槲皮素对高脂日粮小鼠学习记忆能力的影响研究

探讨槲皮素对高脂日粮小鼠学习记忆的影响及可能机制。4周龄C57B/L雌性小鼠45只,随机分为三组:对照组（基础日粮）,高脂组（约20%脂肪）,槲皮素组（高脂日粮+0.01%槲皮素）。第26周进行Morris水迷宫实验,实验结束后取小鼠大脑皮层和海马组织测定氧化应激指标,荧光定量PCR检测海马组织中脑源性神经营养因子（BDNF）、核转录因子Nrf2及血红素单加氧酶（HO-1）的基因表达。结果显示,高脂组小鼠学习记忆能力显著下降,脑组织出现明显的氧化应激,Nrf2、HO-1和BDNF基因表达显著下调;槲皮素干预后,大脑氧化应激程度减轻,Nrf2、HO-1和BDNF基因表达上调,学习记忆能力得到显著改善。槲皮素改善高脂日粮小鼠学习记忆,可能与上调Nrf2/HO-1通路及BDNF的基因表达有关。      

高糖胁迫下槲皮素对酿酒酵母胞内损伤的保护作用与机制

以酿酒酵母S288c为模型,分析高糖胁迫下槲皮素对其胞内损伤的保护作用及机制。结果表明:与对照相比,高糖胁迫不影响酵母胞内活性氧(reactive oxygen species,ROS)水平,但显著降低了胞内酶比活力(P0.05);槲皮素处理后,与对照组和高糖组相比,酿酒酵母胞内ROS水平、超氧化物歧化酶和过氧化氢酶活力均显著下降(P0.05),而过氧化物酶(peroxidase,POD)比活力极显著升高(P0.01),说明POD比活力对高糖耐受性反应更为灵敏,可作为衡量高糖胁迫应激机制的重要生理指标,槲皮素可通过调节胞内POD比活力来提高机体的抗氧化能力。另外,实时荧光定量聚合酶链式反应结果表明高质量浓度葡萄糖显著抑制了酵母中GPD2和SUC2的表达水平(P0.05),并极显著提高了HXT1的表达水平(P0.01),而对GUT1的表达影响不显著;槲皮素处理后,高糖胁迫下酵母中GPD2、SUC2和HXT1的表达水平显著提高(P0.05),而GUT1无显著变化,说明槲皮素可能通过高渗透甘油途径、菊糖水解途径和己糖转运途径等来促进葡萄糖的分解代谢,从而达到保护机体细胞免受伤害的作用。结果表明槲皮素对高糖诱导的酿酒酵母胞内损伤具有保护作用,其作用机制可能与自身的抗氧化作用以及利用调节机体内高渗透甘油途径与糖的分解和转运途径存在一定的关联性。     

Influence of Cultivation System on Bioactive Molecules Synthesis in Strawberries: Spin-off on Antioxidant and Antiproliferative Activity

ABSTRACT:  Strawberries ( Fragaria ananassa  L., cv. favette) were studied to investigate the influence of cultivation practices (biodynamic, conventional) on the synthesis of bioactive molecules (ascorbic acid, ellagic acid, anthocyanins, flavonols) and to evaluate their antioxidant activity. Additionally, the  in vitro  bioactivity, in terms of antioxidant and antiproliferative activity, of the same strawberry samples in human colon carcinoma (Caco-2) cells was also studied. Compared to conventional strawberries, biodynamic fruits had a significantly higher content of ascorbic acid ( P  < 0.01), pelargonidin-3-glucoside ( P  < 0.05), cyanidin-3-glucoside ( P  < 0.01), ellagic acid ( P  < 0.01), quercetin, and kaempferol (both  P  < 0.01). Antioxidant activity of biodynamic strawberry crude extract was significantly higher than that of the conventional one ( P  < 0.05); in addition, while the antioxidant activity of water-soluble fraction was very similar in both biodynamic and conventional strawberries, that of water-insoluble fraction of biodynamic fruits was significantly higher ( P  < 0.05). The same crude extract of biodynamic strawberry samples effectively corresponded to an increase of bioactivity, in terms of both cellular antioxidant activity and antiproliferative activity, in Caco-2 cells differentiated to normal intestinal epithelia and in undifferentiated Caco-2, respectively. Further studies are needed to confirm whether the practice of biodynamic agriculture is likely to increase the bioactivity of other varieties of fruits and vegetables.     

