolipidemic effects of a new piperine derivative GB-N from Piper longum in high-fat diet-fed rats

Context: Long pepper, Piper longum Linn. (Piperaceae), is widely used in traditional Mongolian medicine for treating hyperlipidemia and coronary heart disease.

Objective: To investigate the hypolipidemic effects of a new piperine derivative GB-N isolated from long pepper in high-fat diet-fed rats.

Methods: The levels of serum total cholesterol, triacylglycerols (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were determined by enzymatic colorimetric method. The levels of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA), CYP7A1, lecithin cholesterol acyltransferase (LCAT) and LDL receptor (LDLR) mRNA and protein expression were detected by real-time polymerase chain reaction and western blot analysis.

Results and discussion: Compared with model rats, oral administration of GB-N at doses of 2.5–10?mg/kg to hyperlipidemic rats could significantly decrease the levels of serum TG from 1.54 mmol/L in hyperlipidemic rats to 0.94–1.02 mmol/L, with an increase in serum HDL-C levels from 0.40 mmol/L in hyperlipidemic rats to 1.21–2.26 mmol/L. Treatment with GB-N (10?mg/kg) could also significantly upregulate levels of hepatic HMG-CoA reductase, CYP7A1, LCAT and LDLR mRNA and protein expression.

Conclusion: GB-N had hypolipidemic activity via regulating lipid metabolism pathways in liver of hyperlipidemic rats and could be explored as a potential agent for the prevention of hyperlipidemia diseases.     

瑞香素对血清脂质及脂蛋白胆固醇含量的影响

Daphnetin is one of the components of Daphne koreana Nakai and the sample used in the experiment is the synthesized product. The compound was shown to possess obvious effect on lipid and lipoprotein cholesterol contents in the serum of normal and hyperlipidemic mice or rats. When daphnetin was given orally to rats, the serum level of high density lipoprotein cholesterol and the ratio of high density lipoprotein cholesterol to total cholesterol of normal rats were raised, whereas no significant effect on the level of lipid in normal mice was observed. Daphnetin (800 mg/kg, po for 1 week) decreased significantly the total cholesterol content in the serum of yolk(0.5 ml) treated mice. In addition, when daphnetin was given orally at a dosage of 800 mg/kg day for 2 weeks, the serum level of total cholesterol decreased. The sernm concentration of high density lipoprotein cholesterol and the ratio of high density lipoprotein cholesterol to total cholesterol in rats with hyperlipidemia increased significantly.     

The Hypolipidemic Effects of l-Acetyl-4-phenyl-l,2,4-triazolidine-3,5-dione in Rodents

l-Acetyl-4-phenyl-l ,2,4-triazolidine,5-dione (APTD), a potent hypolipidemic agent, lowered both serum cholesterol and triglyceride levels in normo- and hyperlipidemic rats at 10 or 20 mg/kg/day. The agent effectively lowered VLDL-cholesterol (VLDL-C) and LDL-C content and raised HDL-C content in normal and hyperlipidemic rats treated from 4 to 8 weeks. Similar effects on the incorporation of cholesterol into the lipoprotein fractions were observed after drug treatment. Tissue lipids, e.g. cholesterol, were lowered, whereas fecal cholesterol levels were increased. APTD's primary targets were acyl CoA cholesterol acyl transferase (ACAT) for cholesterol ester synthesis and sn-glycerol-3-phosphate acyl transferase (GPAT) and phosphatidylate phosphohydrolase (PPH) for triglyceride synthesis.     

螺旋藻来源的γ-亚麻酸甲酯调血脂作用研究

利用从螺旋藻中提取的γ-亚麻酸甲酯(GLAME)，分别制成含GLAME0.25％、0．5％、1％的饲料喂饲正常大鼠和高脂膳食喂养形成的高脂血症大鼠，连续4周，测定血脂、肝脂及血浆和肝脏丙二醛(MDA)含量。结果表明：GLAME能显著降低正常大鼠和高脂血症大鼠血浆TC、TG、LDL—C含量和AI，升高HDL—C含量和HDL—C／TC，能降低正常大鼠和高脂血症大鼠血浆和肝脏MDA舍主及肝胆固醇含量，降低高脂血症大鼠肝指数(肝重/体重)，但对正常大鼠的肝指数无明显影响。     

