BACKGROUND & AIMS: :Trichosanlhes kirilowii Maxim seed oil (TSO) is rich in conjugated linolenic acids, and the flavonoids (FLA) combined with n-3 fatty acids can effectively change the plasma antioxidant capacity. Hyperlipidemia and oxidative stress are one of the most important risk factors for cardiovascular disease. This study aims to evaluate the effect of the TSO, FLA, and TSO combined with FLA (TSOFLA) intake on hyperlipemia mice. TSO and TSOFLA administration resulted in a significant decline in serum levels of total cholesterol, triglycerides, and low density lipoprotein-cholesterol. TSOFLA improved the hepatic and serum antioxidant status as assessed by superoxide dismutase, glutathione peroxidase activities, and reduced the levels of lipid peroxidation. Hematoxylin-eosin staining of liver and aorta tissue has shown a marked reduction of the hyperlipidemia-induced lesions by gavage TSOFLA. Compared with TSO and FLA, TSOFLA has more significant hypolipidemic and antioxidant activities, which effects may be correlated to the synergy between TSO and FLA. PRACTICAL APPLICATIONS: Dyslipidemia is a common metabolic disorder, which is characterized by triglyceride levels increased, total cholesterol, and low-density lipoprotein cholesterol. Lipid-lowering treatment can reduce the expansion of coronary atherosclerosis, and particular the dietary lipids have important roles in controlling the concentrations of these risk factors. This is the first study evaluating the hypolipidemic and antioxidant activities effects of Trichosanlhes kirilowii Maxim seed oil (TSO), flavonoids (FLA), and TSO combined with FLA (TSOFLA) intake on hyperlipemia mice caused by a high-fat diet. The pharmacological effects of dietary TSOFLA are correlated to its high content of unsaturated fatty acids and flavonoids. This information can be of interest to the development of food supplements in the field of diseases associated with high-fat intakes such as cardiovascular diseases and adiposis.

背景与目标： ：Trichosanlhes kirilowi​​i Maxim种子油（TSO）富含共轭亚麻酸，而类黄酮（FLA）与n-3脂肪酸结合可有效改变血浆抗氧化能力。高脂血症和氧化应激是心血管疾病最重要的危险因素之一。这项研究旨在评估TSO，FLA和TSO联合FLA（TSOFLA）摄入对高脂血症小鼠的影响。 TSO和TSOFLA给药导致血清总胆固醇，甘油三酸酯和低密度脂蛋白胆固醇水平显着下降。通过超氧化物歧化酶，谷胱甘肽过氧化物酶活性评估，TSOFLA可改善肝和血清抗氧化状态，并降低脂质过氧化水平。食管TSOFLA对肝脏和主动脉组织的苏木精-伊红染色显示出高脂血症诱导的病变的明显减少。与TSO和FLA相比，TSOFLA具有更显着的降血脂和抗氧化活性，其作用可能与TSO和FLA之间的协同作用有关。实际应用：血脂异常是一种常见的代谢紊乱，其特征是甘油三酸酯水平升高，总胆固醇和低密度脂蛋白胆固醇。降脂治疗可以减少冠状动脉粥样硬化的扩展，尤其是饮食中的脂质在控制这些危险因素的浓度方面具有重要作用。这是第一项评估Trichosanlhes kirilowi​​i Maxim籽油（TSO），类黄酮（FLA）和TSO联合FLA（TSOFLA）摄入对高脂饮食引起的高脂血症小鼠降血脂和抗氧化活性影响的研究。膳食TSOFLA的药理作用与其高含量的不饱和脂肪酸和类黄酮有关。在与高脂肪摄入有关的疾病（如心血管疾病和脂肪病）领域，该信息可能对食品补充剂的开发很感兴趣。

BACKGROUND & AIMS: :A series of alpha-asarone isomers was synthesized and investigated for their hypolipidemic and antiplatelet activity. Considering the hypolipidemic activity in rats at a dose of 80 mg/kg/day, some isomers were more potent than clofibrate at 150 mg/kg. Compound 3 was one of the most active agents elevating the HDL cholesterol level by 56% and lowering the LDL cholesterol level by 46.8% in rats after 7 days of administration. The activities of the platelet aggregation test in vitro were significant but lower than those of the reference substances (indomethacine and acetylsalicylic acid). In the pulmonary thromboembolic in vivo test in mice, two compounds (alpha-asarone (6) and compound 4) produced significant antithrombotic effects at 100 mg/kg, namely 44% and 52% protection against lung microembolia, respectively. alpha-Asarone derivatives form a new group of potential hypolipidemic and/or antithrombotic agents. The compounds 3, 4, and 6 may serve as lead substances whose structural modifications may result in original drugs.

