Jiyoung Moon

Antiobesity effects of quercetin-rich onion peel extract on the differentiation of 3T3-L1 preadipocytes and the adipogenesis in high fat-fed rats.

The aim of the present study was to examine the effect of quercetin-rich onion peel extract (OPE) on anti-differentiation in 3T3-L1 preadipocytes and the antiobesity in high-fat fed rats. We found that lipid accumulations and TG contents in 3T3-L1 cells were markedly suppressed by OPE. The mRNA levels of activating protein (AP2) were down-regulated and those of carnitine palmitoyl transferase-1 α (CPT-1α) and fatty acid binding protein 4 (FABP4) were up-regulated by 75 and 100 μg/ml OPE. Body weight, retroperitoneal and mesenteric fat weights of SD rats were significantly lower in the 8 week high fat (HF) diet+0.72% OPE group than in the HF group. Peroxisome proliferator-activated receptor (PPAR)γ mRNA levels were down-regulated in the epididymal fat of OPE than those of control and HF, and significant down-regulation of CCAAT/enhancer binding protein (C/EBP)α mRNA levels in OPE was also observed than the control. The mRNA levels of CPT-1α and uncoupling protein-1 (UCP-1) were up-regulated by the OPE, while those of fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) were down-regulated in HF and OPE groups compared to control group. These results suggest that quercentin-enriched OPE may have antiobesity effects by suppressing preadipocyte differentiation and inhibiting adipogenesis.

Quercetin up-regulates expressions of peroxisome proliferator-activated receptor γ, liver X receptor α, and ATP binding cassette transporter A1 genes and increases cholesterol efflux in human macrophage cell line

Cholesterol-laden macrophages trigger accumulation of foam cells and increase the risk of developing atherosclerosis. We hypothesized that quercetin could lower the content of cholesterol in macrophages by regulating the expression of the ATP binding cassette transporter A1 (ABCA1) gene in differentiated human acute monocyte leukemia cell line (THP-1) cells and thereby reducing the chance of forming foam cells. Quercetin, in concentrations up to 30 μM, was not cytotoxic to differentiated THP-1 cells. Quercetin up-regulated both ABCA1 messenger RNA and protein expression in differentiated THP-1 cells, and its maximum effects were demonstrated at 0.3 μM for 4 to 8 hours in incubation. In addition, quercetin increased protein levels of peroxisome proliferator-activated receptor γ (PPARγ) and liver X receptor α (LXRα) within 2 hours of treatment. Because PPARγ and LXRα are important transcriptional factors for ABCA1, quercetin-induced up-regulation of ABCA1 may be mediated by increased expression levels of the PPARγ and LXRα genes. Furthermore, quercetin-enhanced cholesterol efflux from differentiated THP-1 cells to both high-density lipoprotein (HDL) and apolipoprotein A1. Quercetin at the dose of 0.15 μM elevated the cholesterol efflux only for HDL. At the dose of 0.3 μM, quercetin demonstrated effects both on HDL and apolipoprotein A1. Our data demonstrated that quercetin increased the expressions of PPARγ, LXRα, and ABCA1 genes and cholesterol efflux from THP-1 macrophages. Quercetin-induced expression of PPARγ and LXRα might subsequently affect up-regulation of their target gene ABCA1. Taken together, ingestion of quercetin or quercetin-rich foods could be an effective way to improve cholesterol efflux from macrophages, which would contribute to lowering the risk of atherosclerosis.

Influence of quercetin-rich onion peel extracts on adipokine expression in the visceral adipose tissue of rats.

We examined the effects of quercetin‐rich onion peel extract supplementation on adipokine expressions from adipose tissues in a diet‐induced obese animal model. Male Sprague‐Dawley rats (n = 24) were randomly assigned into control (n = 8), high fat diet (HF, n = 8) and high fat diet with onion peel extract (HFOE, n = 8). After 8 weeks, serum biochemical parameters, weights of adipose tissues (epididymal, perirenal and mesenteric fats) and adipokine mRNA levels (adiponectin, IL (interleukin)‐6 and visfatin) along with PPAR (peroxisome proliferator‐activated receptor) γ2 from adipose tissues were measured. After the 8 week supplementation, mesenteric fat weights were lower in the HFOE group than the HF group (p < 0.05). Adiponectin mRNA levels (mesenteric fats) were remarkably higher in the HFOE group than the other groups (p < 0.05 for both). Levels of PPARγ2 mRNA (mesenteric fats) were significantly higher in the HF group (p < 0.05) than those in the control group, but those in the HFOE group were not different from those in the control group. The IL‐6 mRNA levels (perirenal and mesenteric fats) were higher in the HF and HFOE groups, but those in the HFOE group were slightly lower than those in the HF group. In conclusion, quercetin‐rich onion peel extract supplementation influenced adipokine expressions, particularly from mesenteric fat, addressing the modulatory effect of this substance on obesity‐induced inflammation. Copyright

Inhibitory effect of Jeju endemic seaweeds on the production of pro-inflammatory mediators in mouse macrophage cell line RAW 264.7.

