The secondary metabolite content of cranberry fruits can vary with cultivar and environmental factors, which may in turn impact their potential biological activities. To evaluate the influence of composition on anti-inflammatory activity, cranberry fruits were collected from two major U.S. growing regions. Eight extracts from these fruits were prepared, analyzed for phytochemical composition, and evaluated for their anti-inflammatory effects in human monocytes (THP-1 cells). The extracts varied widely in polyphenol and triterpenoid content. All were able to reduce lipopolysaccharide (LPS)-induced production of pro-inflammatory cytokine interleukin 6 (IL-6) at 100 μg/mL, with inhibition ranging between 18.8 and 48.8%. Of these, three extracts high in anthocyanins, triterpenoids, or total polyphenols decreased levels of IL-6 and tumor necrosis factor alpha (TNF-α) at concentrations of 0.1–10 μg/mL compared to LPS-exposed control. Several individual cranberry phytochemicals were also capable of reducing production of IL-6, IL-1β, and TNF-α. The data suggest that phytochemicals present in varying quantities in cranberry fruits including anthocyanins, hyperoside, ursolic acid, and corosolic acid play a role in the anti-inflammatory effects of cranberry extracts on human monocytes.

This study aimed to evaluate and compare the dried pomace powder of cranberries, lingonberries, sea buckthorns, and black currants as potential food ingredients with functional properties. The composition and several physicochemical and adsorption properties associated with their functionality were investigated. Tested berry pomace powders were rich in dietary soluble fiber (4.92-12.74 g/100 g DM) and insoluble fiber (40.95-65.36 g/100 g DM). The highest level of total phenolics was observed in the black currant pomace (11.09 GAE/g DM), whereas the sea buckthorn pomace revealed the highest protein concentration (21.09 g/100 g DM). All the berry pomace powders that were tested exhibited good water-holding capacity (2.78-4.24 g/g) and swelling capacity (4.99-9.98 mL/g), and poor oil-binding capacity (1.09-1.57 g/g). The strongest hypoglycemic properties were observed for the lingonberry and black currant pomace powders. The berry pomace powders presented effective in vitro hypolipidemic properties. The cholesterol-binding capacities ranged from 21.11 to 23.13 mg/g. The black currant and cranberry pomace powders demonstrated higher sodium-cholate-binding capacity than those of the lingonberry and sea buckthorn pomace powders. This study shows promising results that the powders of tested berry pomace could be used for further application in foods.

Scope: The molecular basis underlying the anti-inflammatory and anticarcinogenic properties of cranberries is incompletely understood. The effects of a cranberry proanthocyanidin-rich extract (PAC) and two of its gut microbial metabolites, 3,4-dihydroxyphenylacetic acid (DHPAA) and 3-(4-hydroxyphenyl)-propionic acid (HPPA), on intestinal epithelial cells microRNA (miRNA) expression and their downstream pathways at homeostasis and in inflammatory conditions, are investigated.Methods and Results: The expression of 799 miRNAs is quantitatively assessed in differentiated Caco-2BBe1 cells pre-treated with PAC, DHPAA, or HPPA and stimulated with interleukin (IL)-1 beta or not. PAC, DHPAA, and HPPA generate subsets of shared and distinct miRNA responses. At homeostasis, miRNAs affected by the metabolites, but not PAC, targeted genes enriched in kinase, Wnt, and growth factor signaling, cell growth and proliferation, apoptosis, and specific cancer pathways. In an inflammatory environment, PAC and DHPAA, but not HPPA, reverses the expression of 16 and two IL-1 beta-induced miRNAs, respectively, regulating inflammatory and cancer pathways.Conclusion: miRNA modulation is a novel mechanism for PAC bioactivity in the gut. The gut microbiota may be necessary to unlock these effects at homeostasis and partially in inflammation.

