Highly water-soluble diacetyl chrysin ameliorates diabetes-associated renal fibrosis and retinal microvascular abnormality in db/db mice

BACKGROUND/OBJECTIVES@#Chronic or intermittent hyperglycemia is associated with the development of diabetic complications. Oxidative stress and inflammation can be altered by hyperglycemia in diverse tissues, including kidneys and eyes, and play a pivotal role in diabetic complications. Our previous studies showed that the water-insoluble 5,7-dihydroxyflvone chrysin effectively combats diabetic damages incurred in diabetic kidneys and retinas. The current study employed the newly-synthesized 5.7-di-O-acetylchrysin, having higher solubility than chrysin, to compare the effects on diabetes-associated renal fibrosis and abnormal retinal neovascularization.MATERIALS/METHODS: In the in vivo study, db/db mice as animal models of type 2 diabetes were orally administrated 10 mg/kg BW diacetylchrysin, daily for 10 weeks. @*RESULTS@#Unlike chrysin, oral administration of 10 mg/kg diacetylchrysin did not lower the blood glucose level and 24 h urine volume in db/db mice. Nevertheless, the urinary albumin excretion was markedly reduced. The administration of diacetylchrysin also diminished the deposition of collagen fibers in diabetic glomeruli and tubules by suppressing the induction of connective tissue growth factor and collagen IV in diabetic kidneys. Supplying diacetylchrysin enhanced the membrane type-1 matrix metalloproteinase (MMP) expression reduced in diabetic kidneys, while the tissue inhibitor of MMP-2 induction was attenuated in diacetylchrysin-challenged diabetic kidneys. In addition, supplementing diacetylchrysin to diabetic mice ameliorated renal injury due to glomerulosclerosis and tubular interstitial fibrosis. Furthermore, the reduced retinal inductions of Zonula occludens-1 and vascular endothelial cadherin in db/db mice were elevated in the retinal tissues of diacetylchrysintreated animals. Oral administration of diacetylchrysin curtailed the induction of vascular endothelial growth factor (VEGF) and VEGF receptor 2 in db/db mice, ultimately retarding diabetes-associated retinal neovascularization. Additionally, the retinal formation of acellular capillaries with leaky vessels was reduced in diacetylchrysin-treated db/db mice. @*CONCLUSION@#Diacetylchrysin may act as a potent pro-health agent for treating renal fibrosisassociated diabetic nephropathy and retinal neovascularization-associated diabetic retinopathy.

Dietary nobiletin suppresses TGF-β1-Src-caveolin-1 dependent signaling involved with high glucose-induced renal mesangial matrix accumulation / 한국영양학회지

PURPOSE: Diabetic nephropathy is one of the most important diabetic complications prompted by chronic hyperglycemia, characterized by glomerulosclerosis, tubular fibrosis, and it eventually causes kidney failure. Nobiletin is a polymethoxyflavone present in tangerine and other citrus peels, and has anti-cancer and anti-inflammatory effects. This study investigated the effects of nobiletin on glomerular fibrosis through inhibition of the transforming growth factor (TGF)-β1-Src-caveolin-1 pathway.METHODS: Human renal mesangial cells (HRMC) were incubated in media containing 33 mM glucose with or without 1–20 uM nobiletin for 3 day. The cellular expression levels of fibrogenic collagen IV, fibronectin, connective tissue growth factor (CTGF), TGF-β1, Src and caveolin-1 were all examined. In addition, TGF-β1, Src and caveolin-1 proteins were screened to reveal the relationship among TGF-β1-Src-caveolin-1 signaling in glomerular fibrosis.RESULTS: High glucose promoted the production of collagen IV, fibronectin and CTGF in HRMC, which was inhibited in a dose dependent manner by 1–20 uM nobiletin. The Western blot data showed that high glucose elevated the expression of TGF-β1, Src, caveolin-1 and Rho GTPase. When nobiletin was treated to the HRMC exposed to high glucose, the expression of TGF-β1-Src-caveolin-1 was dampened. Finally, TGF-β1-Src-caveolin-1 signaling pathway was activated in high glucose-exposed HRMC, and such activation was encumbered by nobiletin.CONCLUSION: These result demonstrated that nobiletin blunted high glucose-induced extracellular matrix accumulation via inhibition of the TGF-β1-Src-caveolin-1 related intracellular signaling pathway. Nobiletin may be a potent renoprotective agent to counteract diabetes-associated glomerular fibrosis that leads to kidney failure.