背景与目标： ：合成了一系列的α-松香油异构体，并研究了它们的降血脂和抗血小板活性。考虑到以80 mg / kg /天的剂量进行的大鼠降血脂活性，某些异构体在150 mg / kg的情况下比氯贝贝酸盐更有效。在给药7天后，化合物3是最活跃的药物之一，可将大鼠的HDL胆固醇水平提高56％，将LDL胆固醇水平降低46.8％。体外血小板聚集试验的活性显着，但低于参考物质（吲哚美辛和乙酰水杨酸）的活性。在小鼠的肺血栓栓塞体内试验中，两种化合物（α-asarone（6）和化合物4）以100 mg / kg的剂量产生了显着的抗血栓形成作用，分别是针对肺微栓子的44％和52％的保护作用。 α-Asarone衍生物形成了一组潜在的降血脂药和/或抗血栓药。化合物3、4和6可以用作先导物质，其结构修饰可能会产生原始药物。

BACKGROUND & AIMS: :The effect of peptide Lys-Glu-Trp-NH2 in doses of 0.2, 20, and 2000 μg/kg on lipid and carbohydrate metabolism was studied in Wistar rats with experimental hyperlipidemia and diabetes mellitus. This tripeptide in a dose of 2000 μg/kg produced a hypolipidemic effect on atherogenic lipoproteins, decreased the intensity of LPO, improved the state of the antioxidant system, and normalized the content of HDL. Treatment with this tripeptide had a hypolipidemic effect and reduced the severity of specifi c morphofunctional changes in the pancreatic and hepatic tissue.

背景与目标： ：在实验性高脂血症和糖尿病的Wistar大鼠中研究了0.2、20和2000μg/ kg剂量的Lys-Glu-Trp-NH2肽对脂质和碳水化合物代谢的影响。这种三肽的剂量为2000μg/ kg，对动脉粥样硬化脂蛋白产生降血脂作用，降低LPO强度，改善抗氧化系统的状态，并使HDL含量正常化。用这种三肽治疗具有降血脂作用，并降低了胰腺和肝组织中特定形态功能改变的严重性。

BACKGROUND & AIMS: :The direct relationship between hypercholesterolemia and atherosclerosis has resulted in formal cholesterol-lowering recommendations for patients at increased risk. The incomplete response to therapy of some forms of hypercholesterolemia as well as not uncommon drug intolerance prompted the development of extracorporeal techniques to reduce serum cholesterol levels. Nonhuman primate data and an analysis of human cholesterol epidemiology and reduction trials were used to establish guidelines that would maximize the likelihood of stabilizing or regressing established coronary artery atherosclerosis. These goals are a total cholesterol (TC) level of less than or equal to 150 mg/dL (3.9 mmol/L) and a ratio of TC to high-density lipoprotein cholesterol (HDL) of less than 2.8. Selective, extracorporeal removal of LDL cholesterol (LDL-pheresis) was combined with diet and hypolipidemic drugs in a pilot study at The Rogosin Institute to achieve these lipid end-points. Technical aspects of LDL-pheresis, the background rationale for its use as part of a combined hypolipidemic therapy, the initial experience at The Rogosin Institute, and plans for future studies and applications are presented.

背景与目标： 高胆固醇血症和动脉粥样硬化之间的直接关系已导致对风险较高的患者正式降低胆固醇的建议。对某些形式的高胆固醇血症的治疗反应不完全，以及不常见的药物耐受性，促使人们开发了降低血清胆固醇水平的体外技术。使用非人类灵长类动物数据以及对人类胆固醇流行病学的分析和减少试验来建立指导方针，以最大程度地稳定或消退已确立的冠状动脉粥样硬化的可能性。这些目标是总胆固醇（TC）含量小于或等于150 mg / dL（3.9 mmol / L），TC与高密度脂蛋白胆固醇（HDL）的比例小于2.8。在Rogosin研究所进行的一项初步研究中，有选择地，体外去除LDL胆固醇（LDL-血液分离）与饮食和降血脂药物相结合，以实现这些脂质终点。介绍了LDL血液分离的技术方面，其作为联合降血脂治疗的一部分的背景原理，在Rogosin研究所的初步经验以及未来研究和应用的计划。

BACKGROUND & AIMS: :α-Glucosidase and lipase inhibitors play important roles in the treatment of hyperglycaemia and dyslipidemia. To identify novel naturally occurring inhibitors, a bioactivity-guided phytochemical research was performed on the pu-erh tea. One new flavanol, named (-)-epicatechin-3-O-(Z)-coumarate (1), and 16 known analogs (2-17) were isolated from the aqueous extract of the pu-erh tea. Their structures were determined by spectroscopic and chemical methods. Furthermore, the water extract of pu-erh tea and its fractions exhibited inhibitory activities against α-glucosidases and lipases in vitro; compound 15 showed moderate inhibitory effect against sucrase with an IC50 value of 32.5 μmol/L and significant inhibitory effect against maltase with an IC50 value of 1.3 μmol/L. Compounds 8, 10, 11 and 15 displayed moderate activity against a lipase with IC50 values of 16.0, 13.6, 19.8, and 13.3 μmol/L, respectively.

