Quercitin Mineralized Tissues

Archives of Oral Biology 169 (2025) 106119
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Archives of Oral Biology

journal homepage: www.elsevier.com/locate/archoralbio
Effects of quercetin on mineralized dental tissues: A scoping review

Gabriel Pereira Nunes a,c , Renata de Oliveira Alves a , Matheus Henrique Faccioli Ragghianti a,
Alexandre Henrique dos Reis-Prado d,e, Priscila Toninatto Alves de Toledo a,e,
Tamires Passadori Martins a,f, Ana Paula Miranda Vieira a , Geórgia Rondó Peres a,c ,
Cristiane Duque a,b,*
a
Department of Preventive and Restorative Dentistry, Araçatuba School of Dentistry, São Paulo State University - UNESP, Araçatuba, SP, Brazil
b
Faculty of Dental Medicine, Centre for Interdisciplinary Research in Health (CIIS), Universidade Católica Portuguesa, Viseu, Portugal
c
Laboratory for Bone Metabolism and Regeneration, University of Porto, Faculty of Dental Medicine, Porto, Portugal
d
Department of Restorative Dentistry, School of Dentistry, Federal University of Minas Gerais (UFMG), Belo Horizonte, Brazil
e
Department of Cariology, Restorative Sciences, and Endodontics, School of Dentistry, University of Michigan, Ann Arbor, MI, United States
f
Department of Preventive Dentistry, Periodontology and Cariology, University Medical Center Göttingen, Göttingen, Germany
A R T I C L E I N F O A B S T R A C T
Keywords: Objective: This scoping review (SR) aimed to investigate the impact of quercetin on mineralized dental tissues
Polyphenols intended to be used in preventive and restorative dentistry.
Enamel Methods: This SR was conducted following the PRISMA-ScR statement. A comprehensive search was performed
Dentin
across databases for articles published up to March 2024. Eligible studies included in vitro and in situ studies and
Tooth erosion
Dental caries
evaluating the potential therapeutic effects of quercetin on dental enamel and dentin. Data were extracted, and
synthesis of study findings was conducted.
Results: Out of the 2322 records screened, 22 studies were included in the review. Quercetin, in solution or into
dental materials increased the bond strength to enamel and dentin. Additionally, quercetin also enhanced the
bond strength of enamel after bleaching. Co-administration of quercetin with fluoride prevented erosive wear
and inhibited the proteolytic activity in dentin more effectively than either agent alone. Hardness and modulus of
elasticity was higher in dentin treated with quercetin compared to placebo. Reduction of nanoleakage at the
composite-dentin interface was reduced in the presence of quercetin as a solution or incorporated into dental
adhesives.
Conclusions: Quercetin exhibits promising therapeutic effects on mineralized dental tissues, including reminer
alization and enhancement of bond strength. It shows potential as a multifunctional agent for improving the
longevity and effectiveness of dental biomaterials, as well as in preventing erosion and dental caries. However, as
these conclusions are largely drawn from lab-based (in vitro) studies, further research, including clinical trials, is
needed to fully explore its therapeutic potential and applications in dentistry.
1. Introduction tissues are crucial in dental practice (Xu et al., 2022). In this context, the
use of therapeutic agents that can prevent or mitigate damage to these
The integrity of mineralized dental tissues, such as enamel and tissues has been widely investigated.
dentin, is fundamental to the longevity and functionality of teeth (Arola Flavonoids are secondary polyphenolic compounds produced by
et al., 2017). These tissues can be compromised by various factors, plants and vegetables to enhance their color and flavor, as well as to
including demineralization processes, dentin erosion and wear caused promote protection against UV damage, toxins, and microbes (Yuan
by chemical and mechanical agents (Chen et al., 2024; Xu et al., 2022). et al., 2024). Dietary flavonoids are associated with reduced disease risk
Advances in understanding the mechanisms of dental tissue degradation and lower mortality rates due to their health benefits (Bondonno et al.,
and the search for more effective therapies to preserve and restore these 2020). Quercetin, the most abundant flavonoid in the human diet, is
* Correspondence to: Faculty of Dental Medicine, Centre for Interdisciplinary Research in Health (CIIS), Universidade Católica Portuguesa, Estrada da
Circunvalação, Viseu 3504-505, Portugal.
E-mail addresses: [email protected], [email protected], [email protected] (C. Duque).
https://doi.org/10.1016/j.archoralbio.2024.106119
Received 30 April 2024; Received in revised form 20 October 2024; Accepted 21 October 2024
Available online 24 October 2024
0003-9969/© 2024 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.
G.P. Nunes et al. Archives of Oral Biology 169 (2025) 106119
found in apples, cranberries, cherries, onions, peppers, asparagus, and 2015), in which the following PCC question was asked: “Does quercetin
medicinal herbs such as Hypericum perforatum and ginkgo (Aghababaei promote beneficial effects when used on mineralized dental tissues?”.
et al., 2023; Yang et al., 2020). This natural compound offers a broad Regarding the criteria, Population: Studies involving mineralized dental
range of therapeutic effects. It has demonstrated antioxidant (Deepika tissues (enamel and dentin) subjected to dental procedures, particularly
and Maurya, 2022), anti-inflammatory (Li et al., 2016), antimicrobial those focusing on in vitro samples (such as extracted teeth or enam
(Nguyen and Bhattacharya, 2022), antiviral (Alam et al., 2021), anti el/dentin discs) or participants undergoing restorative, preventive, or
hypertensive (Popiolek-Kalisz and Fornal, 2022), anticancer therapeutic dental treatments. Concept: Application of quercetin in any
(Popiolek-Kalisz and Fornal, 2022), antidiabetic (Dhanya, 2022), and form (treatment solution, incorporated into dental material, coating,
wound-healing properties (Lu et al., 2020). In 2010, quercetin received etc.) and at any concentration used directly on mineralized dental tis
Generally Recognized As Safe (GRAS) status from the US Food and Drug sues. The comparison groups consisted of either a negative control (e.g.,
Administration, permitting its use as a dietary supplement. placebo or no treatment) or a positive control using another active agent
The multifunctionality of quercetin has been the main impetus for its commonly used in dental practice for similar purposes (e.g., fluoride,
use in the prevention and treatment of oral diseases (Wang et al., 2020). chlorhexidine, or other active substances). Context: The primary out
In animal models of periodontal disease, quercetin reduced the pro comes measured include changes in hard dental tissues, such as alter
duction of pro-inflammatory cytokines and exerted antimicrobial effects ations in mineral content, hardness, demineralization and
against pathogenic microorganisms (Mooney et al., 2021; Wang et al., remineralization rates, resistance to acid attacks, adhesion in restorative
2021). In addition, quercetin inhibited the development of oral squa procedures, and structural or compositional changes in enamel and
mous cell carcinoma, regulated cellular resistance to an antineoplastic dentin after exposure to quercetin. Additionally, outcomes related to the
drug and prevented oral mucositis in irradiated mice (Zhang et al., 2019, organic matrix of dentin were also evaluated.
2021; Chan et al., 2023). Promising results have also emerged high The inclusion criteria were clinical trials on humans, in situ and in
lighting significant beneficial effects that quercetin can exert on vitro studies that evaluated the quercetin use on mineralized dental
mineralized dental tissues (Chen et al., 2024; Moradian et al., 2022; tissues (dental enamel and dentin), without restrictions on the period or
Epasinghe et al., 2016). language of publication. The exclusion criteria were studies that eval
Investigations have indicated that quercetin can promote the remi uated only quercetin use without a control group, animal studies (in
neralization of tooth enamel, controlling mineral loss and enhancing vivo), articles that did not consider dentin or dental enamel tissue, re
resistance against dental caries (Hosseinpour-Nader et al., 2023; Mora views, and studies with data reported in more recent articles. In short,
dian et al., 2022b). Additionally, quercetin has been shown to improve studies that did not meet the above criteria were excluded.
the adhesion of restorative materials to enamel and dentin, thus
increasing the durability of dental restorations (Moradian et al., 2022b; 2.3. Information sources and search strategy
Dávila-Sánchez et al., 2020). In dentin, quercetin exhibits
anti-inflammatory and antioxidant properties that can reduce the A search strategy composed of keywords and free terms was used to
degradation of the organic matrix and mitigate the loss of dentin search for studies in the electronic databases Pubmed/Medline, Web of
structure (Chen et al., 2024; Hong et al., 2022). These effects are Science, Scopus, Embase, and Cochrane, as well as the grey literature
particularly significant for the treatment and prevention of dental dis search through OpenGrey for articles published up to March 11, 2024
eases such as caries and erosion. Moreover, quercetin has demonstrated (Appendix #S1). After that, a reference manager (EndNote, version X9,
to reinforce exceptionally mechanical properties of dentin when com Thomson Reuters, Philadelphia, USA) was used to exclude duplicate
bined with collagen, underscoring its potential importance in clinical citations.
applications (Hong et al., 2022).
