Comparison of Flavonoid Composition of Red Raspberries (Rubus idaeus L.) Grown in the Southern United States

Raspberry flavonoid compounds have significant antioxidant activities, and regular consumption may help prevent and/or moderate chronic diseases. Targeted metabolite profiling is useful to identify compounds contributing to these antioxidant properties and health benefits and for tailored breeding for functional foods. In this study, metabolomic variation was determined among three fall-fruiting red raspberry cultivars (‘Autumn Britten’, ‘Caroline’, ‘Nantahala’) grown at three North Carolina locations differing in elevation and average day/night temperatures. ‘Nantahala’ was specifically bred for the mountainous regions of the southern United States. Ten flavonoid compounds were detected by liquid chromatography–time-of-flight–mass spectrometry (LC-TOF-MS). Of those, cyanidin-3-glucoside, cyanidin-3-sophoroside, cyanidin-3-rutinoside, cyanidin-3-sambubioside, and quercetin-3-glucoside were quantified against external standards. Variation in flavonoid composition was primarily attributed to genotype and associated with night temperature and hours exposed to temperatures over 29 °C. ‘Nantahala’ had particularly high levels of cyanidin-3-sambubioside, indicative of its purple raspberry lineage. Quercetin-3-glucoside levels increased the most with elevated temperatures

Key Role for the 12-Hydroxy Group in the Negative Ion Fragmentation of Unconjugated C24 Bile Acids

Host-gut microbial interactions contribute to human health and disease states and an important manifestation resulting from this cometabolism is a vast diversity of bile acids (BAs). There is increasing interest in using BAs as biomarkers to assess the health status of individuals and, therefore, an increased need for their accurate separation and identification. In this study, the negative ion fragmentation behaviors of C24 BAs were investigated by UPLC-ESI-QTOF-MS. The step-by-step fragmentation analysis revealed a distinct fragmentation mechanism for the unconjugated BAs containing a 12-hydroxyl group. The unconjugated BAs lacking 12-hydroxylation fragmented via dehydration and dehydrogenation. In contrast, the 12-hydroxylated ones, such as deoxycholic acid (DCA) and cholic acid (CA), employed dissociation routes including dehydration, loss of carbon monoxide or carbon dioxide, and dehydrogenation. All fragmentations of the 12-hydroxylated unconjugated BAs, characterized by means of stable isotope labeled standards, were associated with the rotation of the carboxylate side chain and the subsequent rearrangements accompanied by proton transfer between 12-hydroxyl and 24-carboxyl groups. Compared to DCA, CA underwent further cleavages of the steroid skeleton. Accordingly, the effects of stereochemistry on the fragmentation pattern of CA were investigated using its stereoisomers. Based on the knowledge gained from the fragmentation analysis, a novel BA, 3β,7β,12α-trihydroxy-5β-cholanic acid, was identified in the postprandial urine samples of patients with nonalcoholic steatohepatitis. The analyses used in this study may contribute to a better understanding of the chemical diversity of BAs and the molecular basis of human liver diseases that involve BA synthesis, transport, and metabolism

Serum Metabolite Signatures of Type 2 Diabetes Mellitus Complications

A number of metabolic conditions, including hypoglycemia, high blood pressure (HBP), dyslipidemia, nerve damage and amputation, and vision problems, occur as a result of uncontrolled blood glucose levels over a prolonged period of time. The different components of diabetic complications are not independent but rather interdependent of each other, rendering the disease difficult to diagnose and control. The underlying pathogenesis of those components cannot be easily elucidated because of the heterogeneous, polygenic, and multifactorial nature of the disease. Metabonomics offers a snapshot of distinct biochemical variations that may reflect the unique metabolic phenotype under pathophysiological conditions. Here we report a mass-spectrometry-based metabonomic study designed to identify the distinct metabolic changes associated with several complications of type 2 diabetes mellitus (T2DM). The 292 patients recruited in the study were divided into five groups, including T2DM with HBP, T2DM with nonalcoholic fatty liver disease (NAFLD), T2DM with HBP and NAFLD, T2DM with HBP and coronary heart disease (CHD), and T2DM with HBP, NAFLD, and CHD. Serum differential metabolites were identified in each group of T2DM complication, mainly involving bile acid, fatty acid, amino acid, lipid, carbohydrate, steroids metabolism, and tricarboxylic acids cycle. These broad-spectrum metabolic changes emphasize the complex abnormalities present among these complications with elevated blood glucose levels, providing a novel strategy for stratifying patients with T2DM complications using blood-based metabolite markers

Histopathological alterations in the eWAT of mice fed HFD or/and PFOA.

