Boon P. Chew

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.

Effect of dark sweet cherry powder consumption on the gut microbiota, short-chain fatty acids, and biomarkers of gut health in obese db/db mice

Cherries are fruits containing fiber and bioactive compounds (e.g., polyphenolics) with the potential of helping patients with diabetes and weight disorders, a phenomenon likely related to changes in the complex host-microbiota milieu. The objective of this study was to investigate the effect of cherry supplementation on the gut bacterial composition, concentrations of caecal short-chain fatty acids (SCFAs) and biomarkers of gut health using an in vivo model of obesity. Obese diabetic (db/db) mice received a supplemented diet with 10% cherry powder (supplemented mice, n = 12) for 12 weeks; obese (n = 10) and lean (n = 10) mice served as controls and received a standard diet without cherry. High-throughput sequencing of the 16S rRNA gene and quantitative real-time PCR (qPCR) were used to analyze the gut microbiota; SCFAs and biomarkers of gut health were also measured using standard techniques. According to 16S sequencing, supplemented mice harbored a distinct colonic microbiota characterized by a higher abundance of mucin-degraders (i.e., Akkermansia) and fiber-degraders (the S24-7 family) as well as lower abundances of Lactobacillus and Enterobacteriaceae. Overall this particular cherry-associated colonic microbiota did not resemble the microbiota in obese or lean controls based on the analysis of weighted and unweighted UniFrac distance metrics. qPCR confirmed some of the results observed in sequencing, thus supporting the notion that cherry supplementation can change the colonic microbiota. Moreover, the SCFAs detected in supplemented mice (caproate, methyl butyrate, propionate, acetate and valerate) exceeded those concentrations detected in obese and lean controls except for butyrate. Despite the changes in microbial composition and SCFAs, most of the assessed biomarkers of inflammation, oxidative stress, and intestinal health in colon tissues and mucosal cells were similar in all obese mice with and without supplementation. This paper shows that dietary supplementation with cherry powder for 12 weeks affects the microbiota and the concentrations of SCFAs in the lower intestinal tract of obese db/db diabetic mice. These effects occurred in absence of differences in most biomarkers of inflammation and other parameters of gut health. Our study prompts more research into the potential clinical implications of cherry consumption as a dietary supplement in diabetic and obese human patients.

Bixin uptake and antioxidative effect and role in immunoregulation in domestic cats.

Bixin, a carotenoid found in the seed of the Annatto plant, , is a potent antioxidant. Carotenoids are readily absorbed from the diet; therefore, the purpose of this study was to examine uptake of bixin by plasma, lipoproteins, and leukocytes after dietary supplementation in domestic cats and to assess effects on immune response. Female domestic short hair cats (3 yr old; 4.79 ± 0.13 kg BW) were fed a single dose of 0, 1, 5, or 10 mg bixin, and blood was taken at 0, 1, 2, 4 and 8 h after administration ( = 6/treatment) to determine acute absorption rate. Then, bixin was fed daily for 14 d to examine steady-state plasma concentrations and subcellular distribution. Following these preliminary experiments, cats ( = 8/treatment) were fed diets containing 0, 1, 5, or 10 mg bixin/d for 16 wk and blood was collected on wk 0, 6, 12, and 16 for analysis of leukocyte subpopulations, cell-mediated responsiveness, and inflammatory and oxidative biomarkers. Maximal uptake in plasma occurred 1 h after a single oral dose of bixin, with a maximal concentration of 0.119 μ and elimination half-life of 1.8 to 2.2 h. Daily feeding of bixin showed a steady-state plasma concentration of 0.110 μ at the greatest doses. Bixin was primarily associated with the high-density lipoprotein fraction of blood lipoproteins and was primarily distributed in mitochondrial fractions (58-59%) of but also in microsomal and nuclear fractions (37-44%). Leukocyte subpopulations in blood were variably affected by dietary bixin, with an increase ( < 0.05) in total T cells but a concurrent decrease ( < 0.05) in CD18+ and B cell subpopulations. However, plasma IgG increased ( < 0.05) in the 10-mg treatment group by wk 6. Lymphoproliferation was stimulated ( < 0.05) in the 5-mg bixin treatment group by wk 16, and delayed-type hypersensitivity response increased after nonspecific antigenic challenge. Conversely, when a specific challenge of vaccine was assessed on wk 12 and 16, responsiveness decreased ( < 0.05) in the 10-mg bixin treatment group. Bixin supplementation surprisingly caused an increase ( < 0.05) in α-acid glycoprotein but had no effect on natural killer cell activity, other subpopulations of leukocytes, or 8-oxo-2›-deoxyguanosine, a DNA damage biomarker. This experiment demonstrated dose-dependent uptake of bixin in plasma and blood lipoproteins and distribution in leukocyte subcellular components and an impacted immune response through cell-mediated and humoral actions.

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.