褐藻糖胶与海洋深层水联合用药对Ⅱ型糖尿病大鼠认知障碍的干预作用

目的以Ⅱ型糖尿病(Type 2 diabetes mellitus,T2DM)大鼠为模型,研究褐藻糖胶(fucoidan,FPS)与海洋深层水(deep sea water,DSW)联合用药对胰岛素抵抗及认知障碍的干预作用。方法采用高糖高脂饮食联合链脲佐菌素(streptozotocin,STZ)诱导T2DM大鼠模型,然后给予FPS、DSW或DSW与FPS 3个剂量联用,给药期间监测各组大鼠体质量以及摄食摄水等一般情况,给药4周后,进行Morris水迷宫实验。实验结束后取血清,测定空腹血糖(fasting blood glucose,FBG)、空腹胰岛素(fasting insulin,FINS)、血脂四项(总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、低密度脂蛋白胆固醇(low-density lipoproteincholesterol,LDL-C)、高密度脂蛋白胆固醇(high-density lipoprotein-cholesterol,HDL-C))等指标,计算胰岛素抵抗指数(Homeostasis model asses...     

蒙药童格勒格-1对大鼠高脂血症的影响

目的观察蒙药童格勒格-1(TGLG-1)对高脂血症大鼠血清血脂的调节作用。方法建立大鼠高血脂模型。高血脂症大鼠分为四组,一组为实验对照组,其余三组分别以低、中、高剂量TGLG-1灌胃,21d后测定血脂值。结果与高脂对照组相比,中、高剂量TGLG-1能显著降低血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白一胆固醇(LDL-C)水平。结论TGLG-1具有良好的降低血脂浓度和预防高血脂症的作用。     

The in Vitro Plasma Distribution of a Novel Cholesteryl Ester Transfer Protein Inhibitor, Torcetrapib, Is Influenced by Differences in Plasma Lipid Concentrations

Purpose To determine the lipoprotein distribution of Torcetrapib in normolipidemic or hyperlipidemic human plasma and assess any changes in distribution due to lipid profile. Methods Torcetrapib was incubated with human plasma samples, and the distribution was measured across four fractions: triglyceride-rich lipoprotein (TRL), low-density lipoprotein, high-density lipoprotein, and lipoprotein-deficient plasma fraction. Two stocks of human plasma were used, one considered normolipidemic (total cholesterol concentration = 164 mg/dL, triglycerides concentration = 139 mg/dL, protein concentration = 912 mg/dL), the other hyperlipidemic (total cholesterol = 260 mg/dL, triglycerides = 775 mg/dL, protein = 917 mg/dL). The plasma samples were incubated with Torcetrapib at 37°C, and the incubation was stopped with the addition of sodium bromide and cooling to 4°C. The plasma samples were then separated by density gradient ultracentrifugation to their lipoprotein fractions. The resulting lipoprotein fractions and an aliquot of incubated plasma were analyzed by a validated gas chromatography/tandem mass spectrometry analytical method. The distribution of Torcetrapib was determined first with varying incubation times, then with several concentrations. Results At concentrations of 250 and 500 ng/mL, Torcetrapib distributed evenly across the four fractions in normolipidemic plasma. At the same concentrations in hyperlipidemic plasma, approximately 84% of Torcetrapib was found in the TRL fraction, with the remaining 16% evenly partitioned between the low-density lipoprotein, high-density lipoprotein, and lipoprotein-deficient plasma fractions. Conclusions The results suggest that lipid profile affects the distribution of Torcetrapib in hyperlipidemic human plasma lipoprotein fractions. The preferential distribution of Torcetrapib into the TRL fraction in hyperlipidemic plasma needs to be investigated to see if it will affect the pharmacological effect of Torcetrapib in vivo.     

Anti-hyperlipidemic activity of spider brake (Pteris multifida) with rats fed a high cholesterol diet

This study evaluates the possible potency of the anti-hyperlipidemic effect of spider brake [(Pteris multifida Poiret (Pteridaceae)]. We investigated this by feeding the hyperlipidemic Sprague-Dawley rats, caused by a high cholesterol diet, with lyophilized powder of spider brake (LSB) and compared the result with the rats fed with β-sitosterol. The results indicated that the administration of lyophilized powder of spider brake (LSB) lowered the hyperlipidemic level on rats. The relative weights of the liver, adipose tissue, and relative adipose tissue of 10% substitutions of LSB group (LSB-10) showed a significant decrease (P?<?0.05) by 6%, 15.9%, and 14.3% in contrast to the untreated counterparts (control), respectively. A significantly lower (P?<?0.05) plasma TG, low density lipoprotein cholesterol, low density lipoprotein cholesterol/high density lipoprotein cholesterol ratio, liver CH, and TG contents were also observed in LSB-10 compared to the untreated counterparts (by 36.8%, 21%, 18.7%, 10.2% and 14.3% reduction, respectively). Simultaneously, the wet fecal weight, dry fecal weight, nitrogen compounds, excretion of neutral steroids, and bile acids significantly (P?<?0.05) increased by 9.6%, 10.6%, 23.7%, 9.7%, and 3.4% respectively. The results showed that LSB could cause not only a reduction in CH and TG, but also could increase the excretion of lipids and metabolic by-products via the intestinal tract.     

