Animal Model Of Hyperlipidemia Research Articles

Antihyperlipidemic effect of <i>Berberis orthobotrys</i> in hyperlipidemic animal models

The present study was undertaken to evaluate antihyperlipidemic effect of aqueous methanolic extract of Berberis orthobotrys in experimentally induced hyperlipidemic animal models. Atorvastatin was used as standard drug. The crude extract (50 and 100 mg/kg) significantly prevented the increase in low density lipoprotein (LDL), very low density lipoprotein (VLDL), total cholesterol (TC), triglyceride (TG), atherogenic index and coronary risk index in high fat diet, cholesterol, fructose and olive oil-induced hyperlipidemic rat models whereas in ethanol treated mice, the extract reduced VLDL, TG and TC levels. The high density lipoprotein (HDL) level was significantly increased in high fat diet, olive oil and cholesterol induced hyperlipidemic rats. The reduction in serum level of above parameters with 100 mg/kg dose of extract was comparable with atorvastatin. It is concluded, that B. orthobotrys has atheroprotective and lipid lowering potential. DOI: http://dx.doi.org/10.3329/bjp.v9i3.19922

Natural lipid-lowering agents and their effects: an update

Hyperlipidemia is one of the main contributing factors in the development of cardiovascular diseases. The hunt for effective antihyperlipidemic drugs is still on with an intention of finding potent agents with meager adverse effects. For the past several decades, medicinal plants have been evaluated for lipid-lowering effects apart from synthetic approaches to develop newer antihyperlipidemic agents. This article highlights the work carried out on potential antihyperlipidemic agents from plant sources from 2006 till 2012 that were archived in Google Scholar and Science Direct database. Seventy-nine articles were included in the review after manual content curation. The review summarizes the investigations on medicinal plants, compounds and herbal formulations using various hyperlipidemic animal models or in humans, the research findings and possibility of chemotaxonomic occurrence of secondary metabolites responsible for the antihyperlipidemic activities within certain plant families.

Effect of Centella asiatica on oxidative stress and lipid metabolism in hyperlipidemic animal models.

Hyperlipidemia and many other metabolic diseases are related to oxidative stress. Centella asiatica is a traditional Chinese medicine whose antioxidant effect in vitro has been reported. We are interested in whether it possesses this effect in vivo and hence modulates lipid metabolism. Therefore, experiments were carried out on mice and golden hamsters regarding its antioxidant and hypolipidemic effect. We observed that a fraction (CAF3) of the ethanol extract (CAE) of Centella asiatica had a cholesterol decrease of 79% and a triglyceride decrease of 95% in acute mice model, so CAF3 was further investigated in high-fat-fed hamster model. It was shown that CAF3 increased SOD and GSH-Px activities and decreased MDA level, and it also improved TC, TG, LDL-C, HDL-C, AST, and ALT levels. L-CAT and SR-BI gene expression in hamsters were increased. Taken together, our data suggest that the CAF3 fraction of Centella asiatica has antioxidant and hypolipidemic properties.

Chapter Four - Metabolomics in Dyslipidemia

Hyperlipidemia is an important public health problem with increased incidence and prevalence worldwide. Current clinical biomarkers, triglyceride, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol lack the necessary specificity and sensitivity and only increase significantly after serious dyslipidemia. Therefore, sensitive biomarkers are needed for hyperlipidemia. Hyperlipidemia-specific biomarkers would improve clinical diagnosis and therapeutic treatment at early disease stages. The aim of metabolomics is to identify untargeted and global small-molecule metabolite profiles from cells, biofluids, and tissues. This method offers the potential for a holistic approach to improve disease diagnoses and our understanding of underlying pathologic mechanisms. This review summarizes analytical techniques, data collection and analysis for metabolomics, and metabolomics in hyperlipidemia animal models and clinical studies. Mechanisms of hypolipemia and antilipemic drug therapy are also discussed. Metabolomics provides a new opportunity to gain insight into metabolic profiling and pathophysiologic mechanisms of hyperlipidemia.

