High Cholesterol Diet-fed Rats Research Articles

Wax apple (Syzygiumsamarangense) fruit extract ameliorates endothelial dysfunction and liver damage in high cholesterol diet-fed rats

Background and aimWax apple fruit (Syzygium samarangense) is one of the most popular tropical fruit in Asia, and contains several essential nutrients. Therefore, this study explored the effects of the wax apple fruit extract on a high-cholesterol diet-induced vascular endothelial dysfunction and fatty liver in rats. Experimental procedureMale Sprague Dawley rats were fed a diet with 1.5% cholesterol (HCD) for 8 weeks, and were given wax apple fruit extract (50 and 100 mg/kg/day) orally for the last 4 weeks. After 8 weeks, blood sample, thoracic aorta, and liver were collected and processed for biochemical and histological analysis. Additionally, vascular endothelial function and the protein expression of oxidative stress markers in aortae were evaluated. Results and conclusionWax apple reduced serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), aspartate aminotransferase (AST), and alanine aminotransferase (ALT), but increased high-density lipoprotein cholesterol (HDL-C) levels. Furthermore, the liver levels of TG and TC were reduced in wax apple-treated hypercholesterolemic rats. Histological studies revealed that wax apple ameliorated HCD-induced morphologic changes of aortic and liver tissues of rats. In aortic tissues, the impaired endothelium-dependent responses to acetylcholine, the reduced nitric oxide (NO) contents, the elevated endothelin (ET)-1 contents, and the increased expression of NADPH oxidase subunit p47phox and 4-hydroxynonenal in HCD-fed rats were reversed by wax apple treatment. These results suggest that oral administration of wax apple improves vascular dysfunction and damage in hypercholesterolemic rats possibly through increasing NO bioavailability, decreasing ET-1 levels and reducing oxidative stress. Furthermore, wax apple ameliorates the HCD-induced fatty liver in rats.

The Effects of a High-Fat/Cholesterol Diet on the Intestine of Rats Were Attenuated by Sparassis latifolia Polysaccharides.

Sparassis latifolia polysaccharides can regulate lipids and cholesterol in serum and liver. However, little is known about the regulation mechanism of the polysaccharides on cholesterol metabolism and especially the causal relationship with gut microbiota regulation. This study will provide a theoretical basis for the cholesterol-lowering mechanism of S. latifolia polysaccharides and further development of functional foods. In this study, we investigated how the regulation mechanism of Sparassis latifolia polysaccharides affects intestinal cholesterol metabolism in high-fat and high-cholesterol diet-fed rats. Briefly, enzymatic colorimetric microplate assay was used to determine the concentration of faecal bile acid. Gas chromatography-mass spectrometry was used to detect the content of cholesterol and alcohol in faeces. Haematoxylin and eosin staining method was applied to observe the changes in the structure of the small intestine tissue. The related gene expressions in jejunum and ileum were detected by real-time fluorescent quantitative polymerase chain reaction. The related protein expressions in jejunum were studied by using Western blot. High-throughput sequencing was used to detect the intestinal flora changes of the caecal contents. Gas chromatography-mass spectrometry was applied to detect the concentration of short-chain fatty acids in the caecal content. The results showed that Sparassis latifolia polysaccharides could improve the intestinal morphological structure and physiological indices in rats fed high-fat and high-cholesterol diet. Moreover, it could improve intestinal cholesterol metabolism disorder induced by high-fat and high-cholesterol diets via the reduction of the expression of HMGCR, NPC1L1, ACAT2, MTP, ASBT and IBABP mRNA or protein, increasing ABCG8 mRNA expression. In addition, it could also increase the relative abundance of Bacteroides, Butyricicoccus, Parabacteroides, Parasutteerella and Alloprevotella and the short-chain fatty acid concentration, to comprehensively regulate the intestinal cholesterol metabolism. The metabolomics analysis found that Sparassis latifolia polysaccharides could affect lipid, carbohydrate and other related metabolites. Some biomarkers associated with cholesterol metabolism correlated significantly with the abundance of specific intestinal microbiota. These findings indicate that Sparassis latifolia polysaccharides could attenuate intestinal cholesterol metabolism disorder, correlating with modulating gut microbiota and improving host metabolism. They provide theoretical support for the development of Sparassis latifolia as a new food resource.

