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。

BACKGROUND & AIMS: :A study was carried out on the comparative efficacy of Lopid, Mevacor, Bezalip and Lasona in sixteen hyperlipidemic subjects. All the subjects were on Lopid at least for the last 15 days. Lopid therapy was discontinued after determining blood lipid profile of the subjects on day zero (day of 1st contact). The subjects were divided into three groups and after a washout period of 15 days, they were given three different drugs for the next 15 days. Subjects in group a (6), b (5) and c (5) received Mevacor, Bezalip and lasona respectively. In the present study mevacor was found to be the most potent hypolipidemic drug in lowering blood cholesterol and Low density lipoprotein (LDL) while lopid was most effective in keeping blood Triglycerides (TG) and High density lipoproteins (HDL) level within the desired limits. Bezalip and Lasona were also sufficiently effective in changing blood lipid profile, but lasona showed a negligible effect on HDL rise as compared with Bezalip or any other drug used in this study.

背景与目标： ：对Lopid，Mevacor，Bezalip和Lasona在16个高脂血症受试者中的比较疗效进行了研究。至少最近15天，所有受试者均接受Lopid治疗。在第零天（第一次接触的当天）确定受试者的血脂状况后，停止进行大剂量治疗。将受试者分为三组，在15天的冲洗期后，在接下来的15天中给他们三种不同的药物。 A（6），b（5）和c（5）组的受试者分别接受了Mevacor，Bezalip和lasona。在本研究中，发现甲氧萘韦尔是降低血液胆固醇和低密度脂蛋白（LDL）的最有效的降血脂药，而Lopid最有效地将血液甘油三酸酯（TG）和高密度脂蛋白（HDL）的水平保持在所需限度内。 Bezalip和Lasona在改变血脂方面也足够有效，但与Bezalip或本研究中使用的任何其他药物相比，lasona对HDL升高的影响可忽略不计。

BACKGROUND & AIMS: Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors controlling the expression of genes involved in lipid homeostasis. PPARs activate gene transcription in response to a variety of compounds including hypolipidemic drugs as well as natural fatty acids. From the plethora of PPAR activators, Scatchard analysis of receptor-ligand interactions has thus far identified only four ligands. These are the chemotactic agent leukotriene B4 and the hypolipidemic drug Wy 14,643 for the alpha-subtype and a prostaglandin J2 metabolite and synthetic antidiabetic thiazolidinediones for the gamma-subtype. Based on the hypothesis that ligand binding to PPAR would induce interactions of the receptor with transcriptional coactivators, we have developed a novel ligand sensor assay, termed coactivator-dependent receptor ligand assay (CARLA). With CARLA we have screened several natural and synthetic candidate ligands and have identified naturally occurring fatty acids and metabolites as well as hypolipidemic drugs as bona fide ligands of the three PPAR subtypes from Xenopus laevis. Our results suggest that PPARs, by their ability to interact with a number of structurally diverse compounds, have acquired unique ligand-binding properties among the superfamily of nuclear receptors that are compatible with their biological activity.

背景与目标： 过氧化物酶体增殖物激活受体（PPAR）是核激素受体，控制参与脂质体内平衡的基因的表达。 PPAR响应多种化合物（包括降血脂药和天然脂肪酸）激活基因转录。从过多的PPAR激活剂，Scatchard分析受体-配体的相互作用迄今仅鉴定出四个配体。这些是α-亚型的趋化剂白三烯B4和降血脂药Wy 14,643，γ-亚型的是前列腺素J2代谢产物和合成的抗糖尿病噻唑烷二酮。基于配体与PPAR结合会诱导受体与转录共激活因子相互作用的假设，我们开发了一种新型的配体传感器测定法，称为共激活剂依赖性受体配体测定法（CARLA）。通过CARLA，我们筛选了几种天然和合成的候选配体，并将天然存在的脂肪酸和代谢物以及降血脂药鉴定为非洲爪蟾三种PPAR亚型的真正配体。我们的结果表明，PPAR通过与多种结构多样的化合物相互作用的能力，在核受体的超家族中获得了与其生物学活性相适应的独特配体结合特性。