In line with the data above, studies have demonstrated the potential 2.4. Selection of studies
of quercetin to improve the performance of the dental biomaterials and
the longevity of restorative procedures, particularly by its anti The first stage of the article selection was performed by reading the
proteolytic effect and protective role against erosion in dentin (Capalbo titles and abstracts. The remaining studies were read in full to verify
et al., 2022, Jiang et al., 2020). Although a recent scoping review has eligibility. From this stage, the articles selected for this review were
assessed the effects of flavonoids on bacteria associated with periodontal defined, and a manual search was carried out in the references in order
disease and dental caries (Carneiro et al., 2024), and on the adhesion of to find other eligible articles. Two independent authors (GPN and ROA)
caries-affected dentin (Beckman et al., 2024), no study has yet sum carried out the search and selection of studies, and a third reviewer
marized the scientific evidence regarding the potential of quercetin as a evaluated the data in cases of disagreement (AHRP). Agreement be
biomaterial in preventive and restorative dentistry. This scoping review tween the two reviewers regarding title and abstract selection was
aimed to investigate the impact of quercetin on enamel and dentin, by evaluated by Cohen’s kappa coefficient (κ).
assessing the outcomes on mechanical and adhesive properties, remi
neralization, and collagen degradation. 2.5. Data extraction and synthesis
2. Material and methods The following data were extracted from each study: author/year,
country of publication, design study, dental tissue, characteristic inter
2.1. Study design vention (groups – sample), method of administration or use (treatment),
assessment method, results, and conclusion. In cases where some data
This scoping review was conducted following the Preferred Report were missing, the authors were contacted by e-mail once a week for a
ing Items for Systematic Reviews and Meta-Analyses extension for month until the information was obtained. The qualitative synthesis
Scoping Reviews (PRISMA-ScR) guidelines (Tricco et al., 2018) and focused on outcomes related to the application of quercetin on hard
recent studies published (Seron et al., 2024; Nunes et al., 2024; Chalub dental substrates.
et al., 2023).
3. Results
2.2. Eligibility criteria
3.1. Study selection
To define the research question, an approach based on Patient,
Concept, and Context (PCC) mnemonic was considered (Peters et al., A total of 2322 publications were identified across multiple
2
databases, including PubMed (449), Web of Science (718), Scopus Yang et al., 2017; Gotti et al., 2015; Epasinghe et al., 2014), while 9
(289), Embase (856), Cochrane Library (9), and through manual search articles included both controls (placebo and positive control) (Chen
(1). Following the removal of 863 duplicate references, 1459 titles and et al., 2024; Moradian et al., 2022a, 2022b; Li et al., 2022; Liu et al.,
abstracts were screened to identify studies meeting the predetermined 2021; Mehmood et al., 2021; Jiang et al., 2020; Porto et al., 2018;
eligibility criteria. Subsequently, 24 articles were selected for full-text Epasinghe et al., 2016). The primary positive controls were sodium
assessment. Among these, 2 studies were excluded as they did not fluoride (NaF) (Chen et al., 2024; Hosseinpour-Nader et al., 2023;
meet the eligibility criteria. Finally, 22 studies were included in the Capalbo et al., 2022; Li et al., 2022; Jiang et al., 2020; Epasinghe et al.,
scoping review (Chen et al., 2024; Hosseinpour-Nader et al., 2023; Hong 2016), mainly for analyses related to remineralization (mineral con
et al., 2022; Capalbo et al., 2022; Moradian et al., 2022a, 2022b; Fattah tent), and chlorhexidine (CHX) was utilized in four studies (Moradian
et al., 2022; Pourhajibagher et al., 2022; Li et al., 2022, 2017; Lin et al., et al., 2022a; Hong et al., 2022; Li et al., 2022; Porto et al., 2018),
2022; Liu et al., 2021; Porto et al., 2021, 2018; Mehmood et al., 2021; particularly as a positive control in evaluations related to dentin organic
Dávila-Sánchez et al., 2020; Jiang et al., 2020; Yang et al., 2017; matrix (Hong et al., 2022; Porto et al., 2018).
Shamsedin et al., 2017; Epasinghe et al., 2016, 2014; Gotti et al., 2015). In the 22 eligible studies, 18 evaluated the effect of quercetin on
The details of the search strategy are depicted in the flow diagram dentin tissue (Chen et al., 2024; Moradian et al., 2022a; Capalbo et al.,
(Fig. 1). The kappa score for articles included in all databases demon 2022; Fattah et al., 2022; Hong et al., 2022; Li et al., 2022, 2017; Lin
strated an acceptable level of inter-examiner agreement (k = 0.94). et al., 2022; Liu et al., 2021; Mehmood et al., 2021; Porto et al., 2021,
2018; Dávila-Sánchez et al., 2020; Jiang et al., 2020; Yang et al., 2017;
3.2. Characteristics of the included studies Epasinghe et al., 2016, 2014; Gotti et al., 2015), while 4 studies focused
on dental enamel (Hosseinpour-Nader et al., 2023; Moradian et al.,
All the included studies were published in English between 2022b; Pourhajibagher et al., 2022; Shamsedin et al., 2017). Eight
September 2014 and February 2024, and their characteristics are sum studies utilized quercetin as a dentin pre-treatment (Moradian et al.,
marized in Table 1. The eligible studies originated from various coun 2022a; Lin et al., 2022; Porto et al., 2021, 2018; Dávila-Sánchez et al.,
tries, including Brazil (Capalbo et al., 2022; Porto et al., 2021, 2018; 2020; Mehmood et al., 2021; Li et al., 2017; Shamsedin et al., 2017), and
Gotti et al., 2015), Iran (Hosseinpour-Nader et al., 2023; Moradian et al., one study used it as a post-whitening (internal) conditioning agent
2022a, 2022b; Fattah et al., 2022; Pourhajibagher et al., 2022; Sham (Fattah et al., 2022). In 17 studies, quercetin was administered in the
sedin et al., 2017), China (Chen et al., 2024; Hong et al., 2022; Li et al., form of a treatment solution (Chen et al., 2024; Moradian et al., 2022a,
2022, 2017; Lin et al., 2022; Liu et al., 2021; Jiang et al., 2020; Yang 2022b; Fattah et al., 2022; Capalbo et al., 2022; Hong et al., 2022; Li
et al., 2017; Epasinghe et al., 2016, 2014), Ecuador (Dávila-Sánchez et al., 2022, 2017; Lin et al., 2022; Liu et al., 2021; Mehmood et al.,
et al., 2020), and India (Mehmood et al., 2021). Concerning the study 2021; Dávila-Sánchez et al., 2020; Jiang et al., 2020; Porto et al., 2018;
design, all articles utilized an "in vitro" model, with only 2 studies also Shamsedin et al., 2017; Epasinghe et al., 2016, 2014), and five studies
incorporating an "in situ" model (Hong et al., 2022; Jiang et al., 2020). evaluated the incorporation of quercetin into dental materials
Thirteen studies compared quercetin versus a positive control (Capalbo (Hosseinpour-Nader et al., 2023; Pourhajibagher et al., 2022; Porto
et al., 2022; Fattah et al., 2022; Hong et al., 2022; Hosseinpour-Nader et al., 2021; Yang et al., 2017; Gotti et al., 2015), focusing into adhesive
et al., 2023; Lin et al., 2022; Pourhajibagher et al., 2022; Porto et al., systems (Porto et al., 2021; Yang et al., 2017; Gotti et al., 2015) and glass
2021; Dávila-Sánchez et al., 2020; Li et al., 2017; Shamsedin et al., 2017; ionomer cements (Pourhajibagher et al., 2022). The concentrations of
Fig. 1. Flow diagram of search in databases according to PRISMA-ScR Statement.
3
G.P. Nunes et al.
Table 1
General data from included studies.
Author/ year Design Dental G1 - QCT (Intervention group) Method of Administration Assessment Method Results: Outcomes Conclusion
(Country) study Tissue G2 – Control group or use [Mean ± SD] or
(N sample) percentage
Chen et al.,(2024) In vitro Dentin G1: Quercetin 300 μg/ml The samples were immersed in their respective Erosive dentine loss (EDL), Dentin loss (μm): The results suggest that QCT could
(China) Human teeth (QCT): 26 solutions for 2 min each day. release of type I collagen G1 (QCT): 8.13 ± 1.37 effectively inhibit dentine erosion
(Dental erosion and G2.1: Deionized water (DW); 26 telopeptide (ICTP) G2.1 (DW): 17.17 ± and abrasion through tubule
abrasion) G2.2: Sodium Fluoride 1.52 occlusion and demineralized
1.23×104 μg/ml (NaF): 26 G2.2 (NaF): 12.93 ± organic matrix preservation.
0.86
Release of ICTP
G1 (QCT): 19.37 ±
4.38
G2.1 (DW): 44.34 ±
3.37
G2.2 (NaF): 40.13 ±
4.38
Hosseinpour-Nader In vitro Enamel G1.1: NanoQCT (nQCT):10 One layer of nQCT was applied by a sterile Surface topography, and Microhardness PQD-nQCT can improve the
et al., (2023) Human teeth G1.2 Propolis + nanoQCT cotton roll for 60 sec after drying the enamel microhardness. (Remineralized) surface changes and
(Iran) (White spot lesions) (PQD-nQCT): 10 surface and was then washed thoroughly with G1.1 (nQCT): 2.65 ± microhardness in the
G2: Propolis (PQD): 10 PBS (pH 7) to remove any visible remnants of 0.28 remineralization process of
G2.1: 2 % neutral NaF gel: 10 the nQCT and dried G1.2 (PQD-nQCT): demineralized enamel
3.16 ± 0.20 significantly and reduce the
G2.1(PQD): 2.72 ± appearance of white spot lesions
0.31
G2.2 (NaF): 3.28 ±
0.37
DIAGNODent Pen
4
readings
(Remineralized):
G1.1 (nQCT): 8.26 ±
0.47
G1.2 (PQD-nQCT):
7.19 ± 0.54
G2 (PQD): 8.47 ± 0.38
G2.2 (NaF): 6.91 ±
0.53
Fattah et al., (2022) In vitro Dentin Duolink QCT 1 % was applied on the dentine for 10 min Microshear bond strength Microshear bond QCT did not increase the bond
(Iran) Human maxillary G1: Bleaching + QCT after the bleaching and two dual-cure resin types strength values (MPa) strength of both resin cements.
central teeth (Bl/QCT) of cement Duolink
(Bond Strength) G2: Bleaching G1(Bl+QCT): 11.84 ±
Panavia SA 1.7
G1: Bleaching + QCT G2 (Bl): 12.52 ±1.54
G2: Bleaching Panavia

