Hypocholesterolemic effects of a flavonoid-rich extract of Hypericum perforatum L. in rats fed a cholesterol-rich diet

In a previous study, a flavonoid-rich extract of Hypericum perforatum L. (FEHP) was prepared and its antioxidant activity was determined by a series of models in vitro. In this study, the hypocholesterolemic effects of FEHP in rats fed a cholesterol-rich diet were tested. Forty Wistar rats fed a standard laboratory diet or a cholesterol-rich diet for 16 weeks were used. The serum lipid levels, as well as malondialdehyde (MDA) and activity of superoxide dismutase (SOD) and catalase (CAT) in serum and liver, were examined. Cholesterol-rich diet induced hypercholesterolemia was manifested in the elevation of serum lipid levels such as total cholesterol (TC), total triglycerides (TG), and low density lipoprotein cholesterol (LDL-C). Administration of middle-dose (75 mg/kg of BW/day) and high-dose (150 mg/kg of BW/day) FEHP significantly lowered the serum levels of TC, TG, and LDL-C, while increasing the serum level of high density lipoprotein cholesterol (HDL-C). Also, the content of MDA in serum and liver decreased significantly after oral administration of FEHP compared with those of rats fed a cholesterol-rich diet. In addition, FEHP increased the activity of SOD in serum and liver, but the activity of CAT was significantly elevated only in liver. These results suggested that the hypocholesterolemic effects of FEHP might be due to its abilities to lower serum TC, TG, and LDL-C levels as well as to slow the lipid peroxidation process and to enhance the antioxidant enzyme activity.     

Hypocholesterolemic effects of phenolic extracts and purified hydroxytyrosol recovered from olive mill wastewater in rats fed a cholesterol-rich diet

In our previous studies, a phenolic-rich extract of olive mill wastewaters (OMW) was prepared under optimal conditions, using a continuous countercurrent extraction unit, and hydroxytyrosol was purified from the obtained OMW extract. The antioxidant activity of OMW extract and hydroxytyrosol was determined by a series of models in vitro. In this study, the hypocholesterolemic effects of hydroxytyrosol and OMW extract in rats fed a cholesterol-rich diet were tested. Wistar rats, fed a standard laboratory diet or a cholesterol-rich diet for 16 weeks, were used. Serum lipid levels, as well as thiobarbituric acid reactive substances (TBARS) and superoxide dismutase and catalase activities in liver were examined. Cholesterol-rich diet-induced hypercholesterolemia was manifested in the elevation of serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). Administration of a low-dose (2.5 mg/kg of body weight) of hydroxytyrosol and a high-dose (10 mg/kg of body weight) of OMW extract significantly lowered the serum levels of TC and LDL-C while increasing the serum levels of high-density lipoprotein cholesterol (HDL-C). Furthermore, the TBARS contents in liver, heart, kidney, and aorta decreased significantly after oral administration of hydroxytyrosol and OMW extract as compared with those of rats fed a cholesterol-rich diet. In addition, OMW phenolics increased CAT and SOD activities in liver. These results suggested that the hypocholesterolemic effect of hydroxytyrosol and OMW extract might be due to their abilities to lower serum TC and LDL-C levels as well as slowing the lipid peroxidation process and enhancing antioxidant enzyme activity.     

Interactions of lipid metabolism and intestinal physiology with Tremella fuciformis Berk edible mushroom in rats fed a high-cholesterol diet with or without Nebacitin

Male adult Wistar rats were randomly divided into six groups in a 2 x 3 factorial design and fed diets containing different levels of Tremella fuciformis Berk (TFB) dietary fiber (0, 5, or 10%) and 1 g of cholesterol/100 g of diet with or without 0.7% Nebacitin for 4 weeks. TFB contained 6.2% soluble dietary fiber and 57.3% insoluble dietary fiber. The results showed that the serum LDL-cholesterol, hepatic total cholesterol, and triglyceride levels were significantly decreased (P < 0.05) in the rats fed diets with TFB content with or without Nebacitin. However, the serum total cholesterol, VLDL-cholesterol, and triglyceride levels were significantly decreased (P < 0.05) by Nebacitin. In feces, the presence of TFB (T5, T10, AT5, and AT10) in the diet significantly increased the total neutral steroids and bile acid excretions and undigested fiber concentrations as compared to T0 or AT0. In the small intestine, the Nebacitin diets increased the weights of both cecum and colon-rectum contents and lowered short-chain fatty acid (SCFA) concentrations of serum and cecal contents more than no Nebacitin diets did. It was suggested that the hypocholesterolemic effect of TFB dietary fiber may be mediated by the increase in fecal neutral steroids and total bile acids excretion and the increase in SCFA productions. The TFB edible mushroom dietary supplement altered the intestinal physiology of the rats.     

