Non-anthocyanin phenolics in cherry (Prunus avium L.) modulate IL-6, liver lipids and expression of PPARδ and LXRs in obese diabetic (db/db) mice.

Anthocyanin-rich cherries are known for preventing/decreasing risk factors associated with obesity; however, the specific benefits exerted by cherry non-anthocyanin phenolics are not clear. Obese diabetic (db/db) mice fed a diet supplemented with anthocyanin-depleted cherry powder (cherry) were compared to db/db (obese) or lean counterparts (lean) fed a control isocaloric diet for 12 weeks. The reduced plasma interleukin (IL)-6 and improved liver health may be mediated by cherry fibre and non-anthocyanin phenolics. Benefits for liver health included reduction of lipids and protein carbonyls, and modulation of peroxisome proliferator-activated receptor (PPAR)δ mRNA to resemble levels in lean. Lack of plasma antilipidemic, improvement of antioxidant defenses, and PPARα/γ mRNA modulation in liver suggest cherry anthocyanins specific benefits. This is the first study to elucidate in vivo the potential benefits of cherry non-anthocyanin phenolics for diabetes-induced liver disorders and the importance of choosing processing technologies that preserve anthocyanins and health benefits of whole cherries.

Red raspberry (Rubus idaeus L.) intake decreases oxidative stress in obese diabetic (db/db) mice.

Red raspberry fruit intake was investigated on obese diabetic (db/db) mice for 8weeks. Animals fed isocaloric diets (5.3% freeze-dried raspberry, or control) were assessed for obesity-diabetes-disease risk biomarkers. Results showed that raspberry intake improved antioxidant status and lessened plasma interleukin (IL)-6 (0.3-fold of control, p<0.1); most likely through enhancing glutathione peroxidase (GPx) activity in liver (4.3-fold of control), and in blood (2.1-fold of control). Other disease-risk biomarkers were similar between groups (p>0.05). Plasma levels of total cholesterol (T-CHL), low density lipoprotein-cholesterol (LDL-CHL), and resistin were higher in the raspberry group. Overall, the enhanced detoxifying cell defenses exerted by raspberry intake might be due to its polyphenolics and fibre. This study demonstrates in vivo that raspberry intake, at a dose that can be achieved by human consumption, might protect against diabetes-induced oxidative stress.

Red raspberry decreases heart biomarkers of cardiac remodeling associated with oxidative and inflammatory stress in obese diabetic db/db mice.

Early diagnosis of risks of heart disease can be critical to fight cardiovascular diseases (CVD) associated with obesity and diabetes and for the implementation of nutritional interventions. The objective of this study was to investigate the cardioprotective effects of red raspberry consumption in the obese diabetic (db/db) mice using proteomic analysis as a tool. Hearts harvested from db/db mice fed an isocaloric diet (AIN-93G, control group) or AIN-93G supplemented with freeze-dried raspberry (raspberry group) for eight weeks were analyzed for changes in protein expression. Bioinformatics and pathway analysis of proteomic data detected in >50% samples were scrutinized with Database for Annotation, Visualization and Integrated Discovery (DAVID). Histologic analysis, adipokines and lipid quantification in heart tissues were assessed as end points for disease biomarkers. Results from proteomic data identified five proteins unique to the control group involved in cardiac remodeling and one involved in stress response. Twenty-five proteins expressed in both groups were differentially downregulated in the raspberry group (p < 0.05) within 0.25-0.7-fold of control. Out of these, seven were involved in cardiac remodeling (e.g. natriuretic peptide precursor type A, 0.25-fold of control), and five were involved in stress response (e.g. glutathione S-transferase A4, 0.49-fold of control). However, no significant differences between raspberry and control groups were detected in heart lipid composition, adipokines, and morphology within the study timeframe. In conclusion, raspberry consumption may be effective in decreasing the levels of oxidative and inflammatory stress that promote morphological changes in the heart at an older age, thus preventing or delaying heart diseases.

Consumption of cranberry beverage improved endogenous antioxidant status and protected against bacteria adhesion in healthy humans: a randomized controlled trial.