Background: Previous studies indicate cardiovascular health benefits of cranberry juice consumption. However, whether daily consumption of whole cranberries will have sustained vascular benefits in healthy individuals is currently unknown. Objective: To investigate the vascular effects of acute and daily consumption of freeze dried whole cranberry in healthy men and how effects relate to circulating cranberry (poly)phenol metabolites. Methods: A double-blind, parallel-group, randomized controlled trial was conducted in 45 healthy male adults randomly allocated to 1 month daily consumption of either cranberry (9 g powder solubilized in water equivalent to 100 g of fresh cranberries, 525 mg total (poly)phenols) or control (9 g powder, no (poly)phenols). Flow-mediated dilation (FMD, primary outcome), pulse wave velocity (PWV), aortic augmentation index (AIx), blood pressure, heart rate, blood lipids, and blood glucose were assessed at baseline and at 2 h on day 1 and after 1 month. Plasma and 24 h-urine were analyzed before and after treatment using targeted quantitative LC-MS methods including 137 (poly)phenol metabolites. Results: Cranberry consumption significantly increased FMD at 2 h and 1-month (1.1% (95% CI: 1.1%, 1.8%); p(treatment) <= 0.001; p(treatment x time) = 0.606) but not PWV, AIx, blood pressure, heart rate, blood lipids, and glucose. Of the 56 and 74 (poly)phenol metabolites quantified in plasma and urine, 13 plasma and 13 urinary metabolites significantly increased 2 h post-consumption and on day 1, respectively, while 4 plasma and 13 urinary metabolites were significantly higher after 1-month of cranberry consumption, in comparison with control. A multi-variable stepwise linear regression analysis showed that plasma cinnamic acid-4 '-glucuronide, 4-hydroxybenzoic acid-3-sulfate, 2,5-dihydroxybenzoic acid, 3 '-hydroxycinnamic acid, and 5-O-caffeoylquinic acid were significant independent predictors of 2 h FMD effects (R-2 = 0.71), while 3 '-hydroxycinnamic acid, 4-methoxycinnamic acid-3 '-glucuronide, 3-(4 '-methoxyphenyl)propanoic acid 3 '-sulfate, and 3-(4 '-methoxyphenyl)propanoic acid 3 '-glucuronide predicted the 1-month FMD effects (R-2 = 0.52). Conclusions: Acute and daily consumption of whole cranberry powder for 1 month improves vascular function in healthy men and this is linked with specific metabolite profiles in plasma. The National Institutes of Health (NIH)-randomized trial records held on the NIH ClinicalTrials.gov website (NCT02764749). https://clinicaltrials.gov/ct2/show/NCT02764749

The existence of a relationship between the consumption of dietary berries and blood pressure reduction in humans has been repeatedly hypothesized and documented by an increasing body of epidemiological and clinical evidence that has accumulated in recent years. However, results are mixed and complicated by a number of potentially confounding factors. The objective of this article is to review and summarize the available clinical evidence examining the effects of berry consumption on blood pressure regulation as well as the prevention or treatment of hypertension in humans, providing an overview of the potential contribution of distinctive berry polyphenols (anthocyanins, condensed tannins and ellagic acid), and results of dietary interventions with blueberries, bilberries, cranberries, raspberries, strawberries, chokeberries, cherries, blackcurrants and acai berries. We conclude that, while there is insufficient evidence supporting the existence of a direct blood pressure lowering effect, there is stronger evidence for specific types of berries acting indirectly to normalize blood pressure in subjects that are already hypertensive.

PURPOSE: This review aims to compare the magnitude of the effects of chronic consumption of fruits; specifically berries, citrus and cherries on cardiovascular disease (CVD) risk factors. METHODS: PubMed, Web of Science, Scopus, and psycARTICLES were searched from inception until January 2020. Forty-five chronic (>= 1 week) randomised controlled trials assessing CVD risk factors including endothelial (dys)function, blood pressure (BP), blood lipids and inflammatory biomarkers were included. RESULTS: Investigated interventions reported improvements in endothelial function (n = 8), inflammatory biomarkers and lipid status (n = 14), and BP (n = 10). Berries including juice of barberry, cranberry, grape, pomegranate, powder of blueberry, grape, raspberry and freeze-dried strawberry significantly reduced SBP by 3.68 mmHg (95% CI - 6.79 to - 0.58; P = 0.02) and DBP by 1.52 mmHg (95% CI - 2.87 to - 0.18, P = 0.04). In subgroup analysis, these associations were limited to cranberry juice (SBP by 1.52 mmHg [95% CI - 2.97 to - 0.07; P = 0.05], DBP by 1.78 mmHg [95% CI - 3.43 to - 0.12, P = 0.04] and cherry juice (SBP by 3.11 mmHg [95% CI - 4.06 to - 2.15; P = 0.02]). Berries also significantly elevated sVCAM-1 levels by 14.57 ng/mL (85% CI 4.22 to 24.93; P = 0.02). CONCLUSION: These findings suggest that supplementing cranberry or cherry juice might contribute to an improvement in blood pressure. No other significant improvements were observed for other specified fruits. More research is warranted comparing different classes of fruit and exploring the importance of fruit processing on their cardiovascular-protective effects.