Isoflavone-free soy protein prepared by column chromatography reduces plasma cholesterol in rats

To know whether isoflavones are responsible for the hypocholesterolemic effect of soy protein, the effect on plasma cholesterol of isoflavone-free soy protein prepared by column chromatography was examined in rats. Five-week-old male Sprague-Dawley rats were fed cholesterol-enriched AIN-93G diets containing either 20% casein (CAS), 20% soy protein isolate (SPI), 20% isoflavone-free SPI (IF-SPI), 19.7% IF-SPI + 0.3% isoflavone-rich fraction (isoflavone concentrate, IC), or 20% CAS + 0.3% IC for 2 weeks. Plasma total cholesterol concentrations of rats fed SPI and IF-SPI were comparable and were significantly lower than that of rats fed CAS. The addition of IC to the CAS and IF-SPI did not influence plasma cholesterol level. Fecal steroid excretion of the three SPI groups was higher than that of the two CAS groups, whereas the addition of IC showed no effect. Thus, a significant fraction of the cholesterol-lowering effect of SPI in rats can be attributed to the protein content, but the isoflavones and other minor constituents may also play a role.     

Lipid-lowering and antioxidant effects of hydroxytyrosol and its triacetylated derivative recovered from olive tree leaves in cholesterol-fed rats

This study was designed to test the lipid-lowering and antioxidative activities of triacetylated hydroxytyrosol compared with its native compound, hydroxytyrosol, purified from olive tree leaves. Wistar rats fed a standard laboratory diet or a cholesterol-rich diet for 16 weeks were used. The serum lipid levels, the thiobarbituric acid-reactive substances (TBARS) level, as an indicator of lipid peroxidation, and the activity of superoxide dismutase (SOD) as well as that of catalase (CAT) were examined. The cholesterol-rich diet induced hypercholesterolemia that was manifested in the elevation of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C). Administration of hydroxytyrosol and triacetylated hydroxytyrosol (3 mg/kg of body weight) decreased the serum levels of TC, TG, and LDL-C significantly and increased the serum level of high-density lipoprotein cholesterol (HDL-C). Furthermore, the content of TBARS in liver, heart, kidney, and aorta decreased significantly when hydroxytyrosol and its triacetylated derivatives were orally administered to rats compared with those fed a cholesterol-rich diet. In addition, triacetylated hydroxytyrosol and hydroxytyrosol increased CAT and SOD activities in the liver. These results suggested that the hypolipidemic effect of triacetylated hydroxytyrosol and hydroxytyrosol might be due to their abilities to lower serum TC, TG, and LDL-C levels as well as to their antioxidant activities preventing the lipid peroxidation process.     

Effect of different olive oils on bile excretion in rats fed cholesterol-containing and cholesterol-free diets

