Antihyperlipidemic activity of adenosine triphosphate in rabbits fed a high-fat diet and hyperlipidemic patients

Context Recently, adenosine triphosphate (ATP) was occasionally found to decrease the triglyceride (TG) levels in several hyperlipidemic patients in our clinical practice.

Objective The study investigates the anti-hyperlipidemic effects of ATP in a high-fat fed rabbit model and hyperlipidemic patients.

Materials and methods Twenty-four rabbits were randomly divided into three groups of eight animals each as follows: normal diet, high-fat diet and high-fat diet?+?ATP group. ATP supplementation (40?mg/day) was started at the 20th day and lasted for 10 days. Serum concentrations of total cholesterol (TC), TG, LDL-C, HDL-C were measured on the 20th day and 30th day. Heart, liver and aorta were subjected histopathological examination. Twenty outpatients diagnosed primary hyperlipidemia took ATP at a dose of 60?mg twice a day for 1 week.

Results Feeding rabbits with a high-fat diet resulted in a significant elevation of lipid parameters including TC, TG, LDL-C, VLDL-C compared to the normal diet group (p?<?0.01). ATP treatment significantly decreased serum TG level (p?<?0.01), whilst other parameters remained statistically unaltered. Meanwhile, ATP significantly reduced the thickness of fat layer in cardiac epicardium (p?<?0.05) and pathological gradation of ballooning degeneration in hepatocytes (p?<?0.05). After taking ATP for 1 week, hyperlipidemia patients exhibited a significant decrease of TG (p?<?0.01), but other lipid parameters had no significant change.

Discussion and conclusion The study indicates that ATP selectively decreases serum TG levels in high-fat diet rabbits and hyperlipidemic patients. Therefore, ATP supplementation may provide an effective approach to control TG level.     

Hypolipidemic activity of Phellinus rimosus against triton WR-1339 and high cholesterol diet induced hyperlipidemic rats

Patients with the risk for atherosclerotic disease will be targeted to reduce the existing hyperlipidemia. The hypolipidemic activity of Phellinus rimosus was studied using triton WR-1339 and high cholesterol diet (HCD) induced models. The triton induced elevated lipid profile was attenuated by P. rimosus or standard drug atorvastatin. Similarly, administration of P. rimosus along with HCD significantly decline serum triglyceride, total cholesterol, low-density lipoprotein, with elevating the high-density lipoprotein. Thiobarbituric acid reacting substances in heart and liver significantly decreased; where as activity of enzymatic antioxidants and level of reduced glutathione were significantly increased. In both models, P. rimosus extract showed a significant ameliorative effect on the elevated atherogenic index as well as LDL/HDL-C ratio. The hypolipidemic activity of P. rimosus can be ascribed to its inhibitory effect on the liver HMG CoA reductase activity. The results suggest the possible therapeutic potential of this fungus as hypolipidemic agent.     

Effect of vincristine of triton WR-1339 induced hyperlipidemia in mice

The effect of Vincristine sulphate on the hyperlipidemia induced in mice by Triton WR-1339 was studied. A single i.p. dose (1 mg/kg) of Vincristine inhibited the development of hyperlipidemia within 2–4 hr. Vincristine sulphate seems to exert its lipid lowering effect through the liver by inhibiting either the synthesis or the excretion of lipoproteins or both.     

Changes in coagulative and fibrinolytic activities in Triton WR-1339-induced hyperlipidemia in rats

Changes in coagulative and fibrinolytic activities were studied in rats with hyperlipidemia induced by Triton WR-1339 (T-WR). After intravenous injection of T-WR (150, 200 or 300 mg/kg) into S.D. rats, dose-related increases in plasma lipids (total cholesterol, triglyceride, free cholesterol and phospholipid) were observed. In hyperlipidemic rats that received 300 mg/kg of T-WR, decreases in red blood cell count and Hb value were found. Significant increases in the ma value of the thromboelastogram and the fibrinogen level were observed in these T-WR treated rats. The alpha 2-plasmin inhibitor activity was found to decrease dose-relatedly. These results indicate that T-WR induced hyperlipidemia in rats is accompanied with an increase in coagulative activity and an indirect enhancement of fibrinolytic activity.     

Antidiabetic activity of aqueous root extract of Ichnocarpus frutescens in streptozotocin-nicotinamide induced type-II diabetes in rats

Objective:

To evaluate the antidiabetic activity of aqueous extract of roots of Ichnocarpus frutescens in streptozotocin-nicotinamide induced type-II diabetes in rats.