Mangrove (Rhizophora sp.) Fruit Extract Inhibits Tumor Growth Factor (TGF)-β1 Expression in High Cholesterol Diet-Fed Rats

Background: Atherosclerosis is a major finding in cardiovascular disease. One of the pro-fibrotic cytokines that play an important role in the atherosclerosis process is Tumor Growth Factor (TGF)-β1, where the presence of high TGF-β1 secretion due to hypercholesterolemia will trigger excessive collagen matrix formation. Objective: To analyze Rhizophora sp fruit extract effect on TGF-β1 expression in high cholesterol diet-fed rats. Material and Methods: Eighteen 10-week-old rats weighing 150-200 g were used in this study. These animals were grouped into 3 groups, each consisting of 6 rats. Group A (normal control) is a group of rats that received a normal diet. Group B (atherogenic control) received a diet that induces atherosclerosis (atherogenic diet). This diet contains 2% cholesterol, 5% goat fat, 0.2% cholic acid and standard diet up to 100%. Atherogenic diet was given for 3 days, and on the first day this group also received vitamin D3 700,000 IU/kg. Group C (treated), apart from receiving an atherogenic diet, was also given Rhizophora sp fruit extract 500 mg/kg body weight. The Rhizophora sp fruit extract effect on TGF-β1 expression was evaluated by immunohistochemical procedure. The area of ​​the expression is calculated using the ImageJ. Results: The results of this study indicate that the expression of TGF-β1 is higher in the group receiving the atherogenic diet than the normal control group (17.3 vs. 8.9; P=0.000). Rhizophora sp fruit extract reduced this expression remarkably (17.3 vs. 11.4; P=0.001). Conclusion: Rhizophora sp fruit extract inhibits the the expression of TGF-β1 in high cholesterol diet-fed rats.

Pineapple consumption reduced cardiac oxidative stress and inflammation in high cholesterol diet-fed rats

BackgroundHypercholesterolemia is a major risk factor for cardiovascular disease. It has been reported that pineapple contains healthy nutrients and phytochemicals associated with antioxidant and anti-inflammatory capacities. No investigation exists concerning the effect of pineapple consumption modulating hypercholesterolemia-induced cardiac damage in high-cholesterol diet (HCD)-fed rats. This study evaluated the effect of pineapple consumption on lipid-lowering, cardiac oxidative stress and inflammation in HCD-fed rats.MethodsMale Sprague–Dawley rats were fed with HCD, in the presence and absence of Pineapple (Ananas comosus L.) cv. Pattavia powder for 8 weeks. Then, serum lipid profiles, liver and renal function tests, cardiac oxidative stress and pro-inflammatory cytokines were determined.ResultsDaily pineapple consumption reduced weight gain, serum lipid profiles, atherogenic coefficient (AC), cardiac risk ratio (CRR), and liver enzyme activity, without causing renal dysfunction. Pineapple consumption also restores cardiac protein carbonyl (cPC) content, reduces cardiac malondialdehyde (MDA), cardiac pro-inflammation cytokine IL-6 and IL-1β levels.ConclusionPineapple possesses antioxidant and lipid-lowering properties and daily consumption alleviates hypercholesterolemia-induced cardiac lipid peroxidation and pro-inflammation elevation in an in vivo model. This study demonstrates that pineapple is a potential candidate for cardioprotection against hypercholesterolemia.

Sesamol supplementation alleviates nonalcoholic steatohepatitis and atherosclerosis in high-fat, high carbohydrate and high-cholesterol diet-fed rats.