The mechanism of the hypocholesterolemic effect of olive oils was investigated in 60 Wistar rats adapted to cholesterol-containing and cholesterol-free diets. The rats were divided in six diet groups of 10. The control group was fed only basal diet (BD), which contained wheat starch, casein, cellulose, and mineral and vitamin mixtures. For the five other groups, 10 g/100 g virgin (virgin group) or lampante (lampante group) olive oils, 1 g/100 g cholesterol (chol group), or both cholesterol and oil (chol/virgin and chol/lampante groups) were added to the BD. The experiment lasted 4 weeks. Before and after the experiment the bile was collected, and its flow and biliary bile acids and cholesterol concentrations were registered. Plasma lipids, liver cholesterol, plasma antioxidative potential (TRAP), fecal output, fecal bile acids, and fecal cholesterol excretion were measured. Groups did not differ before the experiment. After the experiment significant hypocholesterolemic and antioxidant effects were registered mainly in groups of rats fed cholesterol-containing diets supplemented with both olive oils (chol/virgin and chol/lampante). Significant increases in the bile flow and in the bile cholesterol and bile acids concentrations were observed (19.2% and 16.9%, 30.5% and 18.2%, and 79.6% and 45.6% for the chol/virgin and chol/lampante groups, respectively). Also, significant increases of the fecal output and fecal excretion of bile acids and cholesterol in rats of these groups were found. In conclusion, olive oils positively affect plasma lipid metabolism. The hypocholesterolemic effect of olive oils is genuine and is most likely mediated through increases in bile flow and biliary cholesterol and bile acids concentrations and subsequent increases in their fecal excretion.     

Dietary phosphatidylinositol prevents the development of nonalcoholic fatty liver disease in Zucker (fa/fa) rats

Recent studies have shown that dietary phospholipids, especially phosphatidylcholine and phosphatidylserine, have various beneficial biological effects. However, there are not enough data concerning the physiological function of dietary phosphatidylinositol (PI). The metabolic syndrome, a cluster of metabolic abnormalities such as dyslipidemia, diabetes mellitus, and hypertension, is a widespread and increasingly prevalent disease in industrialized countries. Nonalcoholic fatty liver disease (NAFLD) is often associated with features of the metabolic syndrome. NAFLD describes the spectrum of liver damage ranging from hepatic steatosis to steatohepatitis, liver fibrosis, and cirrhosis, and it is emerging as the most common liver disease worldwide. The present study examined whether dietary PI protects Zucker ( fa/ fa) rats from the metabolic syndrome. For 4 weeks, rats were fed semisynthetic diets containing either 7% soybean oil or 5% soybean oil plus 2% PI. Dietary PI markedly prevented the development of hepatomegaly and hepatic steatosis and lowered hepatic injury markers in serum. Additionally, hyperinsulinemia was relieved by the feeding of dietary PI in Zucker rats. These effects were attributable to an increase in serum adiponectin, enhancement of fatty acid beta-oxidation, and suppression of mRNA expression of inflammatory genes in the liver. This is the first report that dietary PI increases serum adiponectin level and prevents the development of NAFLD in a rat model of the metabolic syndrome.     

Effect of Bran Extract from Pigmented Rice Superjami on the Lipid and Glucose Metabolisms in a Postmenopause‐Like Model of Ovariectomized Rats

The effect of rice bran ethanolic extract from Superjami, a new blackish‐purple pigmented cultivar, on the lipid and glucose metabolisms in a postmenopausal‐like model of ovariectomized rats was investigated. Sprague‐Dawley female rats were subjected to either bilateral ovariectomy or a sham operation and randomly divided into three dietary groups (n = 6): sham‐operated fed with normal diet (SHAM), ovariectomized fed with normal diet (OVX‐AIN76), and ovariectomized fed with normal diet supplemented with Superjami bran extract (OVX‐SJ). The OVX‐AIN76 group showed significantly higher body weight, triglyceride, total cholesterol, blood glucose, and insulin than the SHAM group. On the other hand, supplementation of Superjami bran extract markedly reduced the body weight gain and improved the lipid and glucose profiles in ovariectomized rats through inhibition of hepatic lipogenesis and adipokine production and modulation of glucose‐regulating enzyme activities. These findings demonstrate that extracts from Superjami bran may be useful in the prevention and management of postmenopause‐induced hyperlipidemia and hyperglycemia.     

Hypolipidemic effect of soluble fiber isolated from seeds of Cassia tora Linn. in rats fed a high-cholesterol diet

Soluble fibers isolated from the seeds of Cassia tora Linn. (SFC) have attracted considerable attention in recent years due to their phenomenal rheological behavior. In this study were investigated the effects of SFC on lipid metabolism. Male Sprague-Dawley rats were fed one of three experimental diets, a normal diet, a high-cholesterol diet, or a high-cholesterol diet with 5% SFC, for 5 weeks. The serum concentration of total cholesterol in rats fed SFC was 27% lower (p < 0.05) compared to that of the control group, but the serum high-density lipoprotein cholesterol level was increased in the SFC group. Liver total cholesterol and triglyceride levels were reduced significantly (p < 0.05) in rats fed the SFC diet. In addition, fecal bile acid and lipid excretion was significantly increased by SFC consumption. These results indicate that SFC enhances fecal lipid excretion and may cause a reduction in serum and hepatic lipid concentrations in rats.     