Materials and Methods:

Streptozotocin-nicotinamide induced type-II diabetic rats (n = 6) were administered aqueous root extract (250 and 500 mg/kg, p.o.) of Ichnocarpus frutescens or vehicle (gum acacia solution) or standard drug glibenclamide (0.25 mg/kg) for 15 days. Blood samples were collected by retro-orbital puncture and were analyzed for serum glucose on days 0, 5, 10, and 15 by using glucose oxidase-peroxidase reactive strips and a glucometer. For oral glucose tolerance test, glucose (2 g/kg, p.o.) was administered to nondiabetic control rats and the rats treated with glibenclamide (10 mg/kg, p.o.) and aqueous root extract of Ichnocarpus frutescens. The serum glucose levels were analyzed at 0, 30, 60, and 120 min after drug administration. The effect of the extract on the body weight of the diabetic rats was also observed.

Results:

The aqueous root extract of Ichnocarpus frutescens (250 and 500 mg/kg, p.o.) induced significant reduction (P < 0.05) of fasting blood glucose levels in streptozotocin-nicotinamide induced type-II diabetic rats on the 10^th and 15^th days. In the oral glucose tolerance test, the extract increased the glucose tolerance. It also brought about an increase in the body weight of diabetic rats.

Conclusion:

It is concluded that Ichnocarpus frutescens has significant antidiabetic activity as it lowers the fasting blood sugar level in diabetic rats and increases the glucose tolerance.     

α-Glucosidase inhibitory activity and in vitro antioxidant activities of alcohol-water extract (AWE) of Ichnocarpus frutescens leaves

In this study alcohol–water extract (AWE) of Ichnocarpus frutescens was studied for its α–glucosidase inhibitory activity and antioxidant properties. HAE exhibited the rat intestinal α-glucosidase, sucrase, isomaltase, and maltase activities. Sucrose was administered orally with or without extract to rats at a dose of 1000 mg/kg. The postprandial elevation in the blood glucose level after the administration of sucrose with the extract was significantly suppressed when compared with the control. The antioxidant activity, and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, superoxide anion radical scavenging , and hydrogen peroxide scavenging activities were evaluated to determine the total antioxidant capacity of the alcohol–water extract. HAE exhibited strong activity in phenyl-hydrazine–induced hemolysis. The total amount of polyphenol compounds in HAE was determined as pyrocatechol equivalents per gram of alcohol–water extract.     

高脂所致脂肪肝动物模型建立的动态研究

目的建立大鼠高脂血症及非酒精性脂肪肝模型,观察肝脏脂变程度和时间的动态关系,以找到合适的高脂血症和脂肪肝模型造模时间。方法采用W istar大鼠50只,饲喂高脂饲料,分别检测2~6 wk大鼠血清TG、TC、HDL、LDL、AST、ALT水平,根据肝脏病理切片分析肝脏脂变情况。结果在饲喂高脂饲料2 wk后,大鼠出现高血脂症状并伴有轻度的脂肪肝,随后的几周血脂水平保持稳定上升,肝系数持续增大,肝脏组织细胞脂变程度随造模时间的延长逐渐加重,3~4 wk为中度,5~6 wk为重度,第6周时伴有脂肪纤维化症状。结论经过高脂饲料的喂养,6 wk内可形成不同脂变程度的脂肪肝病理模型,可用于相关药理实验。     

Involvement of IL-6 and IL-6 receptor in fibrinogen synthesis in the liver of Triton WR-1339-induced hyperlipidemic rats

To clarify the mechanisms by which Triton WR-1339 causes an elevation in the plasma fibrinogen level, we studied the time courses of hepatic mRNA expression for beta-chain fibrinogen, interleukin-6 (IL-6) and IL-6 receptor (R) by RT-PCR. After intravenous injection of Triton WR-1339 (150, 300 and 500 mg/kg) in Sprague-Dawley rats, the plasma level of fibrinogen and MCP-1 significantly and dose-relatedly increased from 12 to 24 hours (h). At 3 and 6 hours dose dependent increases were found in hepatic IL-6 and IL-6R mRNA expression with increases in the hepatic mRNA expression for beta-chain fibrinogen as the rate-limiting step in fibrinogen synthesis. These results suggest that the increase in the plasma fibrinogen level is followed by the enhancement of hepatic mRNA expression of beta-chain fibrinogen, IL-6 and IL-6R, that is, IL-6 and IL-6R may partly regulate the plasma fibrinogen level in Triton WR-1339-induced hyperlipidemic rats.     

