Evaluating the Therapeutic Properties of Natural Products in Orthodontic and Surgical Treatment of Dentofacial Deformities: A Systematic Review of Clinical Trials

The use of natural products as alternatives to traditional pharmacological treatments in orthodontics is gaining interest due to their anti-inflammatory, antibacterial, and antioxidant properties. This systematic review synthesizes evidence from clinical trials to evaluate the efficacy of natural products in reducing inflammation and bacterial presence in orthodontic and orthognathic treatment settings. The database search was conducted across PubMed, Scopus, and Embase up to January 2024. The review focused on randomized controlled trials only. The selected studies centered on the anti-inflammatory, antibacterial, and antioxidant effects of natural products, adhering to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines for data extraction. Nine studies, totaling 358 participants, were included. Significant findings demonstrated a reduction in gingival inflammation by over 40% with the use of Aloe vera compared to chlorhexidine. Another study noted a decrease in bleeding on probing by 13.6 points in the treatment group over placebo. Additionally, honey showed a rapid modulation of plaque pH and significantly reduced bacterial counts of Streptococcus mutans. Furthermore, the use of resveratrol emulgel was linked to substantial improvements in gingival health, with a reduction in the gingival index and probing pocket depth. The results indicate that natural products can significantly enhance orthodontic treatment outcomes by reducing inflammation and bacterial levels. These products offer effective alternatives to traditional treatments and show potential for integration into routine orthodontic care protocols. Further research is encouraged to standardize application methods and dosages to maximize clinical benefits and patient satisfaction.


Introduction
Orthodontic treatment, aimed at correcting irregularities in tooth alignment and jaw position, often involves the use of appliances like braces or aligners [1,2].These interventions, while effective, can lead to biological responses such as inflammation, typically characterized by pain, swelling, and redness, which are common side effects experienced by orthodontic patients [3][4][5].Therefore, managing these inflammatory responses is important as they can impact patient comfort and the overall effectiveness of the treatment.
Traditionally, the management of inflammation and pain during orthodontic treatment has relied on the use of non-steroidal anti-inflammatory drugs (NSAIDs) [6,7].While NSAIDs are effective in controlling orthodontic pain and inflammation, their use is often limited by potential side effects, including gastrointestinal issues and cardiovascular risks [8,9].Consequently, there is a growing interest in alternative treatments that are effective yet bear fewer risks, and that could be recommended for patients that have contraindications for NSAIDs [10][11][12].
Natural products have been used medicinally for thousands of years and are known for their pharmacological effects, including anti-inflammatory, anti-bacterial, and anti-oxidant properties [13,14].These products, derived from plants, animal products, or minerals, offer a vast repository of bioactive compounds that could provide therapeutic benefits without the adverse effects associated with synthetic drugs [15,16].The anti-inflammatory mechanisms of natural products often involve modulation of inflammation mediators such as cytokines and enzymes involved in the inflammatory pathway.Many natural extracts and compounds have been documented to inhibit these mediators, thereby reducing inflammation [17,18].For orthodontic patients, the application of such natural agents could potentially accelerate recovery times and improve overall treatment outcomes.
Based on the growing interest and preliminary findings regarding natural products as therapeutic options, this systematic review hypothesizes that natural products are effective in reducing inflammation, provide anti-bacterial and antioxidant effect in patients undergoing orthodontic and dentofacial surgical treatment.This review aims to synthesize existing clinical trial data to provide a clear, evidence-based guide for the use of natural antiinflammatory agents in orthodontics, potentially offering a viable alternative to traditional pharmacological treatments.

Protocol and Registration
For this systematic review, a comprehensive search strategy was implemented across major medical and scientific databases, including PubMed, Scopus, and Web of Science, to gather literature up to January 2024.This search was specifically designed to capture clinical trials evaluating the anti-inflammatory, antibacterial, and antioxidant effectiveness of natural products during orthodontic treatment, recognizing the variability in the types of natural products and the methods of their application in orthodontics, and differentiating studies based on the type of natural product used, the application method, and the stage of orthodontic treatment.
The search was structured around the Population-Intervention-Comparator-Outcome (PICO) framework, targeting the following criteria: orthodontic patients of any age (Population) undergoing treatment with natural products possessing anti-inflammatory properties (Intervention), compared against standard care or placebo (Comparator), to assess outcomes related to inflammation control, pain reduction, and treatment satisfaction (Outcome).
Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines [19], this protocol was established to ensure clarity, structure, and reproducibility in the review process.The review has been registered with the Open Science Framework (OSF) with the registration number osf.io/rvsqb, underscoring our commitment to a transparent and rigorous systematic review process.