Barley intake induces bile acid excretion by reduced expression of intestinal ASBT and NPC1L1 in C57BL/6J mice

To investigate the hypocholesterolemic mechanism of barley in vivo, six-week-old C57BL/6J mice were fed a high-fat diet (HFD) or high-fat diet containing barley (HFD-B) for seven weeks. Total and LDL cholesterol concentrations were significantly reduced in the HFD-B group while fecal cholesterol and bile acid was increased. Real-time PCR and immunoblot analysis revealed the induction of FXR expression, which in turn suppressed the expression of ASBT and NPC1L1 in the HFD-B group compared with the controls. In the liver, the expression of HMG-CoA reductase was significantly reduced while LDL receptor expression was unaltered in the HFD-B group compared with the controls. Our data suggest that the hypocholesterolemic effects of barley are primarily the result of reduced dietary cholesterol uptake and bile acid resorption. Reduced expression of intestinal ASBT and NPC1L1 may play a key role in the regulation of dietary cholesterol and bile acid metabolism in mice consuming a diet containing barley.     

Effect of long-term dietary supplementation of high-gamma-linolenic canola oil versus borage oil on growth, hematology, serum biochemistry, and N-6 fatty acid metabolism in rats

Dietary supplementation of a high-gamma-linolenic acid canola oil (HGCO) containing approximately 36% (w/w) of gamma-linolenic acid (GLA, 18:3n-6) from the seeds of a genetically transformed canola strain, was assessed for its long-term biological effects. Growing Sprague-Dawley rats (n = 30) were fed a purified AIN93G diet containing 5, 10, or 15% (w/w) of HGCO as the fat source. For comparison, a separate group of rats (n = 10) was given the diet containing 15% (w/w) of borage oil (BO), which contained 22% (w/w) of GLA. After 12 weeks of feeding, the growth, relative organ weights, hematology, and serum biochemistry were found to be similar among rats fed the 5, 10, and 15% HGCO diets. The GLA levels in plasma and liver phospholipids (PL) were also similar. However, the levels of GLA in peripheral tissues (muscle PL and adipose triacylglycerols) were significantly higher in rats fed the 10 and 15% HGCO diets than those fed the 5% HGCO diet. When the above biologic parameters were compared between the 15% HGCO and 15% BO dietary groups, there were no significant differences except for lower final body weights and higher tissue levels of GLA, dihomo-gamma-linolenic acid (20:3n-6) and arachidonic acid (20:4n-6) in the 15% HGCO dietary group as compared with the 15% BO dietary group. This is due to a higher GLA content and possibly a more favorable stereospecific distribution of GLA in HGCO. Overall, long-term (12-week) feeding with diets containing up to 15% HGCO resulted in no adverse effects on growth, organ weight, hematology and serum biochemistry as compared to the diet containing 15% BO, suggesting that HGCO may be a safe alternative source of GLA.     

Effect of dietary high-oleic-acid oils that are rich in antioxidants on microsomal lipid peroxidation in rats