17β-Estradiol Inhibits Lysophosphatidylcholine-Induced Apoptosis in Cultured Vascular Smooth Muscle Cells

Objectives@#Coronary heart disease (CHD) risk increases in women after menopause, but menopausal hormone therapy (MHT) helps prevent CHD if started early after menopause. To explore the mechanism underlying the direct vascular actions of estrogen, the effects of 17β-estradiol (E2) on apoptosis of vascular smooth muscle cells (VSMCs) induced with lysophosphatidylcholine (lysoPC), an active component of oxidized low-density lipoprotein, were investigated in the present study. @*Methods@#VSMCs were isolated from rat aortas. Apoptosis and protein expression of caspases were assessed using propidium iodide staining and Western blot analysis, respectively. Intracellular formation of reactive oxygen species (ROS) was examined using dichlorofluorescein diacetate, a cell-permeable oxidation-sensitive probe, and quantitated with flow cytometry. Nuclear factor-κB (NF-κB) activation was determined after transfection with a reporter plasmid containing the luciferase reporter gene. @*Results@#After pre-treatment for 24 hours, 17β-E2 suppressed lysoPC-induced (15 mM) apoptotic cell death in a dose-dependent manner with statistical significance at near physiological concentration. 17β-E2 (10−6 M) also increased protein levels of caspase-9 and -8 precursors and decreased the active form of caspase-3. Western blot analysis using subcellular fractions showed that 17β-E2 decreased mitochondrial Bax levels and concomitantly increased cytosolic Bax expression. Furthermore, intracellular production of ROS and NF- κB-mediated transcriptional activity were reduced with 17β-E2. In addition, estrogen effects on apoptosis were partially blocked by ICI 182,780, a specific estrogen receptor antagonist. @*Conclusions@#In cultured VSMCs treated with lysoPC, 17β-E2 reduced apoptotic cell death by down-regulating both extrinsic and intrinsic apoptosis pathways, contributing to the preventive action of MHT against CHD.

Effects of 17β-Estradiol on the Plasminogen Activator System in Vascular Smooth Muscle Cells Treated with Lysophophatidylcholine

Objectives@#When administered soon after menopause, hormone therapy can prevent coronary heart diseases in women. To explore the mechanism underlying the cardioprotective actions of estrogen, we investigated the effects of 17β-estradiol (17β-E2) on the plasminogen activator system using cultured vascular smooth muscle cells (VSMCs). @*Methods@#VSMCs were isolated from rat aortas. Protein expression of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) were evaluated using Western blotting and enzyme-linked immunosorbent assay, respectively. The enzyme activity of PAI-1 in a conditioned medium was assessed via reverse fibrin overlay zymography and that of t-PA was assessed via fibrin overlay zymography. Gene expression was quantified using real-time reverse transcription-polymerase chain reaction. @*Results@#Following pre-treatment for 24 hours, 17β-E2 suppressed both protein expression and enzyme activity of PAI-1 stimulated by lysophosphatidylcholine (lysoPC) in a significant and dose-dependent manner at a near physiological concentration. Moreover, 17β-E2 (10−7 M) inhibited PAI-1 gene expression, and ICI 182,780—a specific estrogen receptor antagonist—blocked the effects of 17β-E2 on the PAI-1 protein. 17β-E2 did not affect t-PA secretion but significantly enhanced free t-PA activity through reduced binding to PAI-1. Furthermore, 17β-E2 suppressed intracellular reactive oxygen species production and nuclear factor-κB-mediated transcription. @*Conclusions@#In VSMCs stimulated with lysoPC, 17β-E2 reduced PAI-1 expression through a non-receptor-mediated mechanism via antioxidant activity as well as a receptor-mediated mechanism; however, it did not alter t-PA secretion. Of note, 17β-E2 suppressed PAI- 1 activity and concurrently enhanced t-PA activity, suggesting a beneficial influence on fibrinolysis.

Novel glutathione-containing dry-yeast extracts inhibit eosinophilia and mucus overproduction in a murine model of asthma