白藜芦醇对高脂饮食诱导小鼠高脂血症的作用机制研究

目的 考察白藜芦醇对高脂血症小鼠的影响,并探讨其作用机制.方法 按体重将雄性C57BL/6J小鼠随机分为3组:正常组、模型组及实验组,每组10只.正常组正常饲养,模型组及实验组小鼠连续饲喂4周高脂饲料构建高血脂模型.建模后,实验组灌服白藜芦醇(400 mg·kg-1),模型组及空白组灌服等量生理盐水,每天1次,连续干预...     

高脂饮食诱导肥胖大鼠的胰岛素敏感性与FFAs变化的关系

目的 :观察正常大鼠在高脂饮食诱导下形成肥胖后 ,胰岛素敏感性及其FFAs的变化。方法 :9周龄健康雄性Wistar大鼠16只 ,随机分为正常饲养组 (NC,n=8)和高脂饲养组 (HF,n=8)。喂养10周 ,比较两组大鼠体重、HOMA -IR以及FFAs等的变化。结果 :经10周高脂喂养 ,HF组与NC组比较 ,体重和内脏脂肪组织显著增加 (HF组大鼠体重较NC组增加了11 4% ,P<0 05) ;HF组大鼠内脏脂肪组织较NC组增加了20 7% ,P<0 01) ,并出现胰岛素抵抗 (HOMA -IR :HF组8 88±4 25vs3 92±2 26 ,P<0 05) ,空腹FFAs水平显著上升 ,较NC组增加了80 8% (P<0 05) ,但两组空腹血糖差异无显著性 ,HF组 :(7 89±1 46)mmol/LvsNC组 (8 70±1 59)mmol/L,P>0 05。结论 :高脂饮食可诱导大鼠肥胖伴胰岛素抵抗 ,其胰岛素抵抗的形成可能与FFAs水平的升高有关     

Withdrawal from free-choice high-fat high-sugar diet induces craving only in obesity-prone animals

Introduction

Vulnerability for weight gain is an individual trait. Obese people undertake dieting, but permanent weight loss is difficult to attain due to repeated phases of relapse to excess consumption.

Materials and methods

In this study, male Wistar rats were trained to operantly self-administer pellets followed by free-choice access in the homecage to high-fat high-sugar (HFHS) diet consisting of 30% sucrose, lard, standard rodent chow and water. Animals were divided into obesity-prone (OP) and obesity-resistant (OR) groups based on relative weight gain compared to normally fed controls despite equal consumption of HFHS.

Results and discussion

After 4 weeks of HFHS access, OP and OR animals did not differ in motivation for food pellets in terms of progressive ratio break point, lever pressing or response rate. However, upon discontinuation of the HFHS diet, differences between the OP and OR groups were noted. OP animals increased their motivation (i.e. craving) during the second withdrawal week and reduced time spent in the centre of an open field (increased anxiety) compared to the OR animals. Both OP and OR animals consumed less of the standard rodent chow during the first week of withdrawal when compared to normally fed controls. But, while the OR animals quickly returned to control levels of food consumption, OP animals continued to consume less standard rodent chow.

Conclusion

The results show for the first time that withdrawal from free-choice HFHS induces craving that is specific to the OP animals and suggests that OP individuals may have withdrawal symptoms that are similar to those induced by addictive drugs.

     

Cepharanthine action in preventing obesity and hyperlipidemia in rats on a high-fat high sucrose diet

BackgroundIt was demonstrated that cepharanthine (CEP), derived from Stephania cepharantha hayata, is a potent inhibitor of the ABCC10 transmembrane protein. It is approved to be a natural product or remedy. The present study focuses on investigating whether cepharanthine effectively reduces hyperlipidemia and obesity in an experimental hyperlipidemic rat model.MethodFour groups of Wistar rats were assigned randomly to the following groups: a high-fat high sucrose diet (HFHS), normal-fat diet (NFD), HFHS plus cepraranthine (10 mg/kg) (HFHS-C), and a HFHS diet with atorvastatin (HFHS-A). The responses of rats were observed on the basis of serum and hepatic biochemical parameters, food intake, and body weight after CEP treatment, and assessing the histopathological modifications by the optical microscope in the liver and its cells.ResultsSignificant improvement in the serum total cholesterol (TC), serum triglycerides (TG), and serum low-density lipoprotein (LDL) levels were observed following CEP treatment. We have also observed significant improvement in the structure of liver tissue and reduced-fat droplets in the cytoplasm. Moreover, CEP had a significant effect in preventing the gain in body weight of animals, and food intake was not significantly affected.ConclusionOur research results revealed that CEP significantly improved dyslipidemia and prevented the accumulation of fatty deposits in the rats' liver tissue fed an HFHS diet. In addition, CEP exerted an anti-obesity effect.     