G1(Bl+QCT): 2.13 ±
0.69
G2(Bl): 1.58 ± 0.62
Hong et al., (2022) In situ Dentin G1.1QCT 75 (QCT 75):10 Treatment for 2 min and then subjected to in Dentin loss, inhibition of G1.1 / G1.2 / G1.3 / QCT resulted in increased μUTS of
(China) and Human third molar G1.2 QCT 150 μg/ml (QCT situ/in vivo erosive/abrasive challenge for 7 dentin-derived MMPs, G2 the DOM. QCT led to a
In vivo (Erosion and 150):10 days follows: in vivo erosion 4 times a day and degrees of crosslinking, Dentin loss (μm) significantly lower dentin loss
abrasion; G1.3 QCT 300 μg/ml (QCT then in vivo toothbrush abrasion after the first and ultimate microtensile 0.94 ± 0.38 / 0.85 ± after erosive/abrasive challenge
demineralized 300):10 and last erosive challenges of each day 0.39 / 0.73 ± 0.37 / than CHX.
organic matrix G2 CHX 120 μg/ml:10 1.24 ± 0.36
(DOM)) Inhibition of dentin-
derived MMPs (%):
32.2 ± 5.2 / 41. ± 1.7
(continued on next page)
G.P. Nunes et al.
Table 1 (continued )
/ 60.3 ± 5.3 / 59.68 ±

6.0
Degrees of crosslinking
(%) – G2 (Ethanol and
Deionized water)
28.51 ± 2.64 / 43.54
± 1.46 / 54.41 ± 3.3 /
0 ± 0.2
G1.1 / G1.2 / G1.3 /
G2.1 / G2.2
Ultimate microtensile
strength of collagen
(MPa)
23.5 ± 8.6 / 24.3 ±
7.3 / 29.6 ± 8.5 / 9.9
± 3.6 /10.2 ± 3.4
Capalbo et al., In vitro Dentin G1.1 QCT:12 Blocks were treated with each solution (4 ml/ Dentin loss, Zymography, G1.1 / G1.2 / G2 F+QCT led to a superior
(2022) Bovine dentin G1.2 Fuoride + QCT group) for 1 min under and Microhardness Dentin loss (μm): protective effect against dentin
(Brazil) (Erosion) (F+QCT):12 agitation twice a day (Before the first and third 7.9 ± 0.7 / 3.2 ± 0.2 / erosion when compared with QCT
G2 Fluoride (F):12 erosive challenges) and submitted to 4 daily 4.1 ± 0.4 and F alone.
erosive challenges (90 s) for 5 days Zymography (%
inhibition)
MMP− 2
77 ± 0.9 / 100 ± 0.2 /
100 ± 0.3 / Placebo:
5
MMP− 9
76 ± 2.6 / 100 ± 0.2 /
93 ± 2.1
Knoop hardness -
Depth from surface
(μm)
KHN × µm (5–30 µm)
564.3 ± 44.3 / 628.7
± 42.2 / 546.0 ± 34.9
KHN × µm
(30–70 µm):
1422.5 ± 60.2 /
1364.3 ± 71.7 / 1371
± 76.4
Li et al., (2022) In Dentin G1: 300 μg/ml QCT: 20 4 daily erosive challenges for 5d. Treatment for Erosive dentin loss using a G1.1 / G2.1 / G2.2 / CHX and QCT showed the best
(China) vitro Human caries-free G2.1: deionized water (DW 2 min and then immersed in cola drinks for contact profilometer G2.3 performance in controlling dentin

third molars negative control): 20 5 min; and after the erosive challenges. Erosive dentin loss erosion.
(Erosion) G2.2:1.23×104 μg/ml NaF: 20 (μm)
G2.3: 120 μg/ml CHX (CHX): Before the erosive
20 challenges
3.38 ± 0.86 / 8.94 ±
1.07 / 5.03 ± 0.72 /
5.88 ± 0.68
After the erosive
challenges
4.89 ± 0.76 / 8.89 ±
1.07 / 5.17 ± 0.96 /
3.63 ± 0.79
G.P. Nunes et al.
Lin et al., (2022) In Dentin G1.1: 75 μg/ml QCT Superficial The microshear bond G1.1 / G1.2 / G1.3 / The application of QCT prior to
(China) Vitro Human caries-free pretreatment + bleaching:16 Dentin was treated with 2 ml for 2 min, and then strength (μSBS), color G2 bleaching preserved the
third molars G1.2: 150 μg/ml QCT the surfaces opposite to evaluation, and fracture Microshear bond immediate bond strength and
(Bond strength) +bleaching:16 the bonding surfaces were subjected to pattern strength (μSBS) improved the aged bond strength
G1.3: 300 μg/ml QCT bleaching treatment with 40 % hydrogen Immediate: 7.9 ± 1.9 / of bleached dentin while
pretreatment + bleaching:16 peroxide for two 15-min sessions 10.6 ± 3.2 / 8.1 ± 1.7 maintaining the effectiveness of
G2: Deionized water / 3.2 ± 1.7 bleaching.
pretreatment + bleaching Aged: 5.1 ± 3 / 6.3 ±
treatment:16 2.3 / 6.7 ± 1.4 / 3.0 ±
1.1
Color parameters △E
/ △WID
G1.1: 8.3 ± 2.7–50.2
± 7.2; G1.2: 7.7 ±
1.6–47.3 ± 2.5
G1.3: 7.39 ± 2.6–46.4
± 6.1; G2: 8.4 ±
2.4–49.7 ± 5.1
Fracture pattern
analysis (Adhesive)
(%)
nonaging - aging
G1.1: 35–50 / G1.2:
25–35 / G1.3: 25–35 /
G2: 35–50
6
Pourhajibagher In vitro Enamel G1: Modified glass ionomer + Experimental groups: Teeth were etched with Shear bond strength and Shear bond strength It can be concluded that resin-
et al., (2022) Human molar teeth nanoQCT (n-Qct – 2 %): 5/ 20 % polyacrylic acid, and the buccal tubes were Faiulure mode) (MPa) modified glass ionomer
(Iran) (Shear bond group bonded with modified glass ionomer (GC Ortho G1.1: 9.4 ± 2.2 / G1.2: containing QCT presents no
strength) G2: Transbond XT (3 M Unitek, LC, Fuji, Japan). 4.65 ± 1.2 / adverse effect on shear bond
Monrovia, CA, USA): 5 G1.3: 4.59 ± 1.6 / G2: strength.
12 ± 3.1
Faiulure mode (%)
G1 (QCT 2 %) / G2
(Transbond XT)
Adhesive: 7 / 12;
Mixed: 15 / 10;
Cohesive: 5 / 5
Moradian et al., In vitro Dentin G1: QCT 1 %: 24 The pretreatment solutions were actively Shear bond strength Shear bond strength It can be concluded that the
(2022a) Sound molars G2.1: no pretreatments applied to the dentin for 1 min. Then, the teeth (Mpa) solutions used in this study had no
(Iran) (Bond Strength) (negative control): 24 were 24 hours / 6months adverse effect on immediate SBS.
G2.2: CHX 2 % (positive Rinsed, dried and the universal adhesive system G1: 15.77 ± 2.5 / After 6 months, the CHX could

control): 24 was applied. 10.12 ± 3.56 preserve SBS in comparison to
G2.3: α-tocopherol 10 %: 24 G2.1: 13.27 ± 2.09 / other groups.
11.24 ± 2.68
G2.2: 14.08 ± 3.70 /
13.11 ± 1.92
G2.3: 13.02 ± 3.22 /
7.60 ± 4.08
Moradian et al., In vitro Enamel G1: QCT 1 %: 12 Immediately after bleaching: enamel surfaces Shear bond strength Shear bond strength It could be concluded that 10 %
(2022b) Intact human G2.1: only bleached (no were exposed to solutions for 10 min, followed (Mpa) QCT applied for 10 min increased
(Iran) maxillary first treatment): 12 by water-rinsing for 30 s. G1: 15.45 ± 1.58 the bond strength to bleached
premolars G2.2: sodium ascorbate 10 %: G2.1: 12.29 ± 2.20 enamel, but it was not able to
(Shear - Bleaching) reverse it completely.
G.P. Nunes et al.
12 G2.2: 14.56 ± 2.72