BACKGROUND/OBSECTIVE: Airway inflammation by eosinophils, neutrophils and alveolar macrophages is a characteristic feature of asthma that leads to pathological subepithelial thickening and remodeling. Our previous study showed that oxidative stress in airways resulted in eosinophilia and epithelial apoptosis. The current study investigated whether glutathione-containing dry yeast extract (dry-YE) ameliorated eosinophilia, goblet cell hyperplasia and mucus overproduction. MATERIALS/METHOD: This study employed 2 µg/mL lipopolysaccharide (LPS)- or 20 ng/mL eotaxin-1-exposed human bronchial epithelial cells and ovalbumin (OVA)-challenged mice. Dry-YE employed in this study contained a significant amount of glutathione (140 mg in 100 g dry yeast). RESULTS: Human bronchial epithelial cell eotaxin-1 and mucin 5AC (MUC5AC) were markedly induced by the endotoxin LPS, which was dose-dependently attenuated by nontoxic dry-YE at 10-50 µg/mL. Moreover, dry-YE inhibited the MUC5AC induction enhanced by eotaxin-1, indicating that eotaxin-1-mediated eosinophilia may prompt the MUC5AC induction. Oral supplementation with 10-100 mg/kg dry-YE inhibited inflammatory cell accumulation in airway subepithelial regions with a reduction of lung tissue level of intracellular adhesion molecule-1. In addition, ≥ 50 mg/kg dry-YE diminished the lung tissue levels of eotaxin-1, eosinophil major basic protein and MUC5AC in OVA-exposed mice. Alcian blue/periodic acid schiff staining revealed that the dry-YE supplementation inhibited goblet cell hyperplasia and mucus overproduction in the trachea and bronchiolar airways of OVA-challenged mice. CONCLUSIONS: Oxidative stress may be involved in the induction of eotaxin-1 and MUC5AC by endotoxin episode and OVA challenge. Dry-YE effectively ameliorated oxidative stress-responsive epithelial eosinophilia and mucus-secreting goblet cell hyperplasia in cellular and murine models of asthma.

Anti-diabetic effect of purple corn extract on C57BL/KsJ db/db mice

BACKGROUND/OBJECTIVES: Recently, anthocyanins have been reported to have various biological activities. Furthermore, anthocyanin-rich purple corn extract (PCE) ameliorated insulin resistance and reduced diabetes-associated mesanginal fibrosis and inflammation, suggesting that it may have benefits for the prevention of diabetes and diabetes complications. In this study, we determined the anthocyanins and non-anthocyanin component of PCE by HPLC-ESI-MS and investigated its anti-diabetic activity and mechanisms using C57BL/KsJ db/db mice. MATERIALS/METHODS: The db/db mice were divided into four groups: diabetic control group (DC), 10 or 50 mg/kg PCE (PCE 10 or PCE 50), or 10 mg/kg pinitol (pinitol 10) and treated with drugs once per day for 8 weeks. During the experiment, body weight and blood glucose levels were measured every week. At the end of treatment, we measured several diabetic parameters. RESULTS: Compared to the DC group, Fasting blood glucose levels were 68% lower in PCE 50 group and 51% lower in the pinitol 10 group. Furthermore, the PCE 50 group showed 2- fold increased C-peptide and adiponectin levels and 20% decreased HbA1c levels, than in the DC group. In pancreatic islets morphology, the PCE- or pinitol-treated mice showed significant prevention of pancreatic beta-cell damage and higher insulin content. Microarray analyses results indicating that gene and protein expressions associated with glycolysis and fatty acid metabolism in liver and fat tissues. In addition, purple corn extract increased the phosphorylation of AMP-activated protein kinase (AMPK) and decreased phosphoenolpyruvate carboxykinase (PEPCK), glucose 6-phosphatase (G6pase) genes in liver, and also increased glucose transporter 4 (GLUT4) expressions in skeletal muscle. CONCLUSIONS: Our results suggested that PCE exerted anti-diabetic effects through protection of pancreatic beta-cells, increase of insulin secretion and AMPK activation in the liver of C57BL/KsJ db/db mice.

Anti-carcinogenic effects of non-polar components containing licochalcone A in roasted licorice root

BACKGROUND/OBJECTIVE: Licorice has been shown to possess cancer chemopreventive effects. However, glycyrrhizin, a major component in licorice, was found to interfere with steroid metabolism and cause edema and hypertension. The roasting process of licorice modifies the chemical composition and converts glycyrrhizin to glycyrrhetinic acid. The purpose of this study was to examine the anti-carcinogenic effects of the ethanol extract of roasted licorice (EERL) and to identify the active compound in EERL. MATERIALS/METHODS: Ethanol and aqueous extracts of roasted and un-roasted licorice were prepared. The active fraction was separated from the methylene chloride (MC)-soluble fraction of EERL and the structure of the purified compound was determined by nuclear magnetic resonance spectroscopy. The anti-carcinogenic effects of licorice extracts and licochalcone A was evaluated using a MTT assay, Western blot, flow cytometry, and two-stage skin carcinogenesis model. RESULTS: EERL was determined to be more potent and efficacious than the ethanol extract of un-roasted licorice in inhibiting the growth of DU145 and MLL prostate cancer cells, as well as HT-29 colon cancer cells. The aqueous extracts of un-roasted and roasted licorice showed minimal effects on cell growth. EERL potently inhibited growth of MCF-7 and MDA-MB-231 breast, B16-F10 melanoma, and A375 and A2058 skin cancer cells, whereas EERL slightly stimulated the growth of normal IEC-6 intestinal epithelial cells and CCD118SK fibroblasts. The MC-soluble fraction was more efficacious than EERL in inhibiting DU145 cell growth. Licochalcone A was isolated from the MC fraction and identified as the active compound of EERL. Both EERL and licochalcone A induced apoptosis of DU145 cells. EERL potently inhibited chemically-induced skin papilloma formation in mice. CONCLUSIONS: Non-polar compounds in EERL exert potent anti-carcinogenic effects, and that roasted rather than un-roasted licorice should be favored as a cancer preventive agent, whether being used as an additive to food or medicine preparations.