背景与目标： ：α-葡萄糖苷酶和脂肪酶抑制剂在高血糖和血脂异常的治疗中起重要作用。为了鉴定新型的天然抑制剂，对普-茶进行了生物活性指导的植物化学研究。从普-茶的水提取物中分离出一种新的黄烷醇，称为（-）-表儿茶素-3-O-（Z）-香豆酸盐（1）和16种已知的类似物（2-17）。通过光谱和化学方法确定它们的结构。此外，普-茶的水提取物及其馏分在体外对α-葡萄糖苷酶和脂肪酶具有抑制作用。化合物15对蔗糖酶的抑制作用中等，IC50值为32.5μmol/ L，对麦芽糖酶的抑制作用显着，IC50值为1.3μmol/ L。化合物8、10、11和15对脂肪酶表现出中等活性，IC50值分别为16.0、13.6、19.8和13.3μmol/ L。

BACKGROUND & AIMS: :Peroxisome proliferation induced by 2 hypolipidemic agents (clofibrate and ciprofibrate) was studied in rats by complementary approaches, ie cell fractionation, electron microscopy, marker enzyme activities, immunoblotting and nucleic acid hybridization techniques. Administration of clofibrates for 2 and 52 weeks in doses of 500 ppm and 50 ppm respectively, or ciprofibrate for 2,28 and 52 weeks in doses of 250, 25 and 25 ppm respectively, did not alter the behavior of the peroxisomes after induction as shown by ultracentrifugation profiles. The peroxisome mass was increased as shown by the purification procedure. Specific enzymes (catalase and mostly cyanide insensitive palmitoyl CoA oxidase) were induced. A mechanism of peroxisome biogenesis might have been initiated ie cytosolic factor, ligand-receptor interaction and/or post-translational modification of the import. Increase in marker enzyme activities showed that the peroxisomes are the most responsive organelles in comparison to lysosomes, mitochondria and smooth endoplasmic reticulum (except for cytochrome P-450 LA omega-hydroxylase). Peroxisomal integral membrane proteins appeared to be differently induced: some of them were virtually absent in untreated rat liver but were strongly expressed in treated liver. Induction was sustained for 52 weeks, indicating that there was no compensatory mechanism.

背景与目标： 在大鼠中，通过补充方法，即细胞分级分离，电子显微镜，标记酶活性，免疫印迹和核酸杂交技术，研究了由两种降血脂药（氯贝特和环丙贝特）诱导的过氧化物酶体增殖。如图所示，分别以500 ppm和50 ppm的剂量给予氯贝贝特2和52周，或分别以250、25和25 ppm的剂量给予环丙贝特2,28和52周，均未改变过氧化物酶体的行为。通过超速离心曲线。如纯化程序所示，过氧化物酶体质量增加。诱导了特定的酶（过氧化氢酶和大多数对氰化物不敏感的棕榈酰CoA氧化酶）。过氧化物酶体生物发生的机制可能已经开始，即胞质因子，配体-受体相互作用和/或输入的翻译后修饰。标记酶活性的增加表明，与溶酶体，线粒体和平滑的内质网（细胞色素P-450 LAω-羟化酶除外）相比，过氧化物酶体是最敏感的细胞器。过氧化物酶体整合膜蛋白似乎被不同地诱导：其中一些在未经治疗的大鼠肝脏中实际上不存在，但在经过治疗的肝脏中强烈表达。诱导持续52周，表明没有补偿机制。

BACKGROUND & AIMS: :This review addresses the structure-function properties of hypolipidemic peptides. The cholesterol-lowering peptide (lactostatin: IIAEK) operates via a new regulatory pathway in the calcium-channel-related mitogen-activated protein kinase (MAPK) signaling pathway of cholesterol degradation. The bile acid binding peptide (soystatin, VAWWMY) inhibits the micellar solubility of cholesterol in vitro and cholesterol absorption in vivo. VVYP is the most effective peptide having hypotriglyceridemic action in globin digests. The suppressive effect of globin digest on postprandial hyperlipidemia has been reported in humans. The ability of peptides (KRES, Apolipoprotein A-I mimetic peptides) to interact with lipids, remove LOOH and activate antioxidant enzymes associated with high-density lipoprotein determines their anti-inflammatory and anti-atherogenic properties. The β-conglycinin derived peptides KNPQLR, EITPEKNPQLR, and RKQEEDEDEEQQRE inhibit fatty acid synthase in vitro. These promising findings indicate the need for more conclusive molecular, cellular, and animal and human studies to design innovative new peptides that ameliorate cholesterol and lipid metabolism. PRACTICAL APPLICATIONS: Prevention and amelioration of hypercholesterolemia by dietary regulation are important. Dietary protein and peptides are very useful as regulators of serum cholesterol concentration. Diets low in saturated fat and cholesterol that include soy protein may reduce the risk of heart disease. In Japan, the concept of "food for specified health use" has been introduced for the prevention and treatment of life-style related disease. Thus, peptides derived from food proteins and sources other than food proteins such as peptide-rich functional foods and nutraceutical products, have considerable potential to prevent lifestyle-related diseases, especially hyperlipidemia, as discussed in this review. Furthermore, various strategies have been used for the efficient screening, development, and application of new hypolipidemic peptides. These include the use of phage display (for anti-obesity peptide), peptide mimetics (for anti-atherogenic peptide), and molecular targets such as CYP7A1 (for hypocholesterolemic peptide) and prohibitin (for anti-obesity peptide).