G2.3: α-tocopherol 10 %: 12 G2.3: 12.67 ± 2.50
Liu et al., (2021) In vitro Dentin. G1.1 QCT 1 %: 8 The demineralized beams were immersed in Modulus of elasticity Modulus of elasticity QCT showed a mechanical
(China) Human teeth G1.2: QCT 2 %: 8 2 ml irrigants for 3 min, followed by water- (MPa), (MPa) strength, and enhanced
(Auxiliary G1.3: QCT 4 %: 8 rinsing for 1 min. Hydroxyproline (HYP) G1.1: 2.5 ± 0.7 / G1.2: biodegradation resistance.
Endodontic Irrigant G2.1: Sterile Water: 8 Release Assay 2.6 ± 0.6
for Root Canal) G2.2: Ethanol: 8 G1.3: 3.4 ± 0.5 / G2.1:
1.5 ± 0.6
G2.2: 1.5 ± 1.2
Hydroxyproline
Release Assay (µg of
HYP/mg)
G1 (QCT 2 %): 88.2 ±
37.6 / G2
(water):520.9 ± 115.6
Mehmood et al., In vitro Dentin G1.1 QCT 1 % + Ethanol: 22 Application of solution on acid-etched dentin Shear bond strength and Shear bond strength Quercetin showed significantly
(2021) Human third molars G1.2: QCT 1 % + DMSO: 22 surface for 1 min and gently blot dried with failure mode. (Mpa) higher SBS values at 24 h when
(India) (Bond strength) G2.1: Ethanol: 22 filter paper before the application of the Immediate / Delayed compared to the control group,
G2.2: DMSO: 22 adhesive: Scotch bond (3 M, ESPE). G1.1: 54.2 ± 11.9 / but there was no significant
G2.3: Control: 22 39.9 ± 8.9 difference between the two
G1.2: 53.8 ± 11.1 / groups
40.8 ± 8.9
G2.1: 57.7 ± 12.6 / 42
± 6.5
G2.2: 71.4 ± 11.9 /
7
49.8 ± 9.1
G2.3: 35.7 ± 12.7
/22.9 ± 6.3
Porto et al., (2021) In vitro Dentin G1: QCT: 25 35 % phosphoric acid gel for 15 s, then rinsed Microtensile bond Bond strength (MPa) The QCT improved immediate
(Brazil) Human third molars 20 μg/ml QCT for 30 s with distilled water. Two coats of strength, and failure mode. 24 h - 1 Year bond strength and was shown to
(Bond strength) 250 μg/ml QCT adhesive were applied and light-cured for 10 s. G1.1: 38 ± 6–35 ± 3 / maintain the bond strength after
500 μg/ml QCT G1.2: 36 ± 12–32 ± aging for up to 1 year in distilled
G2 (Single Bond 2) – Control: 10 water.
25 G1.3: 38 ± 9–32 ± 11
/ G2: 32 ± 9–22 ± 5
Faiulure mode (%) -
24 h
Mixed - adhesive
G1.1: 50–30 / G1.2:
55–25 / G1.3: 55–30 /
G2: 40–55

Faiulure mode (%) - 1
year
Mixed - adhesive
G1.1: 62–32 / G1.2:
58–38 / G1.3: 60–40 /
G2: 48–50
Dávila-Sánchez In vitro Dentin G1 QCT 6.5 % (QCT):13 The QCT solution was applied for 1 min. Control Microtensile bond strength Microtensile bond QCT exhibited a significant drop
et al., (2020) Caries-free G2 Universal adhesive:13 group - only Universal adhesive for 20 s, dried and strength (μTBS, MPa) in the TBS values. The use of QCT
(Ecuador) extracted human for 5 s and cure for 10 s. nanohardness G1: 24.58 ± 4.90 / G2: as dentin pretreatment may
third molars 14.42 ± 4.43 improve the immediate bonding
(Long-term bonding Microtensile bond performance and the longevity of
stability) strength (μTBS, MPa) universal bonding system.
G.P. Nunes et al.
Aging –
Thermocycling: G1:
12.0 ± 5.2 / G2: 9.4 ±
4.3
Nanohardness GPa
Thermocycling/
average: G1: 0.273 ±
0.072 / 0.420
G2: 0.370 ± 0.084
/0.426
Faiulure Adhesive (%):
24 h / Themocycling:
G1: 95 / 100; G2: 100 /
97
Jiang et al., (2020) In vitro Dentin In vitro In vitro Surface microhardness, In vitro The QCT solutions showed a
(China) and Human third molars G1.1: 75 µg/ml QCT: 12 Specimens (after the formation of an acquired erosive dentin wear (µm), Percentage of surface superior protective effect against
In situ (Erosion) G1.2: 150 µg/ml QCT: 12 pellicle) were treated for 2 min and erosive and demineralized organic microhardness (% erosive dentin wear compared to a
G1.3: 300 µg/ml QCT: 12 challenges. 7-day erosion cycling regimen (4 matrix, and SMH) positive control (NaF). In
G2.1: NaF (NaF, 1.23 × 104 µg/ erosive challenges daily). carboxyterminal G1.1: 18.31 ± 6.40 / addition, regarding the different
ml – positive control): 12 In situ telopeptide of type I G1.2: 15.48 ± 5.41 concentrations, QCT at 300 µg/ml
G2.2: Deionized water Specimens collagen (ICTP). G1.3: 8.75 ± 4.95 / promoted a lower %SHM than 75
(negative control): 12 were treated for 2 min. Then the appliances G2.1: 27.08 ± 4.90 and 150 µg/ml.
G2.3: Ethanol (negative were worn for 2 h, followed by an erosive G2.2: 37.95 ± 7.86 /
control): 12 challenge. G2.3: 39.24 ± 4.69
In situ Erosive dentin wear
8
G1: 300 µg/ml QTC: 10 (µm)

volunteers G1.1: 2.7 ± 0.9 / G1.2:
G2: NaF (NaF, 1.23 × 104 µg/ 2.5 ± 1.0 / G1.3: 2.3 ±
ml): 10 volunteers 1.2 / G2.1: 5.6 ± 1.4 /
G2.2: 7.2 ± 2 / G2.3:
7.4 ± 1.7
Demineralized organic
matrix (DOM)
G1.1: 14.85 ± 5.95 /
G1.2: 14.07 ± 3.69
G1.3: 15.45 ± 2.59 /
G2.1: (6.21 ± 3.92
G2.2: 5.88 ± 4.12 /
G2.3: 5.97 ± 4.68
ICTP
G1.1: 8.49 ± 0.47 /

G1.2: 5.72 ± 0.98
G1.3: 5.97 ± 0.88 /
G2.1 19.27 ± 5.34
G2.2: 22.06 ± 4.05 /
G2.3: 21.44 ± 3.50
In situ
Percentage of surface
microhardness (%
SMH)
G1 QCT 5.22 ± 2.94 /
G2 (NaF): 19.23 ± 5.7
Erosive dentin wear
G.P. Nunes et al.
(µm)
G1 QCT 300: 0.77 ±
0.34 / G2 (NaF): 2.61
± 0.97
Porto et al., (2018) In vitro Dentin G1.1 QCT 100 µg/ml: 6 After acid, 5 µl of experimental solutions was Microtensile bonding Microtensile bond QCT showed higher values than
(Brazil) Human third molars G1.2 QCT 200 µg/ml: 6 dropped onto dentin for 60 s. Then, an adhesive strength, failure mode, and strength (MPa) another groups on the first day.
(Etched with 35 % G1.3 QCT 500 µg/ml: 6 (Single Bond 3 M ESPE) was applied. collagen fibrils stability of 1 day However, a lower bond strength
phosphoric acid gel) G1.4 QCT 1000 µg/ml: 6 the adhesive interface by G1.1: 32.1 ± 8.9; after 120 d of water storage was
G2.1 distilled water: 6 scanning electron G1.2: 27.5 ± 8.7; observed in group QCT100 μg.
G2.2 CHX 2 %: 6 microscopy. G1.3: 31.2 ± 9.9;
G1.4: 31.3 ± 10.3;
G2.1: 23.6 ± 6.7;
G2.2: 27.8 ± 6.9
120 days (Aged)
G1.1: 25.3 ± 8.01;
G1.2: 34.7 ± 16.2;
G1.3: 42.4± 13.6
G1.4: 37.4 ± 11.4;
G2.1: 26.5 ± 8.3;
G2.2: 30.7 ± 8.7
Li et al. (2017) In vitro Dentin G1.1 0.1 % QCT (QCT 0.1 %): 6 The specimens were treated for 60 s with Microtensile bond Microtensile bond Pretreatment with 0.5 and 1.0 %
(China) Human third molars G1.2 0.5 % QCT (QCT 0.5 %): 6 solutions, dried, and bonded with Adper Single strength, failure modes, strength MPa ± SD QCT solutions was effective in
(Etched with 35 % G1.3 1.0 % QCT (QCT 1.0 %): 6 Bond 2 (3 M ESPE, St.Paul, MN, USA), following interfacial nanoleakagee, Immediate preserving the bond strength and
phosphoric-acid gel) G2 Group 1: 100 % ethanol the manufacturer’s instructions. in situ zymography. G1.1 38.6 ± 5.2; G1.2: the integrity of the hybrid layer
(control group): 6 38.1 ± 6.8; G1.3: 37.7 after one month of aging.
9
± 7.0
G2. (ethanol): 37.8 ±
6.7
Aged
G1.1: 27.58 ± 5.91;
G1.2: 36.71 ± 7.86;
G1.3: 36.95 ± 7.24;
G2: 26.18 ± 6.27
Failure frequency (%)
Adhesive /Cohesive /
Mixed failures
Immediate
G1.1: 35/10/15/40;
G1.2: 60/20/0/20
G1.3: 70/10/0/20; G2:
35/10/25/30