Antidiabetic and Beta Cell-Protection Activities of Purple Corn Anthocyanins

Antidiabetic and beta cell-protection activities of purple corn anthocyanins (PCA) were examined in pancreatic beta cell culture and db/db mice. Only PCA among several plant anthocyanins and polyphenols showed insulin secretion activity in culture of HIT-T15 cells. PCA had excellent antihyperglycemic activity (in terms of blood glucose level and OGTT) and HbA1c-decreasing activity when compared with glimepiride, a sulfonylurea in db/db mice. In addition, PCA showed efficient protection activity of pancreatic beta cell from cell death in HIT-T15 cell culture and db/db mice. The result showed that PCA had antidiabetic and beta cell-protection activities in pancreatic beta cell culture and db/db mice.

Cytotoxic Effects of Lysophosphatidylcholine on Vascular Smooth Muscle Cells / 대한폐경학회지

OBJECTIVES: To investigate the cytotoxic effects of lysophosphatidylcholine (lysoPC), an active component of oxidized low-density lipoproteins (LDL), on vascular smooth muscle cells (VSMCs). METHODS: VSMCs were derived from rat aorta. Cell death was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay, lactic dehydrogenase (LDH) assay, and DNA fragmentation assay. Apoptosis was quantified by propidium iodide staining and fluorescent activated cell sorting (FACS) analysis, and intracellular free radical production was determined using 2',7'-dichlorofluorescin diacetate (DCF-DA). In addition, the changes in caspases, bcl-2 and bax proteins were evaluated by western blot analysis. RESULTS: LysoPC over 25 microM induced more than 50% of the cell death at 10 hours on MTT assay with no change in the level of LDH. The DNA ladder pattern showed that cell death induced by lysoPC was caused by apoptosis, which was associated with increased free radical production. Vitamin E, a potent antioxidant and caffeic acid phenylethyl ester (CAPE), an inhibitor of nuclear factor-kappaB (NF-kappaB), blocked apoptosis. The casepase-3 precursor decreased and the active form of caspase-8 increased. Total bcl-2 and bax proteins did not change with lysoPC treatment, but translocation of bax from cytosole to the mitochondria membrane was observed. CONCLUSION: LysoPC induces apoptosis in VSMCs via an oxidant mechanism, dependent on NF-kappaB.

Impact of Lysophosphatidylcholine on the Plasminogen Activator System in Cultured Vascular Smooth Muscle Cells

The balance between tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) regulates fibrinolysis. PAI-1 expression increases in atherosclerotic arteries and vascular smooth muscle cells (VSMCs) are one of major constituents of atheroma. We investigated the impact of lysophosphatidylcholine (lysoPC), an active component of oxidized low-density lipoprotein, on the plasminogen activator system of the rat VSMCs. The lysoPC stimulated the protein and gene expressions of PAI-1 but did not affect the protein expression of t-PA. Fibrin overlay zymography revealed that lysoPC increased the activity of PAI-1 in the conditioned media, while concurrently decreasing that of free t-PA. Vitamin E inhibited the lysoPC-induced PAI-1 expression. Further, lysoPC increased the intracellular reactive oxygen species (ROS) formation. Caffeic acid phenethyl ester, an inhibitor of NF-kappaB, blocked this lysoPC effect. Indeed, lysoPC induced the NF-kappaB-mediated transcriptional activity as measured by luciferase reporter assay. In addition, genistein, an inhibitor of protein-tyrosine kinase (PTK), diminished the lysoPC effect, while 7,12-dimethylbenz[a]anthracene, a stimulator of PTK, stimulated PAI-1 production. In conclusion, lysoPC does not affect t-PA expression but induces PAI-1 expression in the VSMC by mediating NF-kappaB and the genistein-sensitive PTK signaling pathways via oxidative stress. Importantly, lysoPC stimulates the enzyme activity of PAI-1 and suppresses that of t-PA.