Lipid metabolism and inflammation contribute to CVD development. This study investigated whether the consumption of cranberries (CR; Vaccinium macrocarpon) can alter HDL metabolism and prevent inflammation in mice expressing human apo A-I transgene (hApoAITg), which have similar HDL profiles to those of humans. Male hApoAITg mice were fed a modified American Institute of Nutrition-93M high-fat/high-cholesterol diet (16 % fat, 0.25 % cholesterol, w/w; n 15) or the high-fat/high-cholesterol diet containing CR (5 % dried CR powder, w/w, n 16) for 8 weeks. There were no significant differences in body weight between the groups. Serum total cholesterol, non-HDL-cholesterol and TAG concentrations were significantly lower in the control than CR group with no significant differences in serum HDL-cholesterol and apoA-I. Mice fed CR showed significantly lower serum lecithin-cholesterol acyltransferase activity than the control. Liver weight and steatosis were not significantly different between the groups, but hepatic expression of genes involved in cholesterol metabolism was significantly lower in the CR group. In the epididymal white adipose tissue (eWAT), the CR group showed higher weights with decreased expression of genes for lipogenesis and fatty acid oxidation. The mRNA abundance of F4/80, a macrophage marker and the numbers of crown-like structures were less in the CR group. In the soleus muscle, the CR group also demonstrated higher expression of genes for fatty acid beta-oxidation and mitochondrial biogenesis than those of the control. In conclusion, although CR consumption elicited minor effects on HDL metabolism, it prevented obesity-induced inflammation in eWAT with concomitant alterations in soleus muscle energy metabolism.

Background and aim: Dietary strategies that contribute to reducing incidence of Helicobacter pylori infection without negative side effects are highly desirable owing to worldwide bacterial prevalence and carcinogenesis potential. The aim of this study was to determine dosage effect of daily cranberry consumption on H. pylori suppression over time in infected adults to assess the potential of this complementary management strategy in a region with high gastric cancer risk and high prevalence of H. pylori infection. Methods: This double‐blind, randomized, placebo‐controlled trial on 522 H. pylori‐positive adults evaluated dose–response effects of proanthocyanidin‐standardized cranberry juice, cranberry powder, or their placebos on suppression of H. pylori at 2 and 8 weeks by 13C‐urea breath testing and eradication at 45 days post‐intervention. Results: H. pylori‐negative rates in placebo, low‐proanthocyanidin, medium‐ proanthocyanidin, and high‐proanthocyanidin cranberry juice groups at week 2 were 13.24%, 7.58%, 1.49%, and 13.85% and at week 8 were 7.35%, 7.58%, 4.48%, and 20.00%, respectively. Consumption of high‐proanthocyanidin juice twice daily (44 mg proanthocyanidin/240‐mL serving) for 8 weeks resulted in decreased H. pylori infection rate by 20% as compared with other dosages and placebo (P < 0.05). Percentage of H. pylori‐negative participants increased from 2 to 8 weeks in subjects who consumed 44 mg proanthocyanidin/day juice once or twice daily, showing a statistically significant positive trend over time. Encapsulated cranberry powder doses were not significantly effective at either time point. Overall trial compliance was 94.25%. Cranberry juice and powder were well‐tolerated. Conclusions: Twice‐daily consumption of proanthocyanidin‐standardized cranberry juice may help potentiate suppression of H. pylori infection. Trial registration: ChiCTR1800017522, per WHO ICTRP.

