Dietary apigenin suppresses IgE and inflammatory cytokines production in C57BL/6N mice

Flavonoids ubiquitously exist in plants, vegetables, fruits, and teas. We evaluated the effect of dietary apigenin, one of the well-known flavonoids, on the immune system in C57BL/6N mice. Mice were fed experimental diets containing apigenin for 2 weeks. After the experimental period, there was no significant difference in body and organ weights between the control and the apigenin group. The total immunoglobulin (Ig) E levels in mice fed apigenin were significantly suppressed, whereas levels of IgG, IgM, and IgA were not affected. We also examined the effect of the apigenin diet on cytokine expression in mice sera using a cytokine array. The production of regulated upon activation normal T cell expressed and secreted (RANTES) and soluble tumor necrosis factor receptor I (sTNFRI) in mice sera was down-regulated by the apigenin diet. These results suggest that a diet containing apigenin can reduce serum IgE and inflammatory cytokines such as RANTES and sTNFRI in mice.     

Oral administration of kefiran induces changes in the balance of immune cells in a murine model

The aim of the present study was to evaluate the effect of the oral administration of kefiran on the balance of immune cells in a murine model. Six week old BALB/c mice were treated with kefiran (300 mg/L) for 0, 2 and 7 days. Kefiran treatment increased the number of IgA+ cells in lamina propria after 2 and 7 days. Percentage of B220+/MHCII(high) cells in mesenteric lymph nodes (2 days) and Peyer's patches (7 days) was higher compared to untreated control mice. An increase of macrophages (F4/80+ cells) was observed in lamina propria and peritoneal cavity (2 and 7 days). In contrast, at day 7, macrophage population decreased in Peyer's patches. These results show the ability of kefiran to modify the balance of immune cells in intestinal mucosa. This property could be highly relevant for the comprehension of the probiotic effect attributed to kefir.     

Whole berries versus berry anthocyanins: interactions with dietary fat levels in the C57BL/6J mouse model of obesity

Male C57BL/6J mice received diets with either 10% of calories from fat (LF) or a high-fat diet [45% (HF45) or 60% (HF60) calories from fat] for 92 days (expt 1) or 70 days (expt 2). These were given with or without freeze-dried powders from whole blueberries (BB) or strawberries (SB) (expt 1) or purified anthocyanin extracts from BB or SB (expt 2). Body composition was determined utilizing Echo MRI. Berries added to the LF diet did not alter weight gain, final body weights, body fat, or protein (percent body weight) or diet (grams) or energy (kilocalories) intake. However, in both HF45- and HF60-fed mice, weight gain, final weights, body fat (percent), and epididymal fat weights increased and body protein decreased ( p < 0.01) compared to LF mice. In mice fed HF45 diet plus BB, body weight gains, body fat (percent of BW), and epididymal fat weights were significantly greater than those in the HF45-fed controls, whereas weights of mice fed SB HF were similar to those of HF controls. SB or BB feeding did not alter glucose tolerance, although glucose tolerance decreased with age and in HF45 versus LF mice. Baseline plasma glucose was lower in SB- versus HF45-fed mice. After 8 weeks, mice fed the HF60 diet plus purified anthocyanins from BB in the drinking water had lower body weight gains and body fat than the HF60-fed controls. Anthocyanins fed as the whole blueberry did not prevent and may have actually increased obesity. However, feeding purified anthocyanins from blueberries or strawberries reduced obesity.     

A matured fruit extract of date palm tree (Phoenix dactylifera L.) stimulates the cellular immune system in mice

The immunomodulatory effects of a hot water extract from matured fruit of the date palm tree (Phoenix dactylifera L.) were investigated in comparison to those of prune and fig fruit in mice. The number of spleen IFN-γ(+)CD4(+), IFN-γ(+)CD49b(+) and IL-12(+)CD11b(+) cells was highest in mice given the date extract-added diet. Polyphenols identified in the date extract, such as chlorogenic acid, caffeic acid, pelargonin and ferulic acid, stimulated IFN-γ mRNA expression significantly in mouse Peyer's patch cell cultures. Chlorogenic acid and caffeic acid also increased the number of IFN-γ(+)CD4(+) cells significantly, while some polyphenols increased the number of IFN-γ(+)CD49b(+) and IL-12(+)CD11b(+) cells significantly. On the other hand, a 70% ethanol-insoluble date extract treated with trypsin increased the number of IFN-γ(+)CD49b(+) and IL-12(+)CD11b(+) cells significantly. These results indicate that some polyphenols and polysaccharides present in date fruit stimulate the cellular immune system in mice.     