Sesamol, a major ingredient in sesame seeds (Sesamum indicum L.) and its oil, is considered a powerful functional food ingredient. However, few studies have investigated its effects on high-fat, high carbohydrate and high-cholesterol (HF-HCC) diet-induced nonalcoholic steatohepatitis (NASH) complicated with atherosclerosis. The present study elucidates the protective effects of sesamol against NASH and atherosclerosis in HF-HCC diet-fed rats. Sprague-Dawley rats were supplemented with or without sesamol in drinking water (0.05 mg mL-1, 0.1 mg mL-1 and 0.2 mg mL-1) from the beginning to end. At the end of the experiment, sesamol supplementation suppressed HF-HCC diet-induced body weight gain and increased absolute liver and adipose tissue weights in rats. Serum biochemical analyses showed that sesamol supplementation improved HF-HCC diet-induced metabolism disorders and damaged vascular endothelial function. Histological examinations displayed that dietary sesamol not only alleviated hepatic balloon degeneration, steatosis, inflammation and fibrosis, but also mitigated lipid accumulation and fibrous elements in the aorta arch in HF-HCC diet-fed rats. In addition, sesamol supplementation inhibited hepatic NOD-like receptor protein 3 (NLRP3) expression and ERS-IRE1 signaling pathway activation. Moreover, sesamol treatment decreased uric acid levels both in serum and the liver by its effect on the inhibition of xanthine oxidase (XO) activity and/or its expression, which might be closely associated with the inhibitions of NLRP3 expression and ERS-IRE1 signaling pathway activation in HF-HCC diet-fed rats. These findings demonstrated that sesamol alleviated NASH and atherosclerosis in HF-HCC diet-fed rats, and may be a potent dietary supplement for protection against these diseases.

Effect of bile salt hydrolase-active Lactobacillus plantarum KLDS 1.0344 on cholesterol metabolism in rats fed a high-cholesterol diet

• L. plantarum KLDS 1.0344 was assayed for BSH activity and hypocholesterolemic effect. • L. plantarum KLDS 1.0344 improved lipid profiles and metabolic pathway in rats. • L. plantarum KLDS 1.0344 regulated hepatic CYP7A1 and HMGCR expression in rats. • L. plantarum KLDS 1.0344 modulated intestinal NPC1L1, ABCG5/8 and ABCA1 expression. The present study aimed to evaluate bile salt hydrolase (BSH) activity and hypocholesterolemic effect of Lactobacillus plantarum KLDS 1.0344. BSH activity of the strain KLDS 1.0344 varied with different bile salts. High-cholesterol diet-induced male Sprague-Dawley rats were simultaneously administrated with strain KLDS 1.0344 for 4 weeks. The strain KLDS 1.0344 significantly improved lipid profiles in serum and liver, and increased fecal total cholesterol and total bile acids levels in high-cholesterol diet-fed rats ( P < 0.05), and superior to L. rhamnosus GG. Moreover, expressions of genes related to cholesterol metabolism were regulated by the strain KLDS 1.0344, including down-regulation of hepatic HMGCR and FXR and intestinal NPC1L1, and up-regulation of intestinal LXRα, ABCG5, ABCG8 and ABCA1 and hepatic CYP7A1 ( P < 0.05). The hypocholeseterolemic effect of L. plantarum KLDS 1.0344 was modulated most likely by pathway of cholesterol absorption, synthesis, and catabolism, which might be partly due to its BSH activity.

Kidney protective effect of acalypha indica linn. root extract in high-fructose and high-cholesterol diet-fed rats