<p>Adult mice were pair-fed a high-fat diet (HFD) or low fat control diet (CTRL) with or without perfluorooctanoic acid (PFOA) administration at 5 mg/kg/day for 3 weeks. H&E staining of Epididymal white adipose tissue (eWAT). Arrows: Inflammatory cell infiltration.</p

Primer sequences used for qPCR analysis.

<p>Primer sequences used for qPCR analysis.</p

Fold changes of hepatic metabolites in mice fed HFD or/and PFOA exposure for 3 weeks.

<p>Hepatic metabolites were analyzed by GC-TOF MS and HPLC-TOFMS (n = 7–8).</p>a<p>Fold change (FC) was obtained by comparing those metabolites in perfluorooctanoic acid (PFOA) group, high fat diet (HFD) group and HFD-PFOA group to control group (CTRL) or HFD-PFOA group to PFOA group; FC with a value >1 indicates a relatively higher concentration present in PFOA group, HFD group or HFD-PFOA group while a value <1 means a relatively lower concentration as compared to the controls or a relatively higher concentration present in HFD-PFOA group while a value <1 means a relatively lower concentration as compared to the PFOA group.</p>b<p><i>p</i> values from Student’s <i>t</i>-test.</p

Metabonomic Profiling Reveals Cancer Chemopreventive Effects of American Ginseng on Colon Carcinogenesis in <i>Apc</i>^<i>Min/+</i> Mice

American ginseng (<i>Panax quinquefolius</i> L.) is one of the most commonly used herbal medicines in the West. It has been reported to possess significant antitumor effects that inhibit the process of carcinogenesis. However, the mechanisms underlying its anticancer effects remain largely unresolved. In this study, we investigated the cancer chemopreventive effects of American ginseng on the progression of high fat (HF) diet-enhanced colorectal carcinogenesis with a genetically engineered <i>Apc</i>^<i>Min/+</i> mouse model. The metabolic alterations in sera of experimental mice perturbed by HF diet intervention as well as the American ginseng treatment were measured by gas chromatography time-of-flight mass spectrometry (GC-TOFMS) and liquid chromatography time-of-flight mass spectrometry (LC-TOFMS) analysis. American ginseng treatment significantly extended the life span of the <i>Apc</i>^<i>Min/+</i> mouse. Significant alterations of metabolites involving amino acids, organic acids, fatty acids, and carbohydrates were observed in <i>Apc</i>^<i>Min/+</i> mouse in sera, which were attenuated by American ginseng treatment and concurrent with the histopathological improvement with significantly reduced tumor initiation, progression and gut inflammation. These metabolic changes suggest that the preventive effect of American ginseng is associated with attenuation of impaired amino acid, carbohydrates, and lipid metabolism. It also appears that American ginseng induced significant metabolic alterations independent of the <i>Apc</i>^<i>Min/+</i> induced metabolic changes. The significantly altered metabolites induced by American ginseng intervention include arachidonic acid, linolelaidic acid, glutamate, docosahexaenoate, tryptophan, and fructose, all of which are associated with inflammation and oxidation. This suggests that American ginseng exerts the chemopreventive effects by anti-inflammatory and antioxidant mechanisms

Fold changes of serum metabolites in mice subjected to HFD or/and PFOA exposure for 3 weeks.

<p>Serum metabolites were analyzed by GC-TOF MS and HPLC-TOFMS (n = 7–8).</p>a<p>Fold change (FC) was obtained by comparing those metabolites in perfluorooctanoic acid (PFOA) group, high fat diet (HFD) group and HFD-PFOA group to control group (CTRL) or HFD-PFOA group to PFOA group; FC with a value >1 indicates a relatively higher concentration present in PFOA group, HFD group or HFD-PFOA group while a value <1 means a relatively lower concentration as compared to the controls or a relatively higher concentration present in HFD-PFOA group while a value <1 means a relatively lower concentration as compared to the PFOA group.</p>b<p><i>p</i> values from Student’s <i>t</i>-test.</p

Body weights, organ weights and blood parameters in mice subjected to HFD or/and PFOA exposure for 3 weeks.

<p>Data are means ± SD (n = 7–8). Significant differences (<i>p</i><0.05) among a, b, c, d were determined by One-Way ANOVA with Dunnett’s post hoc comparison. eWAT: Epididymal white adipose tissue. sWAT: Subcutaneous white adipose tissue. BW: Body weight. FFAs: Free fatty acids.</p

Fold changes 0f drug metabolism genes in the liver of mice subjected to HFD or/and PFOA exposure for 3 weeks.

<p>The mRNA levels were analyzed by RT² Profiler™ PCR Array (<i>n</i> = 3), and genes with ≥1.5 fold change are listed.</p>*<p>Significant differences (<i>p</i><0.05) were determined by Student’s <i>t</i>-test. CTRL: Control. HFD: High fat diet. HFD-PFOA: High fat diet plus PFOA.</p