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2024

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Identification of antiviral phytochemicals from cranberry as potential inhibitors of SARS-CoV-2 main protease (Mpro)

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Authors
Pillai, U. Jisha; Cherian, Lucy; Taunk, Khushman; Iype, Eldhose; Dutta, Mainak
Journal
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES 10.1016/j.ijbiomac.2024.129655
Abstract

Cranberry phytochemicals are known to possess antiviral activities. In the current study, we explored the therapeutic potential of cranberry against SARS-CoV-2 by targeting its main protease (Mpro) enzyme. Firstly, phytochemicals of cranberry origin were identified from three independent databases. Subsequently, virtual screening, using molecular docking and molecular dynamics simulation approaches, led to the identification of three lead phytochemicals namely, cyanidin 3-O-galactoside, 8-carotene and epicatechin. Furthermore, in vitro enzymatic assays revealed that cyanidin 3-O-galactoside had the highest inhibitory potential with IC50 of 9.98 mu M compared to the other two phytochemicals. Cyanidin 3-O-galactoside belongs to the class of anthocyanins. Anthocyanins extracted from frozen cranberry also exhibited the highest inhibitory potential with IC50 of 23.58 mu g/ml compared to the extracts of carotenoids and flavanols, the class for 8-carotene and epicatechin, respectively. Finally, we confirm the presence of the phytochemicals in the cranberry extracts using targeted LC-MS/MS analysis. Our results, therefore, indicate that the identified cranberry-derived bioactive compounds as well as cranberry could be used for therapeutic interventions against SARS-CoV-2.

Improved in vitro Hemagglutination Assays Utilizing P-Type and Type 1 Uropathogenic Escherichia coli to Evaluate Bacterial Anti-Adhesion Activity of Cranberry Products

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Authors
Bosley, Scott; Krueger, Christian G.; Birmingham, Andrew; Howell, Amy B.; Reed, Jess D.
Journal
JOURNAL OF DIETARY SUPPLEMENTS 10.1080/19390211.2023.2276962
Abstract

Cranberries have a long history of use in the prevention of urinary tract infections. Cranberry products vary in proanthocyanidin content, a compound implicated in preventing the adhesion of uropathogenic Escherichia coli (E. coli) to uroepithelial cells. Testing is routinely done by cranberry product formulators to evaluate in vitro bacterial anti-adhesion bioactivity, shelf-life, and potential efficacy of cranberry products for consumer use to maintain urinary tract health. Hemagglutination assays evaluate the anti-adhesion bioactivity of cranberry products by determining how effectively the products prevent agglutination of specific red blood cells with E. coli expressing P-type and Type 1 fimbriae. The current study sought to improve upon an established anti-adhesion assay method by expanding the number of E. coli strains used to broaden potential in vivo efficacy implications and presenting results using photomicrographic data to improve accuracy and build databases on products that are routinely tested. Different lots of cranberry powder ingredient and two formulated products were tested independently for anti-adhesion activity using the established method and the improved method. Positive harmonization of results on the same samples using rigorous controls was achieved and provides the substantiation needed for the cranberry industry to utilize the improved, rapid in vitro testing method to standardize cranberry products for sufficient anti-adhesion bioactivity and maintain consumer confidence.

Intestinal Microbiome Metabolism of Cranberry (Vaccinium macrocarpon) Proanthocyanidin Dimers, but Not Trimers, Is Altered by Dysbiosis in Ulcerative Colitis Ex Vivo

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Authors
Diaz, Maritza S.; Mertens-Talcott, Susanne U.; Talcott, Stephen T.
Journal
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 10.1021/acs.jafc.4c00042
Abstract

Cranberries contain proanthocyanidins with different interflavan bond types and degrees of polymerization. These chemical differences may impact the metabolism of proanthocyanidins by the intestinal microbiome. In our previous study, we found that healthy microbiomes produced higher concentrations of the phenolic acid metabolites 5-(3',4'-dihydroxyphenyl)-g-valerolactone and 3-hydroxyphenylacetic acid from the cranberry extract in comparison to ulcerative colitis (UC) microbiomes ex vivo. To understand this difference, LC-ESI-MS/MS was utilized to characterize the metabolism of the precursor proanthocyanidins. Healthy microbiomes metabolized procyanidin A2, procyanidin B2, and procyanidin dimeric intermediates but not A-type trimers, to a greater extent than UC microbiomes. The metabolism of procyanidin A2 and procyanidin B2 by fecal microorganisms was then compared to identify their derived phenolic acid metabolites. 5-(3',4'-Dihydroxyphenyl)-g-valerolactone and 3-hydroxyphenylacetic acid were identified as unique metabolites of procyanidin B2. Based on these results, the metabolism of procyanidin B2 contributed to the differential metabolism observed between healthy and UC microbiomes.

