Hypolipidemic and body fat-lowering effects of Fatclean in rats fed a high-fat diet.

The body fat-lowering and hypolipidemic effects of a Fatclean formula were examined in Sprague-Dawley rats fed a high-fat diet. Animals were given a normal control (NC) diet or a 15% high-fat (HF) diet with or without Fatclean (5%, wt/wt) supplement for 6 weeks. Fatclean formula contained phenolic compounds (14.3mg/g) and other functional compounds. Fatclean formula significantly lowered final body weights and visceral fat-pads weights, plasma total cholesterol (TC) and triglyceride (TG) concentrations, hepatic cholesterol and triglyceride levels, and hepatic hydroxyl-3-methylglutaryl-coenzyme A reductase (HMG-CoA) and acyl-coenzyme A:cholesterol acyltransferase (ACAT) activities compared to the HF group. Furthermore, adipocytic lipoprotein lipase (LPL) activity was also significantly elevated in the Fatclean group than in the HF group. The high-density lipoprotein-cholesterol/total-cholesterol (HDL-C/Total-C) ratio and atherogenic index (AI) were significantly improved in the Fatclean group than in the HF group. The accumulation of hepatic lipid droplets and the epididymal white adipocyte size were diminished in the Fatclean group than in the HF group. Accordingly, Fatclean seemed to be beneficial for the reduction of body weight and/or body fat and its hyperlipidemic property was highly active for enhancing the plasma lipids profile.

Anti-obesity and hypolipidemic effects of a proprietary herb and fiber combination (S&S PWH) in rats fed high-fat diets.

The objective of this study was to investigate the effects of S&S PWH, a proprietary herb and fiber combination (Bionutrigen Inc., Daejon, Republic of Korea), on body weight and lipid metabolism in rats fed with a high-fat diet. Three groups of male Sprague-Dawley rats were fed different diets for a 6-week period: normal control diet containing 5% (wt/wt) corn oil (NC group), high-fat diet containing 10% (wt/wt) lard plus 5% (wt/wt) corn oil (HF group), and high-fat diet supplemented with powdered 5% (wt/wt) S&S PWH (S&S PWH group). The body weights and relative weights of the epididymal and perirenal white adipose tissue were significantly lower in the S&S PWH group than in the HF group. S&S PWH supplementation significantly lowered plasma total cholesterol and triglyceride concentrations, whereas it elevated the ratio of high density lipoprotein-cholesterol/total-cholesterol and improved the atherogenic index. The accumulation of hepatic lipid droplets and the epididymal white adipocyte size were less in the S&S PWH group than in the HF group. Hepatic hydroxyl-3-methylglutaryl-coenzyme A reductase and acyl-coenzyme A:cholesterol acyltransferase activities were significantly lower, while adipocyte lipoprotein lipase activity was significantly higher, in the S&S PWH group than in the HF group. These beneficial effects may be due to the combined properties of the phenolic compounds present in high concentrations (1.89 g/100 g) in the S&S PWH. In conclusion, these results suggest that S&S PWH can be considered as an anti-obesity functional formula that is effective for suppressing body weight gain and enhancing lipid profile.

Hypocholesterolemic and antioxidant properties of 3-(4-hydroxyl)propanoic acid derivatives in high-cholesterol fed rats.