Aged
G1.1: 25/15/10/50;
G1.2: 55/10/0/35
G1.3: 55/5/0/40; G2:
25/5/15/55
Shamsedin et., al. In vitro Enamel 0.1 % QCT: G1.1- for 5 min; The solutions were applied for 5 or 10 minutes, Shear bond strength (SBS) Shear bond strength QCT improves the SBS to normal
2017 Intact human G1.2- for 10 min; 0.5/5 QCT: washed and the brackets bonded. and adhesive remnant (MPa) levels, regardless of time, when
(Iran) premolars G1.3 - for 5 min; G1.4 - for index. G1.1: 16.5 ± 10.1; compared to DMSO, immediate or
(Shear bond 10 min; QCT 1 %: G1.5–5 min; G1.2: 20.8 ± 11.7; delayed bleaching.
strength) G1.6 QCT 1 % -for 10 min; G1.3: 21.8 ± 8.8;
DMSO: G2.1 - for 5 min; G2.2 – G1.4: 26.5 ± 8.7;
for 10 min; n = 10 G1.5: 23.2 ± 6.8;
G.P. Nunes et al.
G1.6:26.3 ± 8.6;
G2.1:11.0 ± 5.4;
G2.2:13.0 ± 6.6
Yang et al., (2017) In Dentin G1.1 (Single Bond 2 (SB) with Applied on the blotted water-moist dentin Conversion degree, G1.1 / G1.2 / G1.3 / The QCT-doped adhesive
(China) vitro Human caries-free QCT 100 µg/ml): 10 surface, followed by gently agitated for 10 s and microtensile bond G2 (500 µg/ml) preserved its bonding
third molars G1.2 (SB with QCT 500 µg/ml): air stream for another 10 s. strength, failure modes, in Microtensile bond properties against collagenase
(Bond strength) 10 situ zymography, strength (MTBS) MPa ageing.
G1.3 (SB with QCT 1000 µg/ nanoleakage expression. ± SD
ml): 10 Immediat: 42.8 ±7.8 /
G2 (control - Single Bond 2 - 41.9 ± 7.9 / 35.4
SB): 10 ± 6.1/ 42.3 ± 6.7
Aged: 27.6 ± 6.8 /
39.6 ± 6.9 / 30.9
± 7.7 / 27.8 ± 6.2
Failure frequency (%)
Adhesive failure /
Cohesive failure in
dentin
Immediate: G1.1: 100
/ 0; G1.2: 55 / 15;
G1.3: 75 / 0; G2: 90 / 0
Aged: G1.1: 57.5 / 7.5;
G1.2: 45 / 7.5; G1.3:
35 / 7.5;
G2: 50 / 12.5
10
Nanoleakage Presence
(%)
Immediate / Aged:
G1.1: 100 / 100
G1.2: 80 / 100
G1.3: 75 / 100
G2: 90 / 100
Epasinghe et al., In Dentin G1 (6.5 % QCT): 15 Specimens were pH-cycled through the Knoop microhardness, G1 / G2.1 / G2.2 QCT showed positive effects on
(2016) vitro Human caries-free G2.1 (1000 ppm fluoride): 15 treatment solutions (10 minutes). Six transverse Knoop hardness Depth artificial root caries
(China) third molars G2.2 (Deionized water): 15 demineralization–remineralization cycles were microradiography (lesion from surface (μm) remineralization, which is
(Caries – performed each day and continued for eight depth and mineral loss) 30: 8.98 ± 4.2 / 8.66 significantly lower than that of
remineralization) days ± 1.83 / 3.2 ± 0.55 1000 ppm fluoride.
50: 10.43 ± 2.54 /
11.50 ± 4.75 / 7.42 ±
1.5
80: 25.15 ± 9.37 /

26.95 ± 2.61 / 14.52
± 3.69
110: 37.81 ± 14.81 /
49.97 ± 14.06 / 26.02
± 4.33
140: 48.09 ± 14.76 /
57.97 ± 19.10 / 36.58
± 2.81
170: 69.14 ± 8.44 /
73.62 ± 12.02 / 44.85
± 7.38
Mineral loss (ΔZ, vol
G.P. Nunes et al.
%): G1: 1793.4 ±

606.0; G2.1: 1206.7 ±
396.5; G2.2: 4214.1 ±
707.4
Lesion depth (μm): G1:
93.7 ± 23.1 / G2.1:
62.5 ± 15.8; G2.2:
164.4 ± 40.6
Gotti et al., (2015) In Dentin G1 (5 % QCT): 6 Adper Single Bond 2: Apply for 15 s, Microtensile bond Microtensile bond Quercetin-doped adhesives
(Brazil) vitro Human caries-free G2 Adhesive System: 6 Light cure for 10 s strength, failure mode, strength (MPa) showed varying effects based on
Pre molars Adper Single Bond 2 Clearfil SE Bond: Primer and leave for interfacial nanoleakagee 24 h / 6 months the adhesive system used. Overall,
(Bond strength) (3 M ESPE; St Paul, 20 s, Light cure for 10 s Adper Single Bond 2 they presented a positive impact
MN, USA); Clearfil SE Bond Adper Easy Bond: Apply for 20 s, G1: 31.2 ± 4.8 / 38.3 on adhesive interface durability,
(Kuraray Noritake Dental; Light cure for 10 s ± 5.7 as their bond strength either
Tokyo, Japan); Adper Easy G2: 63.7 ± 4.8 / 50.6 remained stable or increased over
Bond ± 6.2 time, particularly after 24 h.
(3 M ESPE) Clearfil SE Bond
G1: 40.7 ± 8.0 / 69.8
± 5.8
G2: 69.0 ± 4.1 / 69.2
± 4.8
Adper Easy Bond
G1: 46.8 ± 4.3 / 44.2
± 5.8
G2: 48.3 ± 6.6 / 51.1
11
± 5.1
Epasinghe et al., In Dentin G1 (6.5 % QCT): 10 Specimens were kept in their respective Modulus of elasticity and G1 / G2.1 / G2.2 Proanthocyainidin was more
(2014) vitro Human caries-free G2.1 (6.5 % Proanthocyanidin): solutions and tested at baseline, 10 min, 30 min, ultimate tensile strength of Modulus of elasticity effective than QCT and naringin in
(China) third molars 10 1 h and 4 h. demineralised dentine. (MPa) improving biomechanical
(Tensile strength) G2.2 (6.5 % Naringin): 10 Baseline: 12.44 ± 2.19 properties of dentine matrix
/ 11.35 ± 2.55 / 11.06
± 3.16
5 min: 11.49 ± 2.67 /
16.12 ± 4.77 / 11.14
± 2.92
10 min: 12.29 ± 2.55
/ 24.89 ± 6.46 / 13.19
± 3.56
30 min: 16.48 ± 4.68
/ 36.24 ± 8.87 / 17.57
± 4.24

1 h: 26.05 ± 10.65 /
44.05 ± 9.09 / 25.88
± 8.55
4 h: 42.27 ± 17.49 /
86.10 ± 22.11 / 28.38
± 4.73
Ultimate tensile
strength (MPa)
Baseline: 8.05 ± 1.77 /
8.05 ± 1.80 / 8.05 ±
1.80
5 min: 8.66 ± 3.11 /
quercetin tested ranged from 20 to 150 μg/ml (Hong et al., 2022; Lin
et al., 2022; Porto et al., 2021; Jiang et al., 2020), 250 or 300 μg/ml
(Chen et al., 2024; Hong et al., 2022; Li et al., 2022; Lin et al., 2022;
Porto et al., 2021; Jiang et al., 2020), 500 μg/ml (Porto et al., 2021,
2018; Yang et al., 2017), 1000 µg/ml (Porto et al., 2018; Yang et al.,
2017), 0.03–2 % (Hosseinpour-Nader et al., 2023; Moradian et al.,
2022a, 2022b; Capalbo et al., 2022; Fattah et al., 2022; Pourhajibagher
et al., 2022; Liu et al., 2021; Mehmood et al., 2021; Shamsedin et al.,
Conclusion
2017), and 4–6.5 % (Liu et al., 2021; Dávila-Sánchez et al., 2020; Epa
singhe et al., 2016, 2014; Gotti et al., 2015). The concentrations of the
main positive controls were as follows: chlorhexidine 120 µg/ml (Hong
et al., 2022; Li et al., 2022), 2 % (Moradian et al., 2022a; Porto et al.,
10 min: 9.40 ± 3.13 /
/ 12.94 ± 3.30 / 9.55