背景与目标： ：这篇综述解决了降血脂肽的结构功能特性。胆固醇降低肽（lactostatin：IIAEK）通过钙降解相关的钙通道相关的促分裂原活化蛋白激酶（MAPK）信号传导途径中的新调节途径起作用。胆汁酸结合肽（soystatin，VAWWMY）在体外抑制胆固醇的胶束溶解度和在体内抑制胆固醇的吸收。 VVYP是在球蛋白消化物中具有降甘油三酸酯作用的最有效的肽。已经报道了在人体中球蛋白消化对餐后高脂血症的抑制作用。肽（KRES，载脂蛋白A-I模拟肽）与脂质相互作用，清除LOOH并激活与高密度脂蛋白相关的抗氧化酶的能力决定了它们的抗炎和抗动脉粥样硬化特性。 β-伴大豆球蛋白衍生的肽KNPQLR，EITPEKNPQLR和RKQEEDEDEEQQRE在体外抑制脂肪酸合酶。这些令人鼓舞的发现表明，需要进行更多结论性的分子，细胞以及动物和人类研究，以设计出能够改善胆固醇和脂质代谢的创新性新肽。实际应用：通过饮食调节预防和改善高胆固醇血症很重要。饮食中的蛋白质和多肽非常有用，可作为血清胆固醇浓度的调节剂。低饱和脂肪和胆固醇的饮食（包括大豆蛋白）可以减少患心脏病的风险。在日本，为预防和治疗与生活方式有关的疾病引入了“特定健康食品”的概念。因此，正如本综述所讨论的那样，衍生自食物蛋白质的肽以及除食物蛋白质以外的其他来源（例如富含肽的功能性食物和营养产品）具有预防与生活方式有关的疾病（尤其是高脂血症）的巨大潜力。此外，各种策略已用于有效筛选，开发和应用新的降血脂肽。这些措施包括使用噬菌体展示（用于抗肥胖肽），肽模拟物（用于抗动脉粥样硬化肽）和分子靶标，例如CYP7A1（用于降胆固醇的肽）和禁止素（用于抗肥胖肽）。

BACKGROUND & AIMS: :Boussingaultia gracilis Miers var. pseudobaselloides Bailey is used as a Chinese folk medicine for treatment of diabetes, inflammation, and liver disease. The present study is to investigate the anti-obesity and hypolipidemic effects of B. gracilis Miers var. pseudobaselloides Bailey ethanol extract (BGE). Six-week-old Sprague-Dawley male rats were separately fed for 6 weeks with two kinds of diets-a normal diet (ND) and a high-calorie high-fat diet (HD). Then the animals were treated with tea catechin (100 mg/kg) or BGE (300, 600, or 900 mg/kg) for another 6 weeks. BGE significantly lowered body weight gain, fat-pad weights, and serum and hepatic lipid levels in HD-induced obese rats. The lipid droplets in hepatic tissue of BGE-treated groups were also markedly lessened compared with HD group rats via oil red O staining. Significant increases were observed in the expressions of genes for peroxisome proliferator-activated receptor (PPAR) α and for fatty acid oxidation and thermogenesis-related proteins-acyl-coenzyme A oxidase, carnitine palmitoyl transferase-1, and uncoupling protein-2-in the liver of the BGE-treated groups. Moreover, BGE was found to suppress the expression of sterol response element binding protein-1, a lipogenic gene, as well as those of fatty acid synthase and PPARγ in adipose tissue and liver of HD group rats. These results indicate that B. gracilis Miers var. pseudobaselloides Bailey may have an anti-obesity and hypolipidemic effect through regulation of expression of genes involved in lipolysis and lipogenesis.

