OBJECTIVEHypercholesterolemia is one of the well-established risk factors for cardiovascular mortality and morbidity in coronary heart disease. The aim of this study was to investigate the anti-atherogenic effect of Chungtaejeon (CTJ, a Korean fermented tea) aqueous extract on proliferation and migration of human aortic smooth muscle cells (HASMCs) in vivo and in vitro.

METHODSThe authors used high-fat atherogenic diet (HFAD) to induce hyperlipidemia in Wistar rats in in vivo animal experiments and used HASMCs for in vitro cell experiments. For the in vitro cell experiment, the proliferation of HASMCs was evaluated using the MTT assay. Similarly, the expression of matrix metalloproteinases (MMPs) in HASMCs was measured using gelatin zymography. Antimigratory activity of CTJ was revealed using the wound-healing model and Boyden 's chamber assay. In the in vivo experiment, CTJ was administered in three different doses for 20 d from the initiation of the HFAD. After 20 d, the serum lipid profile and total lipid contents in liver were measured.

RESULTSTreatment with CTJ for 24 h dose-dependently inhibited the proliferation and migration of HASMCs and expression of MMP-2 in HASMCs. The oral administration of CTJ at concentrations of 200 and 400 mg/kg decreased the levels of low-density lipoprotein cholesterol, total serum cholesterol and hepatic cholesterol of HFAD-fed rats.

CONCLUSIONCTJ possessed strong antiproliferative, antimigratory, as well as lipid-lowering activities. Thus, CTJ can be considered as a therapeutic option in the treatment of high-fat diet-induced atherosclerosis.

Animals ; Atherosclerosis ; prevention & control ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Diet, Atherogenic ; Fermentation ; Humans ; Male ; Plant Extracts ; pharmacology ; therapeutic use ; Rats ; Rats, Wistar ; Tea

Increased oxidative stress in obese diabetes may have causal effects on diabetic complications, including dyslipidemia. Lipopolysccharides (LPS) along with an atherogenic diet have been found to increase oxidative stress and insulin resistance. Cranberry has been recognized as having beneficial effects on diseases related to oxidative stress. Therefore, we employed obese diabetic animals treated with an atherogenic diet and LPS, with the aim of examining the effects of cranberry powder (CP) on diabetic related metabolic conditions, including lipid profiles, serum insulin and glucose, and biomarkers of oxidative stress. Forty C57BL/KsJ-db/db mice were divided into the following five groups: normal diet + saline, atherogenic diet + saline, atherogenic diet + LPS, atherogenic diet + 5% CP + LPS, and atherogenic diet + 10% CP + LPS. Consumption of an atherogenic diet resulted in elevation of serum total cholesterol and atherogenic index (AI) and reduction of high density lipoprotein (HDL)-cholesterol. However, with 10% CP, the increase in mean HDL-cholesterol level was close to that of the group with a normal diet, whereas AI was maintained at a higher level than that of the group with a normal diet. LPS induced elevated serum insulin level was lowered by greater than 60% with CP (P < 0.05), and mean serum glucose level was reduced by approximately 19% with 5% CP (P > 0.05). Mean activity of liver cytosolic glutathione peroxidase was significantly increased by LPS injection, however it was reduced back to the value without LPS when the diet was fortified with 10% CP (P < 0.05). In groups with CP, a reduction in mean levels of serum protein carbonyl tended to occur in a dose dependent manner. Particularly with 10% CP, a reduction of approximately 89% was observed (P > 0.05). Overall results suggest that fortification of the atherogenic diet with CP may have potential health benefits for obese diabetes with high oxidative stress, by modulation of physical conditions, including some biomarkers of oxidative stress.
Animals ; Biomarkers* ; Blood Glucose ; Cholesterol ; Cytosol ; Diabetes Complications ; Diet ; Diet, Atherogenic ; Dyslipidemias ; Glucose* ; Glutathione Peroxidase ; Insulin ; Insulin Resistance ; Insurance Benefits ; Lipoproteins ; Liver ; Mice* ; Oxidative Stress* ; Vaccinium macrocarpon*

This study investigated the effects of freeze-dried cranberry powder on anti-inflammation and lipid profiles of lipopolysaccharide (LPS)-treated rats fed an atherogenic diet for 6 weeks. Forty Sprague-Dawley male rats (6-weeks-old) were equally divided into the following five groups: 1) normal diet group + saline (NC); 2) atherogenic diet + saline (HFC); 3) atherogenic diet + LPS (HL); 4) atherogenic diet with 5% cranberry power + LPS (C5); 5) atherogenic diet with 10% cranberry power + LPS (C10). LPS (0.5 mg/kg) was injected into the abdominal cavities of rats 18 hours prior to sacrifice. At the end of the experimental period, we measured serum lipid profiles as well as levels of serum C-reactive protein (CRP), nitric oxide (NO), and pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, and IL-10 as an anti-inflammatory cytokine. The mean serum high density lipoprotein (HDL)-cholesterol level in C5 rats was significantly higher than that in NC and HL rats (P < 0.05). The mean serum levels of CRP and IL-1beta were significantly lower (P < 0.05) in the cranberry powder groups compared to those in HL rats. Additionally, mean serum IL-6 levels tended to be lower in the cranberry groups than that in the HL group, whereas serum IL-10 and NO showed 29% and 88% higher mean values in the C5 group and 49% and 24% higher in the C10 group than those in the HL group, respectively. These results suggest that freeze-dried cranberry powder may have beneficial effects on cardiovascular diseases by modifying serum lipids and the early inflammatory response.
Abdominal Cavity ; Animals ; C-Reactive Protein ; Cardiovascular Diseases ; Cytokines ; Diet ; Diet, Atherogenic ; Humans ; Interleukin-10 ; Interleukin-6 ; Interleukins ; Lipoproteins ; Male ; Nitric Oxide ; Rats ; Tumor Necrosis Factor-alpha ; Vaccinium macrocarpon

OBJECTIVETo observe the effects of (-)doxazosin(DOX), (+)DOX and (+/-)DOX on serum lipid levels and the mortality rates of the rabbits fed by an atherogenic diet.

METHODSMale white New Zealand rabbits were fed by an atherogenic diet for 4 weeks. 8 rabbits whose serum TC <10 mmol/L were confirmed as normal diet group and were fed normally. 40 rabbits whose serum TC >10 mmol/L were randomly divided into 4 groups (n=10): atherogenic diet group, atherogenic diet with (-)DOX group, atherogenic diet with (+)DOX group and atherogenic diet with (+/-)DOX group, which were intraperitoneally injected with (-)DOX, (+)DOX and (+/-)DOX for 9 weeks respectively. Normal and atherogenic diet group were intraperitoneally injected with double distilled water. After 9 weeks administration of (+/-)doxazosin and its enantiomers, effects of the three agents on serum levels of total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) were observed.

RESULTSThe mortality rate of the rabbits fed by an atherogenic diet for 13 weeks was 40%, and it was much higher than that of the rabbits fed by a normal diet (10%). The mortality rates in the rabbits treated with (-)DOX and (+/-)DOX were lower than that in the rabbits fed by a normal diet (10%). Serum LDL-C level of the rabbits was increased markedly after 4 weeks of atherogenic diet, and it was further increased significantly (P < 0.05 and P < 0.01) during the continued 9 weeks of atherogenic diet. However, serum LDL-C levels were not further increased significantly (P > 0.05) during the continued 9 weeks of atherogenic diet in the rabbits treated with (-)DOX, (+)DOX and (+/-)DOX, respectively.

CONCLUSION(-)DOX and (+/-)DOX increase the survival rate and improve LDL-C disorder mildly in the rabbits fed by an atherogenic diet. The improvements in LDL-C induced by (-)DOX and (+/-)DOX, however, might not be the reason for exploration about the increased survival rate in the rabbits fed by an atherogenic diet.

Animals ; Cholesterol, Dietary ; administration & dosage ; Diet, Atherogenic ; Doxazosin ; pharmacology ; Hyperlipidemias ; blood ; drug therapy ; etiology ; Lipids ; blood ; Male ; Rabbits ; Stereoisomerism

OBJECTIVETo observe the difference in fatty degree, glucose-lipid disorder and adipose-hormones between diet induced obesity (DIO) rats and diet induced obesity resistance (DIO-R) rats, and to explore the effect and acting mechanism of Chinese drugs for strengthening Pi (CD-SP) and those for both strengthening Pi and dissolving phlegm (CD-SPDP) in inhibiting obesity.

METHODSExcepting eight rats allocated in the blank control group, the other 54 rats were fed with high-lipid forage for 12 weeks to establish models of obesity. Finally, 30 DIO rats and 8 DIO-R rats (shown by their body weight) were obtained. The DIO rats were divided into three groups, which were given gastric perfusion, respectively, with normal saline (Group A), CD-SP (Group B), and CD-SPDP (Group C). Fourteen weeks later, the animals' body weight (BW), length (BL), blood levels of fasting insulin (FIn), fasting glucose (FBG), triglyceride (TG), cholesterol (TC), leptin (LP), neuropeptide Y (NPY), C-reactive protein (CRP), tumor necrosis factor-alpha(TNF-alpha), adiponectin (AN), and resistin (RS) were measured; insulin resistance index (IRI) was calculated, and the degree of obesity and lipid content in abdominal cavity of rats were estimated. Moreover, the levels of LP, CRP, TNF-alpha, AN and RS in homogenate of rats' adipose tissues (ATH) were determined.