Diet high in fructose and cholesterol may lead to the development of diabetic nephropathy (DN). One of the first drugs of choice in DN treatment is captopril. Prolonged use of this drug may lead to some adverse effects and the treatment can be optimized through using other therapy options. Acalypha indica Linn. (AI) may be an alternative herbal therapy for DN. The objective of this research is to investigate the renoprotective effect of AI on DN. For seven weeks, thirty-two Sprague-Dawley rats were divided into groups receiving normal diet and high-fructose and high-cholesterol diet (HFCD). Then, the HFCD-fed rats were divided into four groups receiving different treatment: negative control, AI root extract (250 mg/kgBW), captopril (2.5 mg/kgBW), and combination of captopril and AI. Normal diet group was divided into AI and no treatment. After four weeks of treatment, the rats were terminated and serum urea and creatinine levels were measured. In the normal group, AI therapy decreased serum urea and creatinine levels. In the HFCD groups, AI and captopril monotherapy groups had increased serum urea levels, but lower compared to negative control. Meanwhile, serum creatinine levels decreased in both groups. However, these findings are not statistically significant. We found that combination therapy group had the highest increase in serum urea level, which was significantly different with captopril group (p=0.01). Serum creatinine level was also increased in this group. Our present study showed that AI tend to reduce serum urea and creatinine levels in normal diet group and inhibit the increase of serum urea and creatinine levels in rats fed with HFCD diet. Antagonistic interaction between captopril and AI might be present.

Reshaped fecal gut microbiota composition by the intake of high molecular weight persimmon tannin in normal and high-cholesterol diet-fed rats.

It has been proposed that the gut microbiome may be related to obesity, and diet-induced obesity may induce changes in the gut microbiota composition. Our previous studies suggested that persimmon tannin (PT), which is highly polymerized and non-absorbable in the intestine, showed anti-hyperlipidemic and cholesterol-lowering effects in animal models. Considering that the possible composition modification effects of PT on intestinal bacteria might contribute to its anti-hyperlipidemic and cholesterol-lowering effects in vivo, in this study, we determined whether the PT administration could modify the gut microbiota in both normal diet-fed and high-cholesterol (HC) diet-fed rats, and how PT altered the bacterial composition in both normal and HC fed rats. Sprague-Dawley rats were randomly divided into eight groups, and fed with either a normal or an HC diet supplemented with or without a low/medium/high dose of PT (50 (LPT), 100 (MPT), 200 (HPT) mg per kg body weight (BW) per day, respectively) for 4 weeks. On days 0, 7, 14, 21 and 28, feces were collected and prepared for the microbiota and physicochemical analysis. The results showed that LPT and MPT supplementation significantly altered the gut microbiota composition by increasing the Bacteroidetes/Proteobacteria ratio in both normal diet-fed and HC diet-fed rats. LPT also decreased the Firmicutes/Bacteroidetes ratio in normal diet-fed rats and MPT decreased the Firmicutes/Bacteroidetes ratio in HC diet-fed rats. Both LPT and MPT supplementation induced a significant alteration in specific bacterial species after 14 days of treatment. The relative abundance of Bifidobacterium sp. and Lactobacillus sp. was increased by both LPT and MPT treatment, and that of Escherichia coli and Enterococcus was reduced. Our data also indicate that there is a correlation between the changes in bacterial composition and the changes in short-chain fatty acid (SCFA) metabolism. However, HPT supplementation altered the gut microbiota at the phylum and species levels in an adverse way.

Selection of Cholesterol-Lowering Lactic Acid Bacteria and its Effects on Rats Fed with High-Cholesterol Diet.

High cholesterol level in serum is a major factor of influence for coronary heart disease. The cholesterol-lowering ability of lactic acid bacteria (LAB) without side effects makes them more and more attractive. Seventy-nine strains of LAB isolated from fermented food were screened in vitro for their ability to assimilate cholesterol. Then, ten strains which exhibited higher ability of cholesterol assimilation were investigated with the characteristics of acidic resistance, bile salt tolerance, and cell adhesion. According to the results, the best strain LP96 was picked out, and used to evaluate its effects on the high-cholesterol diet-fed rats. The results demonstrated that the levels of serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol, and liver TC and TG were reduced significantly in the groups that received the strain LP96 solution compared with the model group, and that the serum high-density lipoprotein cholesterol levels were increased without any significant difference. Furthermore, LP96 also showed good antioxidative activity and improvement of intestinal microbial balance in the rats. Thus, LP96 may be a promising probiotics with potential cholesterol-lowering ability.