Effect of Korean Native Cimicifuga Species on Proliferation of Vascular Smooth Muscle Cells / 대한폐경학회지

OBJECTIVES: To examine the effect of extracts of Korean native Cimicifuge species on cell proliferation in vascular smooth muscle cells (VSMC). METHODS: VSMC were isolated from rat aorta. Cell proliferation was assessed by measure of bromodeoxyuridine incorporation into the cells. Differences in Reactive oxygen species (ROS) levels were examined after exposure to the extracts of Korean native Cimicifuge species using the detection reagents dichlorofluorecin diacetate. The rhizomes/roots were air-dried and milled with a commercial food mixer. Milled rhizomes/roots of each Cimicifuga species were separately extracted by 80% ethanol, absolute methanol, and 40% 2-propanol using homogenizer and evaporated under reduced pressure at low temperatures. Effects of extracts dissolved in phosphate-buffered saline (0.3 mg/mL) were examined. RESULTS: Ethanolic, methanolic or propanolic extracts of 4 Korean native Cimicifuge species (Cimicifuga [C] davurica, C. japonica, C. heracleifolia var. bifida Nakai, C. simplex) were screened. The addition of extracts of each Korean native Cimicifuge species to cells in the presence of 10% fetal bovine serum (FBS) potently inhibited cell proliferation. Significant decrease of 23%-30% was observed. Vitamin E, a potent antioxidant, inhibited 10% FBS-stimulated cell proliferation of VSMC. We also demonstrated that extracts of each Korean native Cimicifuge species decreased intracellular ROS generation induced with 10% FBS. The effect of Korean native Cimicifuge species was not species-specific and solvent-specific. CONCLUSION: TExtracts of Korean native Cimicifuge species inhibit VSMC proliferation via inhibition of intracellular ROS. These findings suggest that Cimicifuge species used for reducing menopause symptoms might be cardioprotective in women.

Effects of green tea or Sasa quelpaertensis bamboo leaves on plasma and liver lipids, erythrocyte Na efflux, and platelet aggregation in ovariectomized rats

This study was conducted to investigate the effects of Sasa quelpaertensis bamboo and green tea on plasma and liver lipids, platelet aggregation, and erythrocyte membrane Na channels in ovariectomized (OVX) rats. Thirty female rats were OVX, and ten female rats were sham-operated at the age of 6 weeks. The rats were divided into four groups at the age of 10 weeks and fed the experiment diets: sham-control, OVX-control, OVX-bamboo leaves (10%), or OVX-green tea leaves (10%) for four weeks. Final body weight increased significantly in the OVX groups compared with that in the sham-control, whereas body weight in the OVX-green tea group decreased significantly compared with that in the OVX-control (P < 0.01). High density lipoprotein (HDL)-cholesterol level decreased in all OVX groups compared with that in the sham-control rats (P < 0.05) but without a difference in plasma total cholesterol. Plasma triglycerides in the OVX-green tea group were significantly lower than those in the sham-control or OVX-control group (P < 0.05). Liver triglycerides increased significantly in the OVX-control compared with those in the sham-control (P < 0.01) but decreased significantly in the OVX-green tea group compared with those in the OVX-control or OVX-bamboo group (P < 0.01). Platelet aggregation in both maximum and initial slope tended to be lower in all OVX rats compared with that in the sham-control rats but was not significantly different. Na-K ATPase tended to increase and Na-K cotransport tended to decrease following ovariectomy. Na-K ATPase decreased significantly in the OVX-green tea group compared with that in the OVX-control group (P < 0.01), and Na-K cotransport increased significantly in the OVX-bamboo and OVX-green tea groups compared with that in the OVX-control (P < 0.05). Femoral bone mineral density tended to be lower in OVX rats than that in the sham-control, whereas the green tea and bamboo leaves groups recovered bone density to some extent. The results show that ovariectomy caused an increase in body weight and liver triglycerides, and that green tea was effective for lowering body weight and triglycerides in OVX rats. Ovariectomy induced an increase in Na efflux via Na-K ATPase and a decrease in Na efflux via Na-K cotransport. Furthermore, consumption of green tea and bamboo leaves affected Na efflux channels, controlling electrolyte and body water balance.