Mapping of Dietary Interventions Beneficial in the Prevention of Secondary Health Conditions in Spinal Cord Injured Population: A Systematic Review

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Authors
Stojic, S.; Eriks-Hoogland, I.; Gamba, M.; Valido, E.; Minder, B.; Chatelan, A.; Karagounis, L. G.; Ballesteros, M.; Diaz, C.; Brach, M.; Stoyanov, J.; Diviani, N.; Rubinelli, S.; Perret, C.; Glisic, Marija
Journal
JOURNAL OF NUTRITION HEALTH & AGING 10.1007/s12603-023-1937-6
Abstract

Objectives: Individuals with spinal cord injury are at risk of secondary health conditions (SHC) that develop as a consequence of autonomic dysfunction, prolonged oxidative stress and inflammation, and physical inactivity coupled with inadequate energy and nutritional intake. SHC can be debilitating and even life-threatening, and its prevention remains one of the major challenges in the continuum of medical care of aging SCI population. An unhealthy diet is a major driver of inflammation, oxidative stress, and unfavourable metabolic status and may be a practical preventive target to tackle increased SHC risk post-injury.

Aims: To provide a catalogue of dietary interventions beneficial in prevention of SHC among individuals with SCI by conducting a systematic review of the literature on dietary interventions and dietary supplementation in promoting health and well-being after the injury. In addition, we aimed to provide a summary of observational studies exploring the association between habitual diet (macro- and micronutrients intake and dietary patterns) and health patterns following the injury.MethodThis review was registered at PROSPERO (University of York) with registration number CRD42022373773. Four medical databases (EMBASE.com, MEDLINE [Ovid], Cochrane CENTRAL, and Web of Science Core Collection) and Google Scholar were searched from inception until 11th July 2022. Studies were included if they were clinical trials or observational studies conducted in adult individuals with SCI and provided information of interest. Based on strength of the study design and risk of bias assessment (using the NIH tool), we classified studies from Level 1 (most reliable studies) to Level 4 (least reliable studies).

Results: Of 12,313 unique citations, 47 articles (based on 43 original studies) comprising 32 interventional (22 RCTs, 3 NRCT, and 7 pre-post studies) and 11 observational studies (2 cohort studies, 2 case-control, 1 post-intervention follow-up study, and 6 cross-sectional studies) were included in the present systematic review. Twenty studies (46.5%) were classified as Level 1 or 2, indicating high/moderate methodological quality. Based on those studies, dietary strategies including high protein diet, intermittent fasting, balanced diet in combination with physical conditioning and electrical stimulation, and dietary supplementation including alpha-lipoic acid, creatine, vitamin D, and cranberry-derived supplements and probiotics were mapped as the most promising in prevention of SHC among individuals with SCI.

Conclusions: To develop timely and effective preventive strategies targeting major SHC (e.g., cardiometabolic diseases, urinary tract infections) in SCI, further research is warranted to confirm the effectiveness of dietary strategies/interventions identified through the current systematic review of the literature.

Natural O-6-methylguanine-DNA methyl transferase (MGMT) gene antagonist from Vaccinium oxycoccos: A new hope in Alzheimer's therapeutics

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Authors
Yadav, Pardeep; Panda, Siva Prasad; Soni, Renuka; Kumari, Muskan; Pathak, Lavanya; Jha, Saurabh Kumar
Journal
CHEMICAL BIOLOGY LETTERS (10)3, 549
Abstract