鹅肝酶解物对酒精性脂肪肝的改善作用

为探索鹅肝酶解物对酒精性脂肪肝的防治效果,以6周龄SD大鼠为研究对象,将其随机分为对照组、模型组,以及鹅肝酶解物高(GLH-H)、低剂量处理组(GLH-L),其中对照组以Lieber-DeCarli液体对照饲料喂养,其他各组以Lieber-DeCarli乙醇液体饲料喂养;GLH-H、GLH-L处理组分别给药600、200 mg·kg^-1 BW(体质量)GLH进行干预,对照组和模型组分别给予相同体积的生理盐水灌胃,试验共持续5周。试验结束后测定各试验组大鼠的体质量、肝脏指数、血清中尿素氮、总胆固醇、甘油三酯及炎症因子,分析大鼠肠道微生物的组成,并对各试验组大鼠肝脏病理切片进行观察。结果表明,GLH处理明显降低了酒精性脂肪肝大鼠的肝脏指数(P<0.05),改善了酒精性脂肪肝大鼠肝脏脂肪变性程度,显著降低了大鼠血清中的尿素氮、总胆固醇、甘油三酯及炎症水平(P<0.05)。高通量测序发现,GLH可改善大鼠肠道微生物紊乱的现象。综上,GLH对酒精性脂肪肝的发生具有一定的预防作用。本研究结果为酒精性脂肪肝治疗药物的研究提供了新思路。     

葡萄籽原花青素对肥胖大鼠肠粘膜的影响

为探究葡萄籽原花青素(GSP)对营养肥胖模型大鼠肠粘膜通透性的影响,本试验设置了正常、模型、低剂量、中剂量及高剂量5个处理组,其中正常组投喂普通饲料,灌胃3 mL蒸馏水;模型组和低、中、高剂量组选用32只高脂饲料诱导的肥胖大鼠,模型组灌胃蒸馏水,低、中、高剂量组分别灌胃75、162.5、250 mg·kg^-1BW·d^-1GSP,灌胃处理6周再禁食12 h后处死,经解剖后测定各处理组大鼠的生理生化相关指标。结果表明,高脂饲料造模成功率48.75%;与模型组相比,低、中、高剂量组大鼠D-乳酸、乳果糖/甘露醇排出率显著降低,回肠绒毛高度/隐窝深度、紧密连接蛋白Occludin和 ZO-1 表达量显著升高;高剂量组大鼠的回肠杯状细胞数显著升高。综上,葡萄籽原花青素可以改善肥胖应激导致的大鼠肠道粘膜屏障损伤,这在一定程度上揭示了葡萄籽原花青素减肥降脂的作用机理。     

造血器官机能障碍对家蚕存活性能的影响

为了研究造血器官机能障碍后家蚕免疫机能的变化，用重离子射线局部照射家蚕幼虫的造血器官，调查了造血器官机能障碍后不同饲料饲养条件下家蚕的体重、血淋巴中多酚氧化酶的活性、添食苏云金杆菌后的生存率及大肠杆菌注射后在体内诱导产生的应急蛋白质量的变化。结果表明：造血器官机能障碍后，血淋巴中多酚氧化酶的活性减弱，大肠杆菌注射后在体内诱导产生的应急蛋白质量显著减少，添食苏云金杆菌后的家蚕生存率明显下降；用桑叶饲养时5龄的体重几乎没有增加，而用无菌的人工饲料饲养时体重增加与对照蚕的差异不显著。由此得出结论：家蚕造血器官受到破坏后，引起由血球参与的细胞性反应和体内抗菌蛋白质参与的液性反应减弱，最终导致机体的免疫机能下降；而通过清洁饲养可以改善由造血器官机能障碍所带来的影响。     