Chlamydia pneumoniaeinduces expression of pro-atherogenic factors through activation of the lectin-like oxidized LDL receptor-1

Several lines of evidence have associated Chlamydia pneumoniae with cardiovascular disease including acceleration of atherosclerotic lesion progression in hyperlipidemic animal models by infection. Many of the pro-atherogenic effects of oxidized low-density lipoprotein (ox-LDL) occur through the activation of the lectin-like ox-LDL receptor-1 (LOX-1). Chlamydia pneumoniae upregulates the expression of the LOX-1 mRNA, promotes the uptake of ox-LDL, and utilizes the LOX-1 receptor for infectivity. The overall goal of this study was to determine whether C. pneumoniae organisms upregulated LOX-1 protein expression in vascular cells and whether upregulation of pro-atherogenic factors by C. pneumoniae occurred through LOX-1. Chlamydia pneumoniae induced LOX-1 protein expression in both endothelial cells and RAW macrophages. Upregulation was prevented by preincubation of cells with LOX-1 antibody prior to infection. Similarly, C. pneumoniae upregulated protein expression of adhesion molecules, MMP-1, and MMP-3, which was mitigated by anti-LOX-1 antibody. Prior treatment of organisms with PNGase, which removes the chlamydial glycan that is N-linked to the major outer membrane, abolished C. pneumoniae upregulation of LOX-1. These studies suggest that activation of LOX-1 expression occurs through binding of the chlamydial glycan and provides one mechanism by which C. pneumoniae infection could play a role in the pathogenesis of atherosclerosis.

Protective Effect of Na+/Ca2+ Exchange Blocker KB-R7943 on Myocardial Ischemia–Reperfusion Injury in Hypercholesterolemic Rats

Reverse-mode activation of the Na(+)/Ca(2+) exchanger (NCX) during reperfusion following ischemia contributes to Ca(2+) overload and cardiomyocyte injury. KB-R7943, a selective reverse-mode NCX inhibitor, reduces lethal reperfusion injury under non-ischemic conditions. However, the effectiveness of this compound under ischemic conditions is unclear. In the present study, we studied the effects of KB-R7943 in an animal model of hyperlipidemia. We further assessed whether the K ATP (+) channels are involved in potential protective mechanisms of KB-R7943. Twelve rats were fed normal chow, while 48 animals were fed a high cholesterol diet. The hearts from the control and hypercholesterolemic rats were subjected to 25 min of global ischemia followed by a 120-min reperfusion. Before this, hearts from hypercholesterolemic rats either received no intervention (cholesterol control group) or were pre-treated with 1 μM KB-R7943 and 0.3 μM of K ATP (+) blocker glibenclamide or glibenclamide alone. The infarction sizes (triphenyltetrazolium assay) were 35 ± 5.0 % in the control group, 46 ± 8.7 % in the cholesterol control group (p < 0.05 vs. control group), 28.6 ± 3.3 % in the KB-R7943 group (p < 0.05 vs. cholesterol control group), 44 ± 5 % in the KB-R7943 and glibenclamide group, and 47 ± 8.5 % in the glibenclamide group (p < 0.05 vs. control group). Further, KB-R7943 attenuated the magnitude of cell apoptosis (p < 0.05 vs. cholesterol control group). These beneficial effects were abolished by glibenclamide. In conclusion, diet-induced hypercholesterolemia enhances myocardial injury. Selective reverse-mode NCX inhibitor KB-R7943 reduces the infarction size and apoptosis in hyperlipidemic animals through the activation of K ATP (+) channels.

Synthesis and Anti-hyperlipidemic Activity of 3H-benzo [4, 5] thieno [2, 3-d] [1, 2, 3] triazin-4-ones: Possible Mechanism of Altered Lipid Metabolism