Dietary quercetin alleviates diabetic symptoms and reduces streptozotocin‐induced disturbance of hepatic gene expression in mice

Quercetin is a food component that may ameliorate the diabetic symptoms. We examined hepatic gene expression of BALB/c mice with streptozotocin (STZ)‐induced diabetes to elucidate the mechanism of the protective effect of dietary quercetin on diabetes‐associated liver injury. We fed normal and STZ‐induced diabetic mice with diets containing quercetin for 2 wk and compared the patterns of hepatic gene expression in these groups of mice using a DNA microarray. Diets containing 0.1 or 0.5% quercetin lowered the STZ‐induced increase in blood glucose levels and improved plasma insulin levels. A cluster analysis of the hepatic gene expressions showed that 0.5% quercetin diet suppressed STZ‐induced alteration of gene expression. Gene set enrichment analysis (GSEA) and quantitative RT‐PCR analysis showed that the quercetin diets had greatest suppressive effect on the STZ‐induced elevation of expression of cyclin‐dependent kinase inhibitor p21(WAF1/Cip1) (Cdkn1a). Quercetin also suppressed STZ‐induced expression of Cdkn1a in the pancreas. Dietary quercetin might improve liver and pancreas functions by enabling the recovery of cell proliferation through the inhibition of Cdkn1a expression. Unexpectedly, in healthy control mice the 0.5 and 1% quercetin diets reduced the expression of ubiquitin C (Ubc), which has heat‐shock element (HSE) in the promoter region, in the liver.     

Effects of quercetin supplementation on lipid profile: A systematic review and meta-analysis of randomized controlled trials

Background: In spite of promising experimental findings, randomized controlled trials (RCTs) have yielded mixed results on the impact of quercetin supplementation on plasma lipid levels.

Aim: The present study aimed to quantify the effects of quercetin on plasma lipids using a meta-analysis of RCTs.

Methods: A systematic literature search of Medline was conducted for RCTs that investigated the efficacy of quercetin supplementation on plasma lipids comprising total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides. Weighted mean differences (WMDs) and 95% confidence intervals (CIs) were calculated for net changes in lipid concentrations using a random-effects model. Meta-regression analysis was conducted to assess the effect of quercetin dose and duration of supplementation as moderators on the calculated effect measures.

Results: Five RCTs totaling 442 subjects (221 in the quercetin and 221 in the control group) fulfilled the eligibility criteria and selected for analyses. Combined estimate of effect size for the impact of quercetin on plasma LDL-C (WMD: 1.43 mg/dL, 95% CI: ?0.92–3.78, p = 0.23), HDL-C (WMD: 0.26 mg/dL, 95% CI: ?0.74–1.25, p = 0.61) and triglycerides (WMD: ?9.42 mg/dL, 95% CI: ?27.80–8.96, p = 0.32) was not statistically significant. However, a borderline significant but clinically non-relevant increase in total cholesterol was observed (WMD: 3.13 mg/dL, 95% CI: ?0.01–6.27, p = 0.05). When the analysis was confined to the subgroups of studies with quercetin doses ≥500 mg/day and follow-up of ≥ 4 weeks, a significant increase in total cholesterol (WMD: 3.57 mg/dL, 95% CI: 0.21–6.92, p = 0.04) and a decline in triglycerides (WMD: ?24.54 mg/dL, 95% CI: ?33.09 to ?15.99, p < 0.00001) was observed, but LDL-C and HDL-C concentrations remained unchanged (p > 0.05). Changes in plasma triglycerides, but not other indices of lipid profile, were significantly associated with quercetin dose (slope: ?0.057; 95% CI: ?0.103 to ?0.010; p = 0.02) and duration of supplementation (slope: ?5.314; 95% CI: ?9.482 to ?1.147; p = 0.01).

Conclusion: Available evidence from RCTs does not suggest any clinically relevant effect of quercetin supplementation on plasma lipids, apart from a significant reduction of triglycerides at doses above 50 mg/day.     