The Hypolipidemic Activity of l-N-3-Methylphthalimido-butan-3-semicarbazone in Rodents

l-N-(3-Methylphthalimido)butan-3-one semicarbazone demonstrated potent hypolipidemic activity in normal rats and mice and hyperlipidemic diet-induced mice. The compound decreased tissue lipid levels and increased the fecal excretion of cholesterol and triglycerides. After 2 weeks of administration, serum lipoprotein levels were modulated so that very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) cholesterol concentrations were reduced and high-density lipoprotein (HDL) cholesterol concentrations were elevated to levels unprecedented by the cyclic imide derivatives previously tested. The VLDL triglyceride content was also reduced. Hepatic in vitro enzymatic studies demonstrated that the compound suppressed the activity of enzymes in the early synthesis of fatty acids and cholesterol and the regulatory enzymes for the de novo synthesis of triglycerides.     

瑞香素对血清脂质及脂蛋白胆固醇含量的影响

瑞香素(daphnetin)系瑞香科植物长白瑞香(Daphne koreana Nakai)中的有效单体,化学结构为7,8-二羟基香豆素,并已由长春春城制药厂人工合成。药理实验证明有扩张冠状血管、增加冠脉流量,改善心肌代谢作用,并有抑制实验性“关节炎”及兴奋垂体—肾上     

Effects of oleanolic acid and maslinic acid on hyperlipidemia

In the present study, we examined the therapeutic effects of pentacyclic triterpenes, oleanolic acid (OA) and maslinic acid (MA), on hyperlipidemia in a high‐cholesterol diet model. Hyperlipidemia was induced in male Sprague‐Dawley rats by feeding with a high‐cholesterol diet (HCD) for 30 days. MA and OA were supplemented (100 mg/kg body wt/day) during the last 15 days. The levels of serum total cholesterol (TC), triglyceride (TG), high‐density lipoprotein‐cholesterol (HDL‐C), and low‐density lipoprotein‐cholesterol (LDL‐C) increased in hyperlipidemic rats. An apparent increase in the expression of Acyl‐CoA cholesterol acyltransferase (ACAT) mRNA was seen in HCD‐fed rats. The activities of hepatic marker enzymes that serve as indices of cellular injury were also altered in HCD‐fed rats. Treatment with triterpenes modulated the abnormalities induced by hyperlipidimia. Lipid accumulation was decreased in histological findings. Elevated hepatic glycogen content (P<0.05) in triterpene groups was observed compared with HCD‐fed groups. Furthermore, ACAT gene expression was suppressed compared with hyperlipidemia‐induced groups without triterpenes. It can be concluded that triterpene treatment possesses therapeutic effects on diet‐induced hyperlipidemia by inhibiting the intestinal absorption and storage of cholesterol. Drug Dev Res 68:261–266, 2007. © 2007 Wiley‐Liss, Inc.     

甘糖酯对高脂血症大鼠血脂及脂蛋白脂酶的调节作用

目的探讨甘糖酯调节血脂的分子机制。方法以不同剂量甘糖酯(37.8,75.6 mg·kg^-1·d^-1)给高脂血症大鼠ig给药3周,禁食12 h后,测定大鼠血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)的浓度变化,用反转录聚合酶链式反应(RT-PCR)法检测组织中脂蛋白脂酶(LPL)mRNA的表达。结果甘糖酯有降低血清TC,TG和LDL-C,升高HDL-C的作用,同时提高LPL mRNA的表达,且呈剂量依赖性关系。甘糖酯对LPL mRNA转录的促进作用与其降低TC,TG和LDL-C的作用呈正比关系。结论甘糖酯通过促进LPL mRNA转录而调节血脂水平,这可能是甘糖酯降血脂、预防动脉粥样硬化等心脑血管疾病的机制之一。     

