Tetrahydrocurcumin is more effective than curcumin in preventing azoxymethane-induced colon carcinogenesis

Scope : Tetrahydrocurcumin (THC), a major metabolite of curcumin (CUR), has been demonstrated to be anti‐cancerogenic and anti‐angiogenic and prevents type II diabetes. In this present study, we investigated the chemopreventive effects and underlying molecular mechanisms of dietary administration of CUR and THC in azoxymethane (AOM)‐induced colon carcinogenesis in mice. Methods and results : All mice were sacrificed at 6 and 23 wk, and colonic tissue was collected and examined. We found that dietary administration of both CUR and THC could reduce aberrant crypt foci and polyps formation, while THC showed a better inhibitory effect than CUR. At the molecular level, results from Western blot analysis and immunohistochemistry staining showed that dietary CUR and THC exhibited anti‐inflammatory activity by decreasing the levels of inducible NOS and COX‐2 through downregulation of ERK1/2 activation. In addition, both dietary CUR and THC significantly decreased AOM‐induced Wnt‐1 and β‐catenin protein expression, as well as the phosphorylation of GSK‐3β in colonic tissue. Moreover, dietary feeding with CUR and THC markedly reduced the protein level of connexin‐43, an important molecule of gap junctions, indicating that both CUR and THC might interfer with the intercellular communication of crypt cells. Conclusion : Taken together, these results demonstrated for the first time the in vivo chemopreventive efficacy and molecular mechanisms of dietary THC against AOM‐induced colonic tumorigenesis.     

Protective effects of epigallocatechin gallate (EGCG) derivatives on azoxymethane-induced colonic carcinogenesis in mice

Epigallocatechin gallate (EGCG), the major polyphenol in green tea and a functional food ingredient/nutraceutical with health-promoting properties, was structurally modified by esterification with butyric and docosahexaenoic (DHA) acid in order to improve its lipophilicity and hence bioefficacy in vivo. The lipophilic derivatives of EGCG so-prepared were evaluated for their anticancer activity against azoxymethane (AOM)-induced colon carcinogenesis in mice. Formation of colonic aberrant crypt foci (ACF) was monitored as the biomarker of colorectal cancer (CRC). It was found that oral administration of EGCG derivatives led to reduced size of ACF in the mouse colon. EGCG–DHA esters were more effective than EGCG-butyrate in inhibiting the formation of ACF. The total number of large colonic ACF was remarkably decreased by treatment with EGCG derivatives, especially by the EGCG–DHA esters, which showed a 100% inhibition of large ACF formation. Two tumor-promoting enzymes, iNOS and COX-2 were also inhibited by EGCG derivatives to various extents at the expression level. The results suggest that the lipophilic ester derivatives of EGCG are effective in inhibiting colon carcinogenesis and may be good candidates for colon cancer prevention/treatment.     

The preventive role of breadfruit against inflammation‐associated epithelial carcinogenesis in mice

Artocarpus communis has been identified as a rich source of flavonoids and has been gaining attention for its potential chemopreventive abilities. In this study, methanol extracts from the fruit of A. communis (MEFA) and leaf of A. communis (MELA) were prepared, and their effects on inflammation‐associated skin tumorigenesis were assessed using mouse models, including 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) induced cutaneous inflammation as well as 7,12‐dimethylbenz[α]anthracene (DMBA) initiated and TPA‐promoted skin tumorigenesis. According to the results, both MEFA and MELA decreased the intensity of leukocyte infiltration in mouse dorsal skin and cutaneous edema induced by TPA, which appeared to be mediated by inhibition of proinflammatory genes (inducible nitric oxide synthase, cyclooxygenase‐2 (COX‐2), tumor necrosis factor‐α (TNF‐α), IL‐1β, and IL‐6) and proinflammatory mediators (TNF‐α, IL‐1β, and Prostaglandin E₂). In addition, topical application with MEFA or MELA effectively attenuated tumor incidence, multiplicity, volume, malignancy as well as angiogenesis of TPA‐stimulated skin tumor promotion in DMBA‐initiated mice. Notably, immunohistochemical stain showed that MEFA and MELA attenuated COX‐2 expression of both skin and tumor tissues in different animal tests, which may be closely related to the suppression of nuclear factor kappa B/activator protein signaling networks. These findings first demonstrate that flavonoid‐rich A. communis may exert potent anti‐inflammatory activity through modulation of COX‐2 in TPA‐activated skin and tumor tissues.     