Consumption of polyphenol-rich foods is associated with lower risk from many chronic diseases. We hypothesized that a single dose of cranberry beverage would improve indices of oxidative stress, inflammation, and urinary antibacterial adhesion activity in healthy humans. Six males and 6 females (18-35 years; body mass index, 19-25 kg/m(2)) consumed placebo, cranberry leaf extract beverage, or low-calorie cranberry juice cocktail (LCJC) once in a randomized, double-blind, placebo-controlled cross-over experimental design trial. The washout period between beverages was 1 week. Blood was collected 0, 2, 4, 8, and 24 hours after beverage consumption for measuring oxidative and inflammatory biomarkers. Urine was collected at 0, 0 to 3, 3 to 6, 6 to 9, 9 to 12, and 24 hours postintervention to assess antibacterial adhesion activity. Consumption of cranberry leaf extract beverage elevated (P < .05) blood glutathione peroxidase activity, whereas LCJC consumption increased (P < .05) glutathione concentrations and superoxide dismutase activity compared with placebo. Cranberry leaf extract beverage and LCJC consumption had no effect on the inflammatory biomarkers measured as compared with placebo. At 0 to 3 hours postconsumption, urine from participants who consumed cranberry beverages had higher (P < .05) ex vivo antiadhesion activity against P-fimbriated Escherichia coli compared with placebo. An acute dose of cranberry beverages improved biomarkers of antioxidant status and inhibition of bacterial adhesion in urine.

Development of a fluorometric microplate antiadhesion assay using uropathogenic Escherichia coli and human uroepithelial cells.

A fluorometric microplate assay has been developed to determine Escherichia (E.) coli adhesion to uroepithelial cells (UEC). P-fimbriated E. coli were labeled with BacLight Green and preincubated 30 min with human urine or standard. Fluorescent-E. coli were added to UEC in mircoplates at a 400:1 ratio, incubated 1 h, and washed, and the fluorescence intensity was measured. Specific labeling and adherence were confirmed by flow cytometry. A myricetin (1) standard curve (0-30 µg/mL) was developed; the lower limit of detection was 0.1 µg/mL, and half-maximal inhibitory concentration was 0.88 µg/mL (intra- and interassay coefficients of variance were <10% and <15%, respectively). Vaccinium macrocarpon (cranberry) extracts, quercetin (2), and procyanidins B1 (3), B2 (4), and C1 (5) showed similar inhibition. Antiadhesion activity of urine samples from subjects (n = 12) consuming placebo or V. macrocarpon beverage determined using this assay was positively correlated (R(2) = 0.78; p < 0.01) with a radiolabeled-E. coli assay.

Astaxanthin stimulates cell-mediated and humoral immune responses in cats.

Astaxanthin is a potent antioxidant carotenoid and may play a role in modulating immune response in cats. Blood was taken from female domestic shorthair cats (8-9 mo old; 3.2 ± 0.04 kg body weight) fed 0, 1, 5 or 10mg astaxanthin daily for 12 wk to assess peripheral blood mononuclear cell (PBMC) proliferation response, leukocyte subpopulations, natural killer (NK) cell cytotoxic activity, and plasma IgG and IgM concentration. Cutaneous delayed-type hypersensitivity (DTH) response against concanavalin A and an attenuated polyvalent vaccine was assessed on wk 8 (prior to vaccination) and 12 (post-vaccination). There was a dose-related increase in plasma astaxanthin concentrations, with maximum concentrations observed on wk 12. Dietary astaxanthin enhanced DTH response to both the specific (vaccine) and nonspecific (concanavalin A) antigens. In addition, cats fed astaxanthin had heightened PBMC proliferation and NK cell cytotoxic activity. The population of CD3(+) total T and CD4(+) T helper cells were also higher in astaxanthin-fed cats; however, no treatment difference was found with the CD8(+) T cytotoxic and MHC II(+) activated lymphocyte cell populations. Dietary astaxanthin increased concentrations of plasma IgG and IgM. Therefore, dietary astaxanthin heightened cell-mediated and humoral immune responses in cats.

Dietary fish oil and flaxseed oil suppress inflammation and immunity in cats.

The modulatory activity of dietary n-3 fatty acids on inflammation and immune response in domestic cats is unknown. Mature female cats (n=14/treatment) were fed control, fish oil or flaxseed oil diets with n-6:n-3 fatty acid ratios of 20:1, 5:1 and 5:1, respectively, for 12 wk. Immune response was assessed on wk 0, 6 and 12, and skin hypersensitivity response on wk 6 and 12. Fish oil increased (P<0.01) eicosapentaenoic and docosahexaenoic acids in plasma and skin, whereas flaxseed oil increased α-linolenic acid. Fish and flaxseed oils decreased (P<0.01) skin inflammatory response to histamine. Cats fed fish but not flaxseed oil had higher (P<0.05) skin leukotriene LTB(5), but not LTB(4). Fish and flaxseed oils lowered B, total T and T(h) subset populations, and leukocyte proliferative response to PWM (P<0.05). In contrast, there was no change in ConA- or PHA-induced lymphocyte proliferation, Tc and MHC II cell populations, DTH response, NK cytotoxicity, IL-2 production, or plasma IgG concentrations. Therefore, fish and flaxseed oil can reduce skin inflammatory responses in cats, however, flaxseed oil appears less immunosuppressive than fish oil.

