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1.
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.  相似文献   

2.
Cancer is one of the leading causes of death worldwide. Since dietary factors have been connected to a reduced risk of a diversity of human cancers, in this study we investigated the effects of tomato powder (TP) on the development of azoxymethane (AOM)‐induced colorectal cancer in Wistar rats, and possible mechanism(s) by which TP shows its chemopreventive activity. Here we show that TP added to feed at 5% rate decreases the rate of aberrant crypt foci (ACF) and reduces the development of adenocarcinoma and growth of AOM‐induced colorectal cancer in rats. In addition, we demonstrate that TP supplementation shows its chemopreventive activities through inhibition of cyclooxygenase‐2 (COX‐2) expression via NF‐κB pathway and promotion of apoptosis, as well as regulating Nrf2/HO‐1 signaling pathway in colorectal tissue of AOM‐treated rats. Our findings identify an intimate connection between dietary supplementation of TP and the decreased risk of colorectal cancer in rats, and suggest that consumption of TP would be a natural candidate for the prevention of colorectal cancer in men.  相似文献   

3.
Citrus peel or its extract has been reported to exhibit a broad spectrum of biological activity. Herein, we report the first investigation of inhibitory effects of a formulated product from citrus peel extract, gold lotion (GL), on azoxymethane‐induced colonic tumorigenesis. We have demonstrated that oral feeding of GL decreased the number of aberrant crypt foci (ACF), particularly large size of ACF in colonic tissues of mice. Both gene and protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase‐2 (COX‐2) were suppressed by GL treatment. The in vivo data have revealed for the first time that the citrus peel extract–GL–is an effective antitumor agent mechanistically downregulating the protein levels of iNOS, COX‐2, ornithine decarboxylase, vascular endothelial growth factor, and matrix metallopeptidase 9 in colonic tissues of mice, suggesting that GL is a novel functional natural product capable of preventing inflammation‐associated colon tumorigenesis.  相似文献   

4.
The non-digestible fraction (NDF) of common bean (Phaseolus vulgaris L.) cultivar Bayo Madero was evaluated for its chemopreventive effect on azoxymethane (AOM) induced aberrant crypt foci (ACF) in rats. Diets containing cooked beans (CB) or its non-digestible fraction (NDF) were fed to 72 male rats after 2 azoxymethane injections (15 mg kg(-1) of body weight once a week for 2 weeks). ACF number, short chain fatty acids (SCFA) and β-glucuronidase activity were measured in colon sections from rats sacrificed 7 weeks after the last AOM injection. Food intake and weight gain of rats were unaffected by CB and NDF. CB and NDF suppressed the AOM-induced formation of ACF (0.8 and 1.5 ACF/distal zone, respectively vs. 6.6 ACF/distal zone based on methylene blue stain) and lowered β-glucuronidase activity in cecal, colonic and fecal content compared to AOM group. SCFA production was not significantly different among fecal, cecal and colonic content. These results indicate that CB and NDF from Bayo Madero provide direct chemoprotection against early stage of azoxymethane (AOM)-induced colon cancer in rats.  相似文献   

5.
Cocoa is a rich source of bioactive compounds with potential chemopreventive ability but up to date its effectiveness in animal models of colon carcinogenesis has not been addressed. Herein, we investigated the in vivo effect of a cocoa-rich diet in the prevention of azoxymethane (AOM)-induced colon cancer and the mechanisms involved. Our results showed that cocoa feeding significantly reduced AOM-induced colonic aberrant crypt foci formation and crypt multiplicity. Oxidative imbalance in colon tissues seems to be prevented by cocoa as indicated by reduced oxidation markers levels and increased enzymatic and non-enzymatic endogenous defences. Cocoa-rich diet also exhibited antiproliferative effects by decreasing the levels of extracellular regulated kinases, protein kinase B and cyclin D1 together with pro-apoptotic effects evidenced by reduced Bcl-x(L) levels and increased Bax levels and caspase-3 activity. Our findings provide the first in vivo evidence that a cocoa-rich diet may inhibit the early stage of colon carcinogenesis probably by preventing oxidative stress and cell proliferation and by inducing apoptosis.  相似文献   

