Browsing by Subject "flavonoids"
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Item Apigenin and Naringenin Increase Apoptosis and Decrease Proliferation via Transcriptional Regulation(2014-11-26) Daniels, Wesley DaniellePrevious studies have shown that apigenin and naringenin (flavonoids) suppress colon carcinogenesis by inducing apoptosis and suppressing proliferation in rats. The goal of this thesis was to test the hypothesis that apigenin and naringenin affect colonocyte proliferation and apoptosis by regulating expression of genes involved in microbial recognition (TLR-2, TLR-4), short chain fatty acid transport (MCT-1), cell cycle (p21), and apoptosis (Bax, Bcl-2, Fas, Noxa) as well as to determine if the mechanism of action was p53 dependent. Scraped mucosa was obtained from rats which received diets (0.02% naringenin, 0.1% apigenin, or basal) for 10 wks and were treated with AOM. YAMC and mp53 YAMC cells were treated with apigenin (0.1, 1, and 10 ?M), naringenin (0.1, 1, 10, 25, and 50 ?M), or estradiol (1 nM, positive control) for 96 h at non-permissive conditions. In vivo, apigenin suppressed MCT-1 (p<0.03), Bax (p=0.05), and Fas (p<0.05) expression compared to the control diet; and both flavonoids suppressed p21 (p<0.02) and TLR-4 (p<0.01) expression. Diet did not affect expression of Bcl-2 or TLR-2. 1 ?M or greater apigenin or naringenin treatment exhibited dose-dependent decreases (p<0.005) in cell numbers compared to vehicle in YAMCs, while no differences were identified in the mp53 YAMCs except with the highest treatment concentrations (p< 0.0001). No differences in proliferation were observed with apigenin or naringenin in either cell line, except with 20 ?M apigenin treatment (p< 0.0001). Apoptosis and gene expression data were inconclusive in vitro due to a lack of response in the positive control. Considering MCT-1 is a butyrate transporter and butyrate induces colonocyte p21 expression, the suppression of p21 expression may be a MCT-1 mediated effect. Reduction of MCT-1, p21, and TLR-4 expression by apigenin and naringenin suggests that these flavonoids may be able to reduce colon carcinogenesis through their influence on expression of genes involved in multiple pathways. The dose-dependent reduction in cell number induced by apigenin and naringenin is in part p53-mediated; however, the reduction in mp53 YAMC cells resulting from the greatest concentrations suggests alternate pathways can be induced. These reductions in cell number were not related to changes in proliferation.Item Breeding for Bioactive Compounds in Vigna Unguiculata L. (WALP.)(2013-04-30) Gawde, Archana JairamOne of the many ways to address health, obesity and hunger issues is genetic bio-fortification, a strategy of breeding or transforming staple crops with micronutrients and vitamins. This dissertation details efforts to bio-fortify bioactive compounds (phenols, antioxidants, condensed tannins, flavonoids and anthocyanins) in Vigna unguiculata, a staple legume grain crop. Approaches included screening of genetic variation in polyphenolic compositions to identify potential varieties and phenotypes, evaluating the impact of environment (drought stress) on these compositions and elucidating the underlying genetics of their inheritance. Our screening showed significant diversity among genotypes for phenols (2.05 ?15.48 mg GAE/g), condensed tannin (0.05 -15.29 mg CE/g) and antioxidant activity (4.0 -201.8 ?M TE/g). The highest levels of phenols and antioxidant activity were observed in genotypes with light brown, black and red seed coat color, and those with smooth texture and medium maturity (70-90 days). Red and black phenotypes showed the highest content of flavan-3-ols, flavonols and phenolic acids among all color groups, with values of 169 ?g CE/g, 26.17 ?g QHE/g, 27.14 ?g GAE/g for red and 281 ?g CE/g, 23 ?g QHE/g and 25 GAE/g for black phenotypes. When studying the impact of drought stress, genotypeXtreatment and treatmentXyear interactions for bioactive compounds were significant when tested under irrigated and drought stress conditions. Anthocyanins showed a 14 % decrease under drought stress. The genotypes that were stable to drought stress are favorable for breeding programs in preparation towards climate change. An FTNIR method was established for high-throughput, non-destructive quantification of bioactive compounds. This was used in inheritance studies of bioactive compounds. Phenols, condensed tannins and flavonoids showed heterosis in F1 and exhibit transgressive segregation in F2 populations. The information presented in this manuscript will be useful for nutritional improvement of cowpeas, where potential genotypes and phenotypes with health benefits offered by enhanced contents of bioactive compounds can be improved further upon.Item Citrus Bioactive Compounds: Isolation, Characterization and Modulation of Bacterial Intercellular Communication and Pathogenicity(2012-07-16) Vikram, AmitThe secondary