The present study was aimed to evaluate the anti-hyperlipidemic activity of newly synthesized tricyclic benzothieno 1, 2, 3-triazine derivatives namely CP-1 (3-(methyl)- 5,6,7,8-tetrahydro,3H-benzo[4,5] thieno [2,3-d][1,2,3] triazin-4-one), CP-2 (3-(ethyl)- 5,6,7,8-tetrahydro,3H-benzo[4,5] thieno [2,3-d][1,2,3] triazin-4-one) and CP-6 (3-(2-chloro phenyl)-5,6,7,8-tetrahydro,3H-benzo[4,5] thieno [2,3-d][1,2,3] triazin-4-one) against dexamethasone and Triton WR-1339-induced hyper-lipidemia in rats. Anti-hyperlipidemic activity of the test compounds were evaluated against dexamethasone (10 mg/kg, subcutaneous [s.c.]) and Triton WR-1339 (200 mg/kg, intraperitoneal [i.p]) induced hyperlipidemia in rats. Administration of single dose of Triton WR-1339 (200 mg/kg i.p) and dexamethasone (10 mg/kg s.c.) for 8 consecutive days to adult wistar rats caused severe hyperlipidemia characterized by marked increase in serum cholesterol, LDL-C, VLDL-C and triglyceride levels along with an increase in atherogenic index. Serum HDL-C levels were decreased significantly compared to normal control. Pretreatment with Atorvastatin (10 mg/kg, p.o.), CP-1 (25 and 50 mg/kg), CP-2 (25 and 50 mg/kg) and CP-6 (25 and 50 mg/kg) showed significant and dose-dependent protection against dexamethasone and Triton WR-1339-induced hyperlipidemia in rats by maintaining serum total cholesterol, LDL-C, VLDL-C and HDL-C levels within the normal range. Also, a significant decrease in atherogenic index was observed. The anti-hyperlipidemic effect of CP-6 was comparable with reference standard Atorvastatin. Furthermore, CP-6 was found to be more potent than CP-1 and CP-2. These findings suggest that CP-1, CP-2 and CP-6 possess significant anti-hyperlipidemic activity against experimental animal models of hyperlipidemia.

Effects of Prickly Pear Dried Leaves, Artichoke Leaves, Turmeric and Garlic Extracts, and Their Combinations on Preventing Dyslipidemia in Rats

The successful use of herbal combinations in managing diseases or conditions over a single herb has lead us to evaluate the anti-dyslipidemic properties of the combination of the artichoke leaves extract, turmeric extract, prickly pear dried leaves (PPL) and garlic extract versus each one alone in two different hyperlipidemic animal models. A two-week treatment of each of the natural extracts, combination 1 (artichoke, turmeric and PPL) or combination 2 (artichoke, turmeric, PPL and garlic) prior to a single intraperitoneal injection of Pluronic F-127 resulted in decreasing significantly serum LDL levels by garlic and PPL extracts and serum LDL/HDL ratios by turmeric, PPL, combination 1 and 2. In a 10-day high fat diet model, only the combination 1 and 2 lowered serum cholesterol, LDL by 8–12%, decreased significantly triglycerides, LDL/HDL ratio; and increased significantly HDL (P < 0.0001). However, a long term treatment of each natural product for 7 weeks resulted in decreasing significantly serum LDL levels and LDL/HDL ratio (P < 0.05–0.0001). Furthermore, only artichoke and PPL inhibited significantly HMG-CoA reductase activity (P < 0.05). In conclusion, short term, as well as long term, treatment using the combination of artichoke, turmeric, PPL and garlic extract prevents dyslipidemia; partially through inhibiting HMG-CoA reductase.

Oligonucleotide Microarray Analysis of Dietary-Induced Hyperlipidemia Gene Expression Profiles in Miniature Pigs

BackgroundHyperlipidemia animal models have been established, but complete gene expression profiles of the transition from normal lipid levels have not been obtained. Miniature pigs are useful model animals for gene expression studies on dietary-induced hyperlipidemia because they have a similar anatomy and digestive physiology to humans, and blood samples can be obtained from them repeatedly.MethodologyTwo typical dietary treatments were used for dietary-induced hyperlipidemia models, by using specific pathogen-free (SPF) Clawn miniature pigs. One was a high-fat and high-cholesterol diet (HFCD) and the other was a high-fat, high-cholesterol, and high-sucrose diet (HFCSD). Microarray analyses were conducted from whole blood samples during the dietary period and from white blood cells at the end of the dietary period to evaluate the transition of expression profiles of the two dietary models.Principal FindingsVariations in whole blood gene expression intensity within the HFCD or the HFCSD group were in the same range as the controls provide with normal diet at all periods. This indicates uniformity of dietary-induced hyperlipidemia for our dietary protocols. Gene ontology- (GO) based functional analyses revealed that characteristics of the common changes between HFCD and HFCSD were involved in inflammatory responses and reproduction. The correlation coefficient between whole blood and white blood cell expression profiles at 27 weeks with the HFCSD diet was significantly lower than that of the control and HFCD diet groups. This may be due to the effects of RNA originating from the tissues and/or organs.ConclusionsNo statistically significant differences in fasting plasma lipids and glucose levels between the HFCD and HFCSD groups were observed. However, blood RNA analyses revealed different characteristics corresponding to the dietary protocols. In this study, whole blood RNA analyses proved to be a useful tool to evaluate transitions in dietary-induced hyperlipidemia gene expression profiles in miniature pigs.