Effect of allyl isothiocyanate on antioxidant enzyme activities,flavonoids and post-harvest fruit quality of blueberries (Vaccinium corymbosum L., cv. Duke)

The effect of allyl isothiocyanate (AITC) on antioxidant enzyme activities, flavonoid content, and fruit quality of blueberries var. Duke (Vaccinium corymbosum L.) was evaluated. Results from this study showed that AITC was effective in maintaining higher amounts of sugars and lower organic acids compared to untreated fruit during storage at 10 °C. However, AITC reduced antioxidant enzyme activities [superoxide dismutase (SOD), guaiacol peroxidase (G-POD), glutathione-peroxidase (GSH-POD), ascorbate peroxidase (AsA-POD), dehydroascorbate reductase (DHAR), monodehydroascorbate reductase (MDAR) and glutathione reductase (GR)] and non-enzyme components, ascorbate (AsA) and glutathione (GSH). AITC treatments also reduced the amount of phenolic acids (chlorogenic acid, myricetin 3-arabinoside, quercetin 3-galactoside, quercetin 3-arabinoside, and kaempferol 3-glucoside) and anthocyanins (delphinidin 3-galactoside, delphinidon 3-glucoside, delphinidin 3-arabinoside, petunidin 3-galactoside, petunidin 3-glucoside, petunidin 3-arabinoside, malvidin 3-galactoside, and malvidin 3-arabinoside) during storage at 10 °C. The results from this study indicate that AITC does not promote antioxidant property or scavenge constitutive reactive oxygen species (ROS), but maintain blueberry fruit quality through other mechanisms.     

Antiproliferative mechanisms of quercetin in rat activated hepatic stellate cells

Quercetin, rich in fruits and vegetables, has been used as a nutritional supplement because of its anti-inflammatory and antioxidative properties. Its positive effects on anti-hepatic fibrosis have also been suggested. However the anti-hepatofibrotic mechanisms upon which quercetin acts have yet to be well characterized. In the present study, we investigated the anti-proliferative effect of quercetin on activated hepatic stellate cells (aHSCs), the central role of hepatofibrosis, and evaluated the proteins involved in growth inhibition by a 2D gel electrophoretic analysis. Activated HSCs were isolated from Sprague Dawley rats and were spontaneously activated in vitro. Quercetin restrained the proliferation of aHSCs rather than quiescent HSCs and heptotcytes by inducing a G(1) arrest as examined by cell cycle analysis and evidenced by increased levels of p53, p21(CIP1/WAF1), as well as p27(KIP1), and decreased abundance of cyclins (D(1), D(2), A, E). An apoptosis through extrinsic pathway as demonstrated by elevated expression of Fas/Fas ligand (FasL), annexin V labeling, chromatin condensation, sub-G(1) fraction (7.39%), caspase-3 activity, was also observed. The 2D electrophoresis analysis revealed that quercetin negatively regulated protein molecules associated with metabolism (α-enolase, phosphoglycerate kinase), survival, cytokinesis (tubulin), and protein folding (protein disulfide isomerase A3) leading to cell growth retardation. Furthermore, quercetin might restrain HSC activation through reducing the levels of inflammatory cytokines (CXCL10, Midkine). Taken together, quercetin exerted diverse mechanisms to inhibit the growth of aHSCs. Proper consumption of quercetin could be beneficial to control the progression of heptofibrosis.     

Expression of selenium-binding protein 1 characterizes intestinal cell maturation and predicts survival for patients with colorectal cancer

To identify candidate genes involved in the development of colorectal cancer, we used cDNA microarrays to analyze gene expression differences between human colorectal tumors and paired adjacent normal mucosa. We identified approximately 3.5-fold significant downregulation of selenium-binding protein 1 (SBP1) in colorectal tumors compared to normal mucosa (p = 0.003). Importantly, stage III colorectal cancer patients with low tumor-SBP1 expression had significantly shorter disease-free and overall survival as compared with those patients with high tumor-SBP1 expression (p = 0.04 and 0.03, respectively). We further characterized the role of SBP1 in colorectal cancer in vivo and in vitro. In normal tissue, SBP1 was maximally expressed in terminally differentiated epithelial cells on the luminal surface of crypts in the large intestine. Consistent with this in vivo localization, SBP1 was upregulated during in vitro colonic cell differentiation along the absorptive (Caco-2) and secretory (HT29 Clones 16E and 19A) cell lineages. Downregulation (approximately 50%) of SBP1 expression by small interfering RNA in colonic cancer cells was associated with reduced expression of another epithelial differentiation marker, carcinoembryonic antigen (CEA), although PCNA and p21(WAF1/cip1 )expression were not altered. These data demonstrate that higher expression of SBP1 is associated with differentiation of the normal colonic epithelia and may be a positive prognostic factor for survival in stage III colorectal carcinoma.     