藏波罗花根中两个酚苷的分离纯化、结构鉴定和抗氧化活性研究(英文)

利用生物活性跟踪法,通过硅胶吸附柱色谱、反相C18柱色谱和反相制备型HPLC,从藏波罗花的根中筛选到两个化合物。通过ESI-MS、GC-MS、1D-和2D-NMR进行结构鉴定,确定为acteoside(1)和isoacteoside(2)。1和2的-OH清除活性与苯甲酸接近,1和2的-OH及O-2-清除活性均远远高于维生素C,1和2的肝组织LPO抑制活性也高于BHT或维生素C,1和2在保护红细胞免受氧化损伤的活性也高于维生素C。在0.015 6至0.500 0 mg·mL-1浓度范围,1和2的-OH清除活性与浓度成正相关关系。在0.001 9至0.250 0 mg·mL-1浓度范围,随着浓度的增大,1和2的肝组织LPO抑制活性不断增强;但在0.250 0至1.000 0 mg·mL-1浓度范围,随着浓度的增大,LPO抑制活性反而有轻微的下降。     

高脂诱导性肥胖大鼠的胰岛素敏感性与TNF-α及FFAs水平

目的观察正常大鼠在高脂饮食诱导下形成肥胖后的胰岛素敏感性及其TNF-α、FFAs的变化。方法9周龄健康雄性Wistar大鼠16只,随机分为正常饲养组(NC熏n=8)和高脂饲养组(HF熏n=8)。喂养10周,比较两组大鼠体重、胰岛素抵抗指数(HOMA-IR)、以及TNF-α、FFAs等的变化。结果经10周高脂喂养,HF组与NC组比较,体重和内脏脂肪组织显著增加(HF组大鼠体重较NC组增加了11.4%,P<0.05;HF组大鼠内脏脂肪组织较NC组增加了20.7%,P<0.01),并出现胰岛素抵抗(HOMA-IR:HF组为8.88±4.25,NC组为3.92±2.26熏P<0.05),空腹FFAs和TNF-α水平显著上升,较NC组分别增加了80.8%(P<0.05)和58.4%(P<0.05),但两组空腹血糖差异无显著性(HF组为7.89±1.46mmol/L,NC组为8.70±1.59mmol/L熏P>0.05)。结论高脂饮食可诱导大鼠肥胖伴胰岛素抵抗,其胰岛素抵抗的形成可能与TNFα、FFAs水平的升高有关。     

Effects of high molecular weight water-soluble chitosan on in vitro fertilization and ovulation in mice fed a high-fat diet

A high molecular weight water-soluble chitosan (WSC) with an average molecular weight of 300 kD and a deacethylation level of over 90% was produced using a simple multi-step membrane separation process. It is known that WSC prevents obesity induced by a high-fat diet. Consequently, this study investigated whether or not WSC improved the ovarian dysfunction caused by obesity in mice. The mice were fed a high density protein and lipid diet for 4 weeks, followed by the administration of WSC at 480 mg/kg body weight per day for 4 days. Thereafter, the changes in body weight, ovulation rate, in vivo and in vitro fertilization and embryonic development were measured. WSC markedly reduced the body weight of obese mice fed with a high-fat diet, but not in mice fed with a normal diet. WSC had significant effects on the ovulation rate, both the in vivo and in vitro fertilization rates and embryonic development. These results indicate an improvement in the ovarian and oviduct dysfunction caused by obesity, and suggest an adjustment in the internal secretions and metabolic functions.     

Therapeutic potential of octyl gallate isolated from fruits of Terminalia bellerica in streptozotocin-induced diabetic rats

Abstract

Context: Medicinal plants are a potential source of antidiabetic drugs. Terminalia bellerica Roxb. (Combretaceae) is used in Indian traditional systems of medicine to treat diabetes mellitus.

Objective: The aim of this study was to isolate and identify antihyperglycemic principle(s) from the fruits of T. bellerica and assess the bioactivity in streptozotocin (STZ)-induced diabetic rats.

Materials and methods: Bioassay-guided fractionation was followed to isolate the active compound(s), structure was elucidated using ¹H and ¹³C NMR, IR and mass spectrometry and administered intragastrically to diabetic Wistar rats at different doses (5, 10 and 20?mg/kg, body weight) for 28?d. Plasma glucose, insulin, C-peptide and other biochemical parameters were studied.