复方螺旋藻片对高血脂症小鼠血脂的影响

目的：观察复方螺旋藻片（FST）对高脂血症小鼠血脂的影响。方法：用FST1.5mg/kg,3g/kg分别灌胃给予高脂血症小鼠,连续14d后,眼眶取血测血脂。结果：与高脂血症模型对照组相比,FST高、低剂量能显著降低血清TC、TG和LDL－C水平,明显升高血清HDL－C水平与HDL－C／TC比值。同时FST还能升高血清apoAI并降低apoB(但FST 1.5g/kg对apoB无明显影响）。结论：FST能明显降低高脂血症小鼠血脂水平,并对载脂蛋白有一定的调节作用。     

地龙活性蛋白对实验性高脂血症大鼠的调脂作用及其机制

目的:研究地龙活性蛋白(Earthworm active protein,EWAP)对实验性高脂血症SD大鼠的调脂作用并探讨可能的降脂作用机制。方法:通过高脂饲料及维生素D2联合应用法建立SD大鼠高脂血症模型,以EWAP进行治疗28 d,末次给药后测定大鼠血清中总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白(LDL-c)、低密度脂蛋白(LDL-c)水平、脂蛋白脂酶(LPL)、肝脂酶(HL)活性、粪便胆汁酸(FBA)含量以及大鼠体质量变化。结果:EWAP高、中剂量组与模型组比较,TC、TG、LDL-c水平显著降低,同时HL,LPL活性及粪便中FBA排泄量均显著提高,并且EWAP高剂量组大鼠体质量相比模型组增加趋势明显。结论:EWAP对实验性高脂血症大鼠血脂代谢有调节作用,其作用机制可能与提高脂蛋白脂酶、肝脂酶活性,加强肠内胆固醇代谢转化有关。     

Hypolipidemic Activity of o-(N-Phthalimido)acetophenone in Sprague Dawley Rats

o-(N-Phthalimido)acetophenone has proven to be an effective hypolipidemic agent in rats at 20 mg/kg/ day orally. The agent suppressed the activity of the rate-limiting enzyme of the liver involved in de novo synthesis of triglycerides. The synthetic rate-limiting enzyme for cholesterol esters was also inhibited by the drug in vivo. o-(N-Phthalimido)acetophenone lowered cholesterol in the liver and the aorta wall and generally caused an increase in phospholipids in body tissues. Serum lipoproteins were modulated by the drug with a decrease in cholesterol and triglycerides in the chylomicron, very low-density lipoproteins (VLDL), and low-density lipoproteins (LDL) and an increase in high-density lipoprotein (HDL) cholesterol. The phospholipid content was increased in the chylomicron, VLDL, and LDL fractions. In hyperlipidemic rats, o-(N-phthalimido)acetophenone lowered elevated blood lipid levels at 20 mg/kg/day orally after 3 weeks of administration. The hypolipidemic rat after drug treatment had a lower LDL cholesterol and a higher HDL cholesterol content, which is therapeutically desirable to protect against cardiovascular disease.     

附子多糖对大鼠食诱性高胆固醇血症的预防作用及机制研究

目的探讨附子多糖预防大鼠食诱性高胆固醇血症的作用及其机制。方法 SPF级♂Wister大鼠50只,体质量100 g,随机分为正常组(N)、高胆固醇组(HC)和附子多糖(FPS)低、中、高3个剂量组,每组10只,分别给予正常、高胆固醇及高胆固醇加附子多糖(224、448和896 mg.kg-1.d-1)饮食,持续两周,检测各组的血脂水平,探讨FPS对大鼠高胆固醇血症的预防效应。并观察N组,HC组,FPS(224mg.kg-1.d-1)组大鼠的体重、进食量和粪便量的变化,实验结束后取3组大鼠的肝脏行HE染色;并分别测定3组大鼠肝脏低密度脂蛋白受体(LDL-R)的mRNA水平、蛋白表达及受体活性的改变。结果附子多糖能抑制高胆固醇血症大鼠血清中总胆固醇(TC)和低密度脂蛋白胆固醇(LDL-C)的水平(P<0.05);FPS组大鼠肝细胞脂肪变性较HC组轻微;RT-PCR和Western blot结果显示附子多糖能上调高胆固醇大鼠肝脏LDL-R的mRNA水平和蛋白表达(P<0.05);放射配基结合分析法结果表明FPS组大鼠肝脏LDL-R的密度和亲和力均较HC组明显升高(P<0.01)。结论附子多糖具有明显的降血胆固醇作用,其机制与上调大鼠肝脏LDL-R的基因水平、蛋白表达以及受体的活性有关。     