Abstract 513: Role of Heparanase in Atherosclerotic Plaque Formation

Little is know about the role of enzymatic regulation of glycosaminoglycans in the formation of atherosclerotic plaques. Heparanase is the only known mammalian enzyme that degrades the glycosaminoglycan heparan sulfate. We tested the hypothesis that heparanase could regulate atherogenesis and atherosclerotic plaque severity. We transduced human endothelial cells with lentiviruses expressing one of four different constructs expressing shRNA targeted to heparanase or a scrambled control sequence. These shRNA knocked down the expression of heparanase to 30-50% of wild type expression levels. These lines were selected using puromycin and confirmed for gene modulation using immunostaining and western blotting for heparanase. The ability to uptake lipids was tested using fluorescently labeled, oxidized low-density lipoprotein (OxLDL). We found that cells expressing 30% of the heparanase protein in wild type cells had increased uptake of OxLDL in comparison to wild type cells (1.8+0.1 versus 1.00+0.07 of normalized OxLDL uptake; p &lt;0.05) . We also evaluated the formation of atherosclerosis in transgenic mice overexpressing the human heparanase gene (HPA-Tg). This mouse line was crossed with the ApoE knockout mouse line. We exposed mice from this HPA-Tg/ApoE KO line and from the ApoE KO line of 20 weeks of age to 6 weeks of a high fat diet. At week 2 we surgically implanted an extravascular cuff on the left carotid artery to create a region of disturbed flow and low shear stress. Following the surgery, we used a high resolution combined ultrasound and photoacoustic imaging system to image the flow and plaque morphology after 1 day, 2 weeks and 4 weeks post-implantation of the cuff. Overexpression of heparanase increases the formation and severity of atherosclerosis in this model. Color doppler imaging revealed the existence of oscillatory flow in the left common carotid artery due to the formation of atherosclerotic plaque. This analysis confirmed an increase in the inflammatory response and neointimal formation in response to the low endothelial shear stress induced by the cuff in the HPA models compared to the ApoE. Our studies support that heparanase is a powerful regulator of lipid uptake and atherosclerotic plaque formation in an animal model of hyperlipidemia.

English

The process of microwave-assisted extraction (MAE) of total flavonoids from corn silk and the hypolipidemia in animal models were studied. Influence of solvent concentration, microwave power, extraction time and dose of solvent were investigated and then, the orthogonal experiments were performed. Animal models of hyperlipidemia induced by high-fat diet were established. The serum levels were respectively measured, including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). The optimum extraction parameters were determined as follows: the ethanol concentration (60%); the power (600 W); the extraction time (16 min); the ratio of plant material to solvent (M/S) (1:20), and the yield of extract (4.55%). Corn silk total flavonoids (CSTF) significantly lowered the serum TC, TG and LDL-C levels. The serum lipid level was decreased by CSTF in hyperlipidemic animal models in a dose dependent manner. &nbsp; Key words:&nbsp;Corn silk, total flavonoids, microwave-assisted extraction (MAE), antihyperlipidemia.

A Reappraisal of the Mechanism by Which Plant Sterols Promote Neutral Sterol Loss in Mice