Alzheimer's disease (AD) is a neurodegenerative illness with a complex pathobiology. The pathogenesis of Alzheimer's disease is majorly driven by mutation, overexpression and downregulation of beta-amyloid (A beta) gene that results in the aggregation of a beta-amyloid (A beta) protein within the neocortex. O-6-methylguanine-DNA methyl transferase (MGMT) gene coding for a DNA repair enzyme have found to play an important role in Alzheimer's disease. Some researchers have reported that Tau protein disintegration is directly tied to MGMT gene. An unavoidable, agerelated increase in brain methylation of MGMT gene have shown to upregulate MGMT expression, resulting in Tau dysfunction. Due to the complex underlying pathology of Alzheimer disease (AD), treatment strategies are under extensive research as no new therapies have been approved by the US Food and Drug Administration (FDA) since 2003. Drug repositioning/molecular docking have appeared to be successful techniques to fasten the pharmacological research for AD treatment. In light to the same the study was aimed to evaluate various natural compounds from Vaccinium oxycoccos (cranberry) that are antagonist to MGMT gene. MGMT gene and Compounds structure was retrieved from PDB and PubChem databases and were screened for suitable interactions between them. Out of 23 compounds, four demonstrated strong binding affinity to MGMT gene and thus predicted to use as MGMT gene antagonist in developing the treatment for Alzheimer's disease (AD). These findings may be applicable to other degenerative diseases also where MGMT gene interactions have been involved.

Nonantibiotic prophylaxis for urinary tract infections: a network meta-analysis of randomized controlled trials

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Authors
Han, Zeyu; Yi, Xianyanling; Li, Jin; Liao, Dazhou; Ai, Jianzhong
Journal
INFECTION 10.1007/s15010-024-02357-z
Abstract

Objective: Recent guidelines indicated that, in addition to antibiotics, nonantibiotic interventions serve as available preventive options for urinary tract infections (UTIs). This study aimed to compare the efficacy and safety of various nonantibiotic interventions in preventing UTIs. 

Methods: The authors systematically searched databases for eligible studies. The inclusion criteria encompassed randomized controlled trials (RCTs) focusing on one or more nonantibiotic interventions for UTI prevention, with the incidence of UTIs being a key outcome measure. Subgroup analyses were performed according to age, sex, and follow-up. 

Results: 50 RCTs comprising 10,495 subjects and investigating 14 interventions, were included. Nearly 80% of the RCTs utilized double-blind or triple-blind designs. In the whole group, D-mannose (risk ratio [RR] 0.34, 0.21 to 0.56), vaccine (RR 0.65, 0.52 to 0.82), probiotics (RR 0.69, 0.50 to 0.94), cranberry (RR 0.72, 0.60 to 0.87), and triple therapy (cranberry plus probiotics plus vitamin A) (RR 0.27, 0.09 to 0.87), exhibited a significant reduction in UTI incidence compared to the placebo. Probiotics (RR 0.50, 0.28 to 0.89) were the most effective in the nonadult group, while vitamin D (RR 0.46, 0.27 to 0.81) showed the highest efficacy in the long follow-up group (>= 1 year). There was no significant difference in the incidence of adverse events between the interventions and the placebo group. 

Conclusions: D-mannose, triple therapy, vaccine, probiotics, and cranberry serve as potential nonantibiotic intervention options for clinical UTI prevention.

Polyphenol-Rich Beverage Consumption Affecting Parameters of the Lipid Metabolism in Healthy Subjects

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Authors
Rahn, Celina; Bakuradze, Tamara; Stegmueller, Simone; Galan, Jens; Niesen, Sonja; Winterhalter, Peter; Richling, Elke
Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 10.3390/ijms24010841
Abstract

Polyphenols are a diverse and widely distributed class of secondary metabolites, which possess numerous beneficial properties including a modulation of glucose and lipid metabolism. This placebo-controlled human intervention study was performed to explore effects of polyphenol-rich beverage (PRB) uptake on lipid metabolism, as well as DNA integrity. In this case, 36 healthy men were randomly divided to consume either 750 mL of a PRB (containing 51% chokeberry, cranberry, and pomegranate) or a placebo drink daily for eight weeks. Only PRB consumption was found to decrease fat and protein intakes significantly compared to the preceding one-week washout period. During the intervention with PRB an increased fat-free mass was shown after four weeks, whereas a significant elevation in body weight and leptin was observed in placebo group. Blood lipids were not significantly altered after PRB consumption, while triglyceride levels increased after placebo drink intake. In platelets, a significant inhibition of phosphodiesterase (PDE) activity was observed, more pronounced in test group. Consuming the PRB decreased total DNA strand breaks in whole blood as well as H2O2-induced breaks in isolated lymphocytes. Overall, our study suggested beneficial effects on lipid metabolism by reduced energy intake, modulation of biomarkers such as PDE activity and improved DNA integrity associated with PRB consumption.