Eligibility Criteria
The inclusion criteria were set as follows: (1) Study population: studies must involve patients undergoing orthodontic treatment without restrictions on age, sex, or ethnicity to cover a diverse demographic; (2) Intervention: research explicitly investigating the use of natural products as anti-inflammatory and antioxidant agents in orthodontic care, with effects on inflammation reduction, pain alleviation, and improvement in treatment compliance and patient satisfaction; (3) Study types: only randomized controlled trials (RCTs) were considered, ensuring the highest level of evidence; (4) Outcome measures: studies must utilize validated assessment tools or well-defined parameters for measuring the outcomes of inflammation and pain management; (5) Language and peer review: only peer-reviewed articles published in English were included to ensure accessibility and quality of the data.
Exclusion criteria were also specified to refine the study selection: (1) Non-human studies: in vitro or animal studies were excluded to focus exclusively on human clinical outcomes; (2) Non-specific interventions: studies that did not specifically investigate natural products as the primary intervention for anti-inflammatory purposes in orthodontic treatment were excluded; (3) Insufficient detail: studies lacking specific, quantifiable outcomes related to the effectiveness and safety of the natural products used, or those missing sufficient detail for a thorough evaluation, were excluded; (4) Observational studies, cohort studies, case-control studies, and quasi-experimental studies were excluded to maintain a focus on RCTs; and (5) non-scientific publications: non-peer-reviewed articles, conference proceedings, theses, dissertations, general reviews, commentaries, and editorials were also excluded to ensure that the review was based on scientifically valid and peerevaluated sources.

Data Collection Process
Data was processed using Microsoft Excel version 2023 (Microsoft Corporation, Redmond, WA, USA) and graphics were created using Python version 3.9 (Wilmington, DE, USA).The data collection process for this systematic review commenced with the removal of 77 duplicate entries, followed by a rigorous screening of 133 abstracts by two independent reviewers to assess each study's relevance based on predefined inclusion and exclusion criteria.Of the 71 records assessed for eligibility, 14 were excluded by having no available data or by not matching the inclusion criteria (n = 48).Discrepancies between reviewers were resolved through discussion or, if necessary, consultation with a third reviewer to achieve consensus.The initial database search yielded a number of 605 articles, from which 9 relevant studies were identified for inclusion in the final study, as presented in Figure 1.

Risk of Bias and Quality Assessment
For the systematic assessment of study quality and determination of the risk of bias within the included studies, our review employed a dual approach, integrating both qualitative and quantitative evaluation methods.Initially, the quality and risk of bias of clinical trial studies were evaluated using Cochrane's tool [20].Discrepancies in quality assessment scores were resolved through discussion or, if necessary, consultation with a third researcher.

Risk of Bias and Quality Assessment
For the systematic assessment of study quality and determination within the included studies, our review employed a dual approach, integ itative and quantitative evaluation methods.Initially, the quality and risk trial studies were evaluated using Cochrane's tool [20].Discrepancies ment scores were resolved through discussion or, if necessary, consulta researcher.

Study Characteristics
The systematic review included a total of nine studies [21][22][23][24][25][26][27][28][29], as summarized in Table 1.These studies were conducted in various countries, including Spain [21,23], the United States [22], India [24,27], Brazil [25,26], Egypt [28], and Iran [29], over a period spanning from 2014 to 2022.Each study employed a randomized clinical trial design, focusing on evaluating the therapeutic properties of natural products in orthodontic treatment.The quality assessment of these studies revealed a mix of medium and high ratings.Specifically, five studies [21,[24][25][26]28] were rated as medium quality, indicating satisfactory adherence to standard research methodologies but potentially possessing some limitations in study design or execution.In contrast, four studies [22,23,27,29] received high-quality ratings, suggesting a robust study design, comprehensive methodology, and reliable results that adhere closely to the highest standards of clinical research.This diversity in study quality and geographic distribution underscores the global interest in natural therapies within orthodontic treatment, reflecting a broad academic and clinical investment in exploring alternative and supportive treatment modalities.

