Hypercholesterolemic Hamsters Research Articles

Marine Chitosan-Oligosaccharide Ameliorated Plasma Cholesterol in Hypercholesterolemic Hamsters by Modifying the Gut Microflora, Bile Acids, and Short-Chain Fatty Acids.

This study evaluated the cholesterol-alleviating effect and underlying mechanisms of chitosan-oligosaccharide (COS) in hypercholesterolemic hamsters. Male hamsters (n = 24) were divided into three groups in a random fashion, and each group was fed one particular diet, namely a non-cholesterol diet (NCD), a high-cholesterol diet (HCD), and an HCD diet substituting 5% of the COS diet for six weeks. Subsequently, alterations in fecal bile acids (BAs), short-chain fatty acids (SCFAs), and gut microflora (GM) were investigated. COS intervention significantly reduced and increased the plasma total cholesterol (TC) and high-density lipoprotein-cholesterol (HDL-C) levels in hypercholesteremic hamsters. Furthermore, Non-HDL-C and total triacylglycerols (TG) levels were also reduced by COS supplementation. Additionally, COS could reduce and increase food intake and fecal SCFAs (acetate), respectively. Moreover, COS had beneficial effects on levels of BAs and GM related to cholesterol metabolism. This study provides novel evidence for the cholesterol-lowering activity of COS.

Lycopene from Red Guava (Psidium guajava L.): From Hepatoprotective Effect to Its Use as Promising Self-Emulsifying Drug Delivery System for Anti-Inflammatory and Antioxidant Applications.

Lycopene is a carotenoid with potential use in the treatment of chronic illnesses. Here, different formulations of lycopene were studied: lycopene-rich extract from red guava (LEG), purified lycopene from red guava (LPG) and a self-emulsifying drug delivery system loaded with LPG (nanoLPG). The effects of administering orally various doses of LEG to hypercholesterolemic hamsters were evaluated regarding the liver function of the animals. The cytotoxicity of LPG in Vero cells was analyzed by a crystal violet assay and by fluorescence microscopy. In addition, nanoLPG was employed in stability tests. LPG and nanoLPG were tested for their cytotoxic effect on human keratinocytes and antioxidant capacity on cells in an endothelial dysfunction model in an isolated rat aorta. Finally, the effect of different nanoLPG concentrations on the expression of immune-related genes (IL-10, TNF-α, COX-2 and IFN-γ) from peripheral blood mononuclear cells (PBMC) using real-time PCR was also analyzed. Results suggest that LEG, despite not being able to improve blood markers indicative of liver function in hypercholesterolemic hamsters, reduced hepatic degenerative changes. Additionally, LPG did not show cytotoxicity in Vero cells. In relation to nanoLPG, the effects produced by heat stress evaluated by Dynamics Light Scattering (DLS) and visually were loss of color, texture change and phase separation after 15 days without interfering with the droplet size, so the formulation proved to be efficient in stabilizing the encapsulated lycopene. Although LPG and nanoLPG showed moderate toxicity to keratinocytes, which may be related to cell lineage characteristics, both revealed potent antioxidant activity. LPG and nanoLPG showed vasoprotective effects in aortic preparations. The gene expression assay indicates that, although no significant differences were observed in the expression of IL-10 and TNF-α, the PBMCs treated with nanoLPG showed a reduction in transcriptional levels of IFN-γ and an increased expression of COX-2. Thus, the work adds evidence to the safety of the use of lycopene by humans and shows that tested formulations, mainly nanoLPG due to its stability, stand out as promising and biosafe products for the treatment of diseases that have oxidative stress and inflammation in their etiopathology.

Peony seed oil decreases plasma cholesterol and favorably modulates gut microbiota in hypercholesterolemic hamsters.