Silkworm pupae oil exerts hypercholesterolemic and antioxidant effects in high-cholesterol diet-fed rats.

Silkworm pupae is a good resource of edible oil that is especially rich in unsaturated fatty acids and is considered to be an excellent dietary supplement for hyperlipidemia. Groups fed a high-cholesterol diet (HCD) with silkworm pupae oil (SPO) supplementation (1, 2, or 4 mL kg-1 day-1 ) orally had significantly lower levels of serum total cholesterol (P < 0.05) and low-density lipoprotein cholesterol (P < 0.05) compared to the HCD group. With regard to antioxidant parameters, except for levels of glutathione peroxidase (GSH-Px) in the liver, 2 and 4 mL kg-1 day-1 of SPO supplementation leaded to higher total antioxidant capacity (P < 0.05), superoxide dismutase (P < 0.05) and GSH-Px levels (P < 0.05), as well as lower malondialdehyde levels (P < 0.05), both in serum and liver compared to the HCD group. The results of the present study indicate that supplementation with SPO can improve lipid profiles and alleviate oxidative stress in high-cholesterol diet-fed rats. © 2016 Society of Chemical Industry.

Consumption of Japanese Yam Improves Lipid Metabolism in High-Cholesterol Diet-Fed Rats.

We investigated the effects of dietary Japanese yam (Dioscorea japonica Thunb.) on lipid metabolism. Male Wistar rats (6 wk old) were fed a high-cholesterol diet for 6 wk and then supplemented with 26% of Japanese yam or 0.5% of its constituent diosgenin for a further 4 wk of high-cholesterol feeding (C6-J4 and C6-D4 groups, respectively). In the C6-J4 group, body weight gains significantly decreased, but skeletal muscle fiber sizes in quadriceps significantly increased compared with the other groups. Furthermore, Japanese yam supplementation resulted in the reduction of triglyceride contents in their liver, quadriceps, and intra-abdominal visceral fat. Diosgenin supplementation resulted in an increase in the numbers of skeletal muscle fibers and decrease in the fat accumulations in liver and of the lipid contents in quadriceps. Although quadriceps cholesterol contents decreased concomitantly with increased serum HDL-cholesterol in both the groups, fecal bile acid, fecal cholesterol contents, and fecal weight were higher in the C6-J4 group than in the C6-D4 group. Meanwhile, we demonstrated that Japanese yam inhibited micellar cholesterol solubility in vitro in a concentration-dependent manner. These results suggest that Japanese yam is more effective than diosgenin in reducing fat accumulation and improving cholesterol metabolism during chronic consumption of a high-cholesterol diet.

The effect of hypercholesterolemia on carbachol-induced contractions of the detrusor smooth muscle in rats: increased role of L-type Ca2+ channels

To investigate a possible relation between hypercholesterolemia and detrusor smooth muscle function, we studied the contractile response to potassium challenge, carbachol (CCh), and the components of CCh-induced contractile mechanism in high-cholesterol diet-fed rats. Adult male Sprague-Dawley rats were fed with standard (control group, N = 17) or 4% cholesterol diet (hypercholesterolemia group (HC), N = 16) for 4weeks. Spontaneous contractions of detrusor muscle strips and their responses to potassium chloride (KCl) or cumulative dose-contraction curves to CCh were recorded. The effects of muscarinic receptor antagonists (methoctramin and/or 4-diphenylacetoxy-N-methylpiperidine), L-type Ca(+2) channel blocker (nifedipine), and/or rho-kinase inhibitor Y-27632 were investigated. Blood cholesterol level was increased in the HC group with no sign of atherosclerosis. The KCl-induced detrusor smooth muscle contractions were higher in HC, whereas spontaneous and CCh-induced responses were similar in both groups. Preincubation with receptor antagonist for M(3) but not for M(2) attenuated contraction significantly, shifting the dose-response curve to the right. This response was similar in both groups. Among two effector mechanisms of M(3)-mediated detrusor smooth muscle contraction, rho-kinase pathway was not affected by hypercholesterolemia, whereas blockade of L-type Ca(+2) channels potently reduced contractions. The results of this study point out a relation between hypercholesterolemia and contractile mechanism of detrusor smooth muscle likely to change urinary bladder function, via altering L-type Ca(+2) channels. Taken together with escalating incidence of hypercholesterolemia and lower urinary tract symptoms, it is a field which deserves to be investigated further.