BACKGROUND & AIMS: :Effect of coconut protein in rats fed high fat cholesterol containing diet on the metabolism of lipids and lipid peroxides was studied. In addition, effect of coconut protein were compared with rats fed L-arginine. The results indicate that those fed coconut protein and those fed L-arginine showed significantly lower levels of total cholesterol, LDL+ VLDL cholesterol, Triglycerides and Phospholipids in the serum and higher levels of serum HDL cholesterol. The concentration of total cholesterol, triglycerides and phospholipids in the tissues were lower in these groups. There was increased hepatic cholesterogenesis which is evident from the higher rate of incorporation of labeled acetate into free cholesterol. Increased conversion of cholesterol to bile acids and increased fecal excretion of bile acids were observed. Feeding coconut protein results in decreased levels of Malondialdehyde in the heart and increased activity of Superoxide dismutase and Catalase. Supplementation of coconut protein causes increased excretion of urinary nitrate which implies higher rate of conversion of arginine into nitric oxide. In the present study, the arginine supplemented group and the coconut protein fed group produced similar effects. These studies clearly demonstrate that coconut protein is able to reduce hyperlipidemia and peroxidative effect induced by high fat cholesterol containing diet and these effects are mainly mediated by the L-arginine present in it.

背景与目标： ：研究了高蛋白饮食饮食中椰子蛋白对脂质和脂质过氧化物代谢的影响。另外，将椰子蛋白的作用与饲喂L-精氨酸的大鼠进行了比较。结果表明，喂食椰子蛋白的人和喂食L-精氨酸的人血清中的总胆固醇，LDL VLDL胆固醇，甘油三酸酯和磷脂水平显着降低，而血清HDL胆固醇则升高。这些组中组织中总胆固醇，甘油三酸酯和磷脂的浓度较低。肝胆固醇生成增加，这从标记的乙酸盐掺入游离胆固醇的较高速率中可以明显看出。观察到胆固醇向胆汁酸的转化增加和粪便中胆汁酸的排泄增加。喂养椰子蛋白会导致心脏中丙二醛的水平降低，超氧化物歧化酶和过氧化氢酶的活性增加。补充椰子蛋白会导致尿中硝酸盐的排泄增加，这意味着精氨酸向一氧化氮的转化率更高。在本研究中，精氨酸补充组和椰子蛋白喂养组产生了相似的效果。这些研究清楚地表明，椰子蛋白能够减少高脂胆固醇饮食引起的高脂血症和过氧化作用，这些作用主要是由其中存在的L-精氨酸介导的。

BACKGROUND & AIMS: :The hypoglycemic and hypolipidemic effects of flavonoid rich extract obtained from seeds of Eugenia jambolana (EJ) was analyzed in streptozotocin induced diabetic rats. Hypoglycemic activity was assessed by reduction in fasting blood glucose (FBG) and peak blood glucose level within 60 min of glucose tolerance test (GTT) in mild and severe diabetic (MD and SD respectively) rats. Different biochemical parameters like glycogen biosynthesis, glucose homeostatic enzyme (glucose-6-phosphatase, hexokinase) activities demonstrated significant (p<0.05) improvement as compared to diabetic counter parts. Further, the flavonoids also stimulated 16% increase in insulin release in vitro from pancreatic islets. The hypolipidemic action after this extract supplementation was confirmed by significant (p<0.05) decrease in the levels of LDL (27% MD, 29% SD), triglycerides (about 35% MD, 37% SD) and increase in HDL (21% MD, 34% SD) over untreated diabetic rats. The above mentioned action of this plant extract was found to be through dual up regulation of both the peroxisome proliferators-activated receptors (PPARalpha and PPARgamma) up to about 3-4 folds (over control) and their capacity to differentiate 3T3-L1 preadipocytes. The present data suggests that the flavonoid rich extract from EJ plant has both hypoglycemic and hypolipidemic effects which can help the cure and management of diabetes.