The purpose of the present study was to evaluate the in vivo efficacy of two cinnamic acid synthetic derivatives (allyl 3-[4-hydroxyphenyl]propanoate; HPP304, 1-naphthyl-methyl 3-[4-hydroxyphenyl]propanoate; HPP305) in high-cholesterol fed rats and compare their actions to that of cinnamic acid. Cinnamic acid and its synthetic derivatives were supplemented with a high-cholesterol diet for 42 days at a dose of 0.135 mmol/100g of diet. The supplementation of HPP304 and HPP305 significantly lowered cholesterol and triglyceride levels in the plasma and liver with a simultaneous increase in the HDL-cholesterol concentration, whereas cinnamic acid only lowered the plasma cholesterol concentration. Cinnamic acid lowered hepatic HMG-CoA reductase activity in high-cholesterol fed rats, however, its synthetic derivatives (HPP304 and HPP305) did not affect HMG-CoA reductase activity compared to the control group. Instead, the HPP304 and HPP305 supplements significantly lowered hepatic acyl coenzyme A:cholesterol acyltransferase activity and increased the fecal bile acid. The SOD activity of the erythrocytes and liver was not different between the groups, however, the activities of CAT and GSH-Px, and the level of GSH in the erythrocytes were significantly higher in the HPP304 and HPP305 groups than in the control group. On the other hand, the activities of CAT and GSH-Px, and the level of malondialdehyde in the liver were significantly lower in the HPP304 and HPP305 groups. The antioxidant activities of these cinnamic acid synthetic derivatives were similar to the cinnamic acid in the high-cholesterol fed rats. In addition, HPP304 and HPP305 lowered amniotransferase activity in the plasma. These results suggest that two cinnamic acid synthetic derivatives (HPP304 and HPP305) exert lipid-lowering action and antioxidant properties without hepatotoxicity in high-cholesterol fed rats.

Anticholesterolemic effect of 3,4-di(OH)-phenylpropionic amides in high-cholesterol fed rats.

Two amide synthetic derivatives of 3,4-di(OH)-hydrocinnamate (HC), 3,4-dihydroxyphenylpropionic (l-serine methyl ester) amide (E030) and 3,4-dihydroxyphenylpropionic (l-aspartic acid) amide (E076), were investigated to compare their lipid-lowering efficacy with HC. Male rats were fed a 1 g/100 g high-cholesterol diet for 6 weeks with supplements of either clofibrate (0.02%, w/w), HC (0.025%, w/w), E030 (0.039%, w/w) or E076 (0.041%, w/w). The clofibrate supplement was used as a positive control for the lipid-lowering efficacy. The food intakes and body weight gains were not significantly different among the groups. The plasma and hepatic cholesterol and triglyceride levels were lower in clofibrate, HC, E030, and E076-supplemented groups compared to the control group. The supplementation of HC and its amide derivatives was as effective as clofibrate in increasing the ratio of HDL-cholesterol to total plasma cholesterol and reducing the atherogenic index (AI). The hepatic cholesterol level in the HC and E076 groups was significantly lower than that in the clofibrate group. The hepatic 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA reductase) and acyl-CoA:cholesterol acyltransferase (ACAT) activities were significantly lower in the all test groups than in the control group. The excretion of neutral sterol was significantly higher in the HC, E030, and E076-supplemented groups compared to the control group. The plasma AST and ALT activities, indirect indexes of hepatic toxicity, were significantly lower in the HC, E030, and E076-supplemented groups than in the control group. Accordingly, the current results suggest that E030 and E076, two amide synthetic derivatives of HC, are effective in lowering lipid activity.

Lipid-lowering efficacy of 3,4-di(OH)-phenylpropionic L-leucine in high-cholesterol fed rats.

A preliminary study revealed that 3,4-di(OH)-hydrocinnamate (HC), a polyphenolic compound, lowered the plasma lipids in high-cholesterol fed rats. Accordingly, this study was designed to test the lipid-lowering efficacy of a synthetic derivative, 3,4-di(OH)-phenylpropionic (L-leucine) amide (PPLA), in rats fed a high-cholesterol (1%, wt/wt) diet. As such, HC or PPLA was given as supplement to a high-cholesterol diet for 6 weeks at a dose of 0.137 mmol/100 g diet. The supplementation of HC and PPLA significantly lowered the plasma and hepatic cholesterol and triglyceride levels compared to the control group. The activities of hepatic HMG-CoA reductase (164 +/- 9.12 and 124.74 +/- 17.09 pmol/min/mg protein vs. 245.41 +/- 13.01 pmol/min/mg protein, p < 0.05) and ACAT (411.49 +/- 11.48 and 334.35 +/- 17.68 pmol/min/mg protein vs. 490.41 +/- 16.69 pmol/min/mg protein, p < 0.05) were significantly lower in the HC- and PPLA-supplemented groups than in the control group. However, PPLA was more effective in inhibiting the enzyme activities than HC. The excretion of neutral sterol was significantly higher in HC- and PPLA-supplemented groups than in the control group. Therefore, these results indicate that PPLA, a leucine-attached version of HC, exhibited a similar significant hypocholesterolemic effect to HC in rats fed a high-cholesterol diet.