Potential of Cranberry Jelly to Prevent Urinary Stone Formation After Cutaneous Ureterostomy: A Case Report

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Authors
Kaga, Kanya; Kaga, Mayuko
Journal
CUREUS JOURNAL OF MEDICAL SCIENCE 10.7759/cureus.54819
Abstract

One complication of cutaneous ureterostomy is urinary stone formation, which may lead to recurrent pyelonephritis. Frequent catheter changes and the prophylactic administration of antibiotics are commonly used to prevent stone formation. Cranberry products have been reported to inhibit stone formation in indwelling urethral catheters. We herein examined the inhibitory effects of a cranberry product on stone formation in a case of catheter occlusion due to stone formation after cutaneous ureterostomy. The results obtained indicate the potential of cranberry products to prevent stone formation after cutaneous ureterostomy requiring catheter placement.

Prebiotic proanthocyanidins inhibit bile reflux-induced esophageal adenocarcinoma through reshaping the gut microbiome and esophageal metabolome

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Authors
Weh, Katherine M.; Howard, Connor L.; Zhang, Yun; Tripp, Bridget A.; Clarke, Jennifer L.; Howell, Amy B.; Rubenstein, Joel H.; Abrams, Julian A.; Westerhoff, Maria; Kresty, Laura A.
Journal
JCI INSIGHT 10.1172/jci.insight.168112
Abstract

The gut and local esophageal microbiome progressively shift from healthy commensal bacteria to inflammation -linked pathogenic bacteria in patients with gastroesophageal reflux disease, Barrett's esophagus, and esophageal adenocarcinoma (EAC). However, mechanisms by which microbial communities and metabolites contribute to reflux-driven EAC remain incompletely understood and challenging to target. Herein, we utilized a rat reflux-induced EAC model to investigate targeting the gut microbiome-esophageal metabolome axis with cranberry proanthocyanidins (C -PAC) to inhibit EAC progression. Sprague-Dawley rats, with or without reflux induction, received water or C -PAC ad libitum (700 mu g/rat/day) for 25 or 40 weeks. C -PAC exerted prebiotic activity abrogating reflux-induced dysbiosis and mitigating bile acid metabolism and transport, culminating in significant inhibition of EAC through TLR/NF-kappa B/TP53 signaling cascades. At the species level, C -PAC mitigated reflux-induced pathogenic bacteria (Streptococcus parasanguinis, Escherichia coli, and Proteus mirabilis). C -PAC specifically reversed reflux-induced bacterial, inflammatory, and immune -implicated proteins and genes, including Ccl4, Cd14, Crp, Cxcl1,Il6,Il1b, Lbp, Lcn2, Myd88, Nfkb1, Tlr2, and Tlr4, aligning with changes in human EAC progression, as confirmed through public databases. C -PAC is a safe, promising dietary constituent that may be utilized alone or potentially as an adjuvant to current therapies to prevent EAC progression through ameliorating reflux-induced dysbiosis, inflammation, and cellular damage.

Probiotic set-yogurt fortified with cranberry fruit powder: physicochemical properties and health effect on ulcerative colitis in mice

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Authors
Ruan, Jingxin; Li, Yufeng; Zheng, Jun'an; Yu, Min; Sun, Weihao; Wei, Xiuyan; Zhang, Xiangrong
Journal
INTERNATIONAL JOURNAL OF FOOD ENGINEERING 10.1515/ijfe-2023-0026
Abstract

The aim of the study was to investigate the effect of cranberry fruit powder (CFP) on the physicochemical and bioactive properties of yogurt. The addition of CFP before fermentation enhanced the amount of total flavonoid, proanthocyanidin, antioxidant capacity and elastic modulus of yogurt compared with the control. In the experiment of ulcerative colitis (UC) in mice, the levels of TNF-alpha, IL-6, and IL-1 beta were statistically lower in the CFPY group than that of DSS group. Moreover, the histological lesions of UC mice were significantly ameliorated in the CFPY group. The pH value decreased significantly, but the sugar content, water holding capacity, susceptibility to syneresis improved a little during storage at 4 degrees C. The bacterial counts were more than the minimum recommended daily dose (6 log CFU/g) in CFP yogurt. The findings suggest that addition of CFP into yogurt is a promising option of producing novel yogurts with nutrition value and bioactivity.