Dietary astaxanthin enhances immune response in dogs.

No information is available on the possible role of astaxanthin on immune response in domestic canine. Female Beagle dogs (9-10 mo old; 8.2 ± 0.2 kg body weight) were fed 0, 10, 20 or 40 mg astaxanthin daily and blood sampled on wk 0, 6, 12, and 16 for assessing the following: lymphoproliferation, leukocyte subpopulations, natural killer (NK) cell cytotoxicity, and concentrations of blood astaxanthin, IgG, IgM and acute phase proteins. Delayed-type hypersensitivity (DTH) response was assessed on wk 0, 12 and 16. Plasma astaxanthin increased dose-dependently and reached maximum concentrations on wk 6. Dietary astaxanthin enhanced DTH response to vaccine, concanavalin A-induced lymphocyte proliferation (with the 20mg dose at wk 12) and NK cell cytotoxic activity. In addition, dietary astaxanthin increased concentrations of IgG and IgM, and B cell population. Plasma concentrations of C reactive protein were lower in astaxanthin-fed dogs. Therefore, dietary astaxanthin heightened cell-mediated and humoral immune response and reduced DNA damage and inflammation in dogs.

Pigmented potato consumption alters oxidative stress and inflammatory damage in men.

Pigmented potatoes contain high concentrations of antioxidants, including phenolic acids, anthocyanins, and carotenoids. These bioactive compounds have been implicated in the inhibition or prevention of cellular oxidative damage and chronic disease susceptibility. We assessed the effects of pigmented potato consumption on oxidative stress and inflammation biomarkers in adult males. Free-living healthy men (18-40 y; n = 12/group) consumed 150 g of cooked white- (WP), yellow- (YP), or purple-flesh potatoes (PP) once per day for 6 wk in a randomized study. Blood was collected at baseline and wk 6 to analyze total antioxidant capacity (TAC), DNA damage as assessed by plasma 8-hydroxydeoxyguanosine (8-OHdG), protein oxidation, lipid peroxidation, C-reactive protein (CRP), inflammatory cytokines, lymphoproliferation, NK cytotoxicity, and phenotypes. Potatoes were analyzed for TAC, phenolic acids, anthocyanins, and carotenoids. Compared with the WP group, the YP group had higher concentrations of phenolic acids (P < 0.002) and carotenoids (P < 0.001), whereas the PP group had higher concentrations of phenolic acids (P < 0.002) and anthocyanins (P < 0.001). Men who consumed YP and PP tended to have lower (P < 0.08) plasma IL-6 compared with those consuming WP. The PP group tended to have a lower plasma CRP concentration than the WP group (P = 0.07). The 8-OHdG concentration was lower in men who consumed either YP or PP compared with WP. Pigmented potato consumption reduced inflammation and DNA damage in healthy adult males. This offers consumers an improved nutritional choice in potato consumption.

Effect of astaxanthin supplementation on inflammation and cardiac function in BALB/c mice.

Astaxanthin is an antioxidant with immunomodulatory, anti-inflammatory and anticancer properties. This study evaluated the use of dietary astaxanthin to decrease oxidative stress and improve cardiac function, thereby providing a potential cardioprotective supplement. Female BALB/c mice (8 weeks of age) were fed a semi-synthetic diet containing 0, 0.02 or 0.08% astaxanthin for 8 weeks. Cardiac function was assessed by echocardiography bi-weekly, and blood and tissue samples were collected at 8 weeks. Plasma astaxanthin concentrations increased (p<0.05) dose-dependently to 0.5 and 4 mumol/l in the astaxanthin-supplemented mice. Blood glutathione concentrations and lymphocyte mitochondrial membrane potential were not significantly affected by astaxanthin treatment. However, mice fed 0.08% astaxanthin had higher (p<0.05) heart mitochondrial membrane potential and contractility index compared to the control group. These results support the possible use of dietary astaxanthin for cardiac protection.

Effect of dietary astaxanthin at different stages of mammary tumor initiation in BALB/c mice.