背景与目标： 细小牛海绵菌（Boussingaultia gracilis） pseudobaselloides Bailey被用作治疗糖尿病，炎症和肝病的民间药物。本研究旨在探讨细纹芽孢杆菌Miers var的抗肥胖和降血脂作用。拟贝雷帽贝利乙醇提取物（BGE）。对六周大的Sprague-Dawley雄性大鼠分别饲喂两种饮食6周，即正常饮食（ND）和高热量高脂饮食（HD）。然后用茶儿茶素（100μg/ kg）或BGE（300、600或900μg/ kg）处理动物另外6周。 BGE显着降低了HD诱发的肥胖大鼠的体重增加，脂肪垫重量以及血清和肝脂质水平。通过油红O染色，与HD组大鼠相比，BGE治疗组的肝组织中的脂质滴也显着减少。观察到过氧化物酶体增殖物激活受体（PPAR）α的基因表达以及脂肪酸氧化和生热相关蛋白-酰基辅酶A氧化酶，肉碱棕榈酰转移酶-1和解偶联蛋白-2-的基因表达显着增加。 BGE治疗组的肝脏。此外，发现BGE在HD组大鼠的脂肪组织和肝脏中抑制固醇反应元件结合蛋白-1，一种生脂基因以及脂肪酸合酶和PPARγ的表达。这些结果表明细纹芽孢杆菌Miers var。假单胞属贝利可能通过调节参与脂肪分解和脂肪形成的基因的表达而具有抗肥胖和降血脂的作用。

BACKGROUND & AIMS: :Factors predisposing hormone-dependent tissues to the development of tumors coincide, at least partly, with hormonal-metabolic promoters (like insulin resistance, glucose intolerance, visceral obesity, etc.) of other main non-communicable diseases. This important knowledge poses the question of whether the same approach which is applied for prevention/treatment of a metabolic syndrome and the associated endocrine disorders might also be used in preventive and therapeutic oncology. Whereas an answer to this question remains controversial and is based mainly on experimental evidence, there is accumulating clinical data suggesting a practical significance of such a strategy, even though it is not to be considered as directly cytostatic. Among the many drugs under discussion, three groups of medicines (statins, antidiabetic biguanides, and thiazolidinediones) are the most attractive. The concept of metabolic rehabilitation is proposed and used practically in an adjuvant setting for the correction of the above-mentioned endocrine-metabolic disorders commonly found in cancer patients. The current use and aim of this approach is to improve the survival of patients and limit cancer progression. Nonetheless, it also appears potentially useful as a neoadjuvant therapy as well as a prophylactic treatment earlier in life for specific groups of people with hormone-associated enhanced oncological risk. It seems possible that certain hypolipidemic and antidiabetic medicines with pleiotropic effects might be combined with traditional antisteroid prevention/therapeutic approaches in routine clinical situations as well as for overcoming resistance to standard cancer hormonal therapies including receptor-negative cases. Characteristic at the end of the 20th and at the beginning of the 21st century is an epidemic of diabetes and obesity, which might further increase the incidence of certain cancers. This makes it timely to apply hypolipidemic and antidiabetic drugs (in combination with reasonable dieting, increased physical fitness, and an in-depth knowledge of drug-gene interactions) as an approach warranting further study.

背景与目标： ：促激素依赖型组织参与肿瘤发展的因素至少部分与其他主要非传染性疾病的激素代谢启动子（如胰岛素抵抗，葡萄糖耐量，内脏肥胖等）重合。该重要知识提出了一个问题，即用于预防/治疗代谢综合征和相关内分泌疾病的相同方法是否也可以用于预防和治疗肿瘤学。尽管该问题的答案仍是有争议的，并且主要基于实验证据，但是，尽管不被认为直接抑制细胞生长，但越来越多的临床数据表明了该策略的实际意义。在讨论中的许多药物中，三类药物（他汀类药物，抗糖尿病双胍类药物和噻唑烷二酮类药物）最具吸引力。提出了代谢康复的概念，并在辅助环境中实际用于纠正癌症患者中常见的上述内分泌代谢紊乱。该方法的当前用途和目的是提高患者的存活率并限制癌症的进展。尽管如此，它对于某些早期激素相关的增加的肿瘤风险人群，也可能作为新辅助疗法以及生命早期的预防疗法有用。在常规临床情况下以及为了克服对包括受体阴性病例在内的对标准癌症激素疗法的耐药性，某些具有多效性的降血脂药和抗糖尿病药似乎可以与传统的抗类固醇预防/治疗方法结合使用。 20世纪末和21世纪初的特征是糖尿病和肥胖症的流行，这可能会进一步增加某些癌症的发病率。这使得及时应用降血脂和降糖药（与合理的饮食，增加的身体适应性以及对药物基因相互作用的深入了解相结合）作为值得进一步研究的方法。

BACKGROUND & AIMS: :The advent of safe and effective hypolipidemic therapy has revolutionized the ability of the clinician to optimize abnormalities in the lipid profile. The advent of statin therapy has provided a potent option to decrease low-density lipoprotein and frequently allows achievement of National Cholesterol Education Program target lipid levels with monotherapy. However, lipid goals are frequently not achieved due to inadequate response to therapy or side effects. The role of combination therapy in the optimization of the lipid profile provides a means by which the implementation of pharmacologic agents with synergistic mechanisms of action allows further improvement in circulating levels of low-density lipoprotein cholesterol. Statins have been combined with bile acid resins, fibric acid derivatives, and nicotinic acid. However, bile acid resins, although not systemically absorbed, have significant problems with patient compliance and drug interactions. The implementation of therapy with fibric acid derivatives or nicotinic acid increases the risk of significant side effects such as rhabdomyolysis or liver toxicity. Ezetimibe is a prototype of a new class of agents that specifically block the absorption of cholesterol from the gastrointestinal tract. Ezetimibe has minimal systemic absorption and a metabolic pathway involving enterohepatic circulation that allows for once a day administration due to a prolonged half-life. Ezetimibe lacks the drug interactions that are common with the bile acid resins and it may be utilized as either monotherapy or in combination with other pharmacologic agents. Ezetimibe has a relatively flat dose-response curve and titration is not required. This review centers on the role of pharmacologic agents that act predominantly by the reduction of cholesterol absorption, including colesevelam and ezetimibe.