Dietary plant sterols (PS) reduce serum total and LDL-cholesterol in hyperlipidemic animal models and in humans. This hypocholesterolemic effect is generally ascribed to inhibition of cholesterol absorption. However, whether this effect fully explains the reported strong induction of neutral sterol excretion upon plant sterol feeding is not known. Recent data demonstrate that the intestine directly mediates plasma cholesterol excretion into feces, i.e., without involvement of the hepato-biliary route.ObjectiveAim of this study was to determine whether stimulation of fecal neutral sterol loss during PS feeding is (partly) explained by increased intestinal cholesterol excretion and to assess the role of the cholesterol transporter Abcg5/Abcg8 herein.Methods and ResultsWild-type mice were fed a control diet or diets enriched with increasing amounts of PS (1%, 2%, 4% or 8%, wt/wt) for two weeks. In addition, Abcg5-/- mice were fed either control or 8% PS diet. PS feeding resulted in a dose-dependent decrease of fractional cholesterol absorption (∼2–7-fold reduction) in wild-type mice and ∼80% reduction in Abcg5-/- mice. Furthermore, PS feeding led to a strong, dose-independent induction of neutral sterol excretion (3.4-fold in wild-types and 2.7-fold in Abcg5-/- mice) without changes in biliary cholesterol secretion. It was calculated that PS feeding stimulated intestinal cholesterol excretion by ∼500% in wild-type mice and by ∼250% in Abcg5-/-.ConclusionsOur data indicate that in mice the cholesterol-lowering effects of PS are to a large extent attributable to stimulation of intestinal, non-bile derived, cholesterol excretion. The Abcg5/Abcg8 heterodimer is involved in facilitating this PS-induced flux of cholesterol.

Dietary red palm oil supplementation decreases infarct size in cholesterol fed rats

Background and AimsThe effect of red palm oil (RPO) supplementation on infarct size after ischaemia/reperfusion in a cholesterol enriched diet-induced hyperlipidemic animal model has not been reported. Previous studies reported results on the effect of RPO in a normal diet, whilst evidence of protection has been linked to improved functional recovery, prosurvival kinase, anti-apoptosis and NO-cGMP. Therefore, we aimed to investigate the effects of dietary RPO supplementation in a cholesterol-enriched diet-induced hyperlipidemic rat model and to investigate the involvement of matrix metalloproteinase 2 (MMP2) inhibition as a possible mechanism of protection.Materials and MethodsMale Wistar rats were fed either a standard rat chow diet (Norm) or a 2% cholesterol-enriched diet (Chol) for nine weeks. Additionally, two more groups received the same treatment, however, at the week 4, diet was supplemented with RPO for the last five weeks (Norm+RPO and Chol+RPO), respectively. After the feeding period hearts were isolated, perfused according to Langendorff and subjected to 30 minutes of normothermic global ischaemia followed by two hours of reperfusion. Infarct size was measured by 2,3,5-triphenyltetrazolium chloride staining at the end of reperfusion.ResultsCholesterol-enriched diet increased myocardial infarct size from 23.5 ± 3.0% to 37.2 ± 3.6% (p < 0.05) when compared to normal diet. RPO supplementation significantly reduced infarct size either in Norm+RPO or in Chol+RPO (to 9.2 ± 1.0% and 26.9 ± 3.0%), respectively. Infarct size in Chol+RPO was comparable to the Norm group. MMP2 activity before ischaemia was significantly reduced in the Chol+RPO group when compared to the Chol group. However, the MMP2 activity of the hearts of the RPO fed rats was significantly increased when compared to the normal diet group after ischaemia.ConclusionsFor the first time it was shown that dietary RPO supplementation attenuated the increased susceptibility of the hearts in cholesterol fed rats to ischaemia/reperfusion injury. This was shown by reduced infarct size. For the first time we also show that red palm oil supplementation altered pre-ischaemic levels of MMP-2, which may indicate that myocardial MMP2 may be implicated as a possible role player in RPO mediated protection against ischaemia/reperfusion injury in hearts of cholesterol supplemented rats.

A Potent and Selective AMPK Activator That Inhibits de Novo Lipogenesis.

AMP-activated protein kinase (AMPK) is a heterotrimeric kinase that regulates cellular energy metabolism by affecting energy-consuming pathways such as de novo lipid biosynthesis and glucose production as well as energy-producing pathways such as lipid oxidation and glucose uptake. Accordingly, compounds that activate AMPK represent potential drug candidates for the treatment of hyperlipidemia and type 2 diabetes. Screening of a proprietary library of AMP mimetics identified the phosphonic acid 2 that bears little structural resemblance to AMP but is capable of activating AMPK with high potency (EC50 = 6 nM vs AMP EC50 = 6 μM) and specificity. Phosphonate prodrugs of 2 inhibited de novo lipogenesis in cellular and animal models of hyperlipidemia.