Peony (Paeonia spp.) seed oil (PSO) contains a high amount of α-linolenic acid. The effects of PSO on hypercholesterolemia and gut microbiota remains unclear. The present study was to investigate effects of PSO supplementation on cholesterol metabolism and modulation of the gut microbiota. Male Golden Syrian hamsters (n = 40) were randomly divided into five groups (n = 8, each) fed one of the following diets namely low-cholesterol diet (LCD); high cholesterol diet (HCD); HCD with PSO substituting 50% lard (LPSO), PSO substituting 100% lard (HPSO) and HCD with addition of 0.5% cholestyramine (PCD), respectively, for 6weeks. PSO supplementation dose-dependently reduced plasma total cholesterol (TC) by 9-14%, non-high-density lipoprotein cholesterol (non-HDL-C) by 7-18% and triacylglycerols (TG) by 14-34% (p < 0.05). In addition, feeding PSO diets reduced the formation of plaque lesions by 49-61% and hepatic lipids by 9-19% compared with feeding HCD diet (p < 0.01). PSO also altered relative genus abundance of unclassified_f__Coriobacteriaceae, unclassified_f__Erysipelotrichaceae, Peptococcus, unclassified_f__Ruminococcaceae, norank_o__Mollicutes_RF9 and Christensenellaceae_R-7_group. It was concluded that PSO was effective in reducing plasma cholesterol and hepatic lipids and favorably modulating gut microbiota associated with cholesterol metabolism.

Activation of FXR by obeticholic acid induces hepatic gene expression of SR-BI through a novel mechanism of transcriptional synergy with the nuclear receptor LXR.

The farnesoid X receptor (FXR) is known to regulate the gene expression of SR-BI, which mediates plasma high-density lipoprotein (HDL)-cholesterol uptake. Our previous study demonstrated that the activation of FXR by obeticholic acid (OCA) lowered plasma HDL-cholesterol levels and increased the hepatic mRNA and protein expression levels of SR-BI in hypercholesterolemic hamsters, but not in normolipidemic hamsters, suggesting that dietary cholesterol may be involved in the OCA-induced transcription of SR-BI. In the present study, a functional 90-base-pair regulatory region was identified in the first intron of the SR-BI gene of hamster and mouse that contains a FXR response element (IR-1) and an adjacent liver X receptor (LXR) response element (LXRE). By in vitro DNA binding and luciferase reporter gene assays, it was demonstrated that FXR and LXR bind to their recognition sequences within this intronic region and transactivate the SR-BI reporter gene in a synergistic manner. It was also shown that mutations at either the IR-1 site or the LXRE site eliminated OCA-mediated gene transcription. Utilizing chow-fed hamsters as an in vivo model, it was demonstrated that treating normolipidemic hamsters with OCA or GW3965 alone did not effectively induce levels of SR-BI, whereas their combined treatment significantly increased the mRNA and protein levels of SR-BI in the liver. The study further investigated effects of FXR and LXR coactivation on the gene expression of SR-BI in human liver cells. The intronic FXRE and LXRE regulatory region was not conserved in the human SR-BI genomic sequence, however, higher mRNA expression levels of SR-BI were observed in human primary hepatocytes and HepG2 cells exposed to combined treatments of FXR and LXR agonists, compared with those in cells exposed to individual ligand treatment. Therefore, these results suggest that human SR-BI gene transcription may also be subject to concerted activation by FXR and LXR, mediated via currently unidentified regulatory sequences.

Soy noodles processed from soy flour or tofu affects antioxidant content, lipid accumulation in 3T3-L1 cells, and plasma lipids in hamsters