芦笋对高脂饮食小鼠肠道内容物细菌多样性的影响

为探讨芦笋对高脂饮食小鼠肠道内容物细菌多样性的影响,设计动物试验,试验分成4组,其中,正常对照组饲喂基础饲料,高脂饮食组、高脂饮食芦笋组、高脂饮食降脂理肝汤组均喂食高脂饲料;每只小鼠每天灌胃2次,每次0.35 mL,正常组与高脂饮食组为蒸馏水,高脂饮食芦笋组为2.10 g·kg^-1芦笋液,高脂饮食降脂理肝汤组为1.19 g·kg^-1降脂理肝汤。试验结束后提取肠道内容物微生物总DNA,进行16S rDNA V4区基因组测序。结果表明,从操作分类单元(OTU)总数来看,正常对照组OTU总数有 1 264 种,高脂饮食组OUT总数为1 564 种,高脂饮食降脂理肝汤组和高脂饮食芦笋组OUT总数分别为 1 354 和1 654 种,表明芦笋液抑制、降脂理肝汤能促进肠道细菌OUT总数恢复至正常水平。样本群落(Alpha)多样性分析表明,高脂饮食芦笋组、高脂饮食降脂理肝汤组和正常对照组丰富度估计指数(Chao)、多样性指数(Shannon)、丰富度估计指数(ACE)及多样性指数(Simpson)均低于高脂饮食组,且高脂饮食芦笋组Shannon指数显著低于高脂饮食组。细菌门分类分析表明,高脂饮食芦笋组变形菌门(Proteobacteria)、放线菌门(Actinobacteria)相对丰度介于高脂饮食组与正常对照组之间,高脂饮食降脂理肝汤组厚壁菌门(Firmicutes)、拟杆菌门(Bacteroidetes)相对丰度介于高脂饮食组与正常对照组之间,蓝细菌(Cyanobacteria)相对丰度在各组间有差别,但差异不显著。本研究结果表明,芦笋通过改变肠道菌群结构达到了降脂的效果,为芦笋产品的进一步开发研究提供了理论依据。     

Antihyperlipidemic and body fat-lowering effects of silk proteins with different fibroin/sericin compositions in mice fed with high fat diet

The effect of silk protein with different fibroin/sericin compositions on body weight and lipid metabolism in high fat-fed mice was investigated. The animals were given experimental diets for 6 weeks: normal control (NC), high fat (HF) and high fat diet supplemented with F100 (pure fibroin, HF-F100), F81 (81:19 fibroin/sericin, w/w, HF-F81) or F50 (50:50 fibroin/sericin, w/w, HF-F50). The silk protein-fed mice showed markedly reduced body weight and enhanced lipid profile relative to the HF group. In general, the amount of body fat, triglyceride and total plasma cholesterol levels, atherogenic index and free fatty acid level tended to decrease, while the HDL-cholesterol level increased, with increased amount of sericin in the diet. This hypolipidemic effect was partly due to increased fecal lipid excretion, inhibition of lipogenesis and regulation of adipokine production. These findings illustrate that silk protein, particularly sericin, may be beneficial in the prevention of high fat diet-induced hyperlipidemia and obesity.     

Amelioration of obesity and glucose intolerance in high-fat-fed C57BL/6 mice by anthocyanins and ursolic acid in Cornelian cherry (Cornus mas)

Much attention has been focused on food that may be beneficial in preventing diet-induced body fat accumulation and possibly reduce the risk of diabetes and heart disease. Cornelian cherries (Cornus mas) are used in the preparation of beverages in Europe and also to treat diabetes-related disorders in Asia. In this study, the most abundant bioactive compounds in C. mas fruits, the anthocyanins and ursolic acid, were purified, and their ability to ameliorate obesity and insulin resistance in C57BL/6 mice fed a high-fat diet was evaluated. Mice were initially fed a high-fat diet for 4 weeks and then switched to a high-fat diet containing anthocyanins (1 g/kg of high-fat diet) and ursolic acid (500 mg/kg of high-fat diet) for an additional 8 weeks. The high-fat diet induced glucose intolerance, and this was prevented by anthocyanins and ursolic acid. The anthocyanin-treated mice showed a 24% decrease in weight gain. These mice also showed decreased lipid accumulation in the liver, including a significant decrease in liver triacylglycerol concentration. Anthocyanin and ursolic acid treated mice exhibited extremely elevated insulin levels. Both treatments, however, showed preserved islet architecture and insulin staining. Overall, these data suggest that anthocyanins and ursolic acid purified from C. mas fruits have biological activities that improve certain metabolic parameters associated with diets high in saturated fats and obesity.     