Results: Octyl gallate (OG) isolated first time from the fruit rind of T. bellerica significantly (p?<?0.05) reduced plasma glucose to near normal values (108.47?±?6.9?mg/dl) after 14?d at the dose of 20?mg/kg. In addition, OG significantly increased plasma insulin, C-peptide, total protein, albumin, tissue glycogen, body weight and markedly decreased serum total cholesterol, triglyceride, LDL-cholesterol, urea, uric acid and creatinine in diabetic rats. Also OG restored the altered regulatory enzymes of carbohydrate metabolism.

Discussion and conclusion: OG might have augmented the secretion of insulin by the modulation of cAMP and intracellular calcium levels in the β cells of the pancreas. Our findings indicate that OG isolated first time from the fruit rind of T. bellerica has potential antidiabetic effect as it augments insulin secretion and normalizes the altered biochemical parameters in experimental diabetic rat models.     

Activity-Directed Fractionation of Pleurotus ostreatus. in the Search for Analgesics

Abstract

Pleurotus ostreatus. (Jacquin: Fries) P. Kummer (Tricholomataceae) was subjected to an antinociceptive activity-guided fractionation procedure in order to identify the fraction having highest activity. Three extracts, namely, acetone, dichloromethane, and hexane, were prepared at room temperature using fresh P. ostreatus., and 500 mg/kg was orally administered to male rats. The acetone extract showed significant antinociceptive activity with the hot-plate assay (male, 68%; p < 0.05), whereas dichloromethane and hexane extracts did not show significant activity. The same dose of acetone extract with female rats in the diestrous stage also showed prolongation of reaction time using the hot-plate test (female, 54%; p < 0.05). None of the extracts showed a significant increase in reaction time with the tail-flick test. The acetone extract was further fractionated by solvent partition to obtain four fractions (hexane, dichloromethane, ethyl acetate, and aqueous). Of these extracts, only the aqueous fraction showed marked prolongation in reaction time with the hot-plate test (500 mg/kg dose) on both male rats and on female rats in the diestrous stage (male, 37%; female, 26%). The aqueous fraction, following purification on a reverse phase column, yielded AqFrA-1, AqFrA-2, and AqFrA-3. Oral administration of a 500 mg/kg dose of these three fractions also showed marked prolongation in reaction time with the hot-plate test after 1 h of treatment (AqFrA-1, 26%; AqFrA-2, 69%; AqFrA-3, 101%). The effect was highest in AqFrA-3 at 1 h of treatment, and the effect lasted for 3 h. Hence, we can conclude that the compounds responsible for the activity have very high polarity. The acetone extract of P. ostreatus. did not induce a membrane-stabilizing effect and did not cause prostaglandin inhibition. Naloxone blocked the antinociceptive activity in the hot-plate test upon feeding of 500 mg/kg of acetone extract of P. ostreatus., indicating the mechanism of action is via opioid receptor mediation.     

Glycoprotein (90 kDa) isolated from Opuntia ficus-indica var. saboten MAKINO lowers plasma lipid level through scavenging of intracellular radicals in Triton WR-1339-induced mice

The Opuntia ficus-indica var. saboten MAKINO (OFI) has been traditionally used as health food and herbal agent in folk medicine in Korea. In this study, we investigated whether the OFI glycoprotein has antioxidative activity and hypolipidemic effect on Triton WR-1339-induced A/J mice. The OFI glycoprotein inhibits the production of reactive oxygen species (ROS) generated by glucose/glucose oxidase (G/GO) in BNL CL.2 cells. With its antioxidative property, the mice were orally administered in the OFI glycoprotein [50 mg/kg body weight (BW)] for two weeks. Our finding resulted in a significant decrease of plasma lipid levels in Triton WR-1339-treated mice such as total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL). Indeed, mice which induced by Triton WR-1339 were significantly increased the levels of TC, TG and LDL, whereas the high-density lipoprotein (HDL) level obviously decreased. However, the values were reversed at pretreatment with OFI glycoprotein in Triton WR-1339-treated mice. The data also showed that pretreatment with OFI glycoprotein resulted in decrease of thiobarbituric acid-reactive substances (TBARS) level and in increase of nitric oxide (NO) amount in presence of Triton WR-1339-treated mice, while the activities of antioxidant enzyme [superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)] were augmented. Therefore, we speculate that the OFI glycoprotein would be effective in lowering of plasma lipid levels.