THE ANTIOXIDATIVE POTENTIAL OF LYOPHILIZED CITRUS PEEL EXTRACT IN DIFFERENT MEAT MODEL SYSTEMS DURING STORAGE AT 20C

Antioxidative potential of lyophilized citrus (Citrus unshiu) peel extract in raw and cooked meat systems was investigated. Beef pork, chicken, and salmon patties were prepared without (control), with lyophilized citrus peel extract (0.1%, NICP), and with 20 kGy-irradiated, lyophilized citrus peel extract (0.1%, ICP). TBARS value showed that the addition of lyophilized citrus peel (NICP or ICP) inhibited the development of lipid oxidation of raw and cooked meat patties during storage for 8 days at 20C (P<0.05) except for raw chicken patty. Hunter color a*-values of the cooked meat patties treated with NICP or ICP were higher than those of the control (P<0.05). Irradiation of citrus peel extract did not show any notable changes in its antioxidant effect in the meat systems. Thus, the lyophilized citrus extract could be used as one of the natural antioxidants with the potential of cost-effectiveness and is environmentally friendly.     

微切变-助剂互作技术制备柑橘皮粉的保健功能研究

目的考察微切变-助剂互作技术制备的柑橘皮粉的保健功能,以促进柑橘皮的合理利用。方法将健康昆明小鼠随机分为空白对照组、粗粉组和微切助粉组,每组10只,空白对照组小鼠饲喂商品鼠粮,实验组小鼠分别饲喂含柑橘皮粗粉或经微切变-助剂互作技术处理柑橘皮制备的微切助粉鼠粮。连续饲养小鼠一定周期后,研究柑橘皮微切助粉对小鼠多种保健功能的影响。结果与对照组相比,柑橘皮微切助粉极显著地增加小鼠的体重,免疫器官指数,血清中抗体Ig G、Ig A和Ig M的含量和血清中SOD的水平,说明柑橘皮可提高小鼠免疫力。二甲苯所致小鼠耳肿胀试验证明柑橘皮微切助粉的耳肿胀抑制率为74.3%,且抗炎效果接近阿司匹林,表明柑橘皮具有非常好的抗炎作用。另外,柑橘皮微切助粉组小鼠的负重游泳时间(6.88±0.27 min)是对照组(4.67±0.18 min)的1.47倍,表明柑橘皮具有抗疲劳作用。与对照组相比,柑橘皮微切助粉极显著地缩短了戊巴比妥钠所致小鼠的入睡时间和延长了睡眠持续时间,表明柑橘皮具有镇静催眠作用。结论柑橘皮具有提高小鼠机体免疫力、抗炎、抗疲劳、镇静催眠的作用,且柑橘皮微切助粉的各种保健效果优于其粗粉。     

Effects of adlay bran and its ethanolic extract and residue on preneoplastic lesions of the colon in rats

BACKGROUND: Adlay (Coix lachryma‐jobi L. var. ma‐yuen Stapf) is a cereal crop used in traditional Chinese medicine and as a nutritious food. Epidemiologists have suspected that the low cancer rates in southeastern China might be related to adlay. Previous studies have shown that adlay has anti‐tumour and anti‐inflammatory activity. This study investigated the effect of adlay bran and its fractions on chemically induced colon carcinogenesis in rats. RESULTS: Adlay bran and its ethanolic extract and residue significantly reduced the number of preneoplastic aberrant crypt foci (ACF) and modified their mucin composition. The inhibitory effect of adlay bran ethanolic extract on ACF showed a dose dependence. Adlay bran and its ethanolic extract suppressed small ACF (one, two or three crypts) and ACF in the distal colon, while the residue suppressed large ACF (four or more crypts). CONCLUSION: These findings suggest the possibility that adlay bran and its ethanolic extract and residue inhibit colonic preneoplastic lesions in an early stage. Adlay and its fractions may have the potential to be developed as chemopreventive cereal products. Copyright © 2010 Society of Chemical Industry     

Anti‐inflammatory Potential of Quercetin‐3‐O‐β‐D‐(“2”‐galloyl)‐glucopyranoside and Quercetin Isolated from Diospyros kaki calyx via Suppression of MAP Signaling Molecules in LPS‐induced RAW 264.7 Macrophages