Hypolipidemic Effect of Hexane Fraction from Rhizopus oryzae KSD-815

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcriptional factors that belong to nuclear receptors superfamily and are involved in the regulation of lipid metabolism. In the present study, anti-hyperlipidemic properties of n-hexane fraction (RoHe) from cultures of Rhizopus oryzae KSD-815 (R. oryzae KSD-815), which was isolated from Nuruk, were studied. n-Hexane fraction lowered plasma low-density lipoprotein levels and total cholesterol in high cholesterol diet-fed rats, and showed comparable potency compared with that of gemfibrozil. n-Hexane fraction was further fractionated with hexane in increasing EtOAc gradient using cell-based transactivation assay for PPAR-α. The active subfraction 4 (3 g) was applied to octadecyl silica gel column chromatography (φ 4×4.5 cm) and eluted with MeCN-H2O (3:1, 1.8 L) to provide 14 fractions (RoHe-4–1 to RoHe -4–14). Results showed the 2nd-subfractions, RoHe-4–2 and RoHe-4–6 could activate PPAR-α and PPAR-γ in a dose-dependent manner, and concentrations of fractions RoHe-4–2 and 4–6 to achieve half of GW409544 activity were 12.39 and 13.99 mg/mL, respectively. In functional assay using human hepatoma HepG2 cells, RoHe-4–2 and 4–6 significantly increased apolipoprotein A1 (ApoA1) production and showed more potent stimulation effects compared with fenofibrate. These results indicate that culture of R. oryzae KSD-815 may have a potent hypolipidemic activity through activation of PPAR-α and secretion of ApoA1.

PAR-5359, a well-balanced PPARα/γ dual agonist, exhibits equivalent antidiabetic and hypolipidemic activities in vitro and in vivo

Peroxisome proliferator-activated receptor (PPAR) α and γ are key regulators of lipid homeostasis and insulin resistance. In this study, we characterize the pharmacological profiles of PAR-5359, a dual agonist of PPARα and γ with well-balanced activities. In transient transactivation assay, PAR-5359 (3-(4-{2[4-(4chloro-phenyl)-3,6-dihydro-2H-pyridin-1-yl]-ethoxy}-phenyl)-(2 S)-ethoxy-propionic acid) significantly activated human and mouse PPARα and γ without activating PPARδ. In functional assays using human mesenchymal stem cells and human hepatoma HepG2 cells, PAR-5359 significantly induced adipocyte differentiation and human ApoA1 secretion, which coincided with its transactivation potencies against the corresponding human receptor subtypes. Interestingly, PAR-5359 showed equivalent potencies against the mouse receptor subtypes (α and γ; 2.84 μM and 3.02 μM, respectively), which suggests the possibility that PAR-5359 could simultaneously activates each subtype of receptors subtype in under physiological conditions. In an insulin-resistant ob/ob mouse model, PAR-5359 significantly reduced plasma insulin levels, improved insulin sensitivity (HOMA-IR), and completely normalized plasma glucose levels. In a severe diabetic db/db mouse model, PAR-5359 dose-dependently reduced the plasma levels of glucose (ED 30 = 0.07 mg/kg). Furthermore, it lowered plasma levels of non HDL- (ED 30 = 0.13 mg/kg) and total cholesterol (ED 30 = 0.03 mg/kg) in high cholesterol diet-fed rats for 4 days treatment. These results suggest that PAR-5359 has the balanced activities for PPARα and PPARγ in vivo as well as in vitro. And its balanced activities may render PAR-5359 as a pharmacological tool in elucidating the complex roles of PPARα/γ dual agonists.