背景与目标： ：安全有效的降血脂治疗的出现彻底改变了临床医生优化脂质分布异常的能力。他汀类药物疗法的出现为减少低密度脂蛋白提供了一种有效的选择，并且经常允许通过单一疗法实现国家胆固醇教育计划的目标脂质水平。但是，由于对治疗或副作用的反应不足，经常无法达到脂质目标。组合疗法在优化脂质谱中的作用提供了一种手段，通过该手段，具有协同作用机制的药理剂的实施可进一步改善低密度脂蛋白胆固醇的循环水平。他汀类药物已与胆汁酸树脂，纤维酸衍生物和烟酸结合。然而，胆汁酸树脂尽管未被全身吸收，但是在患者依从性和药物相互作用方面存在重大问题。用纤维酸衍生物或烟酸进行治疗会增加发生严重副作用（如横纹肌溶解或肝毒性）的风险。依泽替米贝是一类新型药物的原型，该药物专门阻断胃肠道中胆固醇的吸收。依泽替米贝具有最小的全身吸收和涉及肝肠循环的代谢途径，由于半衰期延长，因此每天给药一次。依泽替米贝缺乏胆汁酸树脂常见的药物相互作用，可以用作单一疗法或与其他药物组合使用。依泽替米贝具有相对平坦的剂量反应曲线，不需要滴定。这篇综述集中于主要通过降低胆固醇吸收而起作用的药理作用，包括西洛韦仑和依泽替米贝。

BACKGROUND & AIMS: :The effect of taurine on the serum and liver cholesterol and triglyceride levels was studied in rats fed cholesterol plus cholic acid. Four groups of 4 weeks old rats were fed control diet, hypercholesterolemic diet (HCD), HCD + 1% taurine or HCD + 2% taurine for 8 weeks. Addition of taurine in HCD diet showed a significant reduction not only in serum total cholesterol and triglyceride levels but also in liver total cholesterol, lipid and triglyceride contents compared to the animals fed HCD alone. Histological examination of organs of these animals showed severe fatty vacuolation in livers and signet ring type vacuolation in kidneys of rats fed HCD. Taurine showed ameliorating effect on these abnormalities. The animals fed taurine in HCD also showed increased bile and sterol excretion in faeces compared to rats fed HCD alone. Taurine showed significant hypocholesterolemia in rats probably by enhancing the catabolism of cholesterol and reducing the absorption of dietary cholesterol.

背景与目标： ：在饲喂胆固醇加胆酸的大鼠中研究了牛磺酸对血清，肝胆固醇和甘油三酸酯水平的影响。四组4周龄大鼠分别喂食对照饮食，高胆固醇饮食（HCD），1％牛磺酸HCD或2％牛磺酸HCD，持续8周。与单独喂食HCD的动物相比，在HCD饮食中添加牛磺酸不仅显示血清总胆固醇和甘油三酯水平显着降低，而且肝脏总胆固醇，脂质和甘油三酸酯含量显着降低。这些动物器官的组织学检查显示，喂食HCD的大鼠肝脏严重脂肪空泡化，肾上的图章环型空泡化。牛磺酸对这些异常表现出改善作用。与仅喂食HCD的大鼠相比，喂食HCD的牛磺酸的动物粪便中胆汁和固醇的排泄量也增加。牛磺酸可通过增强胆固醇的分解代谢并减少饮食中胆固醇的吸收而显示出明显的低胆固醇血症。

BACKGROUND & AIMS: :Various cellulose and dextran anion exchangers bind bile salts in vitro under conditions of pH and ionic strength resembling those in the lumen of the small intestine. Of these substances, diethylaminoethyl (DEAE) cellulose, guanidoethyl cellulose, and DEAE Sephadex reduced hypercholesterolemia when added to the diet of cholesterol-fed cockerels. In addition, DEAE Sephadex reduced serum sterols in normocholesterolemic cockerels and dogs, lowered serum phospholipids and triglycerides in cholesterol-fed hypercholesterolemic cockerels and in normocholesterolemic dogs, and increased fecal excretion of bile acids in hypercholesterolemic cockerels. The data indicate that these insoluble cationic polymers exert their hypocholesterolemic effects by interrupting the enterohepatic circulation of bile acids.