Ascorbate enhances iron uptake into intestinal cells through formation of a FeCl3–ascorbate complex

It has been well documented that ascorbate enhances iron uptake, with a proposed mechanism based on reduction to the more absorbable ferrous form. We have performed a study on the effects of ascorbate on ferric iron uptake in the human epithelial Caco-2 cell-line. Ascorbate increased uptake in a concentration-dependent manner with a significant difference between iron uptake and reduction. Uptake kinetics are characteristic of a non-essential activator and the formation of an Fe³⁺–ascorbate complex. This investigation provides evidence that ascorbate enhances the apical uptake of ferric iron into Caco-2 cells through the formation of a Fe³⁺–ascorbate complex.     

Normalization genes for quantitative RT-PCR in differentiated Caco-2 cells used for food exposure studies

Exposure of food products to small-intestinal-like Caco-2 cells, combined with a gene expression based response analysis can be a valuable tool to classify potential bioactive effects of food homogenates. In order to study changes in gene expression upon food exposure, a robust set of stably expressed genes is required for normalization. Here we present a set of reference genes suitable for RT-qPCR that has been validated for exposure studies with the intestinal-like Caco-2 cell line. This study identified ribosomal phosphoprotein P0 (RPLP0) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as best reference genes. The set can be extended with β-2-microglobulin (B2M), splicing factor 3A, subunit 1 (SF3A1), and mitochondrial ribosomal protein L19 (MRPL19). Food homogenates did provoke responses in the Caco-2 cells, as was demonstrated by changed expression of NAD(P)H Quinone dehydrogenase 1 (NQO1), Claudin 4 (CLDN4), Nitric Oxide Synthase 2 (NOS2), and ATP-binding cassette, subfamily B, member 1 (ABCB1) in the same experiment. Results indicate that: i) natural food homogenates can exert effects in Caco-2 cells, and ii) stability in expression of the reference genes is not due to a lack of response of the Caco-2 cells.     

中国主要水果抑制肝癌HepG2细胞和结肠腺癌Caco-2细胞增殖活性评价

分别采用Folin-Ciocalteu法测定了水果提取物的总酚含量,采用亚甲基蓝法测定了其抗人肝癌细胞Hep G2和人结肠腺癌细胞Caco-2增殖的活性,分析了总酚含量与抗Hep G2和Caco-2细胞增殖活性之间的相关性。结果显示,25种水果中李子的总酚含量最高(1686.08±96.94μmol GAE/100鲜果),西瓜(83.54±2.10μmol GAE/100 g鲜果)和哈密瓜(79.35±0.76μmol GAE/100 g鲜果)的总酚含量最低;在可测出抗增殖EC50值的水果中,李子(18.99±0.06 mg/m L)和番石榴(20.94±0.09 mg/m L)抗Hep G2细胞增殖的活性最强,梨的活性最弱(389.63±10.82 mg/m L)。李子抗Caco-2细胞增殖的活性最强(8.73±0.11 mg/m L),火龙果的活性最弱(388.07±7.04 mg/m L)。水果的抗Hep G2和Caco-2细胞增殖活性与其总酚含量相关性显著(R2=0.4147,p0.01;R2=0.4071,p0.05),该相关性表明水果中的多酚具有良好的抗肿瘤细胞增值的活性。     

Improved aqueous solubility,bioaccessibility and cellular uptake of quercetin following pH-driven encapsulation in whey protein isolate

The purpose of this study was to increase the water solubility and potential bioavailability of quercetin by encapsulation in whey protein isolate (WPI) based on a green, efficient pH-driven method. According to the results, the water solubility of quercetin increased by 346.9: times after loading into WPI nanoparticles. When the initial quercetin concentration was 0.25 mg mL⁻¹ and WPI was 2% w/v, the encapsulation efficiency reached 94.1%, the Z-average diameter was 36.63 nm, and the zeta potential was −36.4 mV at pH 7.0. The fluorescence spectroscopy assay suggested the molecular complexation of quercetin and WPI at pH 12.0. X-ray diffraction assay indicated the enclosure of amorphous quercetin in WPI. Correspondingly, the bioaccessibility increased from 2.76% to 31.23% and the Caco-2 cell monolayer uptake increased from 0% to 2.12% after nanoencapsulation. This work confirmed that the pH-driven method is an effective approach to prepare WPI–quercetin nanocapsules to improve physical and potentially biological properties of quercetin.     