Hypolipidemic and Body Fat–Lowering Effects of Giant Embryo Brown Rice (Seonong 17 and Keunnunjami) in High‐Fat‐Fed Mice

The effects of giant embryo brown rice Seonong 17 and Keunnunjami, in comparison with that of ordinary normal brown rice, on the body weight and lipid profile in mice under a high‐fat diet condition were investigated. The animals were fed with experimental diets for eight weeks: normal control, high fat (HF), and high fat supplemented with normal brown rice, Seonong 17 rice, or Keunnunjami rice powder. Their body and fat weights, lipid profiles, lipogenic enzyme activities, and adipokine concentrations were determined. Significant differences between the animal groups were analyzed with Tukey's test (P < 0.05). A marked increase in the body weight and fat, plasma triglyceride and total cholesterol concentrations, and free fatty acid level were found in HF mice relative to the control group. On the other hand, diet supplementation with rice, particularly the giant embryo rice samples, significantly suppressed this high‐fat‐induced body weight gain and hyperlipidemia via regulation of lipogenesis and adipokine production. Both the Seonong 17 and Keunnunjami exhibited greater hypolipidemic and body fat–lowering effects than the normal brown rice. The results demonstrate that these giant embryo mutants may be beneficial as biomaterials for functional foods with antiobesity and hypolipidemic effects.     

Critical role of peroxisome proliferator activated receptor-δ on body fat reduction in C57BL/6J and human apolipoprotein E2 transgenic mice fed delipidated soybean

The consumption of soy protein and fiber reduces body fat accumulation; however, the mechanism of this effect has not been clearly understood. We investigated the antiobesogenic effect of soy protein and fiber in two different mouse models. Normolipidemic nonobese C57BL/6J and hyperlipidemic obese human apolipoprotein E2 transgenic mice were fed either delipidated soybean (DLSB) containing soy protein and fiber or a control diet. The DLSB-fed mice showed a significant reduction in body weight gain and adiposity compared with controls, in both C57BL/6J and apoE2 mice. All metabolic parameters were significantly improved in the DLSB group compared with controls: total cholesterol, low-density lipoprotein cholesterol, insulin, and leptin levels were significantly reduced. Adiponectin concentrations were significantly elevated, and glucose tolerance was improved. In both types of DLSB-fed mice, the specific induction of PPAR-δ protein expression was evident in muscle and adipose tissues. The expression of PPAR-δ target genes in the DLSB-fed mice was also significantly altered. Acetyl-CoA carboxylase-1 and fatty acid synthase levels in adipose tissue were downregulated, and uncoupling protein-2 in muscle was upregulated. Intestinal expression of fatty acid transport protein-4, cluster of differentiation-36, and acyl-CoA synthetase were significantly downregulated. We propose that marked activation of PPAR-δ is the primary mechanism mediating the antiobesogenic effect of soybean and that PPAR-δ has multiple actions: induction of thermogenesis in muscle, reduction of fatty acid synthesis in adipose tissue, and reduction of fatty acid uptake in intestinal tissue.     