Diospyros kaki (DK) contains an abundance of flavonoids and has been used in folk medicine in Korea for centuries. Here, we report for the first time the anti‐inflammatory activities of Quercetin (QCT) and Quercetin 3‐O‐β‐(“2”‐galloyl)‐glucopyranoside (Q32G) isolated from DK. We have determine the no cytotoxicity of Q32G and QCT against RAW 264.7 cells up to concentration of 50 μM. QCT and Q32G demonstrated potent anti‐inflammatory activities by reducing expression of nitric oxide (NO), tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β, IL‐6 inducible NO synthase (iNOS), cyclooxygenase (COX)‐2, and mitogen‐activated protein kinase (MAPKs) in mouse RAW 264.7 macrophages activated with lipopolysaccharide (LPS). Both QCT or Q32G could decrease cellular protein levels of COX‐2 and iNOS as well as secreted protein levels of NO, PGE₂, and cytokines (TNF‐α, IL‐1β, and IL‐6) in culture medium of LPS‐stimulated RAW 264.7 macrophages. Immunoblot analysis showed that QCT and Q32G suppressed LPS‐induced MAP kinase pathway proteins p‐p38, ERK, and JNK. This study revealed that QCT and Q32G have anti‐inflammatory potential, however Q32G possess comparable activity as that of QCT and could be use as adjuvant to treat inflammatory diseases.     

D-101大孔吸附树脂分离纯化橘皮中的黄酮类物质

目的:研究D-101大孔吸附树脂分离纯化橘皮黄酮类物质的工艺条件。方法:采用静态和动态吸附-解吸附两种方法,以黄酮类物质吸附率和解吸附率为评价指标,考察橘皮提取液pH值、吸附液料比、静置吸附时间、洗脱液种类和洗脱液料比等影响因素。结果:D-101大孔吸附树脂分离纯化橘皮黄酮类物质的最佳工艺条件为提取液pH4.43,吸附液料比15:1(黄酮类物质溶液:大孔吸附树脂,mL/g)、静置吸附时间90min、洗脱液为95%乙醇溶液、洗脱液料比25:1(95%乙醇溶液:大孔吸附树脂,mL/g)。结论:该方法简单、可行,能够用来分离纯化橘皮中黄酮类物质。     

Isolation and identification of an antioxidant flavonoid compound from citrus-processing by-product

BACKGROUND: Large amounts of citrus by‐products are released from juice‐processing plants every year. Most bioactive compounds are found in the peel and inner white pulp. Flavonoids are a widely distributed group of bioactive compounds. The methanolic extract of citrus peel powder has been shown to possess strong antioxidant activity. Therefore the aim of this study was to isolate the major antioxidant flavonoid compound from Citrus unshiu (satsuma) peel as citrus by‐product and evaluate its antioxidant activity. RESULTS: The major flavonoid isolated from C. unshiu peel was identified as quercetagetin. The structure of the compound was determined by tandem mass spectrometry and ultraviolet spectroscopy. Its antioxidant activity was assessed by assays of 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) radical, hydroxyl radical and intracellular reactive oxygen species (ROS) scavenging and DNA damage inhibition. Quercetagetin showed strong DPPH radical‐scavenging activity (IC₅₀7.89 µmol L^?1) but much lower hydroxyl radical‐scavenging activity (IC₅₀203.82 µmol L^?1). Furthermore, it significantly reduced ROS in Vero cells and showed a strong protective effect against hydrogen peroxide‐induced DNA damage. CONCLUSION: The results of this study suggest that quercetagetin could be used in the functional food, cosmetic and pharmaceutical industries. Copyright © 2011 Society of Chemical Industry     