The ability of <Emphasis Type="Italic">Lactobacillus</Emphasis> adhesin EF-Tu to interfere with pathogen adhesion

Probiotic bacteria play an important role in preventing widespread colonization of enteropathogens in human gastrointestinal tract. Lactobacillus plantarum CS24.2, isolated from child fecal sample, and L. rhamnosus GG, a widely accepted commercial probiotic strain, were examined in vitro for their ability to inhibit the colonization of enteropathogenic Escherichia coli (EPEC) and Salmonella enterica serovar Typhi (S. Typhi) on human intestinal epithelial cell line (Caco-2). Different adhesion assays such as competitive inhibition, adhesion inhibition, and displacement were carried out for the assessment of antagonistic activity of probiotic bacteria toward adhesion of enteropathogens to Caco-2 cells. Both the probiotic bacteria were able to inhibit pathogen colonization between 30–90% under different assay conditions. The gene coding for the known Lactobacillus adhesion factor—elongation factor Tu (EF-Tu)—was amplified from L. plantarum CS24.2 and cloned into E. coli expression vector, pET30(a). The partially purified recombinant EF-Tu was able to inhibit 50% adhesion of L. plantarum CS24.2 to Caco-2 cells but there was no effect on L. rhamnosus GG adhesion under competitive inhibition assay. To investigate the functional role of lactobacilli EF-Tu in pathogen inhibition to Caco-2 cells, competitive adhesion assay was carried out and there was significant reduction in the adhesion of E. coli (35.3%) and S. Typhi (47.7%) to Caco-2 cells.     

Transepithelial transport of 6-O-caffeoylsophorose across Caco-2 cell monolayers

The aim of this study was to clarify the transport behaviour and mechanism of caffeic acid analogue bearing a sugar-moiety, 6-O-caffeoylsophorose (CS), in Caco-2 cells. The absorption of CS was investigated by its transport across Caco-2 cell monolayers using a high-performance liquid chromatography-time-of-flight-mass spectrometry (LC–TOF-MS). The permeation of CS was concentration-dependent and reached the plateau at >6 mM. The apparent permeability (P_app) of CS in the apical-to-basolateral direction was 5.4 × 10⁻⁷ cm/s, while in the reversed direction the P_app value was significantly reduced (1.9 × 10⁻⁷ cm/s). CS transport was competitively inhibited by phloretin, an inhibitor of monocarboxylic acid transporter (MCT). Benzoic acid, an MCT substrate, also reduced CS transport. A less significant change of CS transport was observed across Caco-2 cell monolayers pretreated with quercetin, a suppressor of tight-junction. These findings strongly indicate that CS, a caffeic acid analogue bearing sophorose moiety, can be transported across Caco-2 cell monolayers via the MCT pathway.     

Sulfonation of Lactobacillus plantarum WLPL04 exopolysaccharide amplifies its antioxidant activities in vitro and in a Caco-2 cell model

Exopolysaccharide (EPS) of Lactobacillus plantarum WLPL04 and its sulfated EPS were systematically investigated for their antioxidant activities and effects on protecting the oxidative damage of Caco-2 cells from H₂O₂. Exopolysaccharide was successfully sulfonated from purified EPS as confirmed by Fourier-transform infrared spectroscopy, and the degree of sulfonation was 0.30. Both EPS and sulfated EPS showed antioxidant activities in vitro determined by 1,1-diphenyl-2-picrylhydrazyl, superoxide, and hydroxyl radical scavenging tests, and those activities of sulfated EPS were significantly enhanced at 1,000 μg/mL. Cell viabilities of Caco-2 in the range of 1 to 100 μg/mL of EPS and sulfated EPS showed no significant difference. In H₂O₂-damaged Caco-2 cells models, EPS and sulfated EPS significantly inhibited the enhancement of reactive oxygen species and malondialdehyde levels, and sulfated EPS enhanced the effects by 40.86% and 61.11% when compared with the purified EPS at the same concentration of 100 μg/mL, respectively. For the activities of antioxidant-related enzymes (superoxide dismutase, catalase, and glutathione peroxidase) and expression of genes (SOD2, GPX2, MT1M) on Caco-2 cells, strong protection abilities against the oxidative stress were displayed from both EPS and sulfated EPS, and sulfated EPS exhibited significant enhancement as compared with either EPS or control groups. In summary, sulfonation is an effective strategy for improving the antioxidant activities of EPS from L. plantarum WLPL04 in vitro and on Caco-2 cells.     