Nutritional properties of noodles prepared with soy flour (SN) or soy flour processed into tofu (TN) were compared to wheat noodles (WN) in vitro and in vivo using a hypercholesterolemic hamster model. SN and TN had higher levels of isoflavones, protein, fat, and dietary fiber, but lower levels of carbohydrate than WN. Predicted in vitro glycemic indices followed carbohydrate contents: WN, 88; SN, 30; and TN, 26. Lipid accumulation in 3 T3-L1 cells treated with an alcohol extract of TN was significantly (p < 0.05) lower than that treated alcohol extract of WN or SN. Hamsters fed a high fat diet supplemented with SN or TN had lower plasma total and LDL-cholesterol concentrations, body weight, and adipose weight than those fed a high fat diet supplemented with WN. Results of antioxidant capacity, in vitro glycemic and lipid accumulation, and animal feeding study showed that TN had higher nutritional value and bioactive potential than WN. Practical applications Thermal processing modifies nutritional values and functional properties of food with chemical changes. Soy based noodles were prepared from the same material using different processing methods: raw soy and heat-treated soy (tofu). Results of this study indicated that the soy based noodles showed greater bioactive capacity, leading to lower plasma total and LDL-cholesterol concentrations, less body weight, and less adipose weight than wheat noodles. Based on our results, tofu may be a better soy noodle ingredient than raw soy flour to improve health benefits of noodles.

Isoflavones enhance the plasma cholesterol-lowering activity of 7S protein in hypercholesterolemic hamsters.

Previous studies have shown that 7S protein is the active ingredient responsible for the plasma cholesterol-lowering activity of soybean. It is hypothesized that isoflavones in soybean could enhance the blood cholesterol-lowering activity of 7S protein. Forty-eight hamsters were divided into six groups and fed a non-cholesterol diet or one of the five high-cholesterol diets containing 12.1% 7S protein with 0-15.62 mg g-1 isoflavones. The results showed that addition of isoflavones in diets dose-dependently enhanced the plasma total cholesterol-lowering activity of 7S protein. Addition of isoflavones in 7S protein-based diets significantly reduced hepatic cholesterol accumulation by 12.6-26.1%, compared with the high cholesterol control diet. Isoflavones could also facilitate excretion of neutral sterols in a dose-dependent manner. Supplementation of isoflavones in diets favourably modulated mRNA expression and the protein mass of HMG-CoA reductase. It was concluded that the enhancing effect of isoflavones on the blood cholesterol-lowering activity of 7S protein was mediated by inhibiting the cholesterol absorption and de novo cholesterol synthesis in hypercholesterolemic hamsters.

Effect of Oat and Tartary Buckwheat - Based Food on Cholesterol - Lowering and Gut Microbiota in Hypercholesterolemic Hamsters.

The nutritional components in oat and tartary buckwheat had been assessed to have cholesterollowering effects. However, The effect of oat and tartary buckwheat based-food (OF) on cholesterol-lowering and gut microbiota in hypercholesterole hamsters was still limited studied because they are usually consumed in whole gran as well as after being processed. In this study, normal diets, high fat diet (HFD) with/without OF were fed to hamsters for 30 days respectively and growth parameters, metabolic parameters, and gut microbiota were investigated, respectively. It was found that OF significantly decreased plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-cholesterol), lowered liver TC, cholesterol ester (CE), and triglycerides (TG) concentrations, and increased fecal weight and bile acids (BA) concentrations, compared with HFD (p < 0.05). Moreover, the concentrations of acetate, propionate, butyrate and total short-chain fatty acids (SCFAs) were significantly increased in hamsters fed with OF, compared with HFD (p < 0.05). OF changed the overall structure of gut microbiota. The relative abundances of Erysipelotrichaceae, Ruminococcaceae, and Lachnospiraceae were decreased and the relative abundance of Eubacteriaceae was increased, compared with HFD. These results suggested that OF could reduce the concentrations of plasma lipid by inhibiting cholesterol absorption in liver and promoting excretions of fecal lipid and BA. And it also increased SCFAs and modulated the gut microbiota effectively to exert the hypocholesterolemic effects.

Soybean germ oil reduces blood cholesterol by inhibiting cholesterol absorption and enhancing bile acid excretion.

