Comprehensive Characterization of Bile Acids in Human Biological Samples and Effect of 4-Week Strawberry Intake on Bile Acid Composition in Human Plasma.

Primary bile acids (BAs) and their gut microbial metabolites have a role in regulating human health. Comprehensive characterization of BAs species in human biological samples will aid in understanding the interaction between diet, gut microbiota, and bile acid metabolism. Therefore, we developed a qualitative method using ultra-high performance liquid chromatography (UHPLC) coupled with a quadrupole time-of-flight (Q-TOF) to identify BAs in human plasma, feces, and urine samples. A quantitative method was developed using UHPLC coupled with triple quadrupole (QQQ) and applied to a previous clinical trial conducted by our group to understand the bile acid metabolism in overweight/obese middle-aged adults (n = 34) after four weeks strawberry vs. control intervention. The qualitative study tentatively identified a total of 81 BAs in human biological samples. Several BA glucuronide-conjugates were characterized for the first time in human plasma and/or urine samples. The four-week strawberry intervention significantly reduced plasma concentrations of individual secondary BAs, deoxycholic acid, lithocholic acid and their glycine conjugates, as well as glycoursodeoxycholic acid compared to control (p < 0.05); total glucuronide-, total oxidized-, total dehydroxyl-, total secondary, and total plasma BAs were also lowered compared to control (p < 0.05). The reduced secondary BAs concentrations suggest that regular strawberry intake modulates the microbial metabolism of BAs.

Pharmacokinetic Characterization of (Poly)phenolic Metabolites in Human Plasma and Urine after Acute and Short-Term Daily Consumption of Mango Pulp.

Pharmacokinetic (PK) evaluation of polyphenolic metabolites over 24 h was conducted in human subjects (n = 13, BMI = 22.7 ± 0.4 kg/m2) after acute mango pulp (MP), vitamin C (VC) or MP + VC test beverage intake and after 14 days of MP beverage intake. Plasma and urine samples were collected at different time intervals and analyzed using targeted and non-targeted mass spectrometry. The maximum concentrations (Cmax) of gallotannin metabolites were significantly increased (p < 0.05) after acute MP beverage intake compared to VC beverage alone. MP + VC beverage non-significantly enhanced the Cmax of gallic acid metabolites compared to MP beverage alone. Pyrogallol (microbial-derived metabolite) derivatives increased (3.6%) after the 14 days of MP beverage intake compared to 24 h acute MP beverage intake (p < 0.05). These results indicate extensive absorption and breakdown of gallotannins to galloyl and other (poly)phenolic metabolites after MP consumption, suggesting modulation and/or acclimation of gut microbiota to daily MP intake.

Pharmacokinetic Parameters of Watermelon (Rind, Flesh, and Seeds) Bioactive Components in Human Plasma: A Pilot Study to Investigate the Relationship to Endothelial Function.

This study aimed to investigate the metabolic fate of bioactive components in watermelon and explore their effect on endothelial function. Six healthy overweight/obese (BMI: 28.7 ± 1.6 kg/m2) adults received 100 kcal of watermelon flesh (WF), rind (WR), seeds (WS), or control meal. l-Citrulline, arginine, and (poly)phenolic metabolites were characterized in plasma over 24 h using UHPLC-MS. Endothelial function was assessed using a flow mediated dilation (FMD) technique over 7 h. Maximum concentration (Cmax) and area under the curve (AUC0-8h) of l-citrulline were significantly higher after WF- and WR-containing test meals compared to control (p < 0.05). Likewise, several individual phenolic metabolites in plasma had significantly higher Cmax after WR, WF, or WS intake compared to control. FMD responses were not different among test meals. Our results provide insights on circulating metabolites from watermelon flesh, seed, and rind and lay the foundation for future clinical trials on vascular benefits of watermelon.

Metabolic fate of strawberry polyphenols after chronic intake in healthy older adults.