绿茶、橘皮、大豆中酚类物质体外消化前后稳定性及抗氧化活性的研究

本研究以富含3类代表性酚类化合物（黄烷醇、黄烷酮和异黄酮）的3种食物（绿茶、橘皮、大豆）作为原料,模拟其在人体口胃肠中的体外消化过程。采用高效液相色谱-二极管阵列检测器/电喷雾-四极杆-飞行时间串联质谱检测器（HPLC-DAD/ESI-Q-TOF-MS）检测体外消化前后酚类化合物的种类及含量变化,同时测定不同消化阶段总酚含量（TPC）、总黄酮含量（TFC）以及抗氧化活性（DPPH、ABTS、FRAP、ORAC）的变化。结果表明,绿茶提取物中检测出4种酚类化合物（表没食子儿茶素、(+)-儿茶素、表没食子儿茶素没食子酸酯和表儿茶素没食子酸酯）,大豆提取物中检测出4种酚类化合物（大豆苷、染料木苷、大豆苷元和染料木素）,橘皮提取物中检测出2种酚类化合物（柚皮苷和橙皮苷）;三种食物提取物中,经过体外消化后,绿茶提取物中的酚类化合物最不稳定,除(+)-儿茶素外,其余3种酚类物质几乎降解完全,损失率均达95%以上。绿茶、橘皮、大豆提取物的TPC在胃消化阶段显著升高（P<0.05）,在肠消化阶段显著降低（P<0.05）。绿茶提取物TFC在口腔和胃消化阶段显著升高（P<0.05）,在肠消化阶段显著降低（P<0.05）。橘皮、大豆提取物TFC与TPC变化趋势一致。绿茶提取物的四种抗氧化活性经胃肠消化后呈先升高再降低的趋势。大豆提取液体外消化前后ABTS、FRAP抗氧化活性在口腔阶段显著降低（P<0.05）,DPPH、ORAC抗氧化活性在口腔、胃消化阶段显著升高（P<0.05）,在肠消化阶段显著降低（P<0.05）。橘皮提取液ORAC抗氧化活性在肠消化阶段显著升高（P<0.05）,ABTS、FRAP抗氧化活性在体外消化阶段均表现出和总酚含量变化一致的趋势。     

Polygonum viviparum L. inhibits the lipopolysaccharide‐induced inflammatory response in RAW264.7 macrophages through haem oxygenase‐1 induction and activation of the Nrf2 pathway

BACKGROUND: Polygonum viviparum L. (PV) is a member of the family Polygonaceae and is widely distributed in high‐elevation areas. It is used as a folk remedy to treat inflammation‐related diseases. This study was focused on the anti‐inflammatory response of PV against lipopolysaccharide (LPS)‐induced inflammation in RAW264.7 macrophages. RESULTS: Treatment with PV did not cause cytotoxicity at 0–50 µg mL^?1 in RAW264.7 macrophages, and the IC₅₀ value was 270 µg mL^?1. PV inhibited LPS‐stimulated nitric oxide (NO), prostaglandin (PG)E₂, interleukin (IL)‐1β and tumour necrosis factor (TNF)‐α release and inducible NO synthase (iNOS) and cyclooxygenase (COX)‐2 protein expression. In addition, PV suppressed the LPS‐induced p65 expression of nuclear factor (NF)‐κB, which is associated with the inhibition of IκB‐α degradation. These results suggest that, among mechanisms of the anti‐inflammatory response, PV inhibits the production of NO and these cytokines by down‐regulating iNOS and COX‐2 gene expression. Furthermore, PV can induce haem oxygenase (HO)‐1 protein expression through nuclear factor E2‐related factor 2 (Nrf2) activation. A specific inhibitor of HO‐1, zinc(II) protoporphyrin IX, inhibited the suppression of iNOS and COX‐2 expression by PV. CONCLUSION: These results suggest that PV possesses anti‐inflammatory actions in macrophages and works through a novel mechanism involving Nrf2 actions and HO‐1. Thus PV could be considered for application as a potential therapeutic approach for inflammation‐associated disorders. © 2012 Society of Chemical Industry     

Attenuation of iNOS and COX2 by blueberry polyphenols is mediated through the suppression of NF-κB activation

Treatment of BV2 microglial cells with blueberry extracts has been shown to be effective in reducing lipopolysaccharide (LPS)-induced proinflammatory mediators such as nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), inducible NO synthase (iNOS), and cyclooxygenase 2 (COX2). The current study explored the possibility that the down-regulation of iNOS and COX2 by blueberry extracts was mediated through NF-κB signaling pathway. A column-purified fraction of polyphenol-enriched blueberry extract (PC18) was used to treat LPS-activated BV2 cells. The results thus far showed that blueberry polyphenols significantly suppressed iNOS and COX2 promoter activities. In addition, blueberry polyphenols inhibited NF-κB nuclear translocation in LPS-activated BV2 cells. These findings suggested that the beneficial effects of blueberries may involve direct modulation of oxidative stress and/or inflammatory signaling cascades.     

