This study aimed to determine whether a polyphenol-rich cranberry beverage affects skin properties, lipids, and the microbiome in women using a randomized, double-blinded, placebo-controlled, cross-over design. Twenty-two women with Fitzpatrick skin types 2-3 were randomized to drink a cranberry beverage or placebo for six weeks. After a 21-day washout, they consumed the opposite beverage for six weeks. Six weeks of cranberry beverage significantly reduced UVB-induced erythema, improved net elasticity on the face and forearm, smoothness on the face, and gross elasticity on the forearm compared to the placebo. When stratified by age, these effects of the cranberry beverage were primarily observed in women >40 years old. SOD activities were improved after six weeks of cranberry beverage consumption compared to the placebo, while glutathione peroxide and TNF- alpha were improved compared to baseline. These effects were found to differ by age group. Skin lipid composition was modulated by both the cranberry beverage and the placebo. Cranberry beverages did not change alpha - or beta -diversity but altered the abundance of several skin microbes at the species and strain level. Consumption of a cranberry beverage for six weeks improved specific skin properties and oxidative stress and modulated skin lipids and microbiome compared to placebo.

Objectives: This study examined the effect of a 4-week unsweetened cranberry beverage (CRAN) (317 mg polyphenols) versus placebo beverage (PLAC) ingestion (240 mL/day) on moderating exercise-induced changes in innate immunity. 

Methods: Participants included 25 male and female non-elite cyclists. A randomized, placebo-controlled, double-blind crossover design was used with two 4-week supplementation periods and a 2-week washout period. Supplementation periods were followed by an intensive 2.25 h cycling bout. Six blood samples were collected before and after supplementation (in an overnight fasted state) and at 0 h, 1.5 h, 3 h, and 24 h post-exercise. Stool and urine samples were collected pre- and post-supplementation. Outcome measures included serum creatine kinase, myoglobin, and cortisol, complete blood counts, plasma untargeted proteomics, plasma-targeted oxylipins, untargeted urine metabolomics, and stool microbiome composition via whole genome shotgun (WGS) sequencing. 

Results: Urine CRAN-linked metabolites increased significantly after supplementation, but no trial differences in alpha or beta microbiota diversity were found in the stool samples. The 2.25 h cycling bout caused significant increases in plasma arachidonic acid (ARA) and 53 oxylipins (FDR q-value < 0.05). The patterns of increase for ARA, four oxylipins generated from ARA-cytochrome P-450 (CYP) (5,6-, 8,9-, 11,12-, and 14,15-diHETrEs), two oxylipins from linoleic acid (LA) and CYP (9,10-DiHOME, 12,13-DiHOME), and two oxylipins generated from LA and lipoxygenase (LOX) (9-HODE, 13-HODE) were slightly but significantly higher for the CRAN versus PLAC trial (all interaction effects, p < 0.05). The untargeted proteomics analysis showed that two protein clusters differed significantly between the CRAN and PLAC trials, with CRAN-related elevations in proteins related to innate immune activation and reduced levels of proteins related to the regulation of the complement cascade, platelet activation, and binding and uptake of ligands by scavenger receptors. No trial differences were found for cortisol and muscle damage biomarkers. 

Conclusion: CRAN versus PLAC juice resulted in a significant increase in CRAN-related metabolites but no differences in the gut microbiome. CRAN supplementation was associated with a transient and modest but significant post-exercise elevation in selected oxylipins and proteins associated with the innate immune system.

BACKGROUND/AIMS: Phenobarbital (PB), commonly used for epilepsy management, is associated with testicular dysfunction after prolonged use. This study aimed to evaluate the ameliorative effects of cranberry (CB) and vitamin C (Vit-C) on PB-induced reproductive toxicity in rats. 