Cranberry volatiles have received little attention for health-promoting properties. In this study, we compared the inhibitory effects of cranberry polyphenol and volatile extracts and volatile standards on nitric oxide (NO) production in lipopolysaccharide (LPS) activated RAW 264.7 macrophages. Polyphenols were analyzed by HPLC/HPLC-MS and volatiles were analyzed by GC/GC-MS. The inhibition of NO production of the fresh cranberry polyphenol and volatile extracts and alpha -terpineol, linalool, linalool oxide, and eucalyptol standards at 2, 4, and 8-fold dilutions of their original concentrations in fresh cranberries was evaluated by treating these extracts/standards for 1 h before or after LPS application for 24 h. After inducing inflammation with LPS, the polyphenol treatments (317.8 and 635.7 micro g g-1) and 1.8 micro g g-1 volatile treatment lowered NO levels 46-62% compared to the positive control (P<0.05). When the cells were treated with polyphenol and volatile extracts before inducing inflammation, the 635.7 micro g g-1 and 317.8 micro g g-1 polyphenol treatments and 1.8 micro g g-1 and 0.9 micro g g-1 volatile treatments lowered NO levels (13-52%) compared to the positive control (P<0.05). Polyphenol and volatile extracts from cranberry were effective in reducing NO production whether applied before or after the application of LPS. alpha -Terpineol at a concentration found in fresh cranberries (1.16 micro g mL-1) was also found to be effective in reducing NO production whether cells were treated before or after application of LPS. Future studies are needed to reveal the mechanisms by which volatile compounds, especially alpha -terpineol act to mitigate inflammation and to determine the bioavailability of terpenes.

The present study is designed to investigate the role of certain natural cranberry and rosemary extracts to improve the histological changes in the cardiac muscle toxicity of adult male albino rats weighing 110±5g (aged 3-4 weeks) induced by doxorubicin (DOX). To assessment of cardiotoxicity, the cardiac enzyme creatine kinase (CK-MB) and troponin I protein were measured. The animals were divided into 7 equal groups (10 rats /each); Gp. I: normal control rats group injected with saline solution 0.9 % intraperitoneally (i.p.) for three times per a week for three weeks, Gp. II: cranberry rats group administrated orally with 150 mg/kg/bw for three times per a week for three weeks, Gp III rosemary rats group administrated orally with 2g/kg/bw for three times per a week for three weeks, Gp IV: DOX rats group injected i.p. with 2.5mg/kg three times / week for two weeks, Gps: V, VI & VII: DOX rat groups administrated orally with cranberry or rosemary or both together in the same previous doses and duration. In the present research, the measurement of CK - MB enzyme and troponin I protein are recorded high values in the blood sera in DOX -rats group (Gp IV) in comparison with other control groups (Gps. I, II& III) and treated groups (Gps; V, VI & VII) in which the levels of CK-MP and troponin I are recorded approximately normal values as in control group (Gp. I). Histological study of the cardiac muscle of normal control rats group (Gp.I) revealed normal branched cardiomyocytes with normal striations and normal oval centrally located nuclei. Similar observations are seen in the cranberry and rosemary rat groups (Gps. II& III). In DOX rats group (Gp IV), the histological observations of the cardiac muscle demonstrated many alternations such as disarrangement, degeneration and vacuolation of the cardiomyocytes. The appearance of infiltration of inflammatory cells and necrotic areas in most cardiomyocytes as well as dilation and congestion of blood vessels in the dilated endomysia were also observed. The administration of either cranberry alone or cranberry with rosemary together to DOX rats group revealed an obvious improvement and harmony restoration of the histological structure with normal appearance of the cardiomyocytes with normal oval nuclei, and complete disappearance of dilated and congested blood vessels, more than those given rosemary only. In brief, DOX rats group given either cranberry alone or cranberry with rosemary together recorded marked recovery of the normal values of CK-MB and troponin I as well as the restoration of the architecture of the cardiac muscle to approximately normal form than those given rosemary only.