Effect of 3,4-di(OH)-cinnamate synthetic derivative on plasma and hepatic cholesterol level and antioxidant enzyme activities in high cholesterol-fed rats.

The effect of 3,4-di(OH)-phenylpropionic acid (L-phenylalanine methyl ester) amide (SL-1063), a synthetic derivative of 3,4-di(OH)-cinnamate, on the cholesterol metabolism and antioxidant enzyme system was examined in rats. Diets that included either SL-1063 (0.046%, w/w) or lovastatin (0.02%, w/w) as a supplement, plus 1 g cholesterol/100 g diet were fed to rats ad libitum for 5 weeks. The total plasma cholesterol and triglyceride levels were significantly lowered by the SL-1063 supplement compared to the control group. Meanwhile, the levels of plasma HDL-cholesterol and ratio of HDL-cholesterol/total cholesterol (%) were significantly higher in the SL-1063 group than in the control group. However, the lovastatin supplement did not affect the plasma lipid level. The hepatic cholesterol level and 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase activity were significantly lowered in the lovastatin group compared to the SL-1063 group; however, the hepatic triglyceride level did not differ among the groups. The activity of hepatic acyl CoA: cholesterol acyltransferase (ACAT), the enzyme that catalyzes hepatic cholesterol esterification, was significantly lower in the lovastatin and SL-1063 groups than in the control group. Furthermore, the SL-1063 supplement elevated the excretion of fecal sterols. As regards the hepatic antioxidant enzyme system, the superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione reductase (GR) activities were all significantly higher in the SL-1063 group compared to the control group, whereas only the GR activity was significantly increased by the lovastatin supplement. No marked difference in the GSH levels and glucose-6-phosphate dehydrogenase (G6PD) activities was observed among the groups. The levels of plasma and hepatic thiobarbituric acid reactive substances (TBARS) were lowered by the SL-1063 supplement compared to the control group. Accordingly, the current results suggest that SL-1063, a synthetic derivative of 3,4-di(OH)-cinnamate, is effective in lowering the plasma lipids and improving the antioxidant enzyme system.

Evaluation of hesperetin 7-O-lauryl ether as lipid-lowering agent in high-cholesterol-fed rats.

The lipid-lowering efficacy of hesperetin was revealed in preliminary studies on experimental animals. As such, the current study compared the effect of hesperetin 7-O-lauryl ether, with that of hesperetin and lovastatin on the lipid profile and cholesterol-regulating mechanism in high-cholesterol-fed rats. Male rats were fed a high-cholesterol diet (1%, wt/wt) or high-cholesterol diet supplemented with lovastatin (1, 0.02%, wt/wt), hesperetin (2, 0.02%, wt/wt), or hesperetin 7-O-lauryl ether (3, 0.031%, wt/wt) for six weeks. The supplemental amount of 3 was 0.066mmol/100g diet as an equivalent to the supplemental amount of 2. The plasma total cholesterol and triglyceride levels were significantly lowered by the 2 and 3 supplements compared with the control or 1-supplemented group. The hepatic HMG-CoA reductase activities were also significantly lower in all the supplemented groups compared with the control group, and the hepatic ACAT activity was significantly lower in the 2- and 3-supplemented groups. The supplementation of 3 resulted in a higher excretion of total neutral sterol and total fecal sterol compared with the control or 1-supplemented group. Accordingly, overall, compound 3, exhibited a more potent plasma lipid-lowering effect than compound 1 based on inhibiting cholesterol biosynthesis and esterification, while also increasing the fecal sterol excretion.