RESULTSAfter 12 weeks of high-lipid diet, the BW of DIO rats was higher than that of normal or DIO-R rats. After a 14-week continuous high-lipid diet feeding, in DIO rats, BW, lipid coefficient (LC), and IRI were significantly increased (P<0.01); serum levels of TNF-alpha, LP and AN were lower, NPY was higher, while the ATH levels of LP and AN were lower and TNF-alpha was higher in DIO rats than in DIO-R rats (P<0.05 or P<0.01); blood levels of FBG and lipids in DIO rats showed an increasing trend but was statistically insignificant (P>0.05); no significant difference was found in serum levels of CRP and RS due to the overly high data dispersion. Comparisons of the 3 DIO groups showed that BW, body weight index (BWI), LC and IRI were significantly lowered after treatment (P<0.01) in Group C, while these indexes were not significantly different between Group A and B; the serum levels of TNF-alpha, LP, and AN increased, NPY decreased in Group B and C, ATH levels of LP and AN increased, and TNF-alpha decreased in the two groups; but NPY, LP, and AN in blood and ATH were higher in Group C than those in Group B (P<0.05 or P<0.01).

CONCLUSIONCD-SPDP could inhibit DIO and IR, showing that the effect is better than that of CD-SP, and its mechanism is related to promotion of LP and AN secretion and elevation of serum NPY.

Adipokines ; blood ; Animals ; Blood Glucose ; analysis ; C-Reactive Protein ; analysis ; Diet, Atherogenic ; Dietary Fats ; adverse effects ; Drug Evaluation, Preclinical ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Leptin ; blood ; Male ; Neuropeptide Y ; blood ; Obesity ; blood ; etiology ; pathology ; prevention & control ; Random Allocation ; Rats ; Rats, Wistar ; Syndrome ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVETo study the effect of gamma linolenic acid (GLA) on atherogenesis in rats.

METHODSixty healthy male rats were randomly divided into 6 groups: normal contro 1, fed by normal feed; atherogenesis mode 1, fed by high lipid diet; positive control group 0.9 mg x kg(-1) x d(-1) of lovastatin and group IV 250 mg x kg(-1) x d(-1) duoxikang; high dose of 375 mg x kg(-1) x d(-1) GLA; low dose of 187.5 mg x kg(-1) x d(-1) GLA. After the model group received atherogenic diet for six weeks, serum triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) were detected by enzyme method to confirm the formation of atherogenic. After fed for another five weeks, morphologic atherosclerosis of aorta in rats was observed by HE staining methods. The blood samples were collected and serum TC, TG, HDL-C, LDL-C, T-AOC, HL, LPL, NO, NOS, MDA and GSH were determined.

RESULTGLA attenuated the formation of atherosclerotic plaques, inhibited the level of serum TC, TG, MDA, OX-LDL, NO, NOS, HL, LPL and LDL-C and increased the level of T-AOC.

CONCLUSIONGLA might significantly attenuate the development of atherosclerosis in rats fed with high lipid diet through improving the antioxidation capacity of the body.

Animals ; Atherosclerosis ; blood ; drug therapy ; metabolism ; Cholesterol ; metabolism ; Diet, Atherogenic ; Lipids ; blood ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; gamma-Linolenic Acid

OBJECTIVETo investigate the effect of chronic enhanced external counterpulastion (EECP) on gene expression profiles of arterial endothelial cells (ECs) of pigs fed with high-cholesterol diet.

METHODSEight male pigs were fed with high-cholesterol diet for 12 weeks to induce arteriosclerosis and subjected to EECP for accumulative 36 h (2 h every other day for 18 sessions). Another 8 pigs on cholesterol-enriched diet and 6 normally fed pigs served as the arteriosclerosis model group and normal control group, respectively, and the high-cholesterol diet was maintained until the end of EECP treatment. The coronary artery was then isolated for transmission electro microscopy, and the abdominal aorta was observed using Sudan III staining. The gene expression profiles in ECs from the thoracic aorta using cDNA microarrays.

RESULTSMacrophages and foam cells were detected beneath the ECs in the coronary artery of pigs in the model group, but not in the other two groups. The ratios of Sudan III-positive area in the celiac aorta were significantly lower in normal control and EECP groups than in the model control group (P<0.05). Compared with the normal control group, the gene expressions of integrins-beta1 and CTGF were up-regulated in the model group. Compared with the model group, the expressions of integrins-beta1, CTGF and VCAM-1 were down-regulated and eNOS up-regulated in EECP group.

CONCLUSIONChronic EECP may reduce endothelial injury, down-regulate the gene expression level of integrin-beta1, CTGF and VCAM-1, lower cholesterol uptake and attenuate arterial endothelial inflammation to protect the pigs fed with high-cholesterol diet from arteriosclerosis.