Health benefits of soybean germ oil have not yet been fully explored. The present study examined the blood cholesterol-lowering activity of soybean germ oil and the underlying mechanisms in hypercholesterolemic hamsters. Forty hamsters were randomly assigned into five groups and fed a non-cholesterol diet, a high cholesterol diet and one of three high cholesterol diets containing 0.50% cholestyramine, 4.75% soybean germ oil, and 9.50% soybean germ oil, respectively, for 6 weeks. The result showed that soybean germ oil significantly decreased plasma cholesterol by 18.5-31.5%, which was accompanied by 28.3-62.7% increase in excretion of fecal neutral sterols and bile acids. The effect was mediated by down-regulation of intestinal Niemann-Pick C1-like 1 protein (NPC1L1) and up-regulation of liver cholesterol-7α-hydroxylase (CYP7A1). We concluded that soybean germ oil favorably modulated the blood cholesterol concentration by inhibiting cholesterol absorption through inhibiting gene expression of NPC1L1 and by enhancing bile acid excretion via promoting gene expression of CYP7A1.

Anti-Atherosclerotic Effect of a Polyphenol-Rich Ingredient, Oleactiv®, in a Hypercholesterolemia-Induced Golden Syrian Hamster Model.

The development of nutraceutical ingredients has risen as a nutritional solution for health prevention. This study evaluated the effects of Oleactiv®, an ingredient developed for the prevention of atherogenesis, in hypercholesterolemic hamsters. Oleactiv® is a polyphenol-rich ingredient obtained from artichoke, olive and grape extracts as part of fruit and vegetables commonly consumed within the Mediterranean diet. A total of 21 Golden Syrian hamsters were divided into three groups. The standard group (STD) was fed a normolipidemic diet for 12 weeks, while the control group (CTRL) and Oleactiv® goup (OLE) were fed a high-fat diet. After sacrifice, the aortic fatty streak area (AFSA), plasmatic total cholesterol (TC), high-density lipoproteins (HDL-C), non-HDL-C and triglycerides (TG), were assessed. The cholesterol efflux capacity (CEC) of hamster plasma was quantified using a radiolabeled technique in murine macrophages J774. OLE administration induced a significant reduction of AFSA (−69%, p < 0.0001). Hamsters of the OLE group showed a significant decrease of both non-HDL-C (−173 mmol/L, p < 0.05) and TG (−154 mmol/L, p < 0.05). Interestingly, OLE induced a significant increase of total CEC (+17,33%, p < 0,05). Oleactiv® supplementation prevented atheroma development and had positive effects on the lipid profile of hypercholesterolemic hamsters. The increased CEC underlines the anti-atherosclerotic mechanism at the root of the atheroma reduction observed.

The hypolipidemic effects of Tamarindus indica fruit pulp extract in normal and diet-induced hypercholesterolemic hamsters are associated with altered levels of serum proteins.

The hypolipidemic effects of Tamarindus indica fruit pulp extract (Ti-FPE) have been earlier reported but the underlying molecular mechanisms are still uncertain. In this study, hamsters fed with Ti-FPE, both in the absence and presence of high-cholesterol diet, were shown to have significantly reduced levels of serum triglyceride, LDL-C and total cholesterol. The Ti-FPE-fed non-hypercholesterolemic hamsters also showed significant enhanced levels of serum apolipoprotein A1, antithrombin III, transferrin and vitamin D binding protein. In diet-induced hypercholesterolemic hamsters, apolipoprotein A1, antithrombin III and transferrin, which were relatively low in levels, became significantly enhanced when the hamsters were fed with Ti-FPE. These Ti-FPE-fed hypercholesterolemic hamsters also showed significant higher levels of serum vitamin D binding protein. When the different treated groups of hamsters were analyzed for the levels of the four serum proteins by ELISA, similar altered abundance were detected. Ingenuity Pathway Analysis of the Ti-FPE modulated serum proteins singled out "Lipid metabolism, molecular transport, small molecule biochemistry" as the top network. Our results suggest that the hypolipidemic effects of Ti-FPE are associated with alterations of serum proteins that are known to be cardioprotective and involved in the metabolism of lipids. The MS data have been deposited to the ProteomeXchange Consortium with the dataset identifier PXD010232.