Single intravenous injection of plasmid DNA encoding human paraoxonase-1 inhibits hyperlipidemia in rats

Paraoxonase-1 (PON1, EC 3.1.8.1) is a high-density lipoprotein (HDL)-associated antioxidant enzyme, and its activity correlates negatively with the level of plasma low-density lipoprotein cholesterol (LDL-C) and triglyceridemia (TG). In this study, we examined the therapeutic effect of plasmid DNA containing the human PON1 gene (pcDNA/PON1) in hyperlipidemic model rats. The rats were fed a high-fat and high-cholesterol diet for 25days to produce a hyperlipidemic animal model. Single intravenous injection of pcDNA/PON1 into model rats prevented dyslipidemia and hepatic lipid accumulation. The mechanisms of pcDNA/PON1 in treating hyperlipidemia were associated with increases of serum antioxidant PON1 and SOD activities, and with reduction of the levels of total cholesterol (TC), LDL-C and TG. The results suggest the potential therapeutic effect of pcDNA/PON1 on hyperlipidemia.

Effect of Chinese prescription Kangen-karyu on lipid metabolism in type 2 diabetic db/ db mice

Aim of the study Chinese prescription Kangen-karyu is clinically used as a treatment for cardiovascular diseases, and we have reported the beneficial effects on chemically induced hyperlipidemic animal models. The present study was investigated to evaluate the hypolipidemic effect of Kangen-karyu in type 2 diabetic db/ db mice which has not been explored yet. Materials and methods Male db/ db mice were divided into three groups, vehicle (control), Kangen-karyu 100, or 200 mg/kg body weight/day, and orally administered for 5 weeks every day. Age-matched non-diabetic m/ m mice were used as a normal group. Results Serum triglyceride (TG) and total cholesterol levels in db/ db mice were increased compared with those of m/ m mice. However, the administration of Kangen-karyu reduced hyperlipidemia in db/ db mice through a decline in the serum levels of TG and total cholesterol. The hepatic TG and total cholesterol levels of db/ db mice were markedly higher than those of m/ m mice, but these elevated lipid levels were significantly reduced by 200 mg/kg Kangen-karyu administration. Also, oil red O staining showed that the increased lipid deposition level in the liver of db/ db control mice was improved by Kangen-karyu administration. The expression of sterol regulatory element-binding protein-1 in the liver of db/ db mice was significantly down-regulated by the administration of Kangen-karyu at a dose of 200 mg/kg body weight. Kangen-karyu caused a slight elevation in the expression of peroxisome proliferator-activated receptor α in the liver of db/ db mice. Conclusions This study provides scientific evidence that Kangen-karyu improves hyperlipidemia and lipid deposition via the regulation of hepatic SREBP-1 expression in type 2 diabetic db/ db mice.

A Novel Class of Antihyperlipidemic Agents with Low Density Lipoprotein Receptor Up-Regulation via the Adaptor Protein Autosomal Recessive Hypercholesterolemia

We have previously reported compound 2 as a inhibitor of acyl-coenzyme A:cholesterol O-acyltransferase (ACAT) and up-regulator of the low density lipoprotein receptor (LDL-R) expression. In this study we focused on compound 2, a unique LDL-R up-regulator, and describe the discovery of a novel class of up-regulators of LDL-R. Replacement the methylene urea linker in compound 2 with an acylsulfonamide linker kept a potent LDL-R up-regulatory activity, and subsequent optimization work gave compound 39 as a highly potent LDL-R up-regulator (39; EC(25) = 0.047 microM). Compound 39 showed no ACAT inhibitory activity even at 1 microM. The sodium salts of compound 39 reduced plasma total and LDL cholesterol levels in a dose-dependent manner in an experimental animal model of hyperlipidemia. Moreover, we revealed in this study using RNA interference that autosomal recessive hypercholesterolemia (ARH), an adaptor protein of LDL-R, is essential for compound 39 up-regulation of LDL-R expression.