Saucernetin-7 and saucernetin-8 isolated from Saururus chinensis inhibit the LPS-induced production of nitric oxide and prostaglandin E2 in macrophage RAW264.7 cells.

In the present study, we demonstrate that saucernetin-8 ( 1) and saucernetin-7 ( 2), isolated from the underground parts of Saururus chinensis (Saururaceae), exerted potent inhibitory effects on LPS-induced nitric oxide (NO) and prostaglandin E (2) (PGE (2)) production in RAW 264.7 cells. Both compounds 1 and 2, known as dineolignans, also suppressed the expression of iNOS and COX-2 protein in a dose-dependent manner. Thus, this study suggests that compounds 1 and 2-mediated inhibition of iNOS and COX-2 expression may be one of the mechanisms responsible for the anti-inflammatory effects of the underground parts of Saururus chinensis.

Two cinnamate derivatives produce similar alteration in mRNA expression and activity of antioxidant enzymes in rats.

Cinnamate is a widespread secondary metabolite of phenolic compound synthesized by plants for defensive purposes. The current study was designed to investigate the effect of two structurally related cinnamate derivatives, 4-hydroxycinnamate and 3-(4-hydroxyphenyl)propionic acid (HPP), on the mRNA expression and activity of antioxidant enzymes in high-cholesterol-fed rats. Male rats were fed a 1 g/100 g high-cholesterol diet with supplements of either 4-hydroxycinnamate or HPP (0.135 mmol/100 g diet) for 6 weeks. The plasma paraoxonase activity was found to be higher in the cinnamate-derivative-supplemented groups than in the control group. The erythrocyte superoxide dismutase (SOD) and catalase (CAT) activities, plus glutathione (GSH) level, were all significantly higher in the 4-hydroxycinnamate- and HPP-supplemented groups than in the control group. However, both 4-hydroxycinnamate and HPP supplementation significantly lowered the hepatic activities and mRNA expression of CAT and glutathione peroxidase (GSH-Px) compared to the control group. The hepatic mRNA expression and activity of SOD did not differ between the groups. The hepatic thiobarbituric acid reactive substances (TBARS) level was significantly lowered by the 4-hydroxycinnamate and HPP supplementation. Accordingly, these results indicate that supplementation by 4-hydroxycinnamate and HPP would seem to enhance the antioxidative defense of erythrocyte. Both HPP and 4-hydroxycinnamate would appear to be beneficial in improving the function of antioxidative enzymes on a molecular level in high-cholesterol-fed rats.

Naringenin derivatives as anti-atherogenic agents.

Two classes of naringenin derivatives were evaluated for anti-atherogenic activity. Naringenin 7-O-oleic ester (2) and naringenin 7-O-cetyl ether (3) inhibited the formation of aortic atherosclerotic lesions in high cholesterol-fed rabbits.

Hematein inhibits atherosclerosis by inhibition of reactive oxygen generation and NF-kappaB-dependent inflammatory mediators in hyperlipidemic mice.