Quillaja saponin can modulate ovalbumin-induced IgE allergic responses through regulation of Th1/Th2 balance in a murine model

Quillaja saponin is the extract from the balk of a South American tree, and it is considered to modulate immunological responses. We hypothesized that Quillaja saponin may change allergy-associated cytokine profile and antigen-specific immune responses. The purpose of this study is to investigate whether Quillaja saponin can suppress ovalbumin (OVA)-induced IgE-mediated allergic responses through promoting a dominant Th1 immune response. The spleen cells from BALB/c mice, which were primed by OVA, were used for an in vitro challenge test. The level of total and OVA-specific IgE, IL-4, IFN-gamma, and IL-12 was determined by enzyme-linked immunosorbent assay (ELISA). BALB/c mice were orally administered with saponin for 35 days. The mice were immunized intraperitoneally with OVA on days 14 and 21. After intraperitoneal challenge with OVA on day 35, anaphylactic symptoms were monitored. Total and specific IgE and IgG, specific IgG1 and IgG2a, and histamine levels in serum were analyzed by ELISA. The increase of IL-12 and IFN-gamma levels was observed in the presence of Quillaja saponin, while the IL-4 level was decreased. Furthermore, Quillaja saponin suppressed total and OVA-specific IgE secretion in spleen cells. Balb/c mice that were orally administered Quillaja saponin exhibited lower total and OVA-specific IgE and OVA-specific IgG secretions, whereas total IgG levels remained unchanged. Suppression of OVA-specific IgG1 and an increase of OVA-IgG2a were observed in mice fed saponin. Quillaja saponin also decreased serum histamine levels and diminished anaphylactic symptoms. The present study indicates that Quillajasaponin can suppress allergen-specific IgE-mediated reactivity in a murine model of food allergy, which results from shifting from a Th2-dominated to a Th1-dominated immune response.     

伏马菌素B1人工抗原的合成及鼠源多克隆抗血清的制备

本研究合成并鉴定伏马菌素B₁(FB₁)人工抗原,通过动物免疫制备敏感性高、特异性好的鼠源FB₁多克隆抗血清。采用碳二亚胺(EDC)法将FB₁分别与载体蛋白BSA和OVA偶联,合成免疫抗原FB₁-BSA和检测抗原FB₁-OVA,经鉴定后,分别按10和30μg/只的剂量免疫BALB/c小鼠,共免疫4次,每次间隔3周,最后1次免疫30d后,断尾采血,制备多抗血清。利用间接ELISA方法测定抗血清效价,间接竞争ELISA测定敏感性和特异性。结果表明,免疫的6只小鼠效价均达1∶104以上,3号小鼠多抗血清敏感性最好,半数抑制浓度IC₅₀为61.3ng/ml,且具有良好的特异性。本试验成功合成了FB₁人工抗原,并制备了敏感性高、特异性好的鼠源多克隆抗体血清,为FB₁单克隆抗体制备及其免疫学快速检测方法的建立奠定了基础。     

Dietary anthocyanin-rich tart cherry extract inhibits intestinal tumorigenesis in APC(Min) mice fed suboptimal levels of sulindac

A promising approach for cancer chemoprevention might be a combination therapy utilizing dietary phytochemicals and anticarcinogenic pharmaceuticals at a suboptimal dosage to minimize any potential adverse side effects. To test this hypothesis, various dosages of anthocyanin-rich tart cherry extract were fed in combination with suboptimal levels of the nonsteroidal anti-inflammatory drug sulindac to APCMin mice for 19 weeks. By the end of the feeding period, fewer mice that were fed the anthocyanin-rich extract in combination with sulindac lost more than 10% of body weight than mice fed sulindac alone. Mice that were fed anthocyanin-rich extract (at any dose) in combination with sulindac had fewer tumors and a smaller total tumor burden (total tumor area per mouse) in the small intestine when compared to mice fed sulindac alone. These results suggest that a dietary combination of tart cherry anthocyanins and sulindac is more protective against colon cancer than sulindac alone.     