IN VITRO AND IN VIVO EXPERIMENTAL EFFECT OF KOREAN RED GINSENG ON ERECTION

To elucidate the efficacy of Korean red ginseng (KRG) on penile erectile tissue and erectile response, the effect of ginseng was evaluated in both in vivo and in vitro experiments in laboratory animals. Fifty milligrams of KRG per kilogram in weight was mixed in physiologic saline and given by mouth for 3 months to both rabbits and rats. In vitro experiments were performed by observing the responses to acetylcholine (ACh) and KRG of strips of rabbit corpus cavernosum. In vivo experiments were performed by measuring the cavernosal pressures after the stimulation of pelvic nerves innervating rat corpus cavernosum. On rabbit cavernosal muscle strips precontracted with phenylephrine (5x10(-6) M), increasing concentrations of ACh (10(-7), 10(-6), 10(-5), 10(-4) M) showed dose dependent relaxation in the control group (10(-7) M: 15.32%, 10(-6) M: 35.44%, 10(-5) M: 59.45%, 10(-4) M: 76.54%)(p<0.01). After 3 months of KRG administration, the relaxation responses to ACh were increased significantly (10(-7) M: 34.18%, 10(-6) M: 56.35%, 10(-5) M: 75.33%, 10(-4) M: 89.86%)(p<0.01). Relaxation effects of KRG were significantly increased after administering KRG for 3 months, as evident by the intracavernousal pressure to electrostimulation being 107.52 cm. water in the control group and significantly increased to 138.34 cm. water after 3 months administration of KRG (p<0.01). We confirmed that the long-term administration of KRG enhances erectile capacity and that its action is mediated by endothelium-derived relaxing factor and peripheral neurophysiologic enhancement.

Long-term supplementation with a high cholesterol diet decreases the release of ATP from the caudal artery in aged rats

We examined the effects of high cholesterol (HC) diet on the spontaneous and noradrenaline-induced release of ATP, ADP, AMP and adenosine from caudal arteries and on the plasma levels of these adenyl purines in aged (100-week-old) Wistar rats. Administration of this diet for 12 weeks significantly reduced spontaneous and noradrenaline (1 μmol/L)-evoked release of adenyl purines from the caudal arteries relative to rats given the control diet. The unsaturation index of fatty acids (UI), which gives the average number of double bonds, of both the plasma and the caudal artery was significantly less in the HC diet-fed rats than in those fed the control diet. The HC diet for 12 weeks produced a slight but significant increase in systolic and diastolic blood pressure with advancing age. Regression analysis revealed a significant inverse relationship between the total amount of purines released from the artery and diastolic blood pressure and also a positive relationship between the total amount of purines released and the UI of the caudal artery. These results suggest that the high cholesterol diet decreased the release of adenyl purines from the caudal arteries of aged rats, leading to an increase in blood pressure.

Visualization of the transport pathways of low density lipoproteins across the endothelial cells in the branched regions of rat arteries

The transport pathways of low density lipoproteins (LDL) across the endothelium at the branched and unbranched regions of the artery were studied in high cholesterol diet-fed rats. Rat tissues were analyzed by perfusing in situ human or rat LDL labeled with colloidal gold or fluorescein 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI). Results indicated that more LDL-DiI accumulated in the branched regions than in the unbranched regions of the artery. LDL-gold conjugates were observed in the plasmalemmal vesicles, multivesicular bodies and in the subendothelial space in both the branched and the unbranched regions of the arteries. Quantitative study revealed that the volume densities of plasmalemmal vesicles which contained the LDL-gold particles in the branched regions of the aortic arch were significantly (P < 0.05) higher than the density value in the unbranched regions of the thoracic aorta, whereas there was no marked difference in the density value of multivesicular bodies between these two regions. The open junctions with gap widths of 30–450 nm between adjacent endothelial cells were only observed in the branched regions of the aortic arch, whereas no open junctions were present in the unbranched regions of the thoracic aorta. Moreover, the LDL-gold conjugates were present within most of these open junctions. In all specimens examined, no gold particles were found in the normal intercellular channels (i.e., 25 nm and less) of both regions. These results indicated that the major visible routes for transport of LDL across the endothelium in the branched regions of the arteries are open junctions as well as plasmalemmal vesicles. The region-associated permeability changes of LDL might account for the incidence of atherosclerosis in the branched areas of arteries.