30 min: 10.71 ± 4.01
15.11 ± 4.21 / 10.13
17.45 ± 4.42 / 12.61

8.30 ± 1.54 / 7.89 ±
9.59 ± 4.06 / 9.71 ±
2018), and sodium fluoride 0.24 % (Capalbo et al., 2022; Epasinghe

1 h: 12.76 ± 5.86 /
4 h: 12.76 ± 5.86 /
Results: Outcomes
[Mean ± SD] or
et al., 2016), 1.23 % (Chen et al., 2024; Li et al., 2022; Jiang et al.,
2020), and 2 % (Hosseinpour-Nader et al., 2023). Regarding the mode of
percentage
application, quercetin was primarily used as a treatment solution, with

± 2.61
± 3.79
± 5.04
application times ranging from 1 to 10 min, with most studies employ

2.71
2.11
ing a 1-min application period. In the studies evaluating dental mate

rials, a standardized protocol was followed according to the
manufacturer’s specifications for each procedure type.
The primary conditions evaluated in the dental substrates included
Assessment Method
bond strength (Moradian et al., 2022a, 2022b; Fattah et al., 2022; Lin
et al., 2022; Pourhajibagher et al., 2022; Mehmood et al., 2021; Porto
et al., 2021, 2018; Dávila-Sánchez et al., 2020; Li et al., 2017; Yang
et al., 2017; Shamsedin et al., 2017; Gotti et al., 2015; Epasinghe et al.,
2014), dental erosion (Chen et al., 2024; Capalbo et al., 2022; Hong
et al., 2022; Li et al., 2022; Jiang et al., 2020), and dental caries
(Hosseinpour-Nader et al., 2023; Epasinghe et al., 2016). Among these
studies, the most evaluated methods were microtensile bond strength
testing (Hong et al., 2022; Porto et al., 2021, 2018; Dávila-Sánchez et al.,
Abbreviations: QCT: Quercetin; NaF: Sodium fluoride; CHX = chlorhexidine digluconate; DMSO = dimethyl sulfoxide.
2020; Li et al., 2017; Yang et al., 2017; Gotti et al., 2015), shear bond
strength (Moradian et al., 2022a, 2022b; Fattah et al., 2022; Lin et al.,
2022; Pourhajibagher et al., 2022; Mehmood et al., 2021; Shamsedin
Method of Administration
et al., 2017), erosive dentin wear by profilometry (Chen et al., 2024;

Capalbo et al., 2022; Hong et al., 2022; Li et al., 2022; Jiang et al., 2020),
microhardness evaluation (Hosseinpour-Nader et al., 2023; Capalbo
et al., 2022; Jiang et al., 2020; Epasinghe et al., 2016), modulus of
elasticity (MPa) (Liu et al., 2021; Epasinghe et al., 2014), fracture
or use
pattern (failure mode) via microscopy (Moradian et al., 2022a; Lin et al.,
2022; Pourhajibagher et al., 2022; Mehmood et al., 2021; Porto et al.,
2021, 2018; Dávila-Sánchez et al., 2020; Li et al., 2017; Yang et al.,
G1 - QCT (Intervention group)
2017; Gotti et al., 2015), interfacial nanoleakage (Porto et al., 2021; Li

et al., 2017; Yang et al., 2017; Gotti et al., 2015), and MMPs inhibition
by zymography (Capalbo et al., 2022; Hong et al., 2022; Yang et al.,
G2 – Control group
2017; Li et al., 2017).
3.3. Outcome results of quercetin effect on mineralized dental tissues

(N sample)
3.3.1. Dental adhesion by evaluation of microtensile bond strength

Dentin has been the most frequently evaluated substrate for studying
the effects of quercetin on dental adhesion, specifically by evaluation of
microtensile bond strength. Four studies showed that quercetin treat
ment resulted in significantly greater microtensile bond strength than a
placebo, both in immediate and aged samples, highlighting its potential
Dental
in improving dentin adhesion properties (Hong et al., 2022;

Tissue
Dávila-Sánchez et al., 2020; Porto et al., 2018; Li et al., 2017). Addi

tionally, two studies indicated that a quercetin-containing treatment
Design
solution achieved better bond strength to dentin than chlorhexidine

study
(Hong et al., 2022; Porto et al., 2018). One study found that quercetin’s
effect was comparable to other flavonoids (Epasinghe et al., 2014).
Furthermore, the incorporation of quercetin into dental material

formulation has been also explored, with two studies reporting that the
Author/ year
addition of quercetin into adhesive systems increased its bond strength

(Country)
to dentin, potentially offering a strategy for enhancing the performance