The effects of astaxanthin on tumor growth, cardiac function and immune response in mice were studied. Female BALB/c mice were fed a control diet (diet C) for 8 weeks, 0.005% astaxathin for 8 weeks (diet A), or diet C for weeks 1-5 followed by diet A thereafter (diet CA). Mice were injected with a mammary tumor cell line on day 7 and tumor growth was measured daily. Mice fed diet A had extended tumor latency and lower tumor volume (p<0.05). Interestingly, those fed diet CA showed the fastest tumor growth. Astaxanthin feeding elevated plasma astaxanthin concentrations; there was no difference in plasma astaxanthin between mice fed CA and those fed A. Mice fed diet A, but not CA, had a higher (p<0.05) natural killer cell subpopulation and plasma interferon-gamma concentration compared to those fed diet C. Astaxanthin delayed tumor growth and modulated immune response, but only when astaxanthin was given before tumor initiation. This suggests that an adequate blood astaxanthin status is needed to protect against tumor initiation; conversely, astaxanthin supplementation after tumor initiation may be contraindicated.

Soy isoflavones modulate immune function in healthy postmenopausal women.

BACKGROUND: The immune system may be compromised after menopause because of the effects of aging and diminishing concentrations of estrogen, an immune-modulating hormone. Isoflavones, plant-derived compounds with estrogenic and antioxidant properties, may offer immunologic benefits to women during this stage of life. OBJECTIVE: The objective of this study was to evaluate the effects of soy isoflavones, both in soymilk and in supplement form, on markers of immunity and oxidative stress in postmenopausal women. DESIGN: Postmenopausal women aged 50-65 y (n = 52) enrolled in this 16-wk double-blind, placebo-controlled trial were randomly assigned to 1 of 3 experimental groups: 1) control, 706 mL cow milk/d plus a placebo supplement; 2) soymilk, 71.6 mg isoflavones derived from 706 mL soymilk/d plus a placebo supplement; and 3) supplement, 70 mg isoflavones in a supplement plus 706 mL cow milk/d. Plasma and 24-h urine samples were obtained at baseline and at 16 wk. Immune variables included lymphocyte subsets, cytokine production, and markers of inflammation and oxidative damage. RESULTS: Isoflavone intervention in postmenopausal women resulted in higher (P < 0.05) B cell populations and lower (P < 0.05) plasma concentrations of 8-hydroxy-2-deoxy-guanosine, an oxidative marker of DNA damage. Isoflavone treatment did not significantly influence concentrations of interferon gamma, interleukin 2, tumor necrosis factor alpha, or C-reactive protein in plasma or of 8-isoprostane in urine. CONCLUSIONS: Soymilk and supplemental isoflavones modulate B cell populations and appear to be protective against DNA damage in postmenopausal women.

Dietary lutein inhibits mouse mammary tumor growth by regulating angiogenesis and apoptosis.

Even though we previously reported that dietary lutein can inhibit mammary tumor growth, the mechanism of this action was unknown. Here, we studied the action of dietary lutein through its possible regulation of apoptosis and angiogenesis. Female BALB/c mice were fed a semi-purified diet containing 0 (control), 0.002 or 0.02% lutein (n = 20/treatment) for 2 weeks prior to inoculation with 100,000 -SA mouse mammary tumor cells into the right mammary fat pad. Tumor volume was measured daily until day 50 postinoculation when all mice were killed. Angiogenesis and apoptosis activities in the tumors were measured by immunohistochemistry. Apoptosis and necrosis of blood lymphocytes were quantitated by flow cytometry using Annexin V-FITC and propidium iodide staining. The expression of the p53, Bax and Bcl-2 mRNA was measured by RT-PCR amplification. Lutein was not detectable in the plasma, liver or tumor of unsupplemented mice, but increased in a dose-dependent manner in lutein-supplemented mice. Mice fed lutein had tumors that were 30 to 40% smaller (p < 0.05) on day 50 post-inoculation compared to unsupplemented mice. Final tumor volume was lowest in mice fed 0.002% lutein. Mice fed lutein had higher apoptotic activity in the tumors but lower apoptotic activity in blood lymphocytes as compared to unsupplemented animals. These observations were supported by the observed increase in the expression of the proapoptotic genes, p53 and Bax, together with a decrease in the expression of the antiapoptotic gene, Bcl-2, and consequently an increase in the Bax:Bcl-2 ratio in tumors from lutein-fed mice. Furthermore, lutein-fed mice also had lower (p < 0.05) angiogenic activity in the tumors as compared to unsupplemented mice. The greatest beneficial effect on apoptosis and angiogenesis was observed with mice fed 0.002% lutein. Therefore, dietary lutein, especially at 0.002%, inhibited tumor growth by selectively modulating apoptosis, and by inhibiting angiogenesis.