In contrast to other metabolic functions, the role of dietary antioxidants and oil on microsomal lipid oxidation has been less extensively studied. This study examines ascorbate-Fe(2+) and NADPH-induced lipid peroxidation of hepatic microsomes of rats that were fed for three weeks high-oleic-acid oils (high-oleic sunflower oil, HOSO; olive oil, OO; or olive pomace oil, OPO) containing different concentrations of the antioxidants alpha-tocopherol, erythrodiol, and oleanolic acid. The fatty acid composition of hepatic microsomes of Wistar rats that were fed for three weeks with the above-mentioned oils had lower proportions of C16:0, C18:2n6, and C22:6n3 and higher proportions of C18:0 and C18:1n9 than rats fed the control diet. Light emission by hepatic microsomes increased, in the first 180 min, 2-fold after ascorbate-Fe(2+) addition compared with NADPH addition. Both increases were less pronounced in microsomes of OPO-fed rats and to a smaller extent in microsomes of OO-fed rats. Smaller increases in light emission were associated positively with higher concentrations of dietary alpha-tocopherol, erythrodiol, and oleanolic acid but were not associated with changes in fatty acid composition of hepatic microsomes. Addition of alpha-tocopherol, erythrodiol, or oleanolic acid decreased light emission of hepatic microsomes with a greater inhibition in microsomes of rats fed the control diet. Our data suggest that erythrodiol and oleanolic acids partly explain the protective effect of dietary OPO on microsomal lipid peroxidation in rats.     

Differential effects of powdered whole soy milk and its hydrolysate on antiobesity and antihyperlipidemic response to high-fat treatment in C57BL/6N mice

This study was performed to investigate the beneficial effects of powdered whole soy milk and its hydrolysate, compared to the processed soy milk and its hydrolysate, on the alteration of lipid metabolism and their possible effects on antiobesity in C57BL/6N mice fed a high-fat and -cholesterol diet. The mice were divided into a control group (20% casein) and four test groups for 5 weeks: soy milk (SM, 20% soy milk protein), soy milk hydrolysate (SMH, 20% hydrolyzed soy milk protein), whole soy milk (WSM, 20% whole soy milk protein), and whole soy milk hydrolysate (WSMH, 20% whole soy milk hydrolysate protein). The body weight and adipose tissue weights were significantly lowered in SMH, WSM, and WSMH groups compared to the control group despite providing an isoenergetic diet. Plasma lipid concentrations and hepatic fatty acid synthase (FAS) and glucose-6-phosphate dehydrogenase (G6PD) activities were significantly lowered in all soy milk groups; however, the hepatic lipid contents and malic enzyme (ME) activity were only significantly lowered in the WSM and WSMH groups, compared to the control group. Data suggest that powdered WSM or WSMH appears to be more beneficial than SM or SMH in overall antiobesity and antihyperlipidemic properties following in the order WSMH/WSM, SMH, SM, and casein.     

Antioxidative functions of natto,a kind of fermented soybeans: effect on LDL oxidation and lipid metabolism in cholesterol-fed rats

Natto water-soluble fractions, low-molecular-weight viscous substance, and soybean water extract, which had an inhibitory effect on the oxidation of low-density lipoproteins (LDL) in vitro, were fed to rats for 3 weeks. These fractions had no influence on the growth of rats, which were fed a basal diet containing 1% cholesterol, but lowered plasma triglyceride and total cholesterol. Inhibition of copper-oxidation of plasma and LDL ex vivo, and a reduction in lipid peroxidation in liver and aorta in vivo, were also observed. The antioxidant enzymes were not induced in rats fed natto fraction diets. These results demonstrate that ingestion of the natto fractions led to inhibition of LDL oxidation, and that the fractions perform direct antioxidant action in the body. It is suggested that natto fractions might help to prevent arteriosclerosis, as they appear to reduce lipid peroxidation and improve lipid metabolism.     

Antioxidative activity of green tea polyphenol in cholesterol-fed rats

This study investigated the effects of green tea polyphenol on the serum antioxidative activity and cholesterol levels of cholesterol-fed rats and compared them with those of probucol, an antioxidant hypocholesterolemic agent. To evaluate the antioxidative activity, the susceptibility to oxidative modification of low-density lipoprotein (LDL) isolated from the serum of cholesterol-fed rats was measured, as was the serum antioxidative activity using the spontaneous autoxidation system of brain homogenate. Administration of green tea polyphenol effectively inhibited LDL oxidation and elevated serum antioxidative activity to the same degree as probucol. However, higher amounts of polyphenol than probucol needed to be administered to reduce the total, free, and LDL cholesterol levels. Furthermore, green tea polyphenol increased the levels of high-density lipoprotein (HDL) cholesterol, leading to dose-dependent improvement of the atherogenic index, an effect that was not seen with probucol. Thus, green tea polyphenol may exert an antiatherosclerotic action by virtue of its antioxidant properties and by increasing HDL cholesterol levels.     