and longevity of adhesive restorations (Porto et al., 2021; Yang et al.,
2017). In contrast, one study did not find a significant difference on
12
bond strength to dentin when quercetin was incorporated into dental 2022b; Gotti et al., 2015), and nine months (Mehmood et al., 2021).
adhesives, suggesting that its benefits might depend on specific formu Seven reported that quercetin treatments resulted in low prevalence of
lations or application protocols (Gotti et al., 2015). Regarding to dental restorative failures compared to the control group (Moradian et al.,
enamel, only one study showed that quercetin-loaded glass ionomer 2022b; Lin et al., 2022; Pourhajibagher et al., 2022; Mehmood et al.,
cement significantly increased its bond strength compared to the con 2021; Porto et al., 2021, 2018; Gotti et al., 2015). In these studies, mixed
ventional form of the material (Pourhajibagher et al., 2022). failures, which involve a combination of adhesive and cohesive failures,
were less frequent after quercetin treatment, suggesting improved
3.3.2. Enamel and dentin adhesion in bleaching dental substrates overall adhesion and interface stability. Adhesive failures were primary
The effect of quercetin on adhesion in bleached dental substrates was failure mode in four studies (Moradian et al., 2022a; Dávila-Sánchez
explored in four studies, focusing on both enamel and dentin tissues. In et al., 2020; Li et al., 2017; Yang et al., 2017), and quercetin group
bleached enamel, the application of quercetin after the bleaching pro displayed low percentage of this failure pattern in three of them
cess was found to improve bond strength, indicating a beneficial effect (Moradian et al., 2022a; Dávila-Sánchez et al., 2020; Yang et al., 2017).
on adhesive properties compromised by bleaching (Moradian et al., In one study, adhesive failure was the predominant failure mode in the
2022b; Shamsedin et al., 2017). For bleached dentin, the results were quercetin-pretreated groups, while cohesive failure was more observed
more variable. One study reported that application of quercetin before in dentin increased in the control group (Li et al., 2017).
the bleaching process preserved the immediate bond strength and
enhanced the aged bond strength of bleached dentin, suggesting a pro 3.3.6. Nanoleakage at the composite-dentin interface
tective effect against the adverse impacts of bleaching on adhesive Nanoleakage at the composite-dentin interface was evaluated in four
properties (Lin et al., 2022). In another study, when quercetin was studies (Porto et al., 2021; Li et al., 2017; Yang et al., 2017; Gotti et al.,
applied in dentin after the bleaching procedures, no significant 2015). Of these, three studies incorporated quercetin into commercial
improvement was observed in shear bond strength of resin cements dental adhesives (Porto et al., 2021; Yang et al., 2017; Gotti et al., 2015),
(Fattah et al., 2022). while one study investigated the use of a quercetin solution as a multi
functional primer for pre-treating the dentin surface prior to adhesive
3.3.3. Erosive dentin wear application (Li et al., 2017). In all studies, the incorporation of quercetin
Quercetin has demonstrated a protective effect against erosive resulted in a reduction of nanoleakage compared to the control groups.
dentin wear in several studies. When compared to a placebo (negative Additionally, a dose-dependent effect was observed, with increased
control), quercetin consistently showed superior efficacy in reducing concentrations of quercetin leading to progressively lower levels of
dentin wear caused by erosive challenges (Chen et al., 2024; Capalbo, nanoleakage (Porto et al., 2021; Yang et al., 2017; Li et al., 2017).
2022; Li et al., 2022). Additionally, quercetin also showed a superior
protective effect against erosion when compared to traditionally used 3.3.7. Inhibition of dentin matrix metalloproteinases and release of type I
therapies. For instance, quercetin outperformed sodium fluoride (NaF) collagen telopeptide in dentin
in two studies (Chen et al., 2024; Li et al., 2022) and was more effective Quercetin has been shown to effectively inhibit dentin matrix met
than chlorhexidine in reducing erosive wear (Hong et al., 2022; Li et al., alloproteinases (MMPs), such as MMP-2 and MMP-9, which play a
2022). Conversely, in one study, NaF demonstrated a superior protective crucial role in the degradation of the dentin organic matrix (Capalbo
effect compared to quercetin (Capalbo et al., 2022). Interestingly, the et al., 2022; Hong et al., 2022). The anti-proteolytic effect of quercetin
co-administration of quercetin with NaF exhibited a synergistic effect, against MMPs is dose-dependent, demonstrating a similar inhibitory
enhancing the prevention of erosive wear more effectively than either effect to chlorhexidine (Hong et al., 2022). However, while sodium
agent alone (Capalbo et al., 2022). fluoride exhibited a greater inhibitory effect on MMP-2 and MMP-9 than
quercetin, the combination of quercetin and fluoride was found to
3.3.4. Mechanical properties completely inhibit the proteolytic activity of MMP-9 (Capalbo et al.,
Among the selected studies, only four investigated the effect of 2022).
quercetin on microhardness analyses (Hosseinpour-Nader et al., 2023; In addition, studies evaluating the release of type I collagen telo
Capalbo et al., 2022; Jiang et al., 2020; Epasinghe et al., 2016). Studies peptide (ICTP), a marker of collagen degradation, have shown that both
indicated that quercetin exhibited significant remineralizing potential placebo and sodium fluoride treatments result in a higher release of ICTP
compared to the negative control and lower efficacy than the positive compared to quercetin (Chen et al., 2024; Jiang et al., 2020).
control (NaF) (Epasinghe et al., 2016, Hosseinpour-Nader et al., 2023).
In a dentin erosion model, two studies (Capalbo et al., 2022; Jiang et al., 3.3.8. Dentin organic matrix outcomes
2020), demonstrated that quercetin displayed superior anti-erosive Some outcomes/analyses were reported in only one article. Hong
properties compared to the placebo (Jiang et al., 2020, Capalbo et al., et al. (2022) demonstrated that quercetin exhibits a higher degree of
2022). When compared to NaF, quercetin showed a similar reminer dentin crosslinking compared to the negative control, and this increase
alizating effect in one study (Capalbo et al., 2022) and a superior effect was concentration-dependent (75, 150, 300 µg/ml). Regarding dentin
(Jiang et al., 2020) in another one, irrespective of the concentration used nanohardness, quercetin presented significantly higher values than the
(75, 150, 300 µg/ml). However, only quercetin at 300 µg/ml out control group (universal adhesive system) in nanohardness within the
performed chlorhexidine (Jiang et al., 2020). Regarding the integrated adhesive layer, hybrid layer, and dentin at a depth of 50 μm
hardness of dentin in depth, quercetin demonstrated a similar effect to (Dávila-Sánchez et al., 2020). In their study, Liu et al. (2021) conducted
NaF (Capalbo et al., 2022; Epasinghe et al., 2016). Studies revealed a a Hydroxyproline (HYP) Release Assay in demineralized dentin and
higher modulus of elasticity for dentin treated with quercetin when found that quercetin irrigant (1, 2, and 4 %) increased the biomechan
compared to placebo and naringenin (Liu et al., 2021; Epasinghe et al., ical properties and biodegradation resistance of dentin collagen.
2014), but lower values when proanthocyanidin was applied on dem
ineralized dentin (Epasinghe et al., 2014). 4. Discussion
3.3.5. Failure modes after restorative procedures This scoping review aimed to investigate the impact of quercetin on
Of the 10 studies that evaluated failure modes, all conducted as mineralized dental tissues, assessing its potential preventive and/or
sessments immediately after the restorative procedure or within therapeutic effects on changes in dental substrates. Overall, data from
24 hours, and some included subsequent evaluations at longer intervals, the 22 studies reviewed suggest that quercetin holds promise as a phy
such as at four months (Porto et al., 2018), six months (Moradian et al., totherapeutic agent for therapies involving hard dental tissues.
13
Treatment with quercetin enhanced the mechanical properties of believed to possess antioxidant properties, which can help counteract
mineralized dental tissues, contributing to the prevention of deminer the oxidative stress induced by bleaching agents (Bhuvaneswari et al.,
alization and promoting dental remineralization. It also improved bond 2014). Quercetin’s antioxidant properties are thought to play a key role
strength in restorative procedures and post-whitening treatments and in this protective mechanism by scavenging free radicals generated
exhibited a biological effect by inhibiting enzymatic degradation of the during the bleaching process, thereby reducing oxidative stress and
dentin matrix. preventing enamel damage. However, this effect was not observed in
Quercetin, a flavonoid found abundantly in various fruits, vegeta bleached dentin. The null effect of quercetin on this dental substrate may
bles, and medicinal herbs, has garnered attention for its potential ther be related to the inherent characteristics of dentin, which make adhesion
apeutic properties (Aghababaei et al., 2023). The antioxidant activity of to it more challenging than to enamel.
flavonoids is influenced by their structure and can be evaluated based on In addition, the varying efficacy of quercetin in dentin compared to
their ability to donate hydrogen and electron atoms, the stability of the dental enamel can be ascribed to several factors, mainly including the
formed flavonoyl radical, interaction with other antioxidants, chelation structural and compositional disparities between these dental tissues
of transition metals, and solubility and interaction with cell membranes (Breschi et al., 2018; Chun et al., 2014), as well as the unique properties
(Mondal and Rahaman, 2020). Quercetin demonstrates high antioxidant of quercetin itself (Angellotti et al., 2020). Dentin and enamel possess
capacity, effectively scavenging free radicals and inhibiting the forma distinct compositions (Arola et al., 2017). Its superior performance in
tion of reactive oxygen species (ROS) and cyclooxygenase-2 (COX-2) enamel could be attributed to factors such as surface characteristics,
(Deepika and Maurya, 2022; 10.Mooney et al., 2021; Li et al., 2016). Its remineralization potential, surface roughness, and biological in
rich polyphenol content enables it to stabilize the collagen chain by teractions (Arola et al., 2017; Xu et al., 2022). Furthermore, it is worth
increasing cross-linking in collagen fibrils, thereby reducing biodegra noting that quercetin did not interfere with the effectiveness of
dation. Furthermore, quercetin has the potential to inhibit the activity of bleaching procedures, as observed by Lin et al. (2022). This is an
matrix metalloproteinases (MMPs), suppressing the expression of these important consideration, especially given the concern regarding the
proteins through the extracellular signal-regulated kinase (ERK) and crystalline yellowish coloration of quercetin.
protein kinase B (PKB) pathways (Pan et al., 2015). Regarding dentin erosion, the present results showed that quercetin
The results demonstrated that quercetin enhances bond strength in was able to reduce erosive dentin wear and exhibited a similar effect to
the adhesive procedure. Its ability to mitigate oxidative damage may well-established therapies such as NaF and CHX, indicating the signifi
preserve the integrity of the bonding interface, strengthening bond cant potential of quercetin in preventing dentin erosion. The same result
strength over time. This significantly reduces the risk of nanoleakage, was observed for the remineralization effect in dental caries models.
considered a relevant indicator for estimating the ability of adhesive These effects are possibly attributed to quercetin’s ability to provide a
materials to seal dentin and create an effective bond (Porto et al., 2021; mechanical barrier against acid diffusion (Ganss et al., 2007; Kato et al.,
Li et al., 2017; Yang et al., 2017); restoration failure, and fracture 2010), and also by preserving the demineralized organic matrix as
propagation; in addition to increasing shear bond strength, resulting in previously described (Hong et al., 2022; Jiang et al., 2020), which can
greater bond longevity (Porto et al., 2021; Gotti et al., 2015). Further act as a template for mineral nucleation. This preservation of the matrix
more, quercetin may refine bonding durability by optimizing the elas may protect against dental caries and erosion and maintain the struc
ticity modulus and facilitating the formation of a robust hybrid layer tural integrity of the remaining tissue. Moreover, quercetin can form
between tooth structure and adhesive materials (Yang et al., 2017). A complexes with calcium ions because of the hydroxyl groups in their
well-established hybrid layer ensures stability in dental restorations, molecular structures. This enhances remineralization by facilitating the
minimizing nanoleakage and extending their longevity (Li et al., 2017; deposition of minerals like calcium and phosphate onto the dental sur
Yang et al., 2017). The favorable outcomes of quercetin in the dentin face, thereby strengthening compromised hard dental tissue (Epasinghe
matrix are presumed to be due to its ability to cross-link collagen et al., 2016). Additionally, quercetin’s ability to inhibit MMPs in dentin
through various types of forces: hydrogen bonds, van der Waals forces, plays a significant role in protecting against erosion and caries. This
electrostatic forces, and hydrophobic forces (Yang et al., 2009). Poly inhibition is primarily attributed to its vicinal hydroxyl groups, which
phenols like quercetin are amphiphilic, exhibiting hydrophobic prop effectively chelate metals, and its interaction with the S1’ pocket of
erties due to their planar aromatic nucleus and hydrophilic properties MMPs, crucial for substrate recognition (Saragusti et al., 2010).
due to polar hydroxyl groups. These properties allow polyphenols to In general, the data related to dentin tissue is interesting and
incorporate into the collagen structure, protecting it and facilitating promising. It is recognized that demineralization of dentin brings about
secondary interactions through hydrogen bonding with collagen proline a shift in the organic matrix, carrying significant implications, particu
residues (Haslam, 1996). The results also highlight quercetin’s potential larly in the selection of therapeutic approaches. As dentin minerals
to enhance bond strength between restorative materials and dentin, dissolve, the exposed collagen becomes susceptible to various collage
which is essential for preventing debonding and promoting cohesive nolytic enzymes, leading to enzyme-mediated collagen degradation
failure within the dentin structure (Dávila-Sánchez et al., 2020). Quer (Chen et al., 2024; Yang et al., 2017). Consequently, the restorative
cetin’s bonding promotion may lead to a more favorable fracture pattern treatment of dentin affected by caries or erosion becomes challenging
and failure mode, reducing the risk of restoration failure or fracture due to the compromised integrity of the dentin collagen matrix (Breschi
propagation (Moradian et al., 2022a; Lin et al., 2022; Mehmood et al., et al., 2018). Placing a restoration on a weakened dentin base result in
2021). Therefore, by improving adhesion, quercetin may help prevent premature bond degradation and displacement of the restoration.
debonding or restoration failure, ultimately enhancing treatment out Moreover, the presence of dentin-bound proteoglycans and proteases
comes and patient satisfaction. interferes the durability of resin-dentin bonding (de Mattos Pimenta
Moreover, preserving the bond strength of bleached dental sub Vidal et al., 2017). Hence, given that quercetin has shown potential as a
strates is clinically significant, as patients often require additional strategy for biomodifying the dentin matrix, it fortifies the fibrillar
restorative therapy to restore the natural appearance of their teeth and collagen matrix. This seems to be a logical approach to withstand me
optimize aesthetic outcomes (Olmedo et al., 2021; Baia et al., 2020). The chanical forces, resist degradation by proteases, reduce collagen-bound
results for post-bleaching shear bond tests have shown that the bleached proteoglycans, and, consequently, enhance the longevity and success
groups treated with quercetin exhibited better bond strength in enamel. outlook of treatment in dentin tissue.
This benefit can be attributed to the antioxidant capacity of quercetin, It is known that sodium fluoride is the gold standard agent for pre
which acts on eliminating residual free radicals from bleaching venting dental erosion and caries, reducing dental demineralization, and
(Moradian et al., 2022b; Shamsedin et al., 2017). Thus, quercetin may promoting remineralization (Wierichs et al., 2020; Walsh et al., 2019;
exert protective effects on enamel during bleaching procedures. It is Emerenciano et al., 2018). However, it is also understood that fluoride
14
has a limited remineralizing action on the superficial layers of dental 5. Conclusion