6.
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  相似文献   

7.
Sheep dairy products containing prebiotic and probiotic ingredients may have health-promoting properties. Thus, this study evaluated the effects of sheep milk ice cream [conventional full-fat (CONV), full-fat enriched with probiotic (PROB, 100 mg % wt/wt of Lacticaseibacillus casei 01), or nonfat synbiotic (SYNB, Lacticaseibacillus casei 01 and inulin, 10% wt/wt)] on carcinogen-induced colonic crypt cytotoxicity and premalignant lesion development. Male Swiss mice received 2 doses of colon carcinogen azoxymethane (AOM, 15 mg/kg of body weight) at wk 3 and 4. Two weeks before and during AOM administrations (4 wk) mice were treated with CONV, PROB, or SYNB by gavage (10 mL/kg). Mice were euthanized at wk 4 or 25 (n = 5 or 10 mice/group, respectively). At wk 4, a significant reduction in micronucleated colonocytes was observed in PROB and SYNB groups, and a significant decrease in both p53 expression and apoptosis indexes in colonic crypts was observed in SYNB group. At wk 25, both PROB and SYNB interventions reduced the mean number of colonic premalignant lesions. However, only SYNB group showed lower incidence and number of high-grade premalignant lesions in the colonic mucosa. These findings indicate that PROB or SYNB sheep milk ice cream, especially SYNB intervention, can reduce chemically induced mouse colon carcinogenesis.  相似文献   

8.
The effects of dietary plant cerebroside on colon gene expression by DNA microarray analysis in 1,2-dimethylhydrazine (DMH)-treated mice were investigated. After 9 weeks of feeding with DMH, decreases and increases in the levels of expression of 110 and 145 genes were detected, respectively. Especially, the expression of Soggy-1, which suppresses the Wnt signaling pathway, was increased, while that of Ras-associated protein, which induces the mitogen-activated protein (MAP)-kinase pathway and is responsible for the development of aberrant crypt foci (ACF), was decreased. The results of the present study indicated that dietary cerebroside in DMH-treated mice regulates the Wnt signaling and MAP-kinase pathways, and prevents the development of ACF in the large intestine.

PRACTICAL APPLICATIONS


Dietary plant cerebroside increased expression of Soggy-1 mRNA, which suppresses the Wnt signaling pathway, and decreased expression ofRas-associated protein, which induces the MAP-kinase pathway in 1,2-dimethylhydrazine (DMH)-treated mice. The results of the present study indicated that dietary cerebroside in DMH-treated mice regulates the Wnt signaling and MAP-kinase pathways, and prevents the development of aberrant crypt foci in the large intestine, thus being of potential use for nutraceutical applications.  相似文献   

9.
Male Fischer 344 rats were subcutaneously injected with azoxymethane (AOM) twice weekly at a dose of 15 mg/kg and were fed with freeze-dried (FD) samples of beer brewed without hops (non-hops beer), beer with hops at 4 times the amount of regular lager beer (x 4-hops beer), and isomerized hop extract (IHE) for the whole experimental period (I/PI) or for the post-initiation period (PI) only. Feeding FD beer samples at a dose of 1% significantly decreased the number of aberrant cryp foci (ACF) in the PI protocol over five weeks.x4-hops beer showed stronger inhibitory effects on the development of the numbers of aberrant crypts per focus and large ACF with four or more crypts than non-hops beer. Feeding IHE to rats at a dose of 0.01% or 0.05% in either the I/PI or PI experiment significantly reduced the numbers of ACF. Prostaglandin E2 (PGE2) levels in colonic mucosa of AOM-treated rats were significantly reduced by feeding of IHE. PGE2 production induced by lipopolysaccharide/interferon-gamma (LPS/IFN-gamma) in RAW264.7 cells was also reduced by treatment with IHE and isohumulone in a dose-dependent manner. These observations suggest that isohumulones show chemopreventive effects on ACF formation in rat colon by inhibiting the production of PGE2.  相似文献   

10.
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.  相似文献   

11.
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.  相似文献   

12.
Abstract: The effects of red meat consumption with and without fermentable carbohydrates on indices of large bowel health in rats were examined. Sprague‐Dawley rats were fed cellulose, potato fiber, or potato‐resistant starch diets containing 12% casein for 2 wk, then similar diets containing 25% cooked beef for 6 wk. After week 8, cecal and colonic microbiota composition, fermentation end‐products, colon structure, and colonocyte DNA damage were analyzed. Rats fed potato fiber had lower Bacteroides‐Prevotella‐Porphyromonas group compared to other diet groups. Colonic Bifidobacterium spp. and/or Lactobacillus spp. were higher in potato fiber and potato‐resistant starch diets than in the cellulose diet. Beneficial changes were observed in short‐chain fatty acid concentrations (acetic, butyric, and propionic acids) in rats fed potato fiber compared with rats fed cellulose. Phenol and p‐cresol concentrations were lower in the cecum and colon of rats fed potato fiber. An increase in goblet cells per crypt and longer crypts were found in the colon of rats fed potato fiber and potato‐resistant starch diets. Fermentable carbohydrates had no effect on colonic DNA damage. Dietary combinations of red meat with potato fiber or potato‐resistant starch have distinctive effects in the large bowel. Future studies are essential to examine the efficacy of different types of nondigestible carbohydrates in maintaining colonic health during long‐term consumption of high‐protein diets. Practical Application: Improved understanding of interactions between the food consumed and gut microbiota provides knowledge needed to make healthier food choices for large bowel health. The impact of red meat on large bowel health may be ameliorated by consuming with fermentable dietary fiber, a colonic energy source that produces less harmful by‐products than the microbial breakdown of colonic protein for energy. Developing functional red meat products with fermentable dietary fiber could be one way to promote a healthy and balanced macronutrient diet.  相似文献   