Seaweed has been used in traditional cosmetics and as a herbal medicine in treatments for cough, boils, goiters, stomach ailments, and urinary diseases, and for reducing the incidence of tumors, ulcers, and headaches. Despite the fact that seaweeds are frequently used in the practice of human health, little is known about the role of seaweed in the context of inflammation. This study aimed to investigate the influence of Jeju endemic seaweed on a mouse macrophage cell line (RAW 264.7) under the stimulation of lipopolysaccharide (LPS). Ethyl acetate extracts obtained from 14 different kinds of Jeju seaweeds were screened for inhibitory effects on pro-inflammatory mediators. Our results revealed that extracts from five seaweeds, Laurencia okamurae, Grateloupia elliptica, Sargassum thunbergii, Gloiopeltis furcata, and Hizikia fusiformis, were potent inhibitors of the production of pro-inflammatory mediators such as nitric oxide (NO), prostaglandin E2 (PGE2), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Based on these results, the anti-inflammatory effects and low cell toxicity of these seaweed extracts suggest potential therapeutic applications in the regulation of the inflammatory response.

Acanthoic acid induces cell apoptosis through activation of the p38 MAPK pathway in HL-60 human promyelocytic leukaemia

The present study was designed to evaluate the molecular mechanisms of the action of acanthoic acid (ACAN) from Acanthopanax koreanum (Araliaceae) against HL-60 human promyelocytic leukaemia cells. ACAN reduced the proliferation of HL-60 cells in a dose- and time-dependent manner accompanied by the induction of apoptosis. Possible mechanisms of ACAN-induced apoptosis were also examined. The results showed that ACAN-induced the phosphorylation of members of the mitogen-activated protein kinase (MAPK) family, c-Jun N-terminal kinase (JNK), p38 MAPK (p38), and extracellular signal-regulated kinase (ERK). A specific p38 MAPK inhibitor (SB203580) significantly blocked ACAN-induced apoptosis and cell viability, whereas an ERK inhibitor (PD98059) and JNK inhibitor (SP600125) had no effect. Moreover, ACAN induced the cleavage of caspase-3 and poly-ADP-ribose polymerase (PARP), and decreased the level of Bcl-xL, but these effects were inhibited by SB203580 pre-treatment. These results strongly suggest that ACAN may have cancer chemopreventive and therapeutic potential, due to its ability to activate the p38 MAPK-mediated signalling pathways.

Quercetin Up‐regulates LDL Receptor Expression in HepG2 Cells

Quercetin, an abundant flavonol found in fruits and vegetable, has been implicated in lowering the risk of cardiovascular disease that is often associated with high plasma levels of low density lipoprotein (LDL) cholesterol. Here we investigated whether quercetin could modulate the expression of LDL receptors (LDLR) in HepG2 cells and the possible underlying mechanisms to exert quercetins effects. We found that quercetin was able to induce LDLR expression with at least a 75 µ m concentration, which was accompanied by an increase in nuclear sterol regulatory element binding protein 2 (SREBP2). This effect was mediated by activation of c‐jun‐N‐terminal kinase (JNK) and extracellular signal‐regulated kinase (ERK) signalling pathways as implicated by experiments using chemical inhibitors of each pathway. When cells were challenged with protein synthesis inhibitors in quercetin‐activated LDLR transcription, LDL mRNA levels were not significantly affected by cycloheximide but puromycin abolished quercetin‐induced LDLR transcription. Taken together, we conclude that quercetin can initiate LDLR transcription by enhancing SREBP2 processing, but new protein synthesis might be necessary to exert a maximum effect of quercetin in the up‐regulation of the LDLR gene. Our findings demonstrate that quercetin strongly up‐regulated LDLR gene expression, which might elicit hypolipidemic effects by increasing the clearance of circulating LDL cholesterol levels from the blood. Copyright

Plasma ceruloplasmin as a biomarker for obesity: A proteomic approach☆☆☆

OBJECTIVES This study aimed to investigate new biomarkers of obesity particularly in relation with inflammation-associated proteins using protein differential display techniques. DESIGN AND METHODS Comparison of protein expression in plasma between non-obese (n=109, body mass index, BMI<25kg/m(2)) and obese (n=32, BMI≥25kg/m(2)) groups was carried out using two-dimensional gel electrophoresis (2-DE) analysis. ELISA was also performed for validation. RESULTS Among six differentially expressed protein spots, ceruloplasmin (Cp) and fibrinogen were over-expressed in obese group. Plasma Cp levels were significantly higher in obese group than non-obese group (34.0 ± 8.6 vs. 41.3 ± 12.7mg/dL, p<0.001) and positively correlated with age (r=0.253, p<0.005), BMI (r=0.265, p<0.001) and hsCRP (r=0.385, p<0.001). In stepwise multiple linear regression analysis, plasma Cp along with hsCRP were found predictors for obesity (adjusted β-coefficient=0.266, p<0.01). CONCLUSION Elevated plasma Cp levels were significantly associated with obesity, which may be suggested to be a marker of obesity.

Relationship between the estimates of desaturase activities and cardiometabolic phenotypes in Koreans.

