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Plant Extracts and Natural Compounds for the Treatment of Urinary Tract Infections in Women: Mechanisms, Efficacy, and Therapeutic Potential

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Authors
Hsu Y-T, Wu H-C, Tsai C-C, Tsai Y-C, Kuo C-Y
Journal
Curr. Issues Mol. Biol. 2025, 47(8), 591; https://doi.org/10.3390/cimb47080591
Abstract

Urinary tract infections (UTIs) are among the most prevalent bacterial infections in women, with high recurrence rates and growing concerns over antimicrobial resistance. The need for alternative or adjunctive therapies has spurred interest in plant-based treatments, which offer antimicrobial, anti-inflammatory, antioxidant, and immune-modulatory benefits. This review summarizes the mechanisms of action, clinical efficacy, and therapeutic potential of various medicinal plants and natural compounds for preventing and treating UTIs in women. Notable candidates include cranberry, bearberry, pomegranate, green tea, and other phytochemicals with proven anti-adhesive and biofilm-disrupting properties. Evidence from clinical trials and meta-analyses supports the role of cranberry natural products and traditional herbal medicines (THMs) in reducing UTI recurrence, especially when combined with antibiotics. Notably, A-type proanthocyanidins in cranberry and arbutin in bearberry are key bioactive compounds that exhibit potent anti-adhesive and biofilm-disrupting properties, offering promising adjunctive strategies for preventing recurrent urinary tract infections. Additionally, emerging therapies, such as platelet-rich plasma (PRP), show promise in restoring bladder function and reducing infection in women with lower urinary tract dysfunction. Overall, plant-based strategies represent a valuable and well-tolerated complement to conventional therapies and warrant further investigation through high-quality clinical trials to validate their efficacy, safety, and role in personalized UTI management.

Polyphenol-rich snack consumption during endurance exercise training improves nitric oxide bioavailability but does not improve exercise performance in male cyclists: a randomised controlled trial

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Authors
d'Unienville, Noah Marc Adrian, Coates, Alison M., Hill, Alison M., Nelson, Maximillian J., Croft, Kevin, Yandell, Catherine, Buckley, Jonathan D.
Journal
Current Developments in Nutrition. 2025. 9(5).
Abstract

Background: Antioxidants and nitric oxide (NO) precursors may improve endurance exercise performance by reducing oxidative stress and increasing NO production. Almonds, dried grapes, and cranberries (AGC) are good sources of antioxidants and NO precursors. 

Objectives: To determine whether AGC consumption improved physiological responses and endurance cycling time-trial performance in response to training. 

Methods: After 1 wk of light training (LT), 96 male recreationally trained cyclists consumed 125 g of AGC or control (CON: isocaloric oat bar) daily during 2 wk of heavy training (HT) and a 2-wk taper (T). At the end of LT, HT, and T, endurance exercise performance (5-min cycling time-trial; 5CTT), NO bioavailability (plasma and urine nitrate and nitrite), oxidative stress [plasma F2-isoprostanes (F2-Isop)], muscle damage (creatine kinase) and subjective measures of wellbeing were assessed, as well as physiological responses during exercise at 70% maximal aerobic power output. 

Results: Compared to LT, 5CTT performance was impaired at HT (d = -0.27, P = 0.01) and improved at T (d = 0.79, P < 0.001), with no difference between treatments (P > 0.81). Compared with CON, during submaximal exercise at 70%, maximal aerobic power output AGC demonstrated higher oxygen consumption (HT: d = 0.46; T: d = 0.38, P < 0.001) and lower respiratory exchange ratio (HT: d = -0.61; T: d = -0.23, P < 0.032). At HT, urine F2-Isop was higher compared with LT (d = 0.21, P = 0.036), but plasma F2-Isop was lower (d = -0.22, P = 0.008), with no difference between treatments. At HT, AGC had higher subjective energy concentrations (d = 0.21, P = 0.02) and urinary nitrite (d = 0.23, P = 0.03) compared with CON and higher creatine kinase (d = 0.24, P = 0.02) and less fatigue (d = -0.20; P = 0.05) at T. 

Conclusion: Although not beneficial for 5CTT performance or exercise efficiency, AGC increases fat oxidation during exercise, NO bioavailability, and subjective energy concentrations, which may confer benefits for health and wellbeing..

Polyphenols for the prevention or management of preeclampsia: a systematic review and meta-analysis.

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Authors
Nguyen, Phi-Yen, Sanderson, Ben, Makama, Maureen, Mills, Kate, Ammerdorffer, Anne, Gulmezoglu, A. Metin, Vogel, Joshua P., McDougall, Annie R. A.
Journal
BJOG: An International Journal of Obstetrics and Gynaecology. June 2025. 132(7):867-879.
Abstract

Objectives: To evaluate the effects of polyphenol-containing products during pregnancy on preeclampsia-related maternal and neonatal outcomes. 

Design: Systematic review and meta-analysis. 

Setting: Nine databases and one trial registry, from inception to August 11th, 2023. 

Population/Sample: Randomised controlled trials where women received polyphenolic-containing products (as standardised extracts or dietary supplements) compared to placebo or standard care. 

Methods: All review stages were conducted by two independent reviewers. Random-effects meta-analysis with the Hartung-Knapp-Sidik-Jonkman method using a framework for studies with few events. Main Outcome Measures: Clinical outcomes combining the core outcome set for preeclampsia and WHO's priority outcomes. 

Results: Fourteen trials investigating six candidates were included. In women with preeclampsia, the addition of epigallocatechin gallate (EGCG) to nifedipine may reduce the time needed to achieve blood pressure control (mean difference (MD) = -14.10 min, 95% CI -18.46 to -9.74) and increase the time to the next hypertensive crisis (MD = 3.10 h, 95% CI 2.35 to 3.85) compared to nifedipine alone (1 trial, 349 women; low certainty). Similarly, the addition of resveratrol to nifedipine may reduce the time needed to achieve blood pressure control (MD = -15.50 min, 95% CI -19.83 to -11.17) and increase the time to the next hypertensive crisis (MD = 2.50 h, 95% CI 2.09 to 2.91) (1 trial, 349 women; low certainty). No differences were observed for other outcomes or candidates (Salvia miltiorrhiza, Bryophyllum pinnatum, raspberry and cranberry extracts). 

Conclusion: ECGC and resveratrol supplements have been investigated for potential effects in managing clinical signs and symptoms of preeclampsia; however, evidence on the clinical and adverse effects of polyphenols is limited and uncertain.

Prevention of recurrent urinary tract infection in women: an update.

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Authors
Corrales-Acosta, Elizabeth, Zaragoza, Eulalia Cuartiella, Perez, Mar Monzo, Perdomo, Sheila Benitez, Corrales-Riveros, Juan Guillermo, Corrales, Mariela
Journal
Microbiology Research. 11 March 2025. 16(3).
Abstract

Recurrent urinary tract infection (rUTI) is a significant public health problem in women. General measures to prevent recurrence include behavioral changes and increased fluid intake, cranberry ingest, use of methenamine hippurate, antibiotic prophylaxis, D-mannose, probiotics, or vaccines. We conducted a literature review of the latest updates on preventing rUTI in December 2024. The search concluded with 27 articles that fulfilled our inclusion criteria. Our review demonstrated that behavioral changes such as correct genital hygiene, avoiding postponing micturition or defecation, urinating after sexual intercourse, and ingesting 1.5-2 L of water could prevent rUTI. The ingestion of cranberries reduces the risk of symptomatic, culture-verified urinary tract infections in women with rUTIs. Methenamine hippurate is an alternative to antibiotics to avoid rUTI. Estrogen reduces rUTI in women with hypoestrogenism. Limited evidence supports using D-mannose, probiotics, and vaccines to prevent rUTI. In conclusion, after successful treatment of the acute episode, preventative measures are needed to reduce rUTI frequency and morbidity according to each patient's characteristics and preferences

The impact of cranberry on lower urinary tract function: limitations due to gene expression and pharmacokinetic variability.

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Authors
Veledar-Hamalukic, Anisa
Journal
Journal of Central European Agriculture 2025. 26(2):437-455.
Abstract

Cranberries are well known for their antioxidative, anti-inflammatory, antimicrobial, and anti-biofilm formation properties. Many studies indicate their potential for cancer prevention, blood sugar regulation, gastrointestinal and cardiovascular health, and antiviral properties. Such wide therapeutic potential for human health has made cranberries favourable for dietary formulations. Considering how prone patients are to accept treatment via nature's pharmacy instead of the conventional one, cranberries in the form of juice, tablets, capsules, or extracts are often prescribed alongside antibiotic therapy for urinary tract infection (UTI) treatment. This review paper aims to provide a better understanding of the limitations of the usage of berry dietary formulations for health improvement. The healing potential of cranberries is limited due to the bioaccessibility of their ingredients and their pharmacokinetic properties. Although rich with pharmacologically active substances, including anthocyanins, proanthocyanidins, vitamin C, vitamins (B1, B2, B3, B5, B6, B9), and organic acids, their potential is limited due to low absorption and distribution, extensive metabolism, and elimination. The variability in gene expression affecting the biosynthesis of anthocyanins and proanthocyanidins within the Vaccinium berries results in diminished concentrations of active ingredients within the plant material itself. Also, the results from the clinical trials are inconsistently standardized. This paper offers a comprehensive analysis of the available data and presents a clear direction for future research.

The Synergistic Impact of Vitamin D and Cranberry Coatings on the Antimicrobial Efficacy of Dental Implants

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Authors
Gayathri KE, Suresh N, Gurumoorthy K, Rakshagan V, Ali S, Kannan KP.
Journal
Adv Hum Biol 2025;15:404-8.
Abstract

Introduction: Cranberry (Vaccinium macrocarpon) and Vitamin D have both demonstrated significant potential in combating microbial infections, particularly in the oral environment. Cranberry is known for its bioactive compounds, such as proanthocyanidins, flavonoids and organic acids, which exhibit antibacterial properties, while Vitamin D plays a crucial role in bone metabolism and immune response. This study aims to evaluate the antimicrobial efficacy of dental implants coated with cranberry extract and Vitamin D to inhibit bacterial biofilm formation and improve osseointegration. 

Materials and Methods: Titanium dental implants were coated with a cranberry hydrogel solution containing Vitamin D. The process involved surface preparation, dip coating and curing of the implants. Sub-gingival plaque samples were collected from patients with peri-implantitis for microbial analysis. In vitro biofilm formation was assessed on both coated and uncoated implants, followed by a colony reduction ability assessment where biofilm from the implant surfaces was dislodged and cultured to quantify bacterial colony-forming units (CFUs). 

Results: The results indicated a significant reduction in bacterial colonies in the test group (coated implants) compared to the control group (uncoated implants). The cranberry/Vitamin D coating effectively inhibited the growth of black-pigmented microbes. The test group showed a notable decrease in CFU count, confirming the antimicrobial properties of the coating. 

Conclusion: Cranberry and Vitamin D-coated dental implants exhibit significant antimicrobial activity, reducing bacterial colonisation and promoting better clinical outcomes in terms of infection control and bone healing. The use of natural bioactive compounds on implant surfaces represents a viable option to enhance the success rate of dental implants. However, further clinical trials are needed to validate long-term efficacy.

Whole cranberry fruit powder supplement reduces the incidence of culture-confirmed urinary tract infections in females with a history of recurrent urinary tract infection: a 6-month multicenter, randomized, double-blind, placebo-controlled trial.

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Authors
Stonehouse, Welma, Benassi-Evans, Bianca, Bednarz, Jana, Vincent, Andrew D.
Journal
American Journal of Clinical Nutrition. April 2025. 121(4):932-941.
Abstract

Background: High prevalence of urinary tract infections (UTI), including cystitis, and concern for antimicrobial resistance justify safe and effective nonantibiotic therapies for prevention of recurrent UTI (rUTI). Objectives: This study investigated the effect of a whole cranberry fruit powder supplement on incidence of culture-confirmed UTI (primary outcome) in females with rUTI history.

Methods: This multicenter, 6-mo, randomized, placebo-controlled, double-blind study enrolled 150 healthy females [18-65 y, body mass index (BMI) >17.5 and <35 kg/m2] with rUTI defined as >=3 UTIs in the last year or <=2 UTIs in the last 6 mo, excluding those with >5 UTIs in the last 6 mo. Participants consumed either 1 capsule of 500 mg/d of whole cranberry powder (Pacran) or placebo. Culture-confirmed UTIs (>108cfu/L) were assessed throughout the intervention period at unscheduled clinic visits whenever participants experienced UTI symptoms and at baseline, 3- and 6-mo clinic visits. Symptomatic suspected UTIs were defined as participant-reported UTI-associated symptoms at unscheduled visits. 

Results: Whole cranberry powder capsules reduced culture-confirmed UTI risk compared with placebo by 52% (adjusted relative risk [RR]: 0.48; 95% confidence interval [CI]: 0.26, 0.87; P = 0.01); reduced Escherichia coli UTIs (RR: 0.49; 95% CI: 0.24, 1.01; P = 0.05); reduced incidence of UTI with urinary frequency and urgency symptomatology (RR: 0.29; 95% CI:0.13, 0.63; P < 0.01); delayed time to first UTI episode (adjusted hazard ratio [HR]: 0.36; 95% CI: 0.18, 0.74; P = 0.01); and reduced the mean total number of UTIs per participant (adjusted incidence rate ratio IRR: 0.41; 95% CI: 0.21, 0.79; P = 0.01). Significant differences between groups in incidence of symptomatic suspected UTIs and culture-confirmed dysuria were not observed. Exploratory scores for UTI-related female sexual matters, assessed in a subset of sexually active, consenting females, did not differ significantly between groups. No safety concerns were reported. 

Conclusion: This study shows that whole cranberry powder capsules do not impact safety markers and reduce the incidence of culture-confirmed UTI and several other UTI-related outcomes in healthy females with rUTI history. This trial was registered at clinicaltrials.gov asNCT03042273.

Polyphenol-rich cranberry beverage positively affected skin health, skin lipids, skin microbiome, inflammation, and oxidative stress in women in a randomized controlled trial.

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Authors
Christman, Lindsey, de Benedetto, Anna, Johnson, Elizabeth, Khoo, Christina, Gu, Li-wei
Journal
Nutrients 16 September 2024. 16(18). 53 ref.
Abstract

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.

A multiomics evaluation of the countermeasure influence of 4-week cranberry beverage supplementation on exercise-induced changes in innate immunity.

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Authors
Nieman, David C., Sakaguchi, Camila A., Williams, James C., Woo, Jongmin, Omar, Ashraf M., Mulani, Fayaj A., Zhang, Qi-bin, Pathmasiri, Wimal, Rushing, Blake R., McRitchie, Susan, Sumner, Susan J., Lawson, Jackie, Lambirth, Kevin C.
Journal
Nutrients 26 September 2024. 16(19). 57 ref.
Abstract

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.

Co-Treatment with Cranberry and Vitamin-C Mitigates Reproductive Toxicities Induced by Phenobarbital in Male Rats.

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Authors
El-Rahman HAA, Hasan AF, Alyasiri T, El-Wahsh HM, Althubyani SA, Basyony MA, El-Naggar SA, Mahmod DH
Journal
Cellular Physiology & Biochemistry. 58(6):722-738, 2024 Dec 13.
Abstract

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.