13.
A protective effect of sphingolipids on colorectal cancer (CRC) has been reported in certain mouse strains. It is unknown if sphingolipids are protective in a p53 deficiency mouse model of CRC. This study investigated the effect of sphingomyelin (SM) on intestinal sphingomyelinase (SMase) activity, colonic epithelial biology and azoxymethane (AOM)-induced CRC. Groups of wild-type (C57BL/6J) and p53+/- mice were fed 0.1% SM diet for 4 wk, administered a single AOM injection and then killed 6 h later to measure apoptosis and proliferation. Separately, both mouse types were fed 0.05% SM diet, administered three AOM injections and killed 33-38 wk later to measure tumour formation. SM significantly increased SMase activity and reduced proliferation (p < 0.05) in wild-type and p53+/- mice. SM did not regulate baseline apoptosis, apoptotic response to AOM or apoptosis in tumours, nor did it restore defective apoptosis in p53+/- mice. There was a nonsignificant trend to reduced tumour incidence with SM in wild-type (p = 0.15) and p53+/- (p = 0.12) mice. In conclusion, while increasing intestinal SMase activity and suppressing proliferation, SM did not promote any form of apoptosis and failed to achieve significant protection in these mice. Further investigation to understand the variable effect of SM in preventing CRC is warranted.  相似文献   

14.
Polymethoxyflavones (PMFs) and hydroxylated polymethoxyflavones exist exclusively in citrus genus, especially in the citrus peels which have been used as herbal medicine for several diseases for thousands of years. In this review, the natural occurrence, isolation and separation of PMFs; synthetic scheme of hydroxylated PMF preparation, especially the reaction mechanism of preparation of 5-hydroxylated PMFs; biotransformation and metabolic fate of PMFs; the preliminary study on PMF bioavailability and the close relationship among solubility, permeability, absorption and oral bioavailability are summarized. The published bioactivity data on anti-inflammatory, anti-cancer and anti-atherogenic properties of PMFs have also been detailed along with a report of new findings of hydroxylated PMFs and their potent biological activities.  相似文献   

15.
目的:探讨不同剂量酪蛋白糖巨肽(casein glycomacropeptide,CGMP)干预二甲肼处理的大鼠时,外周血和结肠组织内细胞因子水平的变化情况,从而推断CGMP对二甲肼处理的大鼠细胞因子网络的影响。方法:60 只Wistar雄性大鼠随机分为正常组、模型组、CGMP低剂量组、CGMP中剂量组和CGMP高剂量组。除正常组外,对每只大鼠每周腹腔注射二甲肼,剂量为30 mg/(kg•周),同时,3 个剂量CGMP组注射二甲肼的同时每天灌胃CGMP,剂量分别为10、50、100 mg/(kg•d)。15 周后,处死大鼠,取其结肠组织和血清,首先检测结肠末端异型隐窝灶个数,然后利用液相芯片法检测结肠组织和血清中的细胞因子的表达水平。结果:乳源CGMP对大鼠体质量影响没有显著性差异,乳源CGMP对大鼠内毒素和活性氧簇的水平具有显著的抑制作用,其抑制作用呈剂量依赖趋势。乳源CGMP可显著抑制异型隐窝灶的形成,且异型隐窝灶个数呈剂量依赖性降低。乳源CGMP可以显著抑制大鼠体内Th1/Th2类细胞因子的失衡,且呈剂量依赖趋势。结论:乳源CGMP具有改善二甲肼处理的大鼠结肠组织损伤的功能,其机制为乳源CGMP可以有效抑制二甲肼处理的大鼠体内异型隐窝灶的形成,并呈剂量依赖性,研究显示乳源CGMP可以下调大鼠体内IL-4等Th2类细胞因子的异常升高,促进IL-2等Th1类细胞因子的分泌,改善大鼠体内处于失衡状态的细胞因子网络。  相似文献   