背景与目标： ：在链脲佐菌素诱导的糖尿病大鼠中分析了从Eugenia jambolana（EJ）种子获得的富含类黄酮的提取物的降血糖和降血脂作用。通过在轻度和重度糖尿病（分别为MD和SD）大鼠的葡萄糖耐量测试（GTT）60分钟内降低空腹血糖（FBG）和峰值血糖水平来评估降血糖活性。与糖尿病对应部位相比，糖原生物合成，葡萄糖稳态酶（葡萄糖6磷酸酶，己糖激酶）等不同生化参数表现出显着（p <0.05）改善。此外，类黄酮还刺激了胰岛中胰岛素的体外释放增加了16％。 LDL（27％MD，29％SD），甘油三酸酯（约35％MD，37％SD）和HDL（21％）显着降低（p <0.05）证实了这种提取物补充后的降血脂作用MD，未经治疗的糖尿病大鼠为34％SD）。发现该植物提取物的上述作用是通过过氧化物酶体增殖物激活的受体（PPARα和PPARγ）的双重上调至约3-4倍（过度控制）及其分化3T3-L1前脂肪细胞的能力。目前的数据表明，EJ植物中富含类黄酮的提取物具有降血糖和降血脂作用，可以帮助糖尿病的治疗和控制。

BACKGROUND & AIMS: The effects of the administration of 50 mg of guggulipid or placebo capsules twice daily for 24 weeks were compared as adjuncts to a fruit- and vegetable-enriched prudent diet in the management of 61 patients with hypercholesterolemia (31 in the guggulipid group and 30 in the placebo group) in a randomized, double-blind fashion. Guggulipid decreased the total cholesterol level by 11.7%, the low density lipoprotein cholesterol (LDL) by 12.5%, triglycerides by 12.0%, and the total cholesterol/high density lipoprotein (HDL) cholesterol ratio by 11.1% from the postdiet levels, whereas the levels were unchanged in the placebo group. The HDL cholesterol level showed no changes in the two groups. The lipid peroxides, indicating oxidative stress, declined 33.3% in the guggulipid group without any decrease in the placebo group. The compliance of patients was greater than 96%. The combined effect of diet and guggulipid at 36 weeks was as great as the reported lipid-lowering effect of modern drugs. After a washout period of another 12 weeks, changes in blood lipoproteins were reversed in the guggulipid group without such changes in the placebo group. Side effects of guggulipid were headache, mild nausea, eructation, and hiccup in a few patients.

背景与目标： 在61例高胆固醇血症患者中，将每日两次50毫克的Guggulipid或安慰剂胶囊的治疗效果与富含水果和蔬菜的谨慎饮食作为辅助治疗比较（Guggulipid组为31例，Guggulipid组为30例）。安慰剂组）以一种随机，双盲的方式。 Guggulipid使总胆固醇水平降低了11.7％，低密度脂蛋白胆固醇（LDL）降低了12.5％，甘油三酸酯降低了12.0％，总胆固醇/高密度脂蛋白（HDL）胆固醇的比例比饮食后降低了11.1％，而安慰剂组的水平没有变化。两组的高密度脂蛋白胆固醇水平无变化。指示氧化应激的脂质过氧化物在古格脂组中下降了33.3％，而安慰剂组没有任何下降。患者的依从性大于96％。在第36周时，饮食和含糖脂的联合作用与现代药物报道的降脂作用一样大。在又过了12周的冲洗期后，古吉脂组的血脂蛋白变化被逆转，而安慰剂组则没有这种变化。在少数患者中，古古柏脂的副作用是头痛，轻度的恶心，勃起和打ic。

BACKGROUND & AIMS: :Reinioside C is a triterpene saponin from the the root of Polygala aureocauda Dunn (PAD). This study examined the effects of reinioside C on hyperlipidemic mice in vivo and endothelium cells, macrophages and smooth muscle cells in vitro. Mice were given a hyperlipidemic diet for 30 days, then administered reinioside C (4, 8, 16 mg/kg/day, p.o.) for 30 days. Then the serum lipid, superoxide dismutase (SOD), malonaldehyde (MDA), the total cholesterol (TC) and triglyceride (TG) in the liver extract were measured. Human umbilical vein endothelial (HUVECs), peritoneal macrophages and smooth muscle cells (SMCs) pre-treated with reinioside C were treated with oxidized low-density lipoprotein (OxLDL). The results showed that reinioside C decreased serum and liver tissue lipid profiles in hyperlipidemic mice. Moreover, reinioside C protected the HUVECs against the Ox-LDL induced LDH leakage and exerted a protective effect on oxidative lesions induced by OxLDL, inhibited cholesteryl ester accumulation in macrophages, and decreased [Ca2+](i) and SMC proliferation in vitro. Based on these results, it is suggested that reinioside C is a promising hypolipidemic candidate.