METHODS: Forty male Wistar rats were divided into five groups. G1 was the negative control, while G2 received PB (160 mg/kg orally) for one month. Groups G3 and G4 received PB followed by CB (500 mg/kg) and Vit-C (27 mg/kg) treatments, respectively. G5 received PB followed by a combined CB and Vit-C regimen. The levels of catalase (CAT), superoxide dismutase (SOD), glutathione reduced (GSH), and malondialdehyde (MDA) were determined using standard biochemical assays. Histological changes in testicular tissues were assessed, and caspase-3 expression was quantified via immunohistochemistry. 

RESULTS: PB exposure increased MDA levels, reduced SOD and CAT activity, and disrupted testicular histology, with elevated caspase-3 expression indicating heightened apoptosis. Treatment with CB or Vit-C significantly restored antioxidant enzyme activities, reduced MDA levels, and ameliorated histological abnormalities. Co-treatment with CB and Vit-C yielded the most pronounced protective effects, including reduced caspase-3 expression and improved testicular structure. 

CONCLUSION: CB and Vit-C demonstrate significant protective effects against PB-induced testicular toxicity, likely due to their antioxidative and anti-apoptotic properties. Co-administration of these agents offers an effective strategy to mitigate reproductive toxicities associated with prolonged PB use. © Copyright by the Author(s). Published by Cell Physiol Biochem Press.

Nephrolithiasis is a common disease and incurs a significant burden on the health care system globally. Patients with kidney stones can be treated with natural remedy such as cranberry, pomegranate, and grape juice. Patients with kidney stone experience anxiety and insomnia as a result of the pain caused by the stones. As a result, physicians may prescribe anxiolytics to treat anxiety, among which alprazolam is a commonly prescribed medication. Meanwhile, cranberry and pomegranate juice are prescribed by many herbal specialists for the treatment of renal calculi. The enzyme CYP3A4 primarily metabolizes alprazolam, while fruit juices such as cranberry and pomegranate juices are potent inhibitors of CYP3A4. Therefore, there could be a drug-food interaction between alprazolam and cranberry and pomegranate juices when consumed concomitantly. A detailed pharmacodynamic and pharmacokinetic investigation is required to ascertain the food-drug interaction between alprazolam, cranberry, and pomegranate juice to avoid the possible toxicity of alprazolam. This review article provides insights about the possible CYP3A4-associated drug interactions between alprazolam and juices of cranberry and pomegranate, for the safe and effective usage of alprazolam in treating anxiety disorders caused by kidney stones.

Cranberry-derived proanthocyanidin (PAC) is processed by the gut microbiota to produce 3-(4-hydroxyphenyl)-propionic acid (HPPA), among other metabolites. These data are in support of the article entitled, "Cranberry proanthocyanidin and its microbial metabolite 3,4-dihydroxyphenylacetic acid, but not 3-(4-hydroxyphenyl)-propionic acid, partially reverse pro-inflammatory microRNA responses in human intestinal epithelial cells," published in Molecular Nutrition and Food Research [1]. Here we describe data generated by nCounterR Human v3 miRNA Expression Panel of RNA obtained from Caco-2BBe1 cells exposed to two different concentrations of cranberry extract rich in PAC (50 micro g/ml or 100 micro g/ml) or 3-(4-hydroxyphenyl)-propionic acid (5 micro g/ml or 10 micro g/ml) for 24 h, then stimulated with 1 ng/ml of IL-1 beta or not (mock) for three hours. The raw data are publicly available at the NCBI GEO database GSE237078. This work also includes descriptive methodological procedures, treatment-responsive microRNA (miRNA) expression profiles in Caco-2BBe1 cells, and in silico mRNA gene target and pathway enrichment analyses of significantly differentially expressed miRNAs (q < 0.001). Cranberry and its components have recognized health benefits, particularly in relation to combatting inflammation and pathogenic bacterial adhesion. These data will be valuable as a reference to study the response of intestinal cells to other polyphenol-rich food sources, analyze gut microbial responses to cranberry and its metabolites in different cell lines and mammalian hosts to elucidate individualized effects, and to delineate the role of the gut microbiota in facilitating the benefits of cranberry. Moreover, these data will aid in expanding our knowledge on the mechanisms underlying the benefits of cranberry and its components.