16.
Sweet orange (Citrus sinensis L.) peel is a rich resource of flavonoids, especially polymethoxyflavones (PMFs). Citrus flavonoids exert a broad spectrum of biological activity, including antiproliferative and proapoptotic effects in cancer cells. We have recently shown that individual PMFs from orange peel induce Ca(2+)-mediated apoptosis in human breast cancer cells and that hydroxylation of PMFs is critical for enhancing their proapoptotic activity. Here, we report that the fraction of orange peel extract containing a mixture of non-hydroxylated PMFs (75.1%) and hydroxylated PMFs (5.44%) and the fraction containing only hydroxylated PMFs (97.2%) induce apoptosis in those cells as well. Treatment of MCF-7 breast cancer cells with these fractions inhibited growth and induced apoptosis associated with an increase in the basal level of intracellular Ca(2+). Effective concentrations of the hydroxylated PMFs fraction in inhibiting growth, inducing apoptosis, and increasing intracellular Ca(2+) were lower than those of the non-hydroxylated PMFs fraction. Our results strongly imply that bioactive PMFs from orange peel exert proapoptotic activity in human breast cancer cells, which depends on their ability to induce an increase in intracellular Ca(2+ )and thus, activate Ca(2+)-dependent apoptotic proteases.  相似文献   

17.
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.  相似文献   

18.
Scope : In this study, we evaluated the efficacy of lycopene against the growth of prostate cancer in vivo. Methods and results : Athymic nude mice were implanted subcutaneously with human androgen‐independent prostate carcinoma PC‐3 cells. They were supplemented with a low or a high dose of lycopene (4 and 16 mg/kg) and a single dose of β‐carotene (16 mg/kg) twice a week for 7 wk. At the end of the experiment, both lycopene and β‐carotene strongly inhibited the tumor growth, as evidenced by the decrease in tumor volume and tumor weight. High‐dosage lycopene and β‐carotene significantly decreased the expression of proliferating cell nuclear antigen in tumor tissues and increased the levels of insulin‐like growth factor‐binding protein‐3 in plasma. In addition, high‐dosage lycopene supplementation significantly decreased the vascular endothelial growth factor (VEGF) levels in plasma. In contrast, β‐carotene supplementation significantly increased the VEGF levels, as compared with tumor control group. Conclusion : Lycopene and β‐carotene supplementation suppressed the growth of prostate tumor cells, and the effects are likely associated with reduction of proliferation (attenuation of proliferating cell nuclear antigen expression) and with interference of the insulin‐like growth factor 1 signaling (increased plasma insulin‐like growth factor‐binding protein‐3 levels). Furthermore, the inhibition of VEGF by lycopene suggests that the antitumor mechanisms of lycopene also involve anti‐angiogenesis.  相似文献   

19.
The effects of kiwifruit on large bowel health were investigated in healthy rats. Four‐week old Sprague‐Dawley rats were given diets containing 10% homogenized green kiwifruit, gold kiwifruit or 10% glucose solution (control) over 4 or 6 wk. Green kiwifruit increased the fecal output compared to control. Growth of certain bacterial species in cecum was influenced by both green and gold kiwifruit. A significant increase in cecal Lachnospiraceae in rats fed the green kiwifruit diet was observed at week 4. At week 6, green and gold kiwifruit diets assisted in improving colonic barrier function by upregulating the expression of mucin (MUC)‐2, MUC3, Toll‐like receptor (TLR)‐4 or trefoil factor‐3 genes. Gold kiwifruit consumption increased the colonic goblet cells per crypt at week 6. Significant negative correlations between E. coli and β‐defensin 1 and TLR4 expression were observed. Consuming green and gold kiwifruit for 6 wk significantly altered the biomarkers of large bowel health; indicating that regularly consuming kiwifruit helps attain optimal digestive health.  相似文献   

20.
Scope: Dietary prebiotics show potential in anti‐diabetes. Dietary resistant starch (RS) has a favorable impact on gut hormone profiles, including glucagon‐like peptide‐1 (GLP‐1) consistently released, a potent anti‐diabetic incretin. Also RS reduced body fat and improved glucose tolerance in rats and mice. In the current project, we hypothesize that dietary‐resistant starch can improve insulin sensitivity and pancreatic β cell mass in a type 2 diabetic rat model. Altered gut fermentation and microbiota are the initial mechanisms, and enhancement in serum GLP‐1 is the secondary mechanism. Methods and results: In this study, GK rats were fed an RS diet with 30% RS and an energy control diet. After 10 wk, these rats were mated and went through pregnancy and lactation. At the end of the study, pancreatic β cell mass, insulin sensitivity, pancreatic insulin content, total GLP‐1 levels, cecal short‐chain fatty acid concentrations and butyrate producing bacteria in cecal contents were greatly improved by RS feeding. The offspring of RS‐fed dams showed improved fasting glucose levels and normal growth curves. Conclusion: Dietary RS is potentially of great therapeutic importance in the treatment of diabetes and improvement in outcomes of pregnancy complicated by diabetes.  相似文献   

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