油酰乙醇胺对高脂血症大鼠降血脂及肝脏的保护作用

目的观察油酰乙醇胺(OEA)对高脂血症模型大鼠降血脂及肝脏保护作用。方法高脂饮食建立高脂血症大鼠模型,分别观察OEA(10,203,0 mg/kg)对高脂血症大鼠的血清胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、谷丙转氨酶(ALT)、肝重和肝脏系数、肝脏丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)的影响。制作冰冻切片观察大鼠肝脏脂质变性程度。结果与模型组相比,OEA(20,30mg/kg)具有降血脂作用,同时降低血清ALT、肝脏脂质、肝重和肝脏系数、肝脏MDA水平,升高肝脏GSH-Px活力。结论 OEA能降低高脂血症大鼠血脂、抑制肝脏脂肪沉积,并减轻脂质过氧化物对肝脏的损伤。     

Hypolipidemic Activity of 3-Amino-1-(2,3,4-mononitro-, mono-, or dihalophenyl)propan-1-ones in Rodents

A series of 3-amino-1-(2,3,4-mononitro-, mono-, or dihalophenyl)propan-1-ones were synthesized and shown to be effective in lowering both serum cholesterol and triglyceride levels significantly in CF₁ mice and Sprague-Dawley rats. All analogs showed better activity than the standard drugs, lovastatin and clofibrate, in reducing the serum cholesterol and triglyceride levels in mice at 8 mg/kg/day intraperitoneally. The best active analogs, 3-morpholino-1-(3-nitrophenyl)propan-1-one ( 4 ) and 3-piperidino-1-(3-nitrophenyl)propan-1-one ( 5 ), exhibited 58% and 67% reduction of serum cholesterol levels, respectively, and 42% and 46% reduction of serum triglyceride levels, respectively, after 16 days of administration at 8 mg/kg/day intraperitoneally in CF₁ mice. In Sprague-Dawley rats at 8 mg/kg/day oral administration, both compounds ( 4 and 5 ) significantly decreased the serum cholesterol and triglyceride levels. Rat tissue lipid levels were reduced significantly by compound 4, while less effects resulted from compound 5. The cholesterol and triglyceride levels in chylomicrons, VLDL, and LDL fractions were reduced by both analogs while the HDL cholesterol levels were significantly increased. Compound 5 was also effective in lowering serum cholesterol and triglyceride levels in hyperlipidemic mice, at 8 mg/kg/day intraperitoneally, but not effective in hyperlipidemic rats at 8 mg/kg/day intraperitoneally, but not effective in hyperlipidemic rats at 8 mg/kg/day orally. Cholesterol and triglyceride lowering effects of the agents were correlated with inhibition of the activities of liver acetyl CoA synthetase, HMG CoA reductase, phosphatidylate phosphohydrolase, and lipoprotein lipase, and with elevation of the activity of cholesterol ester hydrolase.     

小檗碱对胆固醇代谢及肝脏Insig-2基因表达的影响

目的研究小檗碱(berberine,Ber)对高脂模型大鼠胆固醇代谢的影响,并探讨其可能的机制是否与胰岛素诱导基因-2(insulin-induced gene 2,Insig-2)基因表达有关。方法♂清洁级SD大鼠40只,随机分为普食组(Normal diet,ND)、高脂饲料组(High fat diet,HFD)、高脂饲料+洛伐他汀组(Lovastatin diet,LD)、高脂饲料+低剂量小檗碱干预组(Berlow dose diet,BLD)、高脂饲料+高剂量小檗碱干预组(Berhigh dose diet,BHD)。Ber干预18 wk后测定大鼠血清总胆固醇(TC)、甘油三脂(TG)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)等血生化指标的含量。RT-PCR和Western blot技术检测各组大鼠肝脏Insig-2 mRNA和蛋白表达变化。结果Ber干预呈剂量依赖性降低高脂模型大鼠血清TC和LDL-C水平;低剂量Ber明显上调高脂血症大鼠肝脏Insig-2基因mRNA和蛋白表达水平,而高剂量Ber则反馈性下调Insig-2基因mRNA和蛋白的表达。结论Ber干预具有明显的调血脂作用,其机制可能是通过上调肝脏Insig-2基因表达,从而抑制肝脏中胆固醇的合成代谢。