Blockade of vascular angiogenesis by Aspergillus usamii var. shirousamii-transformed Angelicae Gigantis Radix and Zizyphus jujuba

The matrix metalloproteinases (MMP) play an important role in tumor invasion, angiogenesis and inflammatory tissue destruction. Increased expression of MMP was observed in benign tissue hyperplasia and in atherosclerotic lesions. Invasive cancer cells utilize MMP to degrade the extracellular matrix and vascular basement membrane during metastasis, where MMP-2 has been implicated in the development and dissemination of malignancies. The present study attempted to examine the antiangiogenic activity of the medicinal herbs of Aspergillus usamii var. shirousamii-transformed Angelicae Gigantis Radix and Zizyphus jujube (tAgR and tZj) with respect to MMP-2 production and endothelial motility in phorbol 12-myristate 13-acetate (PMA)- or VEGF-exposed human umbilical vein endothelial cells (HUVEC). Nontoxic tAgR and tZj substantially suppressed PMA-induced MMP-2 secretion. In addition, 25 microg/mL tAgR and tZj prevented vascular endothelial growth factor-stimulated endothelial cell transmigration and tube formation. The results reveal that tAgR and tZj dampened endothelial MMP-2 production leading to endothelial transmigration and tube formation. tAgR and tZj-mediated inhibition of endothelial MMP may boost a therapeutic efficacy during vascular angiogenesis.

Effect of onion and beet on plasma and liver lipids, platelet aggregation, and erythrocyte Na efflux in simvastatin treated hypercholesterolmic rats

This study was purposed to investigate the effect of onion or beet on plasma and liver lipids, erythrocyte Na efflux channels and platelet aggregation in simvastatin (SIM) treated hypercholesterolemic rats. Forty Sprague Dawley rats were divided into four groups and fed 0.5% cholesterol based diets containing 2 mg/kg BW simvastatin or simvastatin with 5% onion or beet powder. Plasma total cholesterol was significantly increased in SIM group compared with the control (p<0.01), and the elevated plasma total cholesterol of SIM group was significantly decreased in SIM-onion and SIM-beet groups (p<0.05). HDL-cholesterol in SIM-beet group was significantly increased compared with other groups (p<0.05). Platelet aggregation in both the maximum and initial slope was significantly decreased in SIM group compared with SIM-onion group (p<0.05). Na-K ATPase was significantly decreased in SIM group compared with the control, SIM-onion and SIM-beet groups (p<0.05). Na passive leak was significantly increased in all groups treated with SIM compared with the control (p<0.05). The total Na efflux was decreased in SIM group and increased in SIM-onion group and the difference between these two groups was significant (p<0.05). There was no difference in intracellular Na among groups. In present study, simvastatin, a HMG CoA reductase inhibitor at dose of 2mg/kg BW/day rather increased plasma total cholesterol in rats, inferring that the action mechanism of simvastatin on cholesterol metabolism differ between rat and human. Onion and beet play favorable roles in cardiovascular system by restoring the reduced Na efflux through Na-K ATPase and Na-K cotransport in SIM treated rats.

Effects of Cholesterol Diet and Exercise on Plasma and Liver Lipids, Platelet Aggregation and Erythrocyte Na Efflux in Rats

Present study was conducted to investigate the effects of exercise and cholesterol diet on plasma and liver lipids, platelet aggregation, erythrocyte Na efflux and liver index such as GOT and GPT using Sprague Dawley rats. Forty rats were divided into four groups and fed control or 0.5% cholesterol diet with and without treadmill for six weeks. The final body weight of group fed cholesterol diet with exercise was somewhat decreased compared with group fed cholesterol diet without exercise. L.W/B.W ratio was significantly increased in groups fed cholesterol diet (p < 0.01), but exercise tended to decrease this ratio. Plasma total cholesterol was significantly increased and HDL-cholesterol was decreased in groups fed cholesterol diet (p < 0.01). Plasma triglyceride was significantly decreased in groups fed cholesterol diet compared with groups fed control diet (p < 0.01). Plasma triglyceride of groups with exercise was significantly decreased compared with their non exercising counterparts regardless diet (p < 0.05). Liver total cholesterol and triglyceride was significantly increased in groups fed cholesterol diet (p < 0.01), but exercise did not affect on these levels. Na-K ATPase was somewhat decreased in groups fed cholesterol diet, and exercise tended to recover the reduced Na-K ATPase. Na passive transport was significantly decreased in group fed control diet without exercise and significantly increased in group fed cholesterol diet with exercise, there were significant differences between groups (p < 0.05). There were no differences in total Na efflux and intracellular Na among groups, and total Na efflux was not correlated with intracellular Na. Hematocrit was significantly lower (p < 0.05) in group fed cholesterol diet without exercise compared with other groups. Platelet aggregation in the initial slope and the maximum was increased in groups fed cholesterol diet, but not statistically significant. Exercise especially increased the initial slope of aggregation. Plasma GOT and GPT was significantly increased in groups fed cholesterol diet (p < 0.01), and exercise in group fed cholesterol diet significantly decreased both GOT and GPT compared with the non exercising counterpart (p < 0.01). This study showed that cholesterol diet increases plasma and liver lipids and GOT and GPT, and exercise improves plasma and liver lipid profile and liver index of GOT and GPT preventing fatty liver.