Effect of polygona-polysaccharids on atheromatous plaque: experiment with rabbits

To study the effect of polygona-polysaccharids on the elimination of atheromatous plaque. Thirty adult New Zealand rabbits were fed with high-fat and cholesterol forage for 8 weeks to establish hyperlipidemia animal models and then randomly divided into 3 equal groups: model group, simvastatin group receiving simvastatin orally, and polygona-polysaccharids group receiving polygona-polysaccharids orally. Ten rabbits were fed with normal food as control forage. At weeks 0, 2, and 8 the levels of total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), and lipoprotein (a) [Lp (a)] were determined with enzyme method. At the end of the week 8, all rabbits were killed to observe the elimination of aorta atheromatous plaque by microscope. Before the experiment, there were no significant differences in the levels of serum lipids among all groups. At the end of week 2 (before treatment), the levels of serum TC of the model group, simvastatin group, and polygona-polysaccharids group were (10.2 +/- 1.6) mmol/L, (11 +/- 1.8) mmol/L, and (11.2 +/- 1.9) mmol/L respectively, the LDL-C levels of the 3 groups were (9.85 +/- 1.65) mmol/L, (9.80 +/- 1.54) mmol/L, and (10.08 +/- 1.88) mmol/L respectively, the Lp (a) levels of the 3 groups were (656 +/- 106) mmol/L, (700 +/- 151) mmol/L, and (666 +/- 111) mmol/L respectively, all significantly higher than that of the control group [(1.3 +/- 0.3) mmol/L, (0.55 +/- 0.15) mmol/L, and (106 +/- 15) mg/L respectively, all P < 0.01]. At the end of week 8 (after treatment), the levels of serum TC, LDL-C, and Lp (a) of the polygona-polysaccharids group were (6.0 +/- 2.0) mmol/L, (4.25 +/- 1.35) mmol/L, and (55 +/- 14) mg/L respectively, all significantly lower than that at the end of week 2 [(11.2 +/- 1.9) mmol/L, (10.08 +/- 1.88) mmol/L, and (666 +/- 111) mg/L respectively, all P < 0.01]. The aorta atheromatous plaques in the polygona-polysaccharids group were basically eliminated compared with that in the model group. Polygona-polysaccharids (1.6 ml.kg(-1).d(-1)) has the effect of eliminating aorta atheromatous plaques.

Hypolipidemic Effects of Sophora flavescens and Its Constituents in Poloxamer 407-Induced Hyperlipidemic and Cholesterol-Fed Rats

In this study, we investigated the hypolipidemic effects of Sophora flavescens in poloxamer 407-induced hyperlipidemic and cholesterol-fed rats. The MeOH extract and 4 fractions of S. flavescens were administered at doses of 250 and 100 mg/kg body weight, respectively, once a day for 3 d to the poloxamer 407-induced hyperlipidemic rats. Serum lipid levels such as total cholesterol (TC), triglycerides (TG), and low-density lipoprotein-cholesterol (LDL-C) were markedly elevated in the poloxamer 407-induced hyperlipidemic control rats, while lipid levels were significantly decreased in the rats administered the MeOH extract or 4 fractions of S. flavescens. In addition, serum high-density lipoprotein-cholesterol (HDL-C) was reduced in the poloxamer 407-induced hyperlipidemic control rats. However, oral administration of both the MeOH extract and 4 fractions significantly increased HDL-C levels. Of the tested fractions, the EtOAc fraction showed the strongest lipid-lowering effect, as well as a high antiatherogenic potential with atherogenic index (A.I.) values of less than 1.92. We also investigated the hypolipidemic effects of the main compounds of the EtOAc fraction, kurarinol and kuraridinol, using the hyperlipidemic and hypercholesterolemic animal models. Here, elevated TC, TG, and LDL-C levels in the poloxamer 407-induced hyperlipidemic and cholesterol-fed rats were significantly reduced after oral administration of the compounds, and HDL-C levels had a significant increase. Furthermore, A.I. values were lowered by administering kurarinol and kuraridinol. In particular, kuraridinol exhibited stronger protective activities against hyperlipidemia than kurarinol. These results suggest that S. flavescens and its constituents may be effective cholesterol-lowering agents and useful for preventing hypercholesterolemic atherosclerosis.

Different activity profile of β‐cyclodextrin and hydroxypropyl‐β‐cyclodextrin in hyperlipidemic animal models

Different activity profile of β‐cyclodextrin and hydroxypropyl‐β‐cyclodextrin in hyperlipidemic animal models