背景与目标： ：Reinioside C是从远志（Pogalgala aureocauda Dunn，PAD）的根中提取的三萜皂苷。这项研究检查了神经节苷脂C对体内高脂血症小鼠以及体外内皮细胞，巨噬细胞和平滑肌细胞的影响。给予小鼠高脂饮食30天，然后给予雷诺苷C（4、8、16 mg / kg / day，p.o。）30天。然后测量肝提取物中的血清脂质，超氧化物歧化酶（SOD），丙二醛（MDA），总胆固醇（TC）和甘油三酸酯（TG）。用氧化的低密度脂蛋白（OxLDL）处理了用皂苷C预处理的人脐静脉内皮细胞（HUVEC），腹膜巨噬细胞和平滑肌细胞（SMC）。结果表明，皂苷C降低了高脂血症小鼠的血清和肝组织脂质谱。此外，皂苷C保护HUVECs免受Ox-LDL诱导的LDH渗漏，并对OxLDL诱导的氧化损伤发挥保护作用，抑制巨噬细胞中胆固醇酯的积累，并降低[Ca2]（i）和SMC的体外增殖。根据这些结果，提出了皂苷C是有希望的降血脂候选物。

BACKGROUND & AIMS: :The enterohepatic circulation of bile acids is a major regulator of serum cholesterol homeostasis. After biosynthesis from cholesterol in the liver, bile acids are secreted with bile into the lumen of the small intestine to aid in the digestion and absorption of fat and fat-soluble vitamins. The bile acids are nearly quantitatively reabsorbed in the terminal ileum by a Na+-dependent transport system (IBAT) and are transported with portal blood to the liver and taken up by a second Na+-/bile acid cotransporter (LBAT) to be resecreted into bile. In the liver bile acids inhibit the rate-limiting enzyme for the conversion of cholesterol into bile acid: cholesterol-7alpha-hydroxylase; interruption of the enterohepatic circulation of bile acids withdraws this feedback inhibition and leads to an upregulation of hepatic LDL-receptors with a concomitant decrease of serum LDL-levels. Specific inhibitors of the ileal bile acid transporter belonging to different chemotypes have been developed in recent years for this purpose, some now entering clinical stage. To exert a profound systemic effect these compounds do not need to be available systemically but can act from the luminal side of the small intestine, which offers the advantage to avoid the well-known adverse side effects of other hypolipidemic drugs like statins due to metabolism and drug-drug interactions in the liver. This implies several aspects in compound optimization and drug development quite different from standard procedures, for example the concept of low absorption drugs was established to avoid systemic side effects. The review article covers the mechanistic and therapeutic principles of the approach and presents an overview on the molecular target, the discovery of specific inhibitors and respective optimization strategies.

背景与目标： 胆汁酸的肝肠循环是血清胆固醇稳态的主要调节剂。从肝脏中的胆固醇进行生物合成后，胆汁酸与胆汁一起分泌到小肠腔中，以帮助脂肪和脂溶性维生素的消化和吸收。胆汁酸几乎通过Na依赖性转运系统（IBAT）在末端回肠中被定量吸收，并与门静脉血一起转运到肝脏，并被第二个Na /胆汁酸共转运蛋白（LBAT）吸收，再分泌到胆汁中。在肝脏中，胆汁酸抑制胆固醇转化为胆汁酸的限速酶：胆固醇7α-羟化酶；胆汁酸肠肝循环的中断会取消这种反馈抑制作用，并导致肝脏LDL受体上调，同时血清LDL水平降低。为此，近年来已开发出属于不同化学型的回肠胆汁酸转运蛋白的特异性抑制剂，其中一些现已进入临床阶段。为了发挥深远的全身作用，这些化合物无需全身使用，但可以从小肠的腔侧起作用，这具有避免其他降血脂药物（如他汀类药物）因代谢和代谢而引起的众所周知的不良副作用的优点。肝脏中的药物相互作用。这意味着化合物优化和药物开发中的几个方面与标准程序完全不同，例如，建立了低吸收药物的概念以避免系统性副作用。该综述文章涵盖了该方法的机械原理和治疗原理，并对分子靶标，特定抑制剂的发现和各自的优化策略进行了概述。