In the present study, we evaluated the relationships of estimated desaturase activities with cardiometabolic risk factors including abdominal obesity, atherogenic lipoprotein phenotype and inflammation in Koreans. Ninety-three healthy volunteers participated in this cross-sectional study. LDL particle size was determined using gradient gel electrophoresis and inflammatory markers including C-reactive protein, soluble intercellular adhesion molecule-1, and adiponectin were measured. Stearoyl–coA desaturase, delta-6 desaturase and delta-5 desaturase were estimated as precursor to fatty acid ratios. The results showed that stearoyl–coA desaturase was correlated with body mass index (r = 0.235, p<0.05), triglyceride (r = 0.261, p<0.001), and HDL-cholesterol (r = −0.226, p<0.05). Stearoyl–coA desaturase was associated with only triglyceride (r = 0.283, p<0.01). Delta-6 desaturase was correlated with body mass index (r = 0.236, p<0.05), waist circumference (r = 0.218, p<0.05), triglyceride (r = 0.399, p<0.001), C-reactive protein (r = 0.333, p<0.001), soluble intercellular adhesion molecule-1 (r = 0.229, p<0.05), HDL-cholesterol (r = −0.325, p<0.01), LDL particle size (r = −0.297, p<0.01) and adiponectin (r = −0.233, p<0.05). In contrast, delta-5 desaturase was correlated with body mass index (r = −0.324, p<0.01), waist circumference (r = −0.276, p<0.01), triglyceride (r = −0.329, p<0.01), C-reactive protein (r = −0.215, p<0.05), HDL-cholesterol (r = 0.262, p<0.05) and LDL particle size (r = 0.278, p<0.01). Stepwise multiple regression analysis revealed that delta-6 desaturase (p<0.01) together with waist circumference (p<0.001) were found to be independent factors for determining plasma levels of C-reactive protein (R2 = 0.230). Estimated desaturase activities are closely associated with the features of cardiometabolic risk in Koreans.

Effect of quercetin-rich onion peel extracts on arterial thrombosis in rats

The aim of this study was to examine whether oral supplementation of quercetin-rich onion peel extract (OPE) influences blood coagulation and arterial thrombosis in Sprague-Dawley (SD) rats. 24 male rats, 5 weeks old, were divided into three groups with different diets (C: control, 2mg OPE: chow diet with 2mg OPE supplementation, 10mg OPE: chow diet with 10mg OPE supplementation) for 6 weeks. Blood coagulation parameters including prothrombin time (PT), activated partial thromboplastin time (aPTT) and platelet aggregation were examined. The OPE did not affect blood cholesterol levels but significantly decreased blood triglyceride and glucose levels. PT, aPTT and platelet aggregation were not significantly different among all tested groups. However, in vivo arterial thrombosis was significantly delayed in groups that were fed 2mg and 10mg OPE diets compared to the control group. In addition, the OPE greatly diminished thrombin-induced expression of tissue factor in human umbilical vein endothelial cells (HUVECs), a coagulation initiator. In addition, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling pathways activated by thrombin treatment were prevented by the OPE pre-treatment. These results indicate that OPE may have anti-thrombotic effects through restricting the induced expression of tissue factor via down-regulating mitogen-activated protein kinase (MAPK) activation upon coagulation stimulus, leading to the prolongation of time for arterial thrombosis.

Onion peel extract increases hepatic low-density lipoprotein receptor and ATP-binding cassette transporter A1 messenger RNA expressions in Sprague-Dawley rats fed a high-fat diet

In the present study, we hypothesized that onion peel extract (OPE) alters hepatic gene expression to improve blood cholesterol profiles. To investigate the effect of OPE to test our hypothesis, Sprague-Dawley rats were fed ad libitum for 8 weeks with the control, high-fat diet (HFD) or the high-fat diet with 0.2% OPE supplementations (HFD + OPE). Messenger RNA (mRNA) levels of genes in cholesterol metabolism and fatty acid metabolism were examined by semiquantitative reverse transcriptase polymerase chain reaction. The OPE in HFD reverted high fat-induced reduction in mRNA levels of sterol regulatory element-binding protein-2, low-density lipoprotein receptor, and hydroxyl-3-methylglutaryl coenzyme reductase genes in the liver comparable with the levels of the control group. Onion peel extract slightly increased stearoyl-coA desaturase 1 (SCD-1) expression compared with high-fat feeding. However, sterol regulatory element-binding protein-1c and fatty acid synthase were not affected by high-fat or OPE feeding. Onion peel extract also enhanced expression of ATP-binding cassette transporter A1, peroxisome proliferator-activated receptor γ2 and scavenger receptor class B type I genes when compared with high-fat feeding. However, OPE did not influence high fat-triggered changes in apolipoprotein A1 mRNA levels and liver X receptor α were not affected by either high-fat or OPE feeding. Our results suggest that OPE changes the expression of genes associated with cholesterol metabolism in favor of lowering blood low-density lipoprotein cholesterol and enhancing high-density lipoprotein cholesterol through increasing mRNA abundance of low-density lipoprotein receptor and ATP-binding cassette transporter A1 genes.