Cranberry extract-based formulations for preventing bacterial biofilms

Greene, Ashlee C.; Acharya, Abhinav P.; Lee, Sang B.; Gottardi, Riccardo; Zaleski, Erin; Little, Steven R.

doi:10.1007/s13346-020-00837-x

Cited by 6 publications

(5 citation statements)

References 108 publications

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“…A recent 8-week double-blind randomized placebo-controlled trial of C-PAC juice found that 44 mg PAC equivalents twice daily inhibited Helicobacter pylori infection [ 46 ]. C-PACs have also been reported to possess anti-adhesion effects toward Escherichia coli , Streptococcus mutans , and Candida albicans which are implicated in oral biofilms [ 8 , 95 , 96 , 97 , 98 , 99 ]. However, to our knowledge clinical trials delivering cranberry-based products or extracts have not been conducted in patients at increased risk for esophageal cancer.…”

Section: Discussionmentioning

confidence: 99%

Cranberry Polyphenols in Esophageal Cancer Inhibition: New Insights

et al. 2022

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Esophageal adenocarcinoma (EAC) is a cancer characterized by rapidly rising incidence and poor survival, resulting in the need for new prevention and treatment options. We utilized two cranberry polyphenol extracts, one pro-anthocyanidin enriched (C-PAC) and a combination of anthocyanins, flavonoids, and glycosides (AFG) to assess inhibitory mechanisms utilizing premalignant Barrett’s esophagus (BE) and EAC derived cell lines. We employed reverse phase protein arrays (RPPA) and Western blots to examine cancer-associated pathways and specific signaling cascades modulated by C-PAC or AFG. Viability results show that C-PAC is more potent than AFG at inducing cell death in BE and EAC cell lines. Based on the RPPA results, C-PAC significantly modulated 37 and 69 proteins in JH-EsoAd1 (JHAD1) and OE19 EAC cells, respectively. AFG treatment significantly altered 49 proteins in both JHAD1 and OE19 cells. Bioinformatic analysis of RPPA results revealed many previously unidentified pathways as modulated by cranberry polyphenols including NOTCH signaling, immune response, and epithelial to mesenchymal transition. Collectively, these results provide new insight regarding mechanisms by which cranberry polyphenols exert cancer inhibitory effects targeting EAC, with implications for potential use of cranberry constituents as cancer preventive agents.

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Section: Discussionmentioning

confidence: 99%

Cranberry Polyphenols in Esophageal Cancer Inhibition: New Insights

et al. 2022

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“…Oral delivery of C-PAC (690 μg/rat/day) was well tolerated throughout the chemoprevention bioassay and resulted in potent anticancer effects when ingested at behaviorally achievable levels (human equivalent of approximately 39 mg/day based on standard allometric scaling conversion methods from the rat). The totality of published literature on C-PAC in human populations support efficacy targeting microbial and metabolic outcomes at 36 to 211 mg C-PAC/day and when ingested twice a day due to C-PAC’s pharmacokinetics ( 24 – 28 ). Thus, bioactive concentrations of C-PAC (60–80 mg) can be achieved in humans by consuming 2–4 ounces of 100% cranberry juice, 8–10 ounces of a 27% cranberry juice cocktail, or approximately one-quarter cup fresh cranberries ( 24 – 28 ).…”

Section: Discussionmentioning

confidence: 99%

“…The totality of published literature on C-PAC in human populations support efficacy targeting microbial and metabolic outcomes at 36 to 211 mg C-PAC/day and when ingested twice a day due to C-PAC’s pharmacokinetics ( 24 – 28 ). Thus, bioactive concentrations of C-PAC (60–80 mg) can be achieved in humans by consuming 2–4 ounces of 100% cranberry juice, 8–10 ounces of a 27% cranberry juice cocktail, or approximately one-quarter cup fresh cranberries ( 24 – 28 ). While we and others have shown the cancer inhibitory potential of C-PAC in multiple in vitro models ( 36 ), we believe the current study is the first to show that C-PAC inhibits reflux-driven EAC in vivo and to decipher mechanisms of inhibition linked to reflux-driven dysbiosis, transport, and metabolism of bile, and TLR/NF-κB/TP53 signaling.…”

Section: Discussionmentioning

confidence: 99%

“…Cranberry is a fruit rich in polyphenols, including proanthocyanidins (C-PAC) that exert potent antiinflammatory and antibacterial activities ( 24 – 28 ) in human trials ( 26 – 33 ) and anticancer effects in multiple preclinical models, including EAC xenografts ( 34 – 36 ). Historically, C-PAC was considered to have poor bioavailability and remained underexplored for anticancer effects, particularly in vivo.…”

Section: Introductionmentioning

confidence: 99%

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

Weh,

Howard,

Zhang

et al. 2024

JCI Insight

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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 μg/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-κB/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.

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“…Natural substances have been investigated for their ability to interfere with multiple aspects of biofilm development, adhesion of the biofilm to surfaces, quorum sensing, and disruption of established biofilm [18][19][20]. Cranberry prevents both bacterial and fungal biofilm formation by decreasing adherence of biofilm during infections of the urinary tract and oral cavity [21,22]. Herbs such as rosemary and peppermint can block the quorum-sensing communication within biofilm [23].…”

Section: Introductionmentioning

confidence: 99%

Secreted Metabolites from Pseudomonas, Staphylococcus, and Borrelia Biofilm: Modulation of Immunogenicity by a Nutraceutical Enzyme and Botanical Blend

Cruickshank,

Hamilton,

Iloba

et al. 2024

Microorganisms

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Bacterial biofilms are hardy, adaptable colonies, evading immune recognition while triggering and sustaining inflammation. The goals for this study were to present a method for testing the immunogenicity of secreted metabolites from pathogenic biofilm and to document whether biofilm treated with a nutraceutical enzyme and botanical blend (NEBB) showed evidence of reprogrammed bacterial metabolism, potentially becoming more recognizable to the immune system. We screened immune-modulating properties of metabolites from established biofilm from Pseudomonas aeruginosa (Pa), Stapholycoccus simulans (Ss), and Borrelia burgdorferi (Bb). Secreted metabolites significantly increased the cytokine production by human peripheral blood mononuclear cells, including Interleukin-1-beta (IL-1β), Interleukin-6 (IL-6), macrophage inflammatory protein-1-alpha (MIP-1α), tumor necrosis factor-alpha (TNF-α), interleukin-1 receptor antagonist (IL-1ra), and interleukin-10 (IL-10). Pa metabolites triggered the most robust increase in IL-1β, whereas Bb metabolites triggered the most robust increase in IL-10. NEBB-disrupted biofilm produced metabolites triggering altered immune modulation compared to metabolites from untreated biofilm. Metabolites from NEBB-disrupted biofilm triggered increased MIP-1α levels and reduced IL-10 levels, suggesting a reduced ability to suppress the recruitment of phagocytes compared to untreated biofilm. The results suggest that nutraceutical biofilm disruption offers strategies for inflammation management in chronic infectious illnesses. Further clinical studies are warranted to evaluate clinical correlations in infected human hosts.

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Cranberry extract-based formulations for preventing bacterial biofilms

Cited by 6 publications

References 108 publications

Cranberry Polyphenols in Esophageal Cancer Inhibition: New Insights

Cranberry Polyphenols in Esophageal Cancer Inhibition: New Insights

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

Secreted Metabolites from Pseudomonas, Staphylococcus, and Borrelia Biofilm: Modulation of Immunogenicity by a Nutraceutical Enzyme and Botanical Blend

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