Chemopreventive effects of a Tamarindus indica fruit extract against colon carcinogenesis depends on the dietary cholesterol levels in hamsters

Tamarind has significant antioxidant potential. We showed that tamarind protects hypercholesterolemic hamsters from atherosclerosis. Hypercholesterolemia might increase the risk of colon cancer. We investigated whether tamarind extract modulates the risk of colon cancer in hypercholesterolemic hamsters. Hamsters (n = 64) were given tamarind and a hypercholesterolemic diet for 8 weeks. The groups were the control, tamarind treatment, hypercholesterolemic, and hypercholesterolemic treated with tamarind groups. Half of each group was exposed to the carcinogen dimethylhydrazine (DMH) at the 8th week. All hamsters were euthanatized at the 10th week. In carcinogen-exposed hypercholesterolemic hamsters, tamarind did not alter the cholesterol or triglyceride serum levels, but it reduced biomarkers of liver damage (alanine transaminase [ALT], and aspartate aminotransferase [AST]). Tamarind decreased DNA damage in hepatocytes, as demonstrated by analysis with an anti-γH2A.X antibody. In liver and serum samples, we found that this fruit extract reduced lipid peroxidation (thiobarbituric acid reactive substances [TBARS]) and increased endogenous antioxidant mechanisms (glutathione peroxidase [GPx] and superoxide dismutase [SOD]). However, tamarind did not alter either lipid peroxidation or antioxidant defenses in the colon, which contrasts with DMH exposure. Moreover, tamarind significantly increased the stool content of cholesterol. Although tamarind reduced the risk of colon cancer in hypercholesterolemic hamsters that were carcinogenically exposed to DMH by 63.8% (Metallothionein), it was still ∼51% higher than for animals fed a regular diet. Staining colon samples with an anti-γH2A.X antibody confirmed these findings. We suggest that tamarind has chemoprotective activity against the development of colon carcinogenesis, although a hypercholesterolemic diet might impair this protection.

Lactobacillus casei-fermented milk improves serum and hepatic lipid profiles in diet-induced hypercholesterolaemic hamsters

The hypocholesterolaemic effects of milk fermented by Lactobacillus casei F0822 with bile salt hydrolase activity were investigated in hamsters fed a cholesterol-rich diet. Fermented milk (FM) exhibited dose-dependent hypocholesterolaemic activity. Sterilized and low-dose FM did not significantly affect the lipid profile of hamsters, whereas high-dose FM significantly reduced the levels of serum total cholesterol (TC) and non-high-density lipoprotein cholesterol (non-HDL-C), as well as hepatic TC and esterified cholesterol (EC). The daily faecal total bile acid excretion was significantly negatively correlated with the serum TC and non-HDL-C, as well as with the hepatic TC and EC. High-dose FM significantly enhanced daily faecal total bile acid excretion, which attributed to the hydrolysis of conjugated bile acids and the binding of free bile acids by the cells of strain F0822. These data suggest that the FM may serve as a functional food and has the potential to regulate cholesterol metabolism in humans.

Synergetic cholesterol-lowering effects of main alkaloids from Rhizoma Coptidis in HepG2 cells and hypercholesterolemia hamsters