Nutritional quality of sesame seed protein fraction extracted with isopropanol

The nutritional effect of diet containing decorticated sesame seed extracted with isopropanol (DSS-Iso) was evaluated on growth performance, food efficiency ratio, plasma and tissue lipid profile, plasma protein content, and erythrocyte membrane lipid profile of rats on a comparative basis with diets containing casein (control), soybean meal, and decorticated sesame seed extracted with hexane (DSS-Hex). Rats fed a DSS-Iso-based diet showed body weight gain and food efficiency ratio similar to those of the control groups fed diets prepared with casein, soybean meal, and DSS-Hex. However, dietary proteins exerted a separate effect on plasma lipid concentrations of the rats. Rats fed a DSS-Iso-based diet showed significant decreases in plasma total cholesterol (p < 0.01), triglyceride (p < 0.01), and VLDL+LDL cholesterol (p < 0.01) concentrations in comparison to the rats fed diet containing casein. No significant differences in plasma lipid concentrations were observed for the rats fed diets prepared with soybean meal, DSS-Hex, and DSS-Iso. Rats fed the different dietary proteins did not show much variation in plasma proteins, liver lipids, and erythrocyte membrane lipid concentrations, which suggests that DSS-Iso could be a suitable edible protein like casein or soybean meal.     

Preventive effects of taurine on development of hepatic steatosis induced by a high-fat/cholesterol dietary habit

Nonalcoholic fatty liver (NAFL) is also called hepatic steatosis and has become an emergent liver disease in developed and developing nations. This study was to exam the preventive effects of taurine (Tau) on the development of hepatic steatosis via a hamster model. Although hepatic steatosis of hamsters was induced by feeding a high-fat/cholesterol diet, drinking water containing 0.35 and 0.7% Tau improved (p < 0.05) the serum lipid profile. Meanwhile, the smaller (p < 0.05) liver sizes and lower (p < 0.05) hepatic lipids in high-fat/cholesterol dietary hamsters drinking Tau may be partially due to higher (p < 0.05) fecal cholesterol, triacylglycerol, and bile acid outputs. In the regulation of lipid homeostasis, drinking a Tau solution upregulated (p < 0.05) low-density lipoprotein receptor and CYP7A1 gene expressions in high-fat/cholesterol dietary hamsters, which result in increased fecal cholesterol and bile acid outputs. Drinking a Tau solution also upregulated (p < 0.05) peroxisome proliferator-activated receptor-α (PPAR-α) and uncoupling protein 2 (UPC2) gene expressions in high-fat/cholesterol dietary hamsters, thus increasing energy expenditure. Besides, Tau also enhanced (p < 0.05) liver antioxidant capacities (GSH, TEAC, SOD, and CAT) and decreased (p < 0.05) lipid peroxidation (MDA), which alleviated liver damage in the high-fat/cholesterol dietary hamsters. Therefore, Tau shows preventive effects on the development of hepatic steatosis induced by a high-fat/cholesterol dietary habit.     

Isoflavone glycitein diminished plasma cholesterol in female golden Syrian hamsters

The soybean isoflavones, daidzein, genistein, and glycitein, were hypothesized to act as cholesterol-lowering components, separate from soy protein. Pure synthetic daidzein, genistein, or glycitein (0.9 mmol/kg diet) or a casein-based control diet was fed to groups of 10 female Golden Syrian hamsters for 4 weeks. Hamsters fed glycitein had significantly lower plasma total (by 15%) and non-HDL (by 24%) cholesterol compared with those fed casein (P<0.05). Daidzein and genistein's effects on these lipids did not differ from the effects of either casein or glycitein. Plasma HDL cholesterol and triglyceride concentrations were not significantly affected by dietary treatments. The percentage of urinary recovery of the ingested dose of each isoflavone was glycitein>daidzein>genistein (33.2%, 4.6%, 2.2%, respectively), with the apparent absorption of glycitein significantly greater than that of the other isoflavones. These data suggest that glycitein's greater cholesterol-lowering effect was due to its greater bioavailability, as reflected in its urinary recovery compared with that of the other isoflavones.