糖苷结构对苦荞黄酮促进葡萄糖在C2C12小鼠骨骼肌细胞中摄取作用的影响

苦荞是芦丁含量最高的粮食作物,但不同的加工过程会导致芦丁降解为单糖苷结构的异槲皮素及其前体槲皮素,进而影响生物活性。本研究比较芦丁及其降解产物（槲皮素、异槲皮素）这三类含有不同糖苷结构的黄酮在C2C12小鼠骨骼肌细胞中促进葡萄糖摄取的功效差异,并探究其作用机制。研究结果表明,苦荞与水接触会导致苦荞中的核心黄酮组分-芦丁降解为槲皮素。芦丁及其降解产物（槲皮素、异槲皮素）均能有效促进C2C12细胞对葡萄糖的摄取,作用顺序为:槲皮素>异槲皮素>芦丁。糖苷键的增加会降低槲皮素促进骨骼肌细胞糖摄取的效果。芦丁和异槲皮素不能激活胰岛素依赖型信号通路中的IRS-1表达及AKT的磷酸化,但高浓度下（400 μmol/L）,芦丁和异槲皮素可以通过非胰岛素依赖型的信号通路中的p-AMPK/p-ACC促进葡萄糖摄取作用,且异槲皮素的作用大于芦丁。槲皮素虽然抑制了IRS-1的表达及AKT的磷酸化,但槲皮素通过AMPK/ACC的磷酸化显著了促进C2C12细胞对葡萄糖的摄取。本研究揭示芦丁及其降解产物在细胞水平上的降血糖作用及机理的差异,对于充分理解苦荞黄酮降血糖机制提供了科学依据。     

表没食子儿茶素没食子酸酯体内外调节大鼠胆固醇代谢的机制

目的：探讨表没食子儿茶素没食子酸酯（epigallocatechin gallate,EGCG）对大鼠胆固醇代谢的影响及相 关机制。方法：在建立Caco-2细胞和大鼠肝细胞培养以及Wistar大鼠高脂模型基础上,研究胆汁酸跨膜转运抑制、 胆固醇摄取和外排、血清胆固醇水平变化以及胆固醇代谢相关基因表达水平,探讨EGCG对大鼠胆固醇代谢可能 的调节机制。结果：EGCG显著抑制甘氨胆酸钠和牛磺胆酸钠在Caco-2细胞内的跨膜转运（P＜0.05）;显著干预 Caco-2细胞对胆固醇的摄取（P＜0.05）,同时增强胆固醇在大鼠肝细胞中的外排。动物实验结果表明：EGCG组大 鼠血清中总胆固醇、甘油三酯及低密度脂蛋白胆固醇浓度与模型组相比显著下降（P＜0.05）,高密度脂蛋白胆 固醇浓度明显升高（P＜0.05）;肝脏苏木精-伊红染色显示EGCG组大鼠肝细胞脂肪变性程度降低;与模型组相 比,EGCG组大鼠肝脏中羟甲基戊二酸单酰辅酶A还原酶表达水平较低;胆固醇调节结合蛋白2、肝脏X受体α和 胆固醇7α羟化酶基因表达水平显著升高（P＜0.05）。结论：EGCG对体内胆固醇代谢的调节机制与其抑制肠道 胆汁酸重吸收、干扰胆固醇摄取、增强肝脏胆固醇外排以及调控相关基因表达有关,EGCG对胆固醇代谢具有综 合调节功能。     

Soybean (Glycine max L. Merr.) hexane extracts inhibit cellular fatty acid uptake by reducing the expression of fatty acid transporters

Intake of saturated and trans-fatty acids is a strong risk factor for coronary heart disease. We investigated the inhibitory effects of 2 hexane extracts from white (WBE) and black soybeans (BBE) on cellular fatty acid uptake in vitro. Transcellular uptake of elaidic acid (t18:1), a major trans-fatty acid present in processed foods, in Caco-2 monolayers was significantly reduced by 28.3 and 16.7% 60 min after WBE and BBE treatment, respectively. Results of flow cytometry (FACS) analysis showed significant reductions in boron-dipyrromethene (BODIPY) fluorescence-labeled fatty acid uptake by 35.4 and 40.2% with WBE and BBE treatment, respectively. BBE treatment significantly reduced the expression of fatty acid transport protein-4 and CD36 in Caco-2 cells, as determined by quantitative real time-polymerase chain reaction (qRT-PCR). Similar trends were found in WBE treatment, although to a lesser degree. These observations suggest that soybean extract may reduce fatty acid uptake and cellular fat accumulation by altering fatty acid transporter expression.     