Population Characteristics
These studies incorporated a total of 358 participants in the intervention groups, exploring the efficacy of natural products in orthodontic treatment.The age of participants varied widely across the studies.López-Mateos et al. [21] and Kamath et al. [24] reported older intervention groups with mean ages of 32.2 years and 22.5 years, respectively, contrasting sharply with the predominantly adolescent cohorts in studies by Furtado Júnior et al. [25] and Atwa et al. [28], who reported age ranges of 12-16 years and 12-18 years, respectively.The broadest age range was observed in the study by Goes et al. [26], where participants ranged from 10 to 40 years, with a mean age of 28.8 years, illustrating the inclusion of both adolescent and adult orthodontic patients.
The gender distribution also showed considerable variability.The studies by López-Mateos et al. [21] and Kamath et al. [24] demonstrated a higher female participation in the intervention groups, with 85.4% and 60.0%, respectively, reflecting a common trend in orthodontic studies where females often represent a larger proportion of the sample.In contrast, studies by Martin et al. [22] and Yeturu et al. [27] maintained a balanced gender ratio, each with an even 50% distribution, indicating a deliberate design to eliminate gender as a confounding factor.
Control groups varied across studies, providing a spectrum of comparators that enriched the review's insights into the efficacy of natural products.For example, López-Mateos et al. [21] used patients treated with brackets as a control group, whereas Goes et al. [26] included both placebo and chlorhexidine-treated patients, offering a robust basis for comparison against the natural product interventions (Table 2).

Clinical Trial Assessment
Each study varied in the substance tested, the application method, and the frequency and duration of follow-up, providing a comprehensive view of the experimental approaches in the use of natural products for orthodontic care.López-Mateos et al. [21] assessed the impact of orthodontic aligners on saliva's oxidative stress markers, using advanced procedures to collect and analyze saliva samples at baseline and subsequent intervals up to 90 days.They utilized both Invisalign ® and Damon System ® brackets, tracking changes over three months, which is significant for understanding the long-term biochemical impacts of orthodontic appliances on saliva.
Martin et al. [22] focused on an antioxidant essential oil gel, examining its effect on gingival health by applying the gel twice daily, with evaluations every 4-6 weeks.Their use of both active and placebo gels provided a controlled environment to assess the gel's efficacy over a standard follow-up period, ensuring rigorous testing of the product's therapeutic properties.Leiva-Cala et al. [23] and Kamath et al. [24] both utilized Aloe vera in different forms (gel and mouthwash) compared directly against chlorhexidine, a standard in periodontal treatment.Their studies included detailed follow-up assessments to monitor immediate and short-term changes in oral health parameters, essential for evaluating the effectiveness of natural products against established chemical treatments.
Furtado Júnior et al. [25] and Goes et al. [26] both incorporated natural ingredients (Brazilian red propolis and Matricaria chamomilla L., respectively) into daily oral hygiene routines, with Furtado Júnior et al. assessing outcomes after 28 days and Goes et al. after 15 days.These studies provided insight into the practical application and benefits of incorporating natural products into everyday oral care.Atwa et al. [28] utilized a unique approach by integrating dietary natural products (honey) directly compared with traditional dietary sugars (sucrose and sorbitol) to evaluate their effects on plaque pH over a concise timeframe of 30 min, offering immediate biochemical results.Golshah et al. [29] extended their observation period up to 8 weeks to monitor the effectiveness of an emulgel containing 2% resveratrol on gingival health, providing substantial evidence of the long-term benefits of resveratrol in managing gingivitis in orthodontic patients (Table 3).

Assessment of Outcomes
Several studies documented significant outcomes.López-Mateos et al. [21] observed a notable increase in Advanced Oxidative Protein Product (AOPP) levels from 47.1 µM at baseline to 79.5 µM at 90 days in aligners and from 57.8 µM to 80.2 µM in self-ligating brackets.This suggests that both treatments could potentially elevate oxidative stress markers over time.However, changes in myeloperoxidase (MPO) and total antioxidant capacity (TAC) were not statistically significant, indicating a selective impact on specific oxidative stress markers.Martin et al. [22] reported an initial significant decrease in Bleeding on Probing (BOP) from baseline (T1) to the subsequent time points (T2) by 13.6 in the treatment group compared to a decrease of 3.0 in the placebo group.The Gingival Index (GI) slightly improved by 0.02 in the treatment group compared to a worsening of 0.06 in the placebo, suggesting that the topical gel initially reduces inflammation markers effectively.
Leiva-Cala et al. [23] found that Aloe vera gel significantly reduced inflammation by 41.4% compared to chlorhexidine, which underscores the potential of Aloe vera as a more effective and less adverse option for managing oral inflammation in orthodontic patients.Kamath et al. [24] demonstrated a decrease in the Gingival Index (GI) by 0.64 in the Aloe vera group versus 0.54 in the chlorhexidine group over the study duration.The reduction in bleeding on probing (BOP) was also more pronounced in the Aloe vera group (23.7) compared to chlorhexidine (29.2), reinforcing the viability of Aloe vera as an alternative treatment.
Furtado Júnior et al. [25] showed significant reductions in the Gingival Bleeding Index (GBI) and microbial counts with the use of fluoride dentifrice containing Brazilian red propolis.The GBI decreased by 17.35 in the propolis group compared to 11.11 in the control, and reductions in Gram-negative bacteria and S. mutans were also significantly more pronounced in the propolis group, indicating improved clinical and microbiological activity.Goes et al. [26] observed significant reductions in the Visible Plaque Index (VPI) by 25.6% in the Matricaria chamomilla L. (MTC) group and 39.9% in the chlorhexidine group compared to the placebo, alongside notable decreases in the Gingival Bleeding Index (GBI) by 29.9% and 32.0%, respectively, emphasizing the effectiveness of MTC mouthwash as a herbal alternative with fewer side effects.