Animals ; Aorta, Abdominal ; metabolism ; pathology ; Arteriosclerosis ; etiology ; genetics ; pathology ; Coronary Vessels ; metabolism ; pathology ; Counterpulsation ; methods ; Diet, Atherogenic ; Endothelial Cells ; metabolism ; Gene Expression Profiling ; Male ; Oligonucleotide Array Sequence Analysis ; methods ; Swine

This study investigated that the antioxidative effect of freeze-dried cranberry powder against protein and lipid oxidation and ameliorative effect of serum lipid profile in rat fed atherogenic diet. Six weeks old male Sprague-Dawley rats were divided into the following four groups: normal diet group with 5% corn oil (control), atherogenic diet group with 5% corn oil, 10% lard, 1% cholesterol, and 0.5% sodium cholate (HFC), atherogenic plus 2% cranberry powder diet group (HFC + C2), and atherogenic plus 5% cranberry powder diet group (HFC + C5), and respective diet and water were fed daily for 6 weeks. After the experimental period, the serum lipid profile, such as total cholesterol, HDL-cholesterol, LDL-cholesterol, and triglyceride, ferric reducing ability of plasma (FRAP), plasma phenolics content, superoxide dismutase (SOD) activity, serum protein carbonyl and thiobarbituric acid reactive substances (TBARS) levels were examined. Total phenolic compound and total flavonoid levels in freeze-dried cranberry powder were 9.94 mg/g and 8.12 mg/g, respectively. Serum total cholesterol and LDL-cholesterol levels were not significantly different for cranberry powder treatment, but serum HDL-cholesterol level was significantly increased in HFC + C5 group compared with HFC group. Plasma FRAP value tended to be increased by cranberry powder treatment though there was no significant difference. Plasma total phenol concentrations and SOD activities were not significantly different among all groups. Serum protein carbonyl and TBARS levels were significantly decreased in HFC + C5 group compared with HFC group. Overall results suggested that freeze-dried cranberry powder might have the serum lipid improving effect, as well as antioxidative effect demonstrated by its protective effect against protein and lipid oxidation.
Animals ; Biomarkers ; Cholesterol ; Corn Oil ; Diet ; Diet, Atherogenic ; Dietary Fats ; Humans ; Male ; Oxidative Stress ; Phenol ; Plasma ; Rats ; Rats, Sprague-Dawley ; Sodium Cholate ; Superoxide Dismutase ; Thiobarbiturates ; Thiobarbituric Acid Reactive Substances ; Vaccinium macrocarpon ; Water

Animals ; Aorta ; pathology ; Atherosclerosis ; blood ; etiology ; metabolism ; Chemokine CCL2 ; metabolism ; Cholesterol ; blood ; Cholesterol, Dietary ; administration & dosage ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Dehydroepiandrosterone ; pharmacology ; Diet, Atherogenic ; Immunohistochemistry ; Rabbits ; Random Allocation ; Triglycerides ; blood ; Vascular Cell Adhesion Molecule-1 ; metabolism

OBJECTIVETo investigate the effects of the micrometer compound rhizoma coptidis on inflammatory factors and its possible mechanism in rabbit fed with high-lipid food.

METHODThe levels of CRP, IL-1 and TNF-alpha were all determinated by ELISA method. The mRNA and activity of NF-kappaB were determinated by RT-PCR and EMSA, respectively.

RESULTThe level of CRP, IL-1 and TNF-alpha were significantly increased by feeding for 16 weeks with high-lipid diet in rabbit. It was significantly increased that the mRNA and the binging activity with DNA of NF-kappaB in thorax aorta of rabbits fed by high-lipid diet, too. The micrometer compound rhizoma coptidis can reverse the effects of high-lipid diet on CRP, IL-1, TNF-alpha and NF-kappaB.

CONCLUSIONThe micrometer compound rhizoma coptidis can inhibit the expression of inflammatory factor possibly through inhibitting the expression and activity of NF-kappaB.

Animals ; Aorta, Thoracic ; drug effects ; metabolism ; C-Reactive Protein ; metabolism ; Coptis ; chemistry ; Diet, Atherogenic ; Drug Combinations ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacology ; Enzyme-Linked Immunosorbent Assay ; Inflammation Mediators ; blood ; Interleukin-1 ; blood ; Male ; Microspheres ; NF-kappa B ; genetics ; metabolism ; Particle Size ; Plants, Medicinal ; chemistry ; Powders ; RNA, Messenger ; genetics ; metabolism ; Rabbits ; Random Allocation ; Reverse Transcriptase Polymerase Chain Reaction ; Tumor Necrosis Factor-alpha ; blood