Hematein, a natural compound, is a known anti-inflammatory and antiatherogenic agent in the rabbit model. The authors investigated the effects of this compound on atherogenesis and possible mechanisms of the actions in the hyperlipidemic mice. Low-density lipoprotein receptor-deficient (Ldlr-/-) mice fed a high-cholesterol diet alone for 8 weeks developed the fatty streak lesion in the aortic sinus, whereas this lesion was significantly reduced by hematein treatment without a change in plasma lipid levels compared with control mice. Hematein treatment reduced plasma levels of lipid peroxide and superoxide generation in LPS-stimulated peritoneal macrophage. Hematein treatment inhibited NF-kappaB-DNA binding activity in peritoneal macrophages from Ldlr-/- mice and the activation of NF-kappaB in RAW264.7 macrophages. This compound suppressed plasma nitrite/nitrate levels in Ldlr-/- mice and NO production and iNOS expression in LPS+IFNgamma-stimulated peritoneal macrophages. Hematein treatment also suppressed the activity of iNOS promoters in RAW264.7 macrophages, and reduced the plasma levels of TNF-alpha and IL-1beta and the production of these cytokines in LPS+IFNgamma-stimulated peritoneal macrophages. These results suggest that hematein inhibits atherosclerotic lesion formation, possibly by reducing proinflammatory mediators through a decrease in reactive oxygen species generation and NF-kappaB activation.

Hypocholesterolemic activity of hesperetin derivatives.

Hesperetin ester and ether derivatives possessing a long alkyl chain were synthesized for examining their hypocholesterolemic activities in high cholesterol-fed mice. Hesperetin 7-O-lauryl ether (4b) and hesperetin 7-O-oleyl ether (4e) exhibited strong cholesterol-lowering effects.

Anti-atherogenic effects of 3,4-Dihydroxy hydrocinnamides.

3,4-Dihydroxy hydrocinnamides 2 and 3 exhibited the anti-atherogenic activities by inhibiting the formation of aortic fatty streak in high cholesterol-fed rabbits.

4-hydroxycinnamate lowers plasma and hepatic lipids without changing antioxidant enzyme activities.

BACKGROUND/AIMS: The purpose of this study was to investigate the influence of 4-hydroxycinnamate (4-(OH)-C) supplement on the lipid metabolism and antioxidant system of rats fed a high-cholesterol diet. METHODS: Three groups of rats were given a diet containing 1 g cholesterol/kg for 6 weeks. The control group only received a high cholesterol diet, whereas the other two groups received a diet including lovastatin or 4-(OH)-C (0.1 g/100 g). RESULTS: The plasma total cholesterol concentration was significantly lowered by the 4-(OH)-C supplement, whereas the HDL-cholesterol level was higher in this group. The 4-(OH)-C supplement significantly lowered the hepatic cholesterol and triglycerides levels, respectively. Accumulation of hepatic lipid droplet was the highest in control group; however, it was decreased by supplementation of the 4-(OH)-C and the lovastatin. The hepatic HMG-CoA reductase activities were not significantly different between the groups, whereas the ACAT activity was significantly lowered in the lovastatin group. The 4-(OH)-C significantly lowered the hepatic TBARS content. And it did not alter the neutral sterol and total fecal sterol, however, the fecal acidic sterol was higher in the lovastatin and the 4-(OH)-C groups than in the control group. CONCLUSION: These results indicate that 4-(OH)-C was effective in lowering the plasma cholesterol and hepatic lipids.

Quercetin suppresses proinflammatory cytokines production through MAP kinases andNF-kappaB pathway in lipopolysaccharide-stimulated macrophage.

Quercetin is a flavonoid molecule ubiquitous in nature and functions as an anti-oxidant and anti-inflammatory agent with little toxicity in vivo and in vitro. Dose- and time-dependent effect of quercetin has been investigated on proinflammatory cytokine expression and NO production, focusing on its effects on the MAP kinases and the NF-kappaB signal transduction pathways in LPS-stimulated RAW 264.7 cells by using RT-PCR and immunoblotting. Quercetin strongly reduced activation of phosphorylated ERK kinase and p38 MAP kinase but not JNK MAP kinase by LPS treatment. In addition, quercetin treatment inhibited NF-kappaB activation through stabilization of the NF-kappaB/IkappaB complex and IkappaB degradation and proinflammatory cytokines and NO/iNOS expression. Quercetin may exert its anti-inflammatory and immunomodulatory properties in the effect molecules such as proinflammatory cytokines and NO/iNOS by suppressing the activation of ERK and p38 MAP kinase, and NF-kappaB/IkappaB signal transduction pathways.