Strawberries contain a wide array of nutrients and phytochemicals including polyphenols such as anthocyanins, proanthocyanidins and ellagitannins. These polyphenols are absorbed and metabolized to various phenolic metabolites/conjugates in the body, which may play a role in disease risk reduction. In the present study, we investigated the metabolic fate of strawberry polyphenols after chronic (90 days) supplementation of freeze-dried strawberry (24 g d-1, equivalent to 2 cups of fresh strawberries) vs. control powder in 19 healthy older adults. Blood samples were collected at two time-points i.e., fasting (t = 0 h) and 2 h after the breakfast meal. On days 45 and 90 breakfast also included a control or strawberry drink consistent with their treatment randomization. A total of 21 polyphenolic metabolites were quantified in plasma consisting of 3 anthocyanins/metabolites, 3 urolithin metabolites and 15 phenolic acid metabolites. Among anthocyanins/metabolite, pelargonidin glucuronide (85.7 ± 9.0 nmol L-1, t = 2 h, day 90) was present in the highest concentration. Persistent concentrations of anthocyanins/metabolites, urolithins and some phenolic acids were observed in fasting (t = 0 h) plasma samples on day 45 and 90 after strawberry drink consumption suggesting a role of enteric, enterohepatic recycling or upregulation of gut microbial and/or human metabolism of these compounds. Our results suggest that strawberry polyphenols are absorbed and extensively metabolized, and can persist in the circulation.

Muscadine Grape (Vitis rotundifolia) or Wine Phytochemicals Reduce Intestinal Inflammation in Mice with Dextran Sulfate Sodium-Induced Colitis.

The objective of this study was to determine the anti-inflammatory effects of phytochemical extracts from muscadine grapes or wine on dextran sulfate sodium (DSS)-induced colitis in mice and to investigate cellular mechanisms. Two groups of C57BL/6J mice were gavaged with muscadine grape phytochemicals (MGP) or muscadine wine phytochemicals (MWP), respectively, for 14 days. Acute colitis was induced by 3% DSS in drinking water for 7 days. An additional two groups of mice served as healthy and disease controls. Results indicated that MGP or MWP significantly prevented weight loss, reduced disease activity index, and preserved colonic length compared to the colitis group (p ≤ 0.05). MGP or MWP significantly decreased myeloperoxidase activity as well as the levels of IL-1ß, IL-6, and TNF-α in colon (p ≤ 0.05). MGP or MWP caused down-regulation of the NF-κB pathway by inhibiting the phosphorylation and degradation of IκB in a dose-dependent manner. These findings suggest that phytochemicals from muscadine grape or wine mitigate ulcerative colitis via attenuation of pro-inflammatory cytokine production and modulation of the NF-κB pathway.

Red Raspberries and Their Bioactive Polyphenols: Cardiometabolic and Neuronal Health Links.

Diet is an essential factor that affects the risk of modern-day metabolic diseases, including cardiovascular disease, diabetes mellitus, obesity, and Alzheimer disease. The potential ability of certain foods and their bioactive compounds to reverse or prevent the progression of the pathogenic processes that underlie these diseases has attracted research attention. Red raspberries (Rubus idaeus L.) are unique berries with a rich history and nutrient and bioactive composition. They possess several essential micronutrients, dietary fibers, and polyphenolic components, especially ellagitannins and anthocyanins, the latter of which give them their distinctive red coloring. In vitro and in vivo studies have revealed various mechanisms through which anthocyanins and ellagitannins (via ellagic acid or their urolithin metabolites) and red raspberry extracts (or the entire fruit) could reduce the risk of or reverse metabolically associated pathophysiologies. To our knowledge, few studies in humans are available for evaluation. We review and summarize the available literature that assesses the health-promoting potential of red raspberries and select components in modulating metabolic disease risk, especially cardiovascular disease, diabetes mellitus, obesity, and Alzheimer disease-all of which share critical metabolic, oxidative, and inflammatory links. The body of research is growing and supports a potential role for red raspberries in reducing the risk of metabolically based chronic diseases.

Effects of exogenous abscisic acid on fruit quality, antioxidant capacities, and phytochemical contents of southern high bush blueberries.