AimsHyperlipidemia contributes to the progression of cardiovascular diseases. Main alkaloids from Rhizoma Coptidis including berberine (BBR), coptisine (COP), palmatine (PAL), epiberberine (EPI) and jatrorrhizine (JAT), improved dyslipidemia in hypercholesterolemic hamsters to a different degree. In this study, HepG2 cells and hypercholesterolemic hamsters were used to investigate the synergetic cholesterol-lowering efficacy of these five main alkaloids. Main methodsThe cellular lipid and cholesterol accumulation and in HepG2 cells were evaluated by Oil Red O staining and HPLC analysis. LDL receptor, 3-Hydroxy-3-methylglutaryl CoA reductase (HMGCR) and cholesterol 7-alpha-hydroxylase (CYP7A1) that involving cholesterol metabolism in HepG2 cells were measured by qRT-PCR, western blot and immunofluorescence analysis. The serum profiles including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c), as well as TC and total bile acids (TBA) of feces in hypercholesterolemic hamsters were also measured. Key findingAs compared to single alkaloids, the combination of five main alkaloids (COM) reduced the lipid and cholesterol accumulation in HepG2 cells more effectively and performed an advantageous effect on controlling TC, TG, LDL-c and HDL-c in hypercholesterolemic hamsters. More effective reduction of TBA and TC levels in feces of hamsters were achieved after the administration of COM. These effects were derived from the up-regulation of LDL receptor and CYP7A1, as well as HMGCR downregulation. SignificanceOur results demonstrated that COM showed a synergetic cholesterol-lowering efficacy, which was better than single alkaloids and it might be considered as a potential therapy for hypercholesterolemia.

Comparative effects of hawthorn (Crataegus pinnatifida Bunge) pectin and pectin hydrolyzates on the cholesterol homeostasis of hamsters fed high-cholesterol diets

This study aims to compare the effects of feeding haw pectin (HP), haw pectin hydrolyzates (HPH), and haw pectin pentasaccharide (HPPS) on the cholesterol metabolism of hypercholesterolemic hamsters induced by high-cholesterol diets. The animals were fed a standard diet (SD), high-cholesterol diet (HCD), or HCD plus HP, HPH, or HPPS at a dose of 300mg/kg body weight for 4weeks. Results showed that HPPS was more effective than HP and HPH in decreasing the body weight gain (by 38.2%), liver weight (by 16.4%), and plasma and hepatic total cholesterol (TC; by 23.6% and 27.3%, respectively) of hamsters. In addition, the bile acid levels in the feces were significantly higher by 39.8% and 132.8% in the HPH and HPPS groups than in the HCD group. Such changes were not noted in the HP group. However, the HP group had higher cholesterol excretion capacities than the HPH and HPPS groups by inhibiting cholesterol absorption in the diet, with a 21.7% increase in TC excretion and a 31.1% decrease in TC absorption. Thus, HPPS could be a promising anti-atherogenic dietary ingredient for the development of functional food to improve cholesterol metabolism.

Effects of dietary oat proteins on cholesterol metabolism of hypercholesterolaemic hamsters

The aim of present study was to investigate the hypocholesterolaemic effects of oat proteins (OP) in hamsters fed with a hypercholesterolaemic diet. The hamsters were divided into five groups and fed with the experimental diets containing oat, OP, oat β-glucan (OG), or OP+OG for 30 days. OP and the OG significantly lowered the concentrations of plasma low-density lipoprotein-cholesterol and liver total cholesterol (TC), and increased the excretion of faecal bile acid and TC. Plasma and liver TC in the OP+OG group were significantly lower than those in the OP or OG groups. Both OP and OG increased the activity of liver cholesterol 7α-hydroxylase (CYP7A1), while its activity in the OP+OG group was strongly increased compared with the OP or OG groups. These results indicated that dietary OP could improve hypercholesterolaemia, while dietary OP and OG together would have better hypocholesterolaemic effects.

Effects of fish oil and spirulina on oxidative stress and inflammation in hypercholesterolemic hamsters.