Naringenin 7-O-cetyl ether as inhibitor of HMG-CoA reductase and modulator of plasma and hepatic lipids in high cholesterol-fed rats.

Numerous studies in vitro have shown a close relationship between the chemical structure and biologic activity of flavonoids, whereby their basic structure is modified to increase or decrease their biologic activity. The effects of naringenin (1) and its synthetic derivative, naringenin 7-O-cetyl ether (2), on the lipid profile, the cholesterol-regulating enzyme activity and the excretion of sterol were compared in rats fed a high-cholesterol (1% wt/wt) diet. Either 1 or 2 was supplemented with a high-cholesterol diet for 6 weeks at a dose of 0.073 mmol/100g diet. The supplementation of 1 or 2 significantly lowered the levels (mean+/-SE) of the plasma total cholesterol (4.93+/-0.19 and 4.75+/-0.16 mmol/L vs 5.87+/-0.36 mmol/L, p<0.05) and hepatic triglyceride (0.12+/-0.01 and 0.11+/-0.01 mmol/g vs 0.18+/-0.01 mmol/g, p<0.05) and cholesterol (0.23+/-0.01 and 0.21+/-0.01 mmol/g vs 0.31+/-0.01 mmol/g, p<0.05) compared to those of the control. The compound 1 or 2 supplementation appeared to decrease the excretion of neutral sterols. The plasma HDL-cholesterol concentration and ratio of HDL to total cholesterol were significantly higher in 1 and 2 groups than in control group. Although the biological effect of 2 on inhibiting hepatic HMG-CoA reductase and ACAT activities was only significant compared to the control group, both compounds exhibited a significant hypocholesterolemic effect in rats fed a high-cholesterol diet. The results suggest that cholesterol biosynthesis and esterification were concomitantly reduced by 2, as indicated by the decreased HMG-CoA reductase and ACAT activities.

In vivo effects of CETP inhibitory peptides in hypercholesterolemic rabbit and cholesteryl ester transfer protein-transgenic mice.

We previously reported that cholesteryl ester transfer protein (CETP) inhibitory peptides (designated P28 and P10) have anti-atherogenic effects in hypercholesterolemic rabbits (Biochim. Biophys. Acta (1998) 1391, 133-144). To further investigate those effects, we studied rabbit plasma that was collected after 30 h of a P28 or P10 injection. We found that there is a strong correlation between the in vivo CETP inhibition effects and alterations of lipoprotein particle size distribution in rabbit plasma, as determined on an agarose gel electrophoresis and gel filtration column chromatography. In vivo effects of the peptide were observed again in C57BL/6 mice that expressed simian CETP. The P28 or P10 peptide (7 microg/g of body weight) that was dissolved in saline was injected subcutaneously into the mice. The P28 injection caused the partial inhibition of plasma CETP activity up to 50%, decreasing the total plasma cholesterol concentration by 30%, and increasing the ratio of HDL/ total-cholesterol concentration by 150% in the CETPtransgenic (tg) mice. The CETP inhibition by the P28 or P10 made alterations that modulated the size re-distribution of the lipoproteins in the blood stream. Particle size of the very low (VLDL) and low density lipoproteins (LDL) from the peptide-injected group was highly decreased compared to the saline-injected group (determined on the gel filtration column chromatography). In contrast, The HDL particle size of the P28-injected group increased compared to the control group (saline-injected). The expression level of the CETP mRNA of the P28-injected CETP-tg mouse appeared lower than the saline-injected CETP-tg mouse. These results suggest that the injection of the CETP inhibitory peptide could affect the CETP expression level in the liver by influencing lipoprotein metabolism.

Interaction of CETP inhibitory peptide and lipoprotein substrates in cholesteryl ester transfer assay: relationship between association properties and inhibitory activities.