Background: The aim of this double-blind randomized placebo-controlled clinical trial was to evaluate the efficacy of a multinutrient supplement as an add-on therapy to scaling and root planing for patients with periodontitis. 

Methods: Forty-two patients with stage III or IV periodontitis were randomly allocated to a 2-month treatment of either a multinutrient supplement containing vitamin C, vitamin E, zinc, selenium, alpha-lipoic-acid, cranberry extract, grapeseed extract, and coenzyme Q10 or placebo capsules as an adjunct to conservative periodontal therapy. Periodontal parameters, including probing pocket depth, gingival recession, bleeding on probing, approximal plaque index, and papillary bleeding index, were assessed. Clinical attachment loss, periodontal inflamed surface area, periodontal epithelial surface area, and percentages of pocket sites with <=3, <=4, >=5, >=6, >=7, and >=4 mm with bleeding on probing were calculated. 

Results: All clinical parameters significantly improved from baseline to reevaluation within each group (p < 0.05). Multinutrient intake resulted in a significantly higher reduction of probing-pocket-depth (-0.75 +or- 0.42 mm) and bleeding-on-probing (-21.9 +or- 16.1%) from baseline to reevaluation compared with placebo (-0.51 +or- 0.30 mm, p = 0.040 and -12.5 +or- 9.8%, p = 0.046, respectively). All periodontal parameters showed insignificantly higher improvements in patients receiving the supplement compared with those receiving the placebo (p > 0.05). 

Conclusion: Multinutrient supplementation as an adjunct to nonsurgical treatment of periodontitis showed some additional benefit regarding probing-pocket-depth and bleeding-on-probing. However, the clinical relevance needs to be further explored.

A promising approach for managing root caries is the use of cross-linking agents to stabilize collagen. However, despite testing various natural and synthetic agents in vitro, their efficacy remains uncertain. The aim of this review was to examine which cross-linking agent performs better in reducing root caries lesion depth and the release of hydroxyproline, which is a marker of collagen degradation. Studies evaluating the impact of cross-linking agents on dentin were included, while studies performed on enamel surface/cell cultures and studies evaluating collagenase inhibitors were excluded, among others. A comprehensive search covered eight databases, and study quality was assessed using the QUINN Tool for in vitro dental studies. Synthesis of the results was done using a Bayesian network meta-analysis to compare agents. Fifty studies involving 31 cross-linking agents were included for qualitative synthesis. The network meta-analysis for lesion depth involved 284 samples across 36 comparisons and ranked cross-linking agents in terms of their caries lesion depth-reducing effect (from best to worst): naringin > quercetin > riboflavin > proanthocyanidins > hesperidin > glutaraldehyde > cranberry > grape seed extract > untreated controls. Only naringin, quercetin, proanthocyanidins, and glutaraldehyde showed statistically significant efficacy over untreated controls. Cranberry extract excelled in reducing hydroxyproline release, followed by proanthocyanidins. In conclusion, proanthocyanidins positively affected both outcomes, suggesting they are prime candidates for translational research. Clinical studies are now essential to evaluate their real-world effectiveness against root caries. PROSPERO-CRD42023404911. Copyright © 2024 Scandinavian Division of the International Association for Dental Research. Published by John Wiley & Sons Ltd.