NR
Overall, aligners showed a significant increase in AOPP over the 90 days, particularly in the later stages, whereas changes in MPO and TAC were not significant for either orthodontic technique.The plaque index showed no significant differences between the treatment and control groups at any point during the study period.
Topical gel effectively reduced inflammation markers initially; however, the effects were not sustained post-discontinuation of the gel application.

Summary of Evidence
The systematic review underscores the nuanced therapeutic properties of natural products in orthodontic treatment.López-Mateos et al. [21] reported significant increases in oxidative stress markers with both aligners and brackets over 90 days, highlighting the potential long-term biochemical impacts of orthodontic appliances on oral health.This study suggests a pivotal need to explore further the implications of oxidative stress in orthodontic treatments and its management with potentially antioxidative natural interventions.
Martin et al. [22], focusing on the therapeutic effects of an antioxidant essential oil gel, demonstrated short-term effectiveness in reducing gingival inflammation.This suggests that while natural products can initially modulate inflammatory responses effectively, their sustained impact post-discontinuation remains uncertain.This transient nature of effectiveness prompts a discussion on the necessity for ongoing treatment or perhaps the integration of such natural products into regular dental care routines to maintain their beneficial outcomes.
On the other hand, Leiva-Cala et al. [23] and Kamath et al. [24] utilized Aloe vera against chlorhexidine, a standard antiseptic, to underline the potential of natural products as viable alternatives for chemical treatments.Their findings, which favor Aloe vera, challenge the traditional reliance on chemical antiseptics in orthodontics, advocating for a paradigm shift towards integrating bioactive, natural substances that exhibit comparable efficacy with fewer side effects [30][31][32].