背景与目标： ：各种纤维素和葡聚糖阴离子交换剂在pH和离子强度类似于小肠管腔的pH和离子强度条件下在体外结合胆汁盐。在这些物质中，将二乙基氨基乙基（DEAE）纤维素，胍基乙基纤维素和DEAE Sephadex添加到以胆固醇喂养的公鸡饮食中，可降低高胆固醇血症。此外，DEAE Sephadex降低了正常胆固醇的公鸡和狗的血清固醇，降低了胆固醇喂养的高胆固醇公鸡和正常胆固醇的狗的血清磷脂和甘油三酸酯，并增加了高胆固醇血症的鸡粪中胆汁酸的粪便排泄。数据表明这些不溶性阳离子聚合物通过中断胆汁酸的肠肝循环而发挥其降胆固醇作用。

BACKGROUND & AIMS: :An efficient and solely stereoselective synthesis of (E)-alpha-methylcinnamic acids has been accomplished in single pot by reduction of the unmodified Baylis-Hillman adducts, methyl-3-hydroxy-3-aryl-2-methylenepropanoates with I(2)/NaBH(4) reagent system at room temperature followed by hydrolysis. The efficacy of this method has been proved in the total synthesis of 1-[p-(myristyloxy)-alpha-methylcinnamoyl]glycerol, LK-903, a highly active hypolipidemic agent.

背景与目标： ：（E）-α-甲基肉桂酸的有效和单独立体选择性合成已通过用I（2）还原未修饰的Baylis-Hillman加合物，-3-羟基-3-芳基-2-亚甲基丙酸甲酯来在一个锅中完成。 / NaBH（4）试剂系统在室温下进行水解。在高活性降血脂药1- [对-（肉豆蔻酰氧基）-α-甲基肉桂酰基]甘油LK-903的全合成中已证明了该方法的有效性。

BACKGROUND & AIMS: :The hypotensive effect of DC-015, a newly synthesized quinazoline derivative, was investigated and compared with prazosin in spontaneously hypertensive rats (SHR). Intravenous administration of DC-015 and prazosin (both at 0.01, 0.05 and 0.1 mg/kg) induced a dose-dependent reduction of mean arterial pressure (MAP) which reached a maximal effect at 5 min after injection and persisted over 2 h in SHR. Furthermore, at higher doses DC-015 (0.1 mg/kg i.v. and 2.0 mg/kg orally, respectively) did not cause any significant changes in heart rate (HR); whereas the same doses of prazosin (0.1 mg/kg i.v. and 2.0 mg/kg orally, respectively) produced a decrease in HR which seems to parallel the time course of the hypotensive response in SHR. DC-015 and prazosin attenuated pressor responses to phenylephrine (10 &mgr;g/kg) but failed to inhibit the pressor effects of angiotensin II (0.5 &mgr;g/kg) even at the maximal hypotensive dose (0.1 mg/kg). This observation indicates that DC-015 appears to exert its hypotensive effect through alpha(1)-adrenoceptor blockade. On the other hand, in SHR fed a high-fat-high-cholesterol (HF-HC) diet, oral administration of DC-015 and prazosin (both at 1.0 mg/kg, twice a day) for 4 weeks caused significant reductions in total plasma cholesterol (CE), low-density lipoprotein (LDL)-cholesterol and total plasma triglyceride (TG). DC-015 therapy also increased high-density lipoprotein (HLD)-cholesterol levels, thus the ratio of total plasma cholesterol to HDL-CE was improved. In contrast, prazosin did not significantly increase the HDL-CE level in this study. It is concluded that DC-015 decreased MAP, plasma CE, LDL-CE, plasma TG and increased HDL-CE levels. DC-015 may have therapeutic potential as a potent antihypertensive drug via the alpha(1)-adrenoceptor antagonist. Concurrently, DC-015 may thus hold some advantage for the reduction of two of the major risk factors, hypertension and hyperlipidemia, for cardiovascular diseases. Copyright 1996 S. Karger AG, Basel