Improvement of obesity phenotype by Chinese sweet leaf tea (Rubus suavissimus) components in high-fat diet-induced obese rats

Drinking an herbal tea to lose weight is a well-liked concept. This study was designed to examine the possible improvement of obesity phenotype by a new tea represented by its purified components, gallic acid, ellagic acid, and rubusoside (GER). Male obese-prone SD rats were given low-fat diet, high-fat diet, or high-fat diet plus GER at the dose of 0.22 g/kg of body weight for 9 weeks. GER significantly reduced body weight gain by 22% compared to the high-fat diet control group with 48% less abdominal fat gain. Food intake was not affected. Blood glucose was lowered in the GER-treated group, whereas serum triglycerides and cholesterol were significantly reduced by 50%. This improved obesity phenotype may be associated with the attenuated expression of vascular endothelial growth factor in preadipocyte 3T3-L1 cells. Although other underlying, possibly multiple, mechanisms behind the improved phenotype are largely unknown, the observed improvement of multiple obesity-related parameters by the new tea warrants further investigations.     

Similarity of fine specificity of IgA anti-gliadin antibodies between patients with celiac disease and humanized α1KI mice

Gliadins, and primarily α-gliadins containing several sequences such as aa 31-49, aa 56-88 (33-mer), aa 57-68, and aa 69-82, are critical in the induction of immune response or toxic reaction leading to the development of celiac disease (CLD). The role of IgA anti-gliadin antibodies (IgA AGA) is unknown. To this end, we prepared several humanized monoclonal IgA AGA using transgenic α1KI mice. Employing Pepscan with overlapping decapeptides of α-gliadin we observed a robust similarity between the specificity of humanized mouse monoclonal IgA AGA and IgA AGA from patients with florid CLD. The common immunodominant region included several sequential epitopes localized in the N-terminal part of α-gliadin (QFQGQQQPFPPQQPYPQPQPFP, aa 29-50, and QPFPSQQPYLQL, aa 47-58). Notably, IgA AGA produced by clones 8D12, 15B9, 9D12, and 18E2 had significant reactivity against sequences localized in the 33-mer, LQLQPFPQPQ (aa 56-65) and PQLPYPQPQPFL (aa 69-80). Humanized mouse monoclonal IgA AGA that have a known specificity are suitable as standard in ELISAs to detect serum IgA AGA of CLD patients and for studying the AGA pathogenic role in CLD, especially for analyzing the translocation of complex of specific IgA antibodies and individual gliadin peptides through enterocyte barrier.     

Kudzu (Pueraria lobata) vine ethanol extracts improve ovariectomy-induced bone loss in female mice

Bone-loss-improving action of kudzu vine ethanol extracts (PVEE) was clarified. PVEE was composed roughly of 80% fiber, 10% puerarin, 3.6% daidzin, 2.5% 6″-O-malonyldaidzin, and the other minor isoflavones. Ten-week-old ovariectomized (OVX) mice were fed diets containing PVEE (20 mg/kg body weight/day) for 8 weeks. The bone resorption markers (urinary deoxypyridinoline and tartrate-resistant acid phosphatase activity) was elevated in OVX mice and was significantly decreased in OVX mice that consumed PVEE for 8 weeks. Consistent with the decrease in the markers, the number of matured osteoclasts in the distal femur was diminished in OVX mice fed PVEE diets. PVEE diets also suppressed the decrease in femoral bone mineral density (BMD) by OVX. PVEE showed the affinity for estrogen receptor α and β nearly 1/10000 weaker than 17β-estradiol. No hypertrophy in the uterus by the PVEE diet was observed. These results suggest that PVEE could be a promising resource for a functional food that improves osteoporosis.     

Components and activity of polysaccharides from coarse tea

Coarse tea contained a high content of polysaccharide complex. Composed of polysaccharide and protein, the polysaccharide complex from tea (TPS) belonged to glycoprotein with the molecular weight () of (10.7-11.0) x 10(4). When mice (7 weeks old, C57BL/8) were injected with TPS, the levels of blood glucose (BG) in normal mice and model mice with high BG were decreased significantly by averages of 13.54 and 22.18%, respectively. The antibody concentration (OD(413 nm)) in the mice injected with 2.4 mg/mL TPS was increased evidently by 44.93% (p < 0.01). TPS treatment was beneficial not only for the subsequent production of interleukin (IL) 2 in spleen cells of adjuvant arthritis (AA) rats but also because it prohibited the body from producing too much IL-1 in AA rats. Treatment of diabetes with coarse tea in both China and Japan may be related to TPS and the content of TPS in coarse tea.