Summary of Evidence
The systematic review underscores the nuanced therapeutic properties of natural products in orthodontic treatment.López-Mateos et al. [21] reported significant increases in oxidative stress markers with both aligners and brackets over 90 days, highlighting the potential long-term biochemical impacts of orthodontic appliances on oral health.This study suggests a pivotal need to explore further the implications of oxidative stress in orthodontic treatments and its management with potentially antioxidative natural interventions.
Martin et al. [22], focusing on the therapeutic effects of an antioxidant essential oil gel, demonstrated short-term effectiveness in reducing gingival inflammation.This suggests that while natural products can initially modulate inflammatory responses effectively, their sustained impact post-discontinuation remains uncertain.This transient nature of effectiveness prompts a discussion on the necessity for ongoing treatment or perhaps the integration of such natural products into regular dental care routines to maintain their beneficial outcomes.
On the other hand, Leiva-Cala et al. [23] and Kamath et al. [24] utilized Aloe vera against chlorhexidine, a standard antiseptic, to underline the potential of natural products as viable alternatives for chemical treatments.Their findings, which favor Aloe vera, challenge the traditional reliance on chemical antiseptics in orthodontics, advocating for a paradigm shift towards integrating bioactive, natural substances that exhibit comparable efficacy with fewer side effects [30][31][32].
Furtado Júnior et al. [25] and Goes et al. [26] further contribute to this narrative by demonstrating the clinical and microbiological benefits of integrating natural ingredients like Brazilian red propolis and Matricaria chamomilla L. into daily oral hygiene.These studies underscore the significant role that such ingredients can play in enhancing oral health parameters, thus supporting their incorporation into standard oral care products.
In the analysis of natural remedies in orthodontic practice, several studies have attempted to identify effective treatments that mitigate complications associated with fixed appliances.For example, the study by Papadopoulou et al. [33] focused on the impact of organic, unprocessed products like Aloe vera, honey, and chamomile mouthwash on controlling gingivitis among orthodontic patients.They found significant reductions in plaque and gingival bleeding, attributing these benefits to the antimicrobial and anti-inflammatory properties of the natural products used.On the other hand, Inchingolo et al. [34] explored the role of antioxidants such as resveratrol and green tea in countering oxidative stress and reactive oxygen species production induced by orthodontic treatment.These studies suggest that these natural antioxidants and dietary supplements can help restore physio-logical balance, reduce inflammation levels, and prevent damage to dental and periodontal tissues, highlighting a preventive strategy against long-term complications in orthodontic care [35][36][37][38][39].
In examining the impact of orthodontic materials on oxidative stress, other studies provide valuable insights through contrasting methodologies and findings [34,[40][41][42].However, the non-clinical trial study design did not allow for the inclusion of the current systematic review.Portelli et al.'s study [43] measured salivary antioxidants in patients using self-ligating multibracket vestibular orthodontic appliances and found that antioxidant levels slightly decreased from 2971 mEq/L at baseline to 2909 mEq/L after five weeks, then increased to 3332 mEq/L after ten weeks, without statistically significant changes, suggesting minimal impact on oxidative stress.In contrast, Vito Kovac et al. [44] investigated the cytotoxicity and oxidative stress potential of orthodontic alloys in yeast cells, revealing that stainless steel and cobalt-chromium at 1000 µM concentration were cytotoxic, with significant oxidative damage observed even at 100 µM for the cobalt-chromium alloy, highlighting the potential for these materials to induce oxidative stress depending on their composition and exposure levels.
Other studies examined oxidative stress in patients with fixed orthodontic appliances, revealing complex biological responses.Buczko et al. [45] observed significant increases in salivary markers such as tiobarbituric acid reactive substances and total oxidant status shortly after appliance placement, with tiobarbituric acid reactive substances rising one week post-treatment and total protein concentration increasing significantly at twenty-four weeks.On the other hand, Angeles-Estrada et al. [46] reported increases in the oxidative stress marker 8-hydroxy-2 ′ deoxyguanosine and significant changes in antioxidant enzymes, with superoxide dismutase levels increasing by 2.5 times after six months and catalase tripling after six months, then returning to baseline by nine months.
Ozcan et al. [47] and Guler et al. [48] conducted focused studies on the biochemical impacts of fixed orthodontic appliances.Ozcan et al. examined the levels of interleukin-1 beta, tumor necrosis factor alpha, malondialdehyde, nitric oxide, and 8-hydroxydeoxyguanosine in saliva and gingival crevicular fluid over six months.They found that except for interleukin-1 beta in gingival crevicular fluid, which significantly increased by the sixth month, other markers did not change significantly, suggesting minimal systemic oxidative damage.Conversely, Guler et al. evaluated the impact of different orthodontic composites on salivary total oxidant status, total antioxidant status, and 8-hydroxy-2 ′ -deoxyguanosine in children, finding that while total antioxidant status significantly decreased over time in composites like Kurasper F and GrenGloo, 8-hydroxy-2 ′ -deoxyguanosine initially decreased and then significantly increased by the third month, indicating dynamic changes in oxidative stress related to material composition and treatment duration.
Other studies investigated the effectiveness of different dental hygiene products with natural components in managing oral health in the context of orthodontic treatment.Santamaria et al. [49] studied the antimicrobial effects of Melaleuca alternifolia essential oil gel compared to Colgate Total toothpaste.Over a four-week period involving a crossover design, they found that the melaleuca gel significantly reduced dental biofilm and bacterial colonies more effectively than Colgate Total.However, in terms of sensory attributes such as flavor and initial taste sensation, Colgate Total was preferred by volunteers (p < 0.05).Conversely, Masou et al. [50] conducted a pilot study on the use of xylitol, delivered through chewing gum and dissolvable tablets, to assess its impact on dental plaque and bacterial levels in patients with fixed orthodontic appliances.Their study, which also included oral hygiene instruction and fluoride treatments, found no significant difference in plaque scores or bacterial counts between the xylitol groups and a control group over a 12-month period, suggesting that xylitol did not provide additional clinical or bacterial benefits in this context.However, the study design did not allow for inclusion and detailed analysis in the current systematic review because it was not a clinical trial.
Aloe vera has been extensively studied for its therapeutic effects in oral health, being rich in bioactive compounds such as glycoproteins, which help to reduce pain and inflammation, and polysaccharides, which promote healing and moisturize the tissues [51].Many studies have demonstrated that Aloe vera can significantly reduce gingival inflammation and bleeding, which are common complications in orthodontic treatments.Its antimicrobial properties, attributed to compounds such as barbaloin and acemannan, also make it effective against common oral pathogens, enhancing its suitability for dental applications [52,53].
A formulation based on a fluoride dentifrice enhanced with Brazilian red propolis is another notable natural product in orthodontic care [54].Brazilian red propolis contains unique compounds such as formononetin, biochanin A, and medicarpin, which are known for their anti-inflammatