Non-Cochrane · intervention · PM38840232
Effect of flavonoids from grape seed and cranberry extracts on the microbiological activity of Streptococcus mutans: a systematic review of in vitro studies.
Castellanos Jeison Stiven, Betancourt Diego Enrique, Díaz-Báez David, et al. · BMC oral health · 2024 · PubMed · doi:10.1186/s12903-024-04263-0
Full textEvery question was extracted from the full text, figures and supplements by two independent LLM extractors, disagreements adjudicated. Rows cite where in the review the value comes from.
Questions
26
current version
GRADE rated
0
No studies
0
Included studies
22
linked below
No studies 0 · 0%Ungraded 26 · 100%Very low 0 · 0%Low 0 · 0%Moderate 0 · 0%High 0 · 0%
Ungraded means an effect was reported without a GRADE rating; it is not a gap. No studies means the review found nothing to answer the question. The six categories are a display order, not a score.
Review question
| Element | Planned (methods) | Found (results) |
|---|---|---|
| Population | In vitro cultures/biofilms of Streptococcus mutans | 22 in vitro studies of S. mutans (n=22) |
| Intervention | Flavonoids from grape seed extract (GSE) and cranberry extract (proanthocyanidins) | Cranberry extract/juice and PAC fractions (n=15 studies); grape seed extract and PAC fractions (n=7 studies) |
| Comparison | Other antimicrobial agents and/or untreated/vehicle controls | Untreated/vehicle controls; positive controls where used (chlorhexidine, sodium fluoride, ciprofloxacin) |
| Outcomes | (1) bacterial proliferation of S. mutans; (2) biofilm formation; (3) effective concentrations and times for inhibition of microbiological activity | Bacterial growth inhibition (MIC/MBC); biofilm formation; antioxidant capacity; GtfB/C & F-ATPase activity; biofilm morphology; pH/acidogenicity; adhesion; cell death/cytotoxicity |
| Study designs | In vitro studies | In vitro experimental studies (n=22) |
| Timing | Not specified (no year restriction; in vitro incubation not prespecified) | Incubation 18-72 h (mostly 24-48 h) at 37 C where reported |
Search date: 2023-12-30. Databases: PubMed; Elsevier; Scopus; ScienceDirect; Web of Science; EBSCO; Cochrane; OpenGray (grey literature); reference lists of included articles
Questions and results
Cranberry extract / juice and proanthocyanidin (flavonoid) fractions vs Untreated or vehicle control (some studies vs positive antimicrobial controls, e.g. chlorhexidine/fluoride)
Population: Streptococcus mutans (in vitro cultures and biofilms)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
pH drop / acidogenicity buffering Cranberry extract reduces S. mutans acidogenicity / glycolytic pH drop in vitro (5 studies; ungraded). Source: Results 'Effects of extracts on pH change'; Tables 12-15 (pH drop column) · same question in other reviews | Cranberry PAC buffered acidogenesis: final pH 5.6 vs 5.2 control (Koo), lactic acid reduced 44% (Philip 2019) and 46% at 500 ug/mL (Philip 2019 EJOS), final pH 4.7-4.9 vs 3.7 control (Duarte), and disrupted glycolytic… | 5 studies | Ungraded |
Bacterial cell death Population: Streptococcus mutans cultures and biofilms No meta-analysis was conducted; one included study reported time- and concentration-dependent bacterial-count reduction with cranberry extract. Source: Induction of cell death and cytotoxicity; Table 12 · same question in other reviews | no estimate extracted | 1 study | Ungraded |
pH change or lactic acid production Population: Streptococcus mutans cultures and biofilms No meta-analysis was conducted; five included studies reported buffering of pH drop or reduced lactic acid production with cranberry extract or fractions. Source: Effects of extracts on pH change; Tables 12-14 · same question in other reviews | no estimate extracted | 5 studies | Ungraded |
Biofilm formation (reduction) Cranberry extract reduces S. mutans biofilm formation in vitro (10 studies; ungraded). Source: Results 'Effect of extracts on biofilm formation'; Tables 12-15 (Biofilm formation column) · same question in other reviews | Cranberry extract/PAC reduced S. mutans biofilm formation: 51% at 500 ug/mL (Philip 2019), 95.2% at 50 mg/mL (Sumathi), 50-70% of preformed biofilm at 16.67-20.83 mg/dL (Singhal), 32%/29%/14% at 500/250/125 ug/mL… | 10 studies | Ungraded |
Biofilm morphological changes Cranberry extract alters S. mutans biofilm morphology/architecture (4 studies; ungraded). Source: Results 'Morphological changes associated with exposure to flavonoids'; Tables 12-15 (Biofilm morphological changes column) · same question in other reviews | Cranberry treatment disrupted biofilm integrity with agglutination/cell degradation at higher concentrations (Singhal), reduced polymicrobial biomass 38% at 96 h (Philip 2019), produced defective accumulation and… | 4 studies | Ungraded |
Bacterial growth inhibition (MIC/MBC) Cranberry extract inhibits S. mutans growth in vitro (MIC ~0.5-60 mg/mL across 7 studies; ungraded). Source: Results 'Effect of extracts on bacterial growth inhibition (MIC, MBC)'; Tables 12-15 (Bacterial Inhibition column); Abstract · same question in other reviews | Cranberry extract inhibited S. mutans growth across ~0.5-25 mg/mL (Abstract): MIC 12.5 mg/dL and MBC 25 mg/dL (Singhal), MIC 60 mg/mL (Sumathi), MIC 0.5-0.75 mg/mL (Prince); 2 mg/mL PAC enhanced photo-irradiated H2O2… | 7 studies | Ungraded |
Biofilm formation Population: Streptococcus mutans cultures and biofilms No meta-analysis was conducted; ten included studies reported reduced or inhibited Streptococcus mutans biofilm formation with cranberry extract or fractions. Source: Effect of extracts on biofilm formation; Tables 12-15 · same question in other reviews | no estimate extracted | 10 studies | Ungraded |
Antioxidant capacity One study reported antioxidant activity of cranberry polyphenol fractions (ungraded). Source: Results 'Antioxidant capacity of the test extracts'; Tables 12-15 (Antioxidant Capacity column) · same question in other reviews | Cranberry non-dialyzable fractions showed antioxidant activity; the acetone-eluted NDMac fraction was ~twice as rich in polyphenols and had ~twice the antioxidant activity of the ethanol-eluted fraction (Neto 2017). | 1 study | Ungraded |
GtfB/C and F-ATPase activity Cranberry proanthocyanidins downregulate GtfB/C and F-ATPase activity of S. mutans (5 studies; ungraded). Source: Results 'Effect of the extracts on the expression of GtfB and C. F-ATPase'; Tables 12-15 (Effect on Gtfs and F-ATPase column) · same question in other reviews | Cranberry PAC reduced extracellular polysaccharides 35-40% and inhibited GtfB 40-70% (Koo); decreased EPS formation (Philip 2019); inhibited F-ATPase up to 85% and GtfB up to 70% (Duarte); F-ATPase 18-33% and GtfB… | 5 studies | Ungraded |
Bacterial growth inhibition Population: Streptococcus mutans cultures and biofilms No meta-analysis was conducted; seven included studies reported inhibition of Streptococcus mutans growth with cranberry extract or fractions. Source: Effect of extracts on bacterial growth inhibition (MIC and MBC); Tables 12-15 · same question in other reviews | no estimate extracted | 7 studies | Ungraded |
Bacterial adhesion or initial colonization Population: Streptococcus mutans cultures and biofilms No meta-analysis was conducted; three included studies reported reduced adhesion or initial colonization with cranberry extract or fractions. Source: Effect of extracts on bacterial adhesion; Tables 12-15 · same question in other reviews | no estimate extracted | 3 studies | Ungraded |
Bacterial adhesion (inhibition) Cranberry extract inhibits S. mutans adhesion / initial colonization in vitro (3 studies; ungraded). Source: Results 'Effect of extracts on bacterial adhesion'; Tables 12-15 (Adhesion column) · same question in other reviews | Cranberry formulations adhered to and prevented biofilm on saliva-coated hydroxyapatite (Greene); reduced adhesion via inhibited glucan synthesis (Feng); reduced initial S. mutans colonization 40-60% through reduced… | 3 studies | Ungraded |
Cell death / cytotoxicity induction One study reported time-dependent cell-death induction (50% at 10 h) with cranberry extract (ungraded). Source: Results 'Induction of cell death and cytotoxicity'; Tables 12-15 (Cell death induction column) · same question in other reviews | Cranberry extract produced a time- and concentration-dependent reduction in bacterial count, with a 50% reduction after 10 h (Singhal). | 1 study | Ungraded |
Biofilm morphology or biomass Population: Streptococcus mutans cultures and biofilms No meta-analysis was conducted; four included studies reported disrupted biofilm structure or reduced biomass with cranberry extract or fractions. Source: Morphological changes associated with exposure to flavonoids; Tables 12-14 · same question in other reviews | no estimate extracted | 4 studies | Ungraded |
Antioxidant capacity Population: Streptococcus mutans cultures and biofilms No meta-analysis was conducted; one included study reported antioxidant properties of cranberry fractions. Source: Antioxidant capacity of the test extracts; Table 14 · same question in other reviews | no estimate extracted | 1 study | Ungraded |
Grape seed extract or grape seed flavonoid fractions vs No extract or vehicle control; other antimicrobial agents
Population: Streptococcus mutans cultures and biofilms
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Bacterial growth inhibition No meta-analysis was conducted; five included studies reported inhibition of Streptococcus mutans growth with grape seed extract or fractions. Source: Effect of extracts on bacterial growth inhibition (MIC and MBC); Tables 12-14 · same question in other reviews | no estimate extracted | 5 studies | Ungraded |
Gtf activity Population: Streptococcus mutans (in vitro cultures and biofilms) One study reported grape seed extract inhibits S. mutans Gtf activity (ungraded). Source: Results 'Effect of the extracts on the expression of GtfB and C. F-ATPase'; Tables 12-15 (Effect on Gtfs and F-ATPase column) · same question in other reviews | GSE inhibited glucosyltransferase activity 43.9%, rising to 65.7% when combined with amine fluoride (Furiga). | 1 study | Ungraded |
Antioxidant capacity Population: Streptococcus mutans (in vitro cultures and biofilms) One study reported high antioxidant capacity of grape seed extract (ungraded). Source: Results 'Antioxidant capacity of the test extracts'; Tables 12-15 (Antioxidant Capacity column) · same question in other reviews | GSE had the highest Trolox-equivalent antioxidant capacity (6.99 ug/mL) among the tested agents (Furiga). | 1 study | Ungraded |
Biofilm morphological changes Population: Streptococcus mutans (in vitro cultures and biofilms) Grape seed extract alters S. mutans biofilm morphology (2 studies; ungraded). Source: Results 'Morphological changes associated with exposure to flavonoids'; Tables 12-15 (Biofilm morphological changes column) · same question in other reviews | GSE decreased microcolony number and biofilm thickness at 2000 ug/mL (Furiga) and significantly altered bacterial cell structure with 50 ug/2 mL GSE candy (Nowaczyk). | 2 studies | Ungraded |
Biofilm morphology No meta-analysis was conducted; two included studies reported reduced microcolonies or altered bacterial structure with grape seed extract. Source: Morphological changes associated with exposure to flavonoids; Tables 13 and 15 · same question in other reviews | no estimate extracted | 2 studies | Ungraded |
Bacterial adhesion (inhibition) Population: Streptococcus mutans (in vitro cultures and biofilms) Grape seed extract inhibits S. mutans adhesion to hydroxyapatite in vitro (2 studies; ungraded). Source: Results 'Effect of extracts on bacterial adhesion'; Tables 12-15 (Adhesion column) · same question in other reviews | GSE inhibited S. mutans adhesion to hydroxyapatite by 81.5% (polymeric PAC, 0.125 mg/mL) vs 25% for dealcoholized wine (Daglia); adhesion decreased at MIC 0.5 mg/mL (Smullen). | 2 studies | Ungraded |
Cell death / cytotoxicity Population: Streptococcus mutans (in vitro cultures and biofilms) One study reported minimal cytotoxicity (<1% cell damage) with grape seed extract (ungraded). Source: Results 'Induction of cell death and cytotoxicity'; Tables 12-15 (Cell death induction column) · same question in other reviews | GSE showed a very low level of cell damage (<1%, few visible dead cells) (Furiga). | 1 study | Ungraded |
Biofilm formation (reduction) Population: Streptococcus mutans (in vitro cultures and biofilms) Grape seed extract reduces S. mutans biofilm formation in vitro (5 studies; ungraded). Source: Results 'Effect of extracts on biofilm formation'; Tables 12-15 (Biofilm formation column) · same question in other reviews | GSE reduced biofilm formation: 89% (polymeric PAC) vs 79% (dealcoholized wine) (Daglia), inhibition at 4 mg/mL (Zhao), decreased microcolonies with 2000 ug/mL GSE + fluorinol (Furiga), reduction within 30 min… | 5 studies | Ungraded |
Cell damage or cytotoxicity No meta-analysis was conducted; one included study reported very low cell damage with grape seed extract. Source: Induction of cell death and cytotoxicity; Table 13 · same question in other reviews | no estimate extracted | 1 study | Ungraded |
Bacterial growth inhibition (MIC/MBC) Population: Streptococcus mutans (in vitro cultures and biofilms) Grape seed extract inhibits S. mutans growth in vitro (MIC ~0.5 mg/mL to 250 mg/mL across 5 studies; ungraded). Source: Results 'Effect of extracts on bacterial growth inhibition (MIC, MBC)'; Tables 12-15 (Bacterial Inhibition column); Abstract · same question in other reviews | GSE inhibited S. mutans growth across ~0.5-250 mg/mL (Abstract): inhibition at 250-500 mg/mL (Swadas), 4 mg/mL (Zhao), MIC 1000 ug/mL and MBC 4000 ug/mL (Furiga), MIC 0.5 mg/mL (Smullen), and MIC 19.07 mg/mL for… | 5 studies | Ungraded |
Bacterial adhesion No meta-analysis was conducted; two included studies reported reduced Streptococcus mutans adhesion with grape seed extract or fractions. Source: Effect of extracts on bacterial adhesion; Tables 13-14 · same question in other reviews | no estimate extracted | 2 studies | Ungraded |
AMSTAR 2 appraisal
Two independent extractors rated each item. Their ratings are shown side by side because they have not been reconciled yet. The overall rating follows Shea et al. 2017: one critical flaw gives Low, more than one gives Critically Low.
| Item | Extractor A | Extractor B | Agree |
|---|---|---|---|
| 1Research question includes PICO components | Yes | Yes | yes |
| 2Protocol established before the reviewcritical | No | No | yes |
| 3Choice of study designs explained | Yes | No | no |
| 4Comprehensive literature searchcritical | Partial Yes | Partial Yes | yes |
| 5Study selection in duplicate | Yes | Yes | yes |
| 6Data extraction in duplicate | Yes | Yes | yes |
| 7List of excluded studies with reasonscritical | Yes | No | no |
| 8Included studies described in detail | Yes | Yes | yes |
| 9Risk of bias assessed satisfactorilycritical | RCT: N/A · NRSI: No | NRSI: Yes · RCT: N/A | no |
| 10Funding of included studies reported | No | No | yes |
| 11Appropriate meta-analysis methodscritical | RCT: N/A · NRSI: N/A | NRSI: N/A · RCT: N/A | no |
| 12Impact of risk of bias on the pooled results | N/A | N/A | yes |
| 13Risk of bias accounted for in interpretationcritical | Yes | Yes | yes |
| 14Heterogeneity explained | Yes | Yes | yes |
| 15Publication bias investigatedcritical | N/A | N/A | yes |
| 16Conflicts of interest reported | Yes | Yes | yes |
| Overall | Critically Low | Critically Low | yes |
Included primary studies 22
Open as a trial list| Study | Also included by | Outcomes it informs here | Trial PICO | Results |
|---|---|---|---|---|
| Abu-Obaid 2020 A Comparative Evaluation of the Antimicrobial Effects of Different Mouthrinses against Oral Pathogens: An In Vitro Study1. PMID:32690831 | this review only | not stated | not extracted yet | not extracted yet |
| Daglia 2010 Isolation of red wine components with anti-adhesion and anti-biofilm activity against Streptococcus mutans DOI:10.1016/j.foodchem.2009.08.037 | this review only | not stated | not extracted yet | not extracted yet |
| Duarte 2006 Inhibitory effects of cranberry polyphenols on formation and acidogenicity of Streptococcus mutans biofilms. PMID:16553831 | this review only | not stated | not extracted yet | not extracted yet |
| Elgamily 2023 Laboratory evaluation of anti-plaque and remineralization efficacy of sugarless probiotic jelly candy supplemented with natural nano… PMID:37414826 | this review only | not stated | not extracted yet | not extracted yet |
| Feng 2013 The specific degree-of-polymerization of A-type proanthocyanidin oligomers impacts Streptococcus mutans glucan-mediated adhesion and… PMID:23697791 | this review only | not stated | not extracted yet | not extracted yet |
| Furiga 2013 Preventive effects of an original combination of grape seed polyphenols with amine fluoride on dental biofilm formation and oxidative… PMID:24251548 | this review only | not stated | not extracted yet | not extracted yet |
| Greene 2020 Cranberry extract-based formulations for preventing bacterial biofilms. PMID:32783154 | this review only | not stated | not extracted yet | not extracted yet |
| Gregoire 2007 Influence of cranberry phenolics on glucan synthesis by glucosyltransferases and Streptococcus mutans acidogenicity. PMID:17953606 | this review only | not stated | not extracted yet | not extracted yet |
| Ikai 2013 Synergistic effect of proanthocyanidin on the bactericidal action of the photolysis of H2O2. PMID:24077536 | this review only | not stated | not extracted yet | not extracted yet |
| Kokubu 2019 Inhibitory Effects of Lingonberry Extract on Oral Streptococcal Biofilm Formation and Bioactivity. PMID:30700643 | this review only | not stated | not extracted yet | not extracted yet |
| Koo 2010 Influence of cranberry proanthocyanidins on formation of biofilms by Streptococcus mutans on saliva-coated apatitic surface and on dental… PMID:20234135 | this review only | not stated | not extracted yet | not extracted yet |
| Neto 2017 Characterization of non-dialyzable constituents from cranberry juice that inhibit adhesion, co-aggregation and biofilm formation by oral… PMID:28470309 | this review only | not stated | not extracted yet | not extracted yet |
| Nowaczyk 2021 The effect of cranberry juice and a cranberry functional beverage on the growth and metabolic activity of selected oral bacteria. PMID:34930215 | this review only | not stated | not extracted yet | not extracted yet |
| Philip 2019 Inhibitory effects of fruit berry extracts on Streptococcus mutans biofilms. PMID:30592324 | this review only | not stated | not extracted yet | not extracted yet |
| Philip 2019 Effect of polyphenol-rich cranberry extracts on cariogenic biofilm properties and microbial composition of polymicrobial biofilms. PMID:30951891 | this review only | not stated | not extracted yet | not extracted yet |
| Prince 2022 Exploration of the Antimicrobial Synergy between Selected Natural Substances on Streptococcus mutans to Identify Candidates for the… PMID:35446116 | this review only | not stated | not extracted yet | not extracted yet |
| Singhal 2020 Antimicrobial and Antibiofilm Effect of Cranberry Extract on Streptococcus mutans and Lactobacillus acidophilus: An In Vitro Study. PMID:32581471 | this review only | not stated | not extracted yet | not extracted yet |
| Smullen 2007 The antibacterial activity of plant extracts containing polyphenols against Streptococcus mutans. PMID:17713333 | this review only | not stated | not extracted yet | not extracted yet |
| Sumathi 2019 matched by author and year (probable) | this review only | not stated | not extracted yet | not extracted yet |
| Swadas 2016 Evaluation and Comparison of the Antibacterial Activity against Streptococcus mutans of Grape Seed Extract at Different Concentrations… PMID:27843246 | this review only | not stated | not extracted yet | not extracted yet |
| Yamanaka 2004 Inhibitory effects of cranberry juice on attachment of oral streptococci and biofilm formation. PMID:15107065 | this review only | not stated | not extracted yet | not extracted yet |
| Zhao 2014 The preventive effect of grape seed extract on artificial enamel caries progression in a microbial biofilm-induced caries model. PMID:24863939 | this review only | not stated | not extracted yet | not extracted yet |