substrates (Nunes et al., 2022; Wierichs et al., 2020). Moreover, its ef
fects on dental erosion are less notable (Lussi et al., 2019) due to the Within the limitations of this review, which is primarily based on
much lower pH of erosive acids compared to those involved in dental laboratory-based (in vitro) studies, these findings suggest that quercetin
caries (i.e., bacterial acids) (Lussi et al., 2019). Therefore, it is important holds promise as a multifaceted agent in mineralized dental tissues. It
to find therapies/agents that minimize this limitation of fluoride. Only shows potential applications in enhancing bond strength, preserving
one of the included studies (Capalbo et al., 2022) evaluated the effect of dental structure, and protecting against erosion and dental caries.
co-administered quercetin associated with fluoride, and a synergistic However, further research, including clinical studies, is warranted to
effect between the agents was observed. This result was interesting, as validate these findings and optimize the clinical use of quercetin in
the solutions tested individually showed similar dentin integrated dental practice.
hardness; however, the effect was optimized when both agents were
evaluated together. The synergistic action of fluoride and quercetin, is Funding
clinically important, considering that the treatments were effective not
only in reducing dentin loss but also resulted in less softened dentin This study was not supported by funding.
(Capalbo et al., 2022). This data is extremely important as it directly
impacts the resistance of the remaining dentin that is constantly exposed CRediT authorship contribution statement
to erosive challenges. This approach has been little explored in the
literature; therefore, it would be interesting for future studies to assess Geórgia Rondó Peres: Writing – original draft, Visualization, Vali
the supplementary/adjuvant effect of quercetin to these active agents in dation, Methodology, Investigation, Formal analysis, Data curation. Ana
the process of controlling changes in mineralized dental substrates. Paula Miranda Vieira: Writing – original draft, Visualization, Valida
Despite all the precautions taken by the studies to mimic the con tion, Methodology, Investigation, Formal analysis, Data curation.
ditions found in the oral environment, this scoping review predomi Tamires Passadori Martins: Writing – original draft, Visualization,
nantly included in vitro studies, which inherently have limitations Validation, Methodology, Investigation, Formal analysis, Data curation.
related to biological events. This imbalance limits the generalizability of Priscila Toninatto Alves de Toledo: Writing – original draft, Visuali
our conclusions to clinical settings. In vitro studies often serve as pre zation, Validation, Methodology, Investigation, Formal analysis, Data
liminary investigations to highlight potential efficacy but may not fully curation, Conceptualization. Alexandre Henrique dos Reis-Prado:
capture the complexities of clinical scenarios. Additionally, there is a Writing – original draft, Visualization, Validation, Methodology, Inves
potential for publication bias in in vitro studies, where positive results tigation, Formal analysis, Data curation. Matheus Henrique Faccioli
are more likely to be reported than negative ones. Therefore, further Ragghianti: Writing – original draft, Visualization, Validation, Meth
research is needed, focusing on well-designed clinical trials that consider odology, Investigation, Formal analysis, Data curation, Conceptualiza
the protocols and safety measures necessary to translate in vitro findings tion. Renata de Oliveira Alves: Writing – original draft, Visualization,
into effective clinical interventions. It is crucial to conduct studies that Validation, Methodology, Investigation, Formal analysis, Data curation,
not only confirm the efficacy of quercetin in clinical settings but also Conceptualization. Gabriel Pereira Nunes: Writing – review & editing,
assess its safety and practical benefits. Writing – original draft, Visualization, Validation, Software, Methodol
It is also important to note that, while in vitro protocols can minimize ogy, Investigation, Funding acquisition, Formal analysis, Data curation,
confounding factors and isolate the effects of quercetin, these conditions Conceptualization. Cristiane Duque: Writing – review & editing,
may lead to an overestimation of its efficacy and an underestimation of Writing – original draft, Visualization, Validation, Supervision, Re
potential adverse effects in clinical settings. This limitation is particu sources, Project administration, Methodology, Investigation, Formal
larly relevant for compounds like quercetin, where interactions with analysis, Data curation, Conceptualization.
other dental materials, variations in the oral microenvironment, and
individual patient behaviors (such as dietary habits and oral hygiene Declaration of Competing Interest
practices) could significantly affect its effectiveness and safety. Thus,
well-designed clinical trials that closely mimic real oral conditions are The authors declare that they have no known competing financial
crucial to validate the findings from in vitro studies. Future research interests or personal relationships that could have appeared to influence
should aim to bridge this gap by employing study designs that better the work reported in this paper.
reflect clinical scenarios, including diverse patient populations, longer
observation periods, and varied application methods. These studies Acknowledgments
should focus on determining the optimal concentration, vehicle of de
livery, and mode of application to achieve the most effective and safe The authors thank Ana Claúdia Martins Grieger Manzatti for the
outcomes for quercetin in practical use. excellent technical support.
Furthermore, this review emphasizes the need for methodological
standardization and more clearly defined protocols in future studies.
Appendix A. Supporting information
Although we grouped the data as closely as possible, the included studies
used different dental materials and varied in their application protocols
Supplementary data associated with this article can be found in the
and analysis methods, making homogeneous data comparison chal
online version at doi:10.1016/j.archoralbio.2024.106119.
lenging. Future research should standardize factors such as treatment
time and quercetin concentration to produce more reliable and com
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Archives of Oral Biology 169 (2025) 106119

Contents lists available at ScienceDirect

Archives of Oral Biology

Effects of quercetin on mineralized dental tissues: A scoping review

Fig. 1. Flow diagram of search in databases according to PRISMA-ScR Statement.

Archives of Oral Biology 169 (2025) 106119

/ 60.3 ± 5.3 / 59.68 ±

Archives of Oral Biology 169 (2025) 106119

Archives of Oral Biology 169 (2025) 106119

12 G2.2: 14.56 ± 2.72

Archives of Oral Biology 169 (2025) 106119

G1: 300 µg/ml QTC: 10 (µm)

Archives of Oral Biology 169 (2025) 106119

Archives of Oral Biology 169 (2025) 106119

Archives of Oral Biology 169 (2025) 106119

%): G1: 1793.4 ±

Archives of Oral Biology 169 (2025) 106119

/ 12.94 ± 3.30 / 9.55

15.11 ± 4.21 / 10.13

17.45 ± 4.42 / 12.61

9.59 ± 4.06 / 9.71 ±

2018), and sodium fluoride 0.24 % (Capalbo et al., 2022; Epasinghe

application, quercetin was primarily used as a treatment solution, with

application times ranging from 1 to 10 min, with most studies employ­

ing a 1-min application period. In the studies evaluating dental mate­

et al., 2017), erosive dentin wear by profilometry (Chen et al., 2024;

2017; Gotti et al., 2015), interfacial nanoleakage (Porto et al., 2021; Li

2017; Li et al., 2017).

3.3. Outcome results of quercetin effect on mineralized dental tissues

3.3.1. Dental adhesion by evaluation of microtensile bond strength

in improving dentin adhesion properties (Hong et al., 2022;

Dávila-Sánchez et al., 2020; Porto et al., 2018; Li et al., 2017). Addi­

solution achieved better bond strength to dentin than chlorhexidine

Furthermore, the incorporation of quercetin into dental material

addition of quercetin into adhesive systems increased its bond strength

to dentin, potentially offering a strategy for enhancing the performance

has a limited remineralizing action on the superficial layers of dental 5. Conclusion

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application times ranging from 1 to 10 min, with most studies employ

ing a 1-min application period. In the studies evaluating dental mate

Dávila-Sánchez et al., 2020; Porto et al., 2018; Li et al., 2017). Addi