BackgroundAltered plasma lipids, oxidative stress, and inflammation have been involved in the pathogenesis of cardiovascular disease. Fish oil has shown inconclusive effects on plasma lipids and oxidative stress. Spirulina has both cholesterol lowering and antioxidant properties. However, the effect of fish oil and spirulina on hypercholesterolemia has not been studied. We investigated the effects of fish oil, spirulina, and their combination on hypercholesterolemia.MethodsThe hamsters were divided into 7 groups: control, high cholesterol (HF), fish oil (post FO), spirulina (post SP), and a combination of fish oil and spirulina (post SF, pre-SF, and HF + SF) groups. The HF and HF + SF groups were given a high cholesterol diet for 8 weeks. The post FO, post SP, and post SF groups were given a high cholesterol diet for 4 weeks and then the treatment for 4 weeks. The pre-SF group was given the combined treatment for 4 weeks and then a high cholesterol diet for 4 weeks.ResultsThe HF and HF + SF groups altered plasma lipids, increased oxidative stress, inhibited antioxidants, and increased inflammation. While the post FO group increased plasma lipids and was more atherogenic. The vice versa was observed in spirulina-treated group. Both the post SP and post SF groups inhibited oxidative stress and increased antioxidant status, and post FO and post SP diets regulated pro-inflammatory cytokines to near the control levels.ConclusionsBoth single treatment of fish oil or spirulina inhibit oxidative stress and inflammation. Treatment with a combination of fish oil and spirulina (post SF) may be beneficial for diet-induced hypercholesterolemic hamsters.

Effects of dietary hull-less barley β-glucan on the cholesterol metabolism of hypercholesterolemic hamsters

The aim of the present study is to investigate the hypocholesterolemic effects of dietary hull-less barley β-glucan (HBG) on cholesterol metabolism in hamsters which were fed a hypercholesterolemic diet. The hamsters were divided into 3 groups and fed experimental diets, containing 5‰ HBG or 5‰ oat β-glucan (OG), for 30days. The HBG, as well as OG, lowered the concentration of plasma LDL-cholesterol significantly. The excretion of total lipids and cholesterol in feces were increased in HBG and OG groups compared with the control group. The activity of 3-hydroxy-3-methyl glutaryl-coenzyme A (HMG-CoA) reductase in liver was reduced significantly in the HBG group compared with the control and OG groups. The activity of cholesterol 7-α hydroxylase (CYP7A1) in the liver, in the HBG and OG groups, was significantly increased compared with the control group. The concentrations of acetate, propionate and total short chain fatty acids (SCFAs) were not significantly different between the HBG and control groups. These results indicate that dietary HBG reduces the concentration of plasma LDL cholesterol by promoting the excretion of fecal lipids, and regulating the activities of HMG-CoA reductase and CYP7A1 in hypercholesterolemic hamsters.

Effects of dietary wheat bran arabinoxylans on cholesterol metabolism of hypercholesterolemic hamsters

The aim of the present study is to investigate the effects of dietary wheat bran arabinoxylans (AXs) on cholesterol metabolism in hypercholesterolemic hamsters. The hamsters were divided into 3 groups and fed the experimental diets containing AXs or oat β-glucan at a dose of 5g/kg for 30 days. As the results, the AXs lowered plasma total cholesterol and LDL-cholesterol concentrations, and increased excretions of total lipids, cholesterol and bile acids, as well as oat β-glucan. The AXs reduced the activity of 3-hydroxy-3-methyl glutaryl-coenzyme A (HMG-CoA) reductase, and increased the activity of cholesterol 7-α hydroxylase (CYP7A1) in liver. Moreover, the AXs increased propionate and the total short-chain fatty acids (SCFAs) concentrations. These results indicated that dietary AXs reduced the plasma total cholesterol and LDL-cholesterol concentrations by promoting the excretion of fecal lipids, regulating the activities of HMG-CoA reductase and CYP7A1, and increasing colonic SCFAs in hamsters.

ProAlgaZyme subfraction improves the lipoprotein profile of hypercholesterolemic hamsters, while inhibiting production of betaine, carnitine, and choline metabolites