Alcohol Consumption and the Coronary Heart Disease-Related Risk Factors in Korean Adults: the Third Korea National Health and Nutrition Examination Survey (KNHANES III), 2005

Moderate alcohol consumption has been known to be associated with reduced risk for coronary heart disease (CHD). We assessed the association between alcohol consumption and CHD-related risk factors [hypertension, diabetes mellitus (DM), high total cholesterol, high triglyceride (TG), low HDL-cholesterol (HDL-C), and high LDL-cholesterol (LDL-C)] in Korean. After excluding those with extreme intake values, the number of final subjects included in the analysis was 4,662 Korean adults aged over 20 years (1,961 men, 2,701 women) who participate in the 2005 Korean National Health and Nutrition Examination Survey. The subjects were divided into four or five groups; none-alcohol consumption group, moderate alcohol consumption group ( or = 70 g/d in men, > or = 30 g/d in women). Odds ratios (ORs) were estimated from logistic regression adjusting for potential covariates. Alcohol consumption was inversely associated with low HDL-C in both men and women. However, heavy alcohol intake (> or = 70 g/d) significantly increased risk for hypertension, DM, and hypertriglyceridemia in men. The frequency of alcohol intake was also associated with CHD risk. The risk for low HDLC was decreased with alcohol consumption (> or = 1 times/wk), but frequent alcohol intake (> or = 4 times/wk) increased the risk for hypertension. This study revealed that moderate alcohol consumption has protective effect on CHD-related risk factors in Korean population.

Protective actions of Rubus coreanus ethanol extract on collagenous extracellular matrix in ultraviolet-B irradiation-induced human dermal fibroblasts

Solar ultraviolet (UV) irradiation leads to distinct changes in the skin connective tissues by degradation of collagen, which is a major structural component in the extracellular matrix. UV irradiation induces the production of matrix metalloproteinases (MMP) capable of attacking native fibrillar collagen and responsible for inhibiting the construction of collagenous extracellular matrix. In this study, we attempted to investigate the protective actions of Rubus coreanus ethanol extract (RCE) on the MMP production and the consequent procollagen/collagen degradation in UV-B-irradiated human dermal fibroblasts. The analytical data showed that Rubus coreanus ethanol extract was mostly comprised of cyanidin 3-rutinoside. Pre-treatment of fibroblasts with this extract inhibited UV-B-induced production of MMP-1, MMP-8 and MMP-13 in dose-dependent manners. In addition, Western blot analysis and immunocytochemical staining assay revealed that RCE markedly augmented the cellular levels of procollagen/collagen declined in UV-B-exposed dermal fibroblasts. These results demonstrate that RCE blocks UV-B-induced increase of the collagen degradation by inhibiting MMP production. Thus, RCE may act as an agent inhibiting excessive dermal collagen degradation leading to the skin photoaging.

Resveratrol blunts tumor necrosis factor-alpha-induced monocyte adhesion and transmigration

The leukocyte recruitment and transmigration across the endothelial barrier into the vessel wall are crucial steps in atherosclerosis. Leukocyte trafficking on the endothelium is elicited by induction of endothelial adhesion molecules, and its transmigration is mediated by degradation of basement membrane proteins through enzymatic activity of matrix metalloproteinases (MMP). The current study investigated whether resveratrol, a polyphenol present in grapes and red wine, was capable of inhibiting leukocyte adhesion to tumor necrosis factor (TNF)-alpha-activated endothelium. It was found that resveratrol inhibited the TNF-alpha-activated endothelial expression of vascular cell adhesion molecule-1 in a dose-dependent manner. In addition, resveratrol hampered THP-1 monocyte adhesion to activated endothelial cells. This study further examined whether resveratrol interfered with transendothelial migration of leukocytes. The MMP-2 gelatinolytic activity of endothelial cells was enhanced by TNF-alpha, which was attenuated by an addition of > or =25 micrometer resveratrol. In addition, 25 micrometer resveratrol mitigated the MMP-9 activity of THP-1 cells, followed by a marked inhibition of transendothelial migration. These results demonstrated that resveratrol suppressed monocyte adhesion and migration induced by TNF-alpha through modulating expression of adhesion molecules and gelatinolytic activity of MMP. These findings suggest that dietary resveratrol may be therapeutic agent for inhibiting leukocyte recruitment into the subendothelium during inflammatory atherosclerosis.