背景与目标： ：对新合成的喹唑啉衍生物DC-015的降压作用进行了研究，并与哌唑嗪在自发性高血压大鼠（SHR）中进行了比较。静脉内施用DC-015和哌唑嗪（分别为0.01、0.05和0.1 mg / kg）导致剂量依赖性平均动脉压（MAP）降低，在注射后5分钟达到最大作用，并在SHR中持续2小时以上。此外，在较高剂量下，DC-015（静脉内分别为0.1 mg / kg和2.0 mg / kg口服）不会引起心率（HR）的任何显着变化；而相同剂量的哌唑嗪（分别为0.1 mg / kg静脉内和2.0 mg / kg口服）可导致HR降低，这似乎与SHR中降压反应的时间过程一致。 DC-015和哌唑嗪减弱了对去氧肾上腺素（10μg/ kg）的升压反应，但即使在最大降压剂量（0.1 mg / kg）下也未能抑制血管紧张素II（0.5μg/ kg）的升压作用。该观察结果表明DC-015似乎通过α（1）-肾上腺素受体阻滞发挥其降压作用。另一方面，在以高脂高胆固醇（HF-HC）饮食喂养的SHR中，口服DC-015和哌唑嗪（1.0 mg / kg，每天两次），持续4周，可导致SHR的显着降低。总血浆胆固醇（CE），低密度脂蛋白（LDL）-胆固醇和总血浆甘油三酸酯（TG）。 DC-015治疗还增加了高密度脂蛋白（HLD）-胆固醇的水平，因此总血浆胆固醇与HDL-CE的比率得到了改善。相反，在本研究中，哌唑嗪并未显着增加HDL-CE水平。结论是DC-015降低MAP，血浆CE，LDL-CE，血浆TG和增加HDL-CE水平。 DC-015通过α（1）-肾上腺素受体拮抗剂可能作为强效降压药具有治疗潜力。同时，DC-015因此对于减少心血管疾病的两个主要危险因素高血压和高脂血症可能具有一定的优势。版权所有1996 S. Karger AG，巴塞尔

BACKGROUND & AIMS: :Diabetes is often accompanied by lipid abnormalities, which contribute significantly to cardiovascular (CV) morbidity and mortality in diabetic patients. The plant Ajuga iva (L.) Schreiber (Labiatea) is used in the treatment of diabetes in Moroccan folk medicine. Previously, we have demonstrated potent hypoglycemic activity and relatively non-toxic nature of a lyophilized aqueous extract of the whole plant (AI-extract) in normal (normoglycemic) and streptozotocin (STZ)-diabetic rats. In this study, we examined the AI-extract for its possible lipid-lowering activity in normal and STZ-diabetic rats. Taurine (TR) and glibenclamide (GLB) were used as reference substances. As shown previously, the AI-extract (10 mg/kg; oral) reduced plasma glucose levels after acute (single) and sub-chronic (3 weeks) dosing both in normal and diabetic rats. In normal rats, single and repeated oral administration of the AI-extract, at a dose of 10 mg/kg produced a small but significant decrease in plasma CHL levels (P<0.05). A single dose of the AI-extract did not produce a significant change in plasma TG, but sub-chronic dosing (for up to 21 days) caused a significant decrease in plasma TG (P<0.05). In STZ-diabetic rats, a single dose as well as repeated (3 weeks) treatment with the AI-extract produced a significant decrease in plasma CHL (P<0.01), and triglyceride (P<0.01) levels. The AI-extract also prevented weight loss in the diabetic animals. In summary, an aqueous extract of the Ajuga iva whole plant showed hypolipidemic activity, in addition to its hypoglycemic effect in normoglycemic and diabetic rats. In view of the hypoglycemic and hypolipidemic activity, and its relatively non-toxic nature (shown previously), Ajuga iva may be a candidate for development as an anti-diabetic agent in humans. Further studies are warranted to confirm our results and fractionate the AI-extract to isolate and identify the active principle(s), and to determine the exact mechanism(s) of action.

背景与目标： ：糖尿病常伴有脂质异常，这极大地增加了糖尿病患者的心血管（CV）发病率和死亡率。 Ajuga iva（L.）Schreiber（Labiatea）植物在摩洛哥民间医学中用于治疗糖尿病。以前，我们已经证明了正常（正常血糖）和链脲佐菌素（STZ）糖尿病大鼠中整个植物的冻干水提取物（AI提取物）的强降血糖活性和相对无毒的性质。在这项研究中，我们检查了AI提取物在正常和STZ糖尿病大鼠中可能的降脂活性。牛磺酸（TR）和格列本脲（GLB）被用作参考物质。如前所述，在正常和糖尿病大鼠中，急性（单次）和亚慢性（3周）给药后，AI提取物（10 mg / kg；口服）降低了血浆葡萄糖水平。在正常大鼠中，以10 mg / kg的剂量单次和重复口服AI提取物可使血浆CHL水平出现少量但显着的下降（P <0.05）。单一剂量的AI提取物不会使血浆TG发生显着变化，但亚慢性给药（长达21天）则导致血浆TG显着下降（P <0.05）。在STZ糖尿病大鼠中，单次剂量以及AI提取物的重复（3周）治疗可显着降低血浆CHL（P <0.01）和甘油三酸酯（P <0.01）水平。 AI提取物还防止了糖尿病动物的体重减轻。总之，除了在正常血糖和糖尿病大鼠中具有降血糖作用外，Ajuga iva整个植物的水提取物还具有降血脂活性。考虑到降血糖和降血脂的活性及其相对无毒的性质（如前所示），Ajuga iva可能是发展为人类抗糖尿病药的候选药物。有必要做进一步的研究来证实我们的结果，并对AI提取物进行分级分离，以分离和鉴定有效成分，并确定确切的作用机理。