BackgroundPreviously, we reported that ProAlgaZyme (PAZ) and its biologically active fraction improved plasma lipids in hypercholesterolemic hamsters, by significantly increasing the high density lipoprotein cholesterol (HDL-C) while reducing non-HDL cholesterol and the ratio of total cholesterol/HDL-C. Moreover, hepatic mRNA expression of genes involved in HDL/reverse cholesterol transport were significantly increased, while cholesteryl ester transfer protein (CETP) expression was partially inhibited. In the current study, we investigated the therapeutic efficacy of the biologically active fraction of PAZ (BaP) on the plasma lipid and plasma metabolomic profiles in diet induced hypercholesterolemic hamsters.MethodsFifty male Golden Syrian hamsters were fed a high fat diet for 4 weeks prior to randomization into 6 groups, based on the number of days they received subsequent treatment. Thus animals in T0, T3, T7, T10, T14, and T21 groups received BaP for 0, 3, 7, 10, 14, and 21 days, respectively, as their drinking fluid. Plasma lipids were assayed enzymatically, while real-time reverse transcriptase polymerase chain reaction (RT-PCR) provided the transcription levels of the Apolipoprotein (Apo) A1 gene. The plasma metabolomic profile was determined using 1H nuclear magnetic resonance (NMR) spectroscopy in conjunction with multivariate analysis.ResultsPlasma HDL-C was significantly increased in T3 (P < 0.05) and T21 (P < 0.001), while non-HDL cholesterol was significantly reduced in T3, T7, T10 (P < 0.001) and T14, T21 (P < 0.01). Moreover, the ratio of total cholesterol/HDL-C was significantly lower in all BaP treated groups (P < 0.001) as compared with T0. Quantitative RT-PCR showed an increase in Apo A1 expression in T10 (3-fold) and T21 (6-fold) groups. NMR data followed by multivariate analysis showed a clear separation between T0 and T21 groups, indicating a difference in their metabolomic profiles. Plasma concentrations of metabolites associated with a risk for atherosclerosis and cardiovascular disease, including choline, phosphocholine, glycerol-phosphocholine, betaine and carnitine metabolites were significantly lower in the T21 group.ConclusionTreatment with BaP significantly improved the plasma lipid profile by increasing HDL-C and lowering non-HDL cholesterol. In addition, BaP potentially improved the plasma metabolomic profile by reducing the concentration of key metabolites associated with risk for atherosclerosis and cardiovascular disease.

In vivo biochemical and gene expression analyses of the antioxidant activities and hypocholesterolaemic properties of Tamarindus indica fruit pulp extract.

Background Tamarindus indica (T. indica) is a medicinal plant with many biological activities including anti-diabetic, hypolipidaemic and anti-bacterial activities. A recent study demonstrated the hypolipidaemic effect of T. indica fruit pulp in hamsters. However, the biochemical and molecular mechanisms responsible for these effects have not been fully elucidated. Hence, the aims of this study were to evaluate the antioxidant activities and potential hypocholesterolaemic properties of T. indica, using in vitro and in vivo approaches.Methodology/Principal FindingsThe in vitro study demonstrated that T. indica fruit pulp had significant amount of phenolic (244.9±10.1 mg GAE/extract) and flavonoid (93.9±2.6 mg RE/g extract) content and possessed antioxidant activities. In the in vivo study, hamsters fed with high-cholesterol diet for ten weeks showed elevated serum triglyceride, total cholesterol, HDL-C and LDL-C levels. Administration of T. indica fruit pulp to hypercholesterolaemic hamsters significantly lowered serum triglyceride, total cholesterol and LDL-C levels but had no effect on the HDL-C level. The lipid-lowering effect was accompanied with significant increase in the expression of Apo A1, Abcg5 and LDL receptor genes and significant decrease in the expression of HMG-CoA reductase and Mtp genes. Administration of T. indica fruit pulp to hypercholesterolaemic hamsters also protected against oxidative damage by increasing hepatic antioxidant enzymes, antioxidant activities and preventing hepatic lipid peroxidation.Conclusion/SignificanceIt is postulated that tamarind fruit pulp exerts its hypocholesterolaemic effect by increasing cholesterol efflux, enhancing LDL-C uptake and clearance, suppressing triglyceride accumulation and inhibiting cholesterol biosynthesis. T. indica fruit pulp has potential antioxidative effects and is potentially protective against diet-induced hypercholesterolaemia.