Exercise-induced muscle damage is common in athletes and recreational exercisers and can lead to muscle soreness, weakness, and impaired muscle function. The precise mechanisms are unclear but oxidative stress and inflammation are thought to play a role. (Poly) phenols are substances abundant in Vaccinium berries that have been suggested to possess antioxidant and anti-inflammatory effects that could help improve exercise performance and/or recovery from exercise. The objective of this systematic review was to evaluate the benefits of Vaccinium berry supplementation on exercise performance and recovery, as well as on exercise-induced oxidative and inflammatory biomarkers in healthy individuals. A comprehensive search was conducted in PubMed, ProQuest Medline, Web of Science, Cochrane Library, and Scopus. Studies were included if the participants were healthy individuals who were supplemented with any Vaccinium berry or Vaccinium berry-based products in comparison to a control group. Of the 13 articles included in this review, no significant differences in the exercise performance were found and only one study reported benefits for markers of recovery. Interleukins and c-reactive protein were the most frequently reported biomarkers, but there was limited evidence that Vaccinium berry supplementation impacted them post-exercise. Most studies were of high quality and showed a low risk of bias. Vaccinium berry supplementation is not effective in modulating markers of exercise-induced inflammation and oxidative distress in healthy individuals; nevertheless, more studies are required to evaluate their effects on exercise performance and recovery in this population.

Phenol-pyranoanthocyanins, a structurally modified type of anthocyanin, has higher stability than anthocyanins. However, their conversion occurs slowly. Therefore, it is crucial to improve the conversion efficiency and production of pyranoanthocyanins. In this study, cranberry anthocyanin (CRAN) was fermented using two Lactobacillus strains along with caffeic acid to form cranberry-derived pyranoanthocyanins (PY-CRAN). PY-CRAN was characterized and identified. The physicochemical properties, antioxidant activity, and tyrosinase inhibitory capacity of PY-CRAN were assessed. The results showed that phenol-pyranoanthocyanins can be rapidly produced through fermentative transformation using Lactiplantibacillus plantarum and Lacticaseibacillus paracasei. Lacticaseibacillus paracasei exhibits a higher propensity for producing phenol-pyranoanthocyanins. PY-CRAN exhibits high stability under light and various pH conditions. Moreover, they possess excellent antioxidant properties and the ability to inhibit tyrosinase. These results suggest that fermentative biotransformation conducted by Lactobacillus is an ideal method for producing cranberry pyranoanthocyanins. The resulting anthocyanins have potential as antioxidant and whitening agents, making them promising bioactive ingredients.

Background: Although a high-fat and high-sugar diet (HFHS) can induce ovarian insufficiency and premature ovarian failure (POF)-making the treatment difficult-plant-derived exosome-like nanovesicles manifest numerous therapeutic effects on various diseases. 

Purpose: To explore the therapeutic effects and the molecular biology mechanism of exosomes derived from Vaccinium macrocarpon Ait (cranberry) (Va-exos) in the treatment of murine HFHS-POF. 

Methods: The exosomes from cranberry (Va-exos) were isolated, purified and fed to HFHS-POF model mice. The pathological changes in ovaries, livers, intestines were detected by H&E and Masson staining. The 16s rRNA-seq technique was used to investigate the changes in the gut microbiota and microecology. The mRNA and protein expressions of PANoptosis and their phosphorylation levels in ovarian granulosa cells were detected by qPCR and western blot. 

Results: Pathological examination showed that Va-exos not only significantly alleviated the symptoms of POF in model mice but also improved the intestinal barrier function and inhibited the production of inflammatory factors. The high-throughput sequencing results of 16s rRNA indicated that the relative abundances of Akkermansia and Allobaculum microorganisms in the intestines of the Va-exos group of mice significantly increased, while the relative abundances of uncultured-bacterium_f-Muribaculaceae, Dubosiella, and uncultured-bacterium_f-Lachnospiraceae microorganisms were significantly reduced. The FCM test results indicated that Va-exos significantly reduced necrosis, apoptosis, and accumulation of reactive oxygen species in ovarian granulosa cells (OGCs) of the HFHS POF mice. Finally, both qPCR and western-blot analyses indicated that Va-exos significantly attenuated the expression levels of key regulatory factors in the PANoptosis of OGCs in HFHS POF mice. 

Conclusion: We confirmed that oral administration of cranberry-derived exosomes attenuated murine POF by modulating the gut microbiota and decreasing ovarian granulosa cell PANoptosis.