In a previous study, CETP inhibitory peptide (3 kDa) was isolated from hog plasma. The peptide, synthesized chemically according to the amino acid sequence of the 3-kDa peptide (designated P28), showed CETP inhibitory activity both in vitro and in vivo ICho et al. (1998) Biochim. Biophys. Acta 1391, 133-144]. We report herein further unique features of P28 when it was associated with the cholesteryl ester (CE)-donor and -acceptor lipoproteins. Lipoprotein substrates with P28 present in both HDL (as a CE-donor) and LDL (as a CE-acceptor) served as poor substrates, with CE-transfer activity decreased up to 60% compared to normal substrates without P28. P28 was found to be located in HDL fractions of hog plasma and showed the same electromobility as that visualized by PAGE on 7% polyacrylamide gel under nondenaturing conditions. Addition of apolipoprotein A-1 (apoA-1) or apoB antibody to a normal CE-transfer mixture did not alter CE-transfer activity. However, addition of apoA-1 or -B antibody to a CETP-inhibition mixture decreased the inhibitory activity of P28 by ca. 20%. Western blot analysis revealed that P28 was associated only with human and hog HDL among several lipoproteins purified from human, hog, and rabbit. CETP-inhibition assays with various lipoprotein substrates revealed that P28 exhibited substrate-specific inhibitory activity. The inhibitory activity of P28 was highly dependent on the type of lipoprotein substrate (whether CE-donor or -acceptor); P28 inhibited CE transfer from HDL to LDL, but it did not inhibit CE transfer from HDL to HDL.

Quercetin dihydrate and gallate supplements lower plasma and hepatic lipids and change activities of hepatic antioxidant enzymes in high cholesterol-fed rats.

This study was designed to test the lipid-lowering and antioxidant activity of two bioflavonoids, quercetin dihydrate and gallate. Four groups of rats were given a semisynthetic diet containing 10 g cholesterol/kg for six weeks. The control group received only a high-cholesterol diet, whereas the other three groups received a diet including 1 g lovastatin, 1 g quercetin dihydrate, or 1 g gallate/kg. The quercetin dihydrate and gallate supplements both significantly lowered the plasma lipid and hepatic cholesterol levels compared to those of the control. The hepatic 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase activity was significantly lowered by the quercetin dihydrate when compared to the other groups, while the hepatic acyl CoA: cholesterol acyltransferase (ACAT) activity was only significantly higher in the control group. The overall potential for antioxidant protection was significantly enhanced by the quercetin dihydrate and gallate supplements through lowering the plasma and hepatic thiobarbituric acid reactive substances (TBARS) levels and increasing the hepatic superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in high-cholesterol-fed rats. These results suggest that the supplementation of quercetin dihydrate and gallate promotes an increase in fecal sterols, which in turn leads to a decreased absorption of dietary cholesterol as well as lower plasma and hepatic cholesterol.

Rab7 gene is up-regulated by cholesterol-rich diet in the liver and artery.

To identify genes responding to the cholesterol-rich diet, differentially expressed hepatic genes have been searched from a diet-induced hypercholesterolemic rabbit by differential display reverse transcription-polymerase chain reaction (DDRT-PCR). Among the many screened genes, Rab7 gene was shown to be distinctively up-regulated in response to the cholesterol-loading into the rabbit. To visualize the location of elevated Rab7 expression in tissues, patterns of the gene expression were monitored within hepatic and aortic tissues by in situ hybridization and immunohistochemistry. The expression of Rab7 was obviously increased in the hepatic tissues, especially in the endothelial cells and hepatocytes around central veins of the high cholesterol-fed rabbit, compared to the tissues from rabbit fed a normal diet. To find out a potential relationship between the Rab7 and the atherogenesis, the same experiments were conducted with the atherosclerotic plaques obtained from rabbit and human. The elevated expression of Rab7 gene was clearly evident in both tissues, suggesting that the Rab7 may be involved in the process of atherogenesis.