Hypolipidemic effect of ethyl all-cis-5,8,11,14,17-eicosapentaenoate (EPA-E) in rats.

We examined the effect of ethyl all-cis-5,8,11,14,17-eicosapentaenoate (EPA-E) with high purity on circulating lipids in rats under several experimental conditions. In normolipidemic rats, EPA-E decreased the lipids in a dose-dependent manner. Clofibrate (100 mg/kg/day) was more potent in lowering the lipids than EPA-E (1000 mg/kg/day). In high cholesterol diet-fed rats, EPA-E (300 mg/kg/day) decreased the total cholesterol. However, clofibrate (300 mg/kg/day) had little effect on the total cholesterol. In hypertriglycemic rats induced by corn oil, EPA-E (300 mg/kg/day) or clofibrate (100 mg/kg/day) reduced the rise of triglycerides. EPA-E (300 mg/kg/day), clinofibrate (100 mg/kg/day) or clofibrate (300 mg/kg/day) caused a significant reduction in the lipids induced by the injection of Triton WR-1339. Furthermore, EPA-E (300 mg/kg/day) or clinofibrate (100 mg/kg/day) decreased the elevation of lipids produced by feeding the rats a casein-rich diet. These results show that EPA-E possesses potent inhibitory activity on experimental hyperlipidemia induced either exogenously or endogenously.

Hypolipidemic Effect of Ethyl all-cis-5,8,11,14,17-Icosapentaenoate (EPA-E) in Rats

We examined the effect of ethyl all-cis-5,8,11,14,17-icosapentaenoate (EPA-E) with high purity on circulating lipids in rats under several experimental conditions. In normolipidemic rats, EPA-E decreased the lipids in a dose-dependent manner. Clofibrate (100 mg/kg/day) was more potent in lowering the lipids than EPA-E (1000 mg/kg/day). In high cholesterol diet-fed rats, EPA-E (300 mg/kg/day) decreased the total cholesterol. However, clofibrate (300 mg/kg/day) had little effect on the total cholesterol. In hypertriglycemic rats induced by corn oil, EPA-E (300 mg/kg/day) or clofibrate (100 mg/kg/day) reduced the rise of triglycerides. EPA-E (300 mg/kg/day), clinofibrate (100 mg/kg/day) or clofibrate (300 mg/kg/day) caused a significant reduction in the lipids induced by the injection of Triton WR-1339. Furthermore, EPA-E (300 mg/kg/day) or clinofibrate (100 mg/kg/day) decreased the elevation of lipids produced by feeding the rats a casein-rich diet. These results show that EPA-E possesses potent inhibitory activity on experimental hyperlipidemia induced either exogenously or endogenously.

Serum HDL-cholesterol-increasing and fatty liver-improving actions of Panax ginseng in high cholesterol diet-fed rats with clinical effect on hyperlipidemia in man.

Effects of Panax ginseng on plasma and hepatic lipids were investigated in the high cholesterol diet-fed rats and in patients with hyperlipidemia. Oral administration of red ginseng powder reduced plasma total cholesterol, triglyceride and NEFA, while plasma HDL-cholesterol was elevated. Platelet adhesiveness was also reduced by ginseng administration. The plasma lipid-improving actions were also observed in patients with hyperlipidemia. Hepatic cholesterol and triglyceride contents were decreased and phospholipid increased by ginseng administration in the high cholesterol diet-fed rats, corresponding to improvement of the fatty liver.