metabolites of citrus such as limonoids and flavonoids constitute an important part of human diet. The present work was undertaken to elucidate the effect of citrus limonoids and flavonoids on the bacterial cell-cell signaling in Vibrio harveyi, Escherichia coli O157:H7 and Salmonella Typhimurium LT2. The first experiment was focused on purification of limonoids from grapefruit and sour orange seeds. The limonoids were extracted using organic solvents and purified by chromatographic techniques. A total of ten limonoids (7 aglycones and 3 glucosides) were purified. Currently, simultaneous measurement of aglycones and glucosides of limonoids is not available. To address this limitation, an analytical method using high performance liquid chromatography was developed with the capability of measuring both aglycones and glucosides in a single run. Furthermore, its applicability in the fruit and juice samples was demonstrated. The third study investigated the V. harveyi cell-cell signaling inhibitory potential of purified limonoids. Isolimonic acid, ichangin, obacunone and nomilin were showed potent inhibitory activity. Furthermore, isolimonic acid and ichangin inhibit the signal transduction pathway by up-regulating the response regulator luxO. Isolimonic acid was also found to be a potent inhibitor of Escherichia coli O157:H7 cell-cell signaling in the fourth study. The results demonstrated that isolimonic acid inhibits the autoinducer/epinephrine mediated cell-cell signaling, biofilm and virulence in QseBC and QseA dependent fashion. Further investigations using limonin analogues, in the fifth study, demonstrated that the analogue limonin-7-methoxime inhibited the E. coli biofilm in type 1 pili and antigen 43 dependent-fashion, by preventing the binding of the adhesins to plastic surfaces. Another limonoid, obacunone was demonstrated to attenuate the Salmonella virulence by repressing Salmonella Pathogenicity Island 1 (SPI-1) in EnvZ/OmpR dependent mecahnism. The seventh study showed that naringenin, among the flavonoids, was the most potent inhibitor of V. harveyi and E. coli O157:H7 cell-cell signaling. Furthermore, naringenin was found to repress the (SPI-1) in PstS-HilD dependent fashion in the eighth study. In conclusion, the current project identified several limonoids and flavonoids with cell-cell signaling inhibitory property in three bacterial species.Item Postharvest irradiation treatment effect on grapefruit functional components and their role in prevention of colon cancer(Texas A&M University, 2005-11-01) Vanamala, Jairam Krishna PrasadThis dissertation examines the effects of postharvest treatment and processing on biologically active compounds of orange juice, and ??Rio Red?? grapefruit and their ability to prevent chemically induced colon cancer in rat model. The first study evaluated the differences in flavonoid content of commercial ??made from concentrate?? (MFC) orange juices and ??not from concentrate?? (NFC) orange and grapefruit juices. Total flavonoid content of MFC orange juices (53 mg/100 mL; n = 12) was significantly (P ≤ 0.05) higher than NFC orange juices (36.5 mg/100 mL; n = 14). The second study investigated the ionizing radiation and storage effects on bioactive compounds and quality of ??Rio Red?? grapefruit. Results showed that storage and irradiation significantly (P ≤ 0.05) affected the bioactive compounds in grapefruit, however, the effect of storage was prominent. The third study examined the influence of irradiation and freeze drying on bioactive compounds of grapefruit. Irradiation of grapefruit prior to freeze drying resulted in enhanced (P ≤ 0.05) flavonoid content (naringin and narirutin). Freeze drying markedly reduced (P ≤ 0.05) lycopene content. Freeze drying and irradiation reduced (P ≤ 0.05) volatile compounds (d-limonene and myrcene), with the exception of ethanol. In the fourth study suppression of colon cancer development in Sprague Dawley rats by natural and irradiated grapefruits and their functional compounds, naringin and limonin, were evaluated.The total number of aberrant crypts (AC; P = 0.02), number of high multiplicity AC foci (ACF; P = 0.01), and proliferative index (P = 0.02) were lower and apoptosis (P = 0.02) was higher in azoxymethane (AOM) injected rats on experimental diets. However, only natural grapefruit and limonin only suppressed AOM induced expansion (P = 0.008) of proliferative zone and also enhanced apoptosis more effectively than other experimental diets indicating that natural grapefruit and limonin may serve as better chemopreventive agents compared to IGFPP and naringin. The present study indicates that postharvest quarantine doses of irradiation slightly alter composition of bioactive compounds and in turn marginally reduce the chemopreventive ability of grapefruit against the promotion stage of colon cancer. These results warrant the necessity of testing the impact of post harvest treatments on fruits and vegetables chemopreventive ability.