Effects of flavonoids on the expression of the pro-inflammatory response in human monocytes induced by ligation of the receptor for AGEs

Increasing evidence has shown advanced glycation end products (AGEs) receptor ligation (RAGE) to be an important part of complex interactions of the oxidative stress and pro-inflammatory responses. In this study, flavonoids were used to monitor the protective effects against the oxidative damage and inflammation mediated by AGEs in human monocytes. S100B (RAGE ligand) treatment in human THP-1 monocytic cells (THP-1) significantly increased gene expression of the pro-inflammatory cytokines TNF-alpha and IL-1beta; chemokines MCP-1 and IP-10; adhesion factors platelet endothelial cell adhesion molecule (PECAM-1) and beta2-integrin; and pro-inflammatory cyclooxygenase-2 (COX-2). S100B treatment with quercetin and catechin in THP-1 cells had inhibitory effects on the expression of pro-inflammatory genes and protein levels. Quercetin and catechin could regulate S100B-activated oxidant stress-sensitive pathways through blocking p47phox protein expression. Treatment with quercetin and catechin could eliminate reactive oxygen species (ROS) to reduce oxidative stress stimulated by S100B in THP-1 cells. Quercetin and catechin also showed different regulatory abilities on mitogen-activated protein kinase (MAPK) signaling pathways by inhibiting protein expression in S100B-stimulated inflammatory responses in THP-1 cells. This study suggests that quercetin and catechin may be of benefit for diabetic vascular complications due to its antioxidant abilities against AGE-mediated oxidative stress through oxidative stress-sensitive and oxidative stress-responsive signaling pathways, which lead to inflammation in human monocytes.     

Protective effects of fermented onion juice containing higher amount of querectin aglycone against oxidative stress by 2,2′-azobis (2-amidinopropane) dihydrochloride (AAPH) treatment in Sprague–Dawley rats

It has been reported on beneficial effects of onion extracts containing a large amount of quercetin glucosides for several decades. This study was performed to investigate antioxidative and hepatoprotective effects of fermented onion (Allium cepa L.) extracts containing higher amount of quercetin aglycone (FOQ) against oxidative stress by 2,2′-azobis (2-amidinopropane) dihydrochloride (AAPH) treatment in rats. RP-HPLC analysis elucidated that the fermented onions contain larger amount of quercetin aglycone than that of fresh onions, and the content of quercetin aglycone in 1.0 kg of fresh and fermented onion pickles was 261.34 ± 19.47 and 360.25 ± 27.32 mg, respectively. In vitro free radical scavenging assay showed potently radical-quenching ability of FOQ against reactive oxygen species (ROS) such as hydroxyl, superoxide, and carbon-centered radical using electron spin resonance (ESR) spectroscopy. Biological parameters in plasma and liver tissue were evaluated with 36 healthy Sprague–Dawley rats in the experimental groups (n = 6); control (basal diet), AAPH treated, quercetin aglycone treated, ascorbate-AAPH treated, quercetin aglycone-AAPH treated and FOQ-AAPH treated group. The results revealed that quercetin aglycone or FOQ intakes could increase the level of glutathione (GSH), enzymatic activity of glutathione reductase (GSSG-R), and catalase (CAT), but could decrease the level of glutamate oxaloacetic transaminase (GOT), glutamate pyruvate transaminase (GPT), thiobarbituric acid reactive substance (TBARS) production with the abnormal levels caused by AAPH induced oxidative stress. Moreover, histological study for central vein (CV) area of hepatic lobule was illustrated that cytoplasmic phase near the CV in the qurecetin and FOQ pretreated before AAPH injection could be maintained with normal morphology like that of the control. The present study illustrated that the fermented onion extracts containing larger amount of quercetin aglycone (FOQ) have antioxidative activities against AAPH-induced carbon-centered radical, and its activity can present the protective effect against hepatic damage by oxidative stress similar with the ability of ascorbate (vitamin C).