Effect of Coenzyme Q10 and green tea on plasma and liver lipids, platelet aggregation, TBARS production and erythrocyte Na leak in simvastatin treated hypercholesterolmic rats

This study was conducted to investigate the hypocholesterolemic effect of simvastatin (30 mg/kg BW) and antioxidant effect of coenzyme Q10 (CoQ10, 15 mg/kg BW) or green tea (5%) on erythrocyte Na leak, platelet aggregation and TBARS production in hypercholesterolemic rats treated with statin. Food efficiency ratio (FER, ADG/ADFI) was decreased in statin group and increased in green tea group, and the difference between these two groups was significant (p<0.05). Plasma total cholesterol was somewhat increased in all groups with statin compared with control. Plasma triglyceride was decreased in statin group and increased in groups of CoQ10 and green tea, and the difference between groups of statin and green tea was significant (p<0.05). Liver total cholesterol was not different between the control and statin group, but was significantly decreased in the group with green tea compared with other groups (p<0.05). Liver triglyceride was decreased in groups of statin and green tea compared with the control, and the difference between groups of the control and green tea was significant (p<0.05). Platelet aggregation of both the initial slope and the maximum was not significantly different, but the group with green tea tended to be higher in initial slope and lower in the maximum. Intracellular Na of group with green tea was significantly higher than the control or statin group (p<0.05). Na leak in intact cells was significantly decreased in the statin group compared with the control (p<0.05). Na leak in AAPH treated cells was also significantly reduced in the statin group compared with groups of the control and CoQ10 (p<0.05). TBARS production in platelet rich plasma was significantly decreased in the groups with CoQ10 and green tea compared with the control and statin groups (p<0.05). TBARS of liver was significantly decreased in the group with green tea compared with the statin group (p<0.05). In the present study, even a high dose of statin did not show a cholesterol lowering effect, therefore depletion of CoQ10 following statin treatment in rats is not clear. More clinical studies are needed for therapeutic use of CoQ10 as an antioxidant in prevention of degenerative diseases independent of statin therapy.

Effects of taurine on plasma and liver lipids, erythrocyte ouabain sensitive Na efflux and platelet aggregation in Sprague Dawley rats

The effects of taurine on plasma and liver cholesterol, erythrocyte ouabain sensitive Na efflux and platelet aggregation were examined in Sprague Dawley rats fed control or 0.5% cholesterol with 0.2% cholate diet. Plasma and liver levels of total cholesterol were increased significantly (p<0.05) in rats fed cholesterol diet compared to the control, and taurine significantly decreased the elevated plasma level of cholesterol in rats fed cholesterol diet (p<0.05). HDL-cholesterol was decreased in groups fed the cholesterol diet regardless of taurine supplementation and the difference between groups with and without cholesterol was significant (p<0.01). Plasma triglyceride was decreased and liver triglyceride was increased both significantly (p<0.05) in rats fed cholesterol compared to the control. Plasma and liver triglyceride in rats fed taurine was decreased significantly compared to the control (p<0.05). Intracellular Na tended to be lower in rats fed cholesterol or taurine and higher in rats fed cholesterol plus taurine compared to the control. Na efflux through Na-K ATPase and the passive leak of Na was somewhat reduced in rats fed cholesterol or taurine and was augmented in rats fed cholesterol plus taurine compared to the control, which showed a similar trend to the intracellular Na. Taurine supplementation caused a suppression of Na efflux in groups fed control diet and restored the suppressed Na efflux in groups fed cholesterol. Platelet aggregation was significantly decreased in the group fed taurine compared to the control (p<0.05) and the group fed cholesterol plus taurine was also a little lower in aggregation than the group fed cholesterol. Microscopic examination showed that taurine prevented fatty liver in rats fed cholesterol diet. Taurine known for stimulating Na-K ATPase in some cell types rather decreased erythrocyte ouabain sensitive Na-K ATPase in the present study. Taurine had hypolipidemic and hypocholesterolemic effects and inhibited platelet aggregation which may be favorable for prevention of cardiovascular diseases.