Abscisic acid (ABA) is a plant growth regulator that has a potential to increase antioxidant capacity and phenolic content of fruits and vegetables. The objective of this study was to examine whether an exogenous ABA application can positively affect fruit quality, antioxidant capacity, and phytochemical content of southern high bush blueberries (Vaccinium darrowii). Two varieties, namely Star and Windsor, were tested with ABA water solutions of three concentrations (0, 200, and 400ppm) using a randomised complete block design. Results showed that ABA significantly increased the firmness of berries in both varieties, suggesting a ripening delay effect. Such effect was more pronounced in Windsor variety as reflected by a lower percentage of ripe berries and smaller sized berries on ABA treated bushes. In conclusion, ABA delayed the ripening of blueberries, but did not affect total phenolic content, antioxidant capacity, or the content of individual phytochemicals in ripe blueberries.

Effects of exogenous abscisic acid on yield, antioxidant capacities, and phytochemical contents of greenhouse grown lettuces.

Antioxidants and phytochemicals in vegetables are known to provide health benefits. Strategies that enhance these properties are expected to increase the nutritional values of vegetables. The objective of this research is to assess the effects of exogenous abscisic acid (ABA) on yield, antioxidant capacities, and phytochemical content of lettuces grown in a greenhouse. Red loose leaf lettuce (cv. Galactic) and green loose leaf lettuce (cv. Simpson Elite) were cultivated using a randomized complete block design. Three concentrations of ABA in water [0 (control), 150, 300 ppm] were sprayed on the 30th and 39th days after sowing, and lettuces were harvested on the 46th day. Exogenous ABA significantly decreased yield of green and red lettuces. Total phenolic and total anthocyanin contents in red lettuce treated with ABA were significantly higher than in controls, whereas no significant differences were observed in green lettuce. ABA significantly induced the accumulation of chlorophyll b and total carotenoids in lettuces. The phenolic compounds identified and quantified in red and green lettuces included caffeoyltartaric acid, 5-O-caffeoylquinic acid, dicaffeoyltartaric acid, 3,5-dicaffeoylquinic acid, and quercetin 3-(6''-malonyl)-glucoside. Additionally, cyanidin 3-glucoside, cyanidin 3-(3''-malonoyl)-glucoside, and cyanidin 3-(6''-malonoyl)-glucoside in red lettuces were quantified. No significant effects of ABA on these individual phytochemicals were observed in green lettuces, whereas ABA significantly elevated the content of individual phytochemicals in red lettuces except for 5-O-caffeoylquinic acid. Differences among red lettuces with or without exogenous ABA were visualized on the score plots of principal component analyses. Loading plot indicated that multiple phenolic compounds contributed to the observed differences in red lettuces.

Antioxidant capacity, phenolic content, and profiling of phenolic compounds in the seeds, skin, and pulp of Vitis rotundifolia (Muscadine Grapes) As determined by HPLC-DAD-ESI-MS(n).

The objective of this study was to determine and compare the total phenolic content and antioxidant capacity in the seeds, skin, and pulp of eight cultivars of Florida-grown muscadine grapes and to identify the phenolic compounds in these respective portions. Total phenolic contents were determined colorimetrically using Folin-Ciocalteu reagent, and antioxidant capacity was determined by oxygen radical absorbance capacity (ORAC). High-performance liquid chromatography equipped with diode array (HPLC-DAD) and electrospray ionization mass spectrometric detection (ESI-MS(n)) was used to identify the phenolic compounds in the seeds, skin, and pulp of muscadine grapes. The total phenolic content and antioxidant capacity, based on fresh weight, were highest in seeds followed by skin and pulp. On average, 87.1, 11.3, and 1.6% of phenolic compounds were present in seeds, skin, and pulp, respectively. A total of 88 phenolic compounds of diverse structures were tentatively identified in muscadines, which included 17 in the pulp, 28 in the skin, and 43 in the seeds. Seventeen compounds were identified for the first time in muscadine grapes. The compounds identified in seeds included hydrolyzable tannins, flavan-3-ols and condensed tannins, ellagic acid derivatives, and quercetin rhamnoside. The skin contained hydrolyzable tannins, flavonoids, including anthocyanin 3,5-diglucosides, quercetin, myricetin, and kaempferol glycosides.