Inhibition of lipid peroxidation,cyclooxygenase enzyme and human tumor cell proliferation by compounds in herbal water

A powdered mixture of dried herbs, “Panamrutham”, is sold in India for the preparation of “herbal drinking water”. The hot water extract of this herbal mixture gave lipid peroxidation (LPO), cyclo‐oxygenase (COX‐1 and ‐2) enzyme and human tumor cell proliferation inhibitory activities between 25 and 250 μg/mL. The bioassay‐guided purification of the water extract afforded a novel compound (1), along with phenolics (2, 4, 6, and 7) and sesquiterpenoids (3 and 5). The isolates were evaluated for LPO, COX‐1 and ‐2 enzyme and human tumor cell proliferation inhibitory activities. At 25 μg/mL, compounds 1–7 inhibited LPO by 22–73% and COX‐1 and ‐2 enzymes by 3–14% and 14–74%, respectively. Compounds 5 and 6 at 25 μg/mL showed growth inhibition of colon, gastric, lung, breast and central nervous system human tumor cell lines by 60 and 67, 43 and 60, 24 and 64, 34 and 65, 6 and 27%, respectively. Compounds 2, 4 and 7 displayed weak or moderate growth inhibition of colon, gastric and breast human tumor cell lines. This is the first report on the LPO inhibitory activities of compounds 1 and 3–7 and the COX and tumor cell proliferation inhibitory activities of compounds 1, 3–5 and 7.     

Protective effect of dried safflower petal aqueous extract and its main constituent,carthamus yellow,against lipopolysaccharide‐induced inflammation in RAW264.7 macrophages

BACKGROUND: Safflower, whose botanic name is Carthamus tinctorius L., is a member of the family Compositae or Asteraceae. Carthamus yellow (CY) is the main constituent of safflower and is composed of safflomin A and safflomin B. Dried safflower petals are used in folk medicine and have been shown to invigorate blood circulation, break up blood stasis, and promote menstruation. In addition, dried safflower petals contain yellow dyes that are used to color food and cosmetics. In this study, we investigated the effects of dried safflower petals aqueous extracts (SFA) and CY on lipopolysaccharide (LPS)‐induced inflammation using RAW264.7 macrophages. RESULTS: Our data showed that treatment with SFA (1–1000 µg mL^?1) and CY (1–2000 µg mL^?1) does not cause cytotoxicity in cells. SFA and CY inhibited LPS‐stimulated nitric oxide (NO), prostaglandin E₂ (PGE₂), and interleukin 1β (IL‐1β) release, through attenuation of inducible nitric oxide synthase (iNOS) and cyclooxygenase‐2 (COX‐2) protein expression. Further, SFA and CY suppressed the LPS‐induced phosphorylation of nuclear factor‐κB, which was associated with the inhibition of IκB‐α degradation. CONCLUSION: These results suggest that SFA and CY provide an anti‐inflammatory response through inhibiting the production of NO and PGE₂ by the downregulation of iNOS and COX‐2 gene expression. Thus safflower petals have the potential to provide a therapeutic approach to inflammation‐associated disorders. Copyright © 2010 Society of Chemical Industry     

Dietary grape seed extract ameliorates symptoms of inflammatory bowel disease in IL10‐deficient mice

Grape seed extract (GSE) is a by‐product of the wine industry, with abundant polyphenolic compounds known for their anti‐inflammatory and anti‐oxidative effects. Using IL10‐deficient mice (IL10KO), here we showed that GSE (1% of dry feed weight) ameliorated inflammatory bowel disease indices, increased colonic goblet cell numbers and decreased myeloperoxidase levels in the large intestine. Concomitantly, GSE supplementation attenuated inflammation, decreased the expression of pore forming tight junction protein claudin2, and increased levels of Lactobacilli and Bacteroides in the gut microbiota of IL10KO mice. In summary, our study shows that GSE has protective roles on inflammatory bowel disease through altering gut inflammation, tight junction protein expression, and gut microbiota composition.     

Chinese bayberry fruit extract alleviates oxidative stress and prevents 1,2-dimethylhydrazine-induced aberrant crypt foci development in rat colon carcinogenesis

The effects of Chinese bayberry fruit extract (CBFE) ingestion on hepatic and colonic oxidative stress and 1,2-dimethylhydrazine (DMH)-induced intestinal aberrant crypt foci (ACF) development in rats were investigated. Rats were administered DMH (35 mg/kg body weight) and were supplemented with CBFE (50 or 500 mg/kg body weight every day) for 16 weeks. Results showed that DMH consumption induced intestinal ACF development and adenoma or adenocarcinoma formation, which were significantly reduced with CBFE supplement. The CBFE treatments increased reduced glutathione levels and activities of superoxide dismutase, catalase and glutathione reductase, in both hepatic and colonic tissues; however, the activities of glutathione-S-transferase and glutathione peroxidase were inhibited. These results indicate that CBFE, rich in phenolic compounds, effectively inhibits DMH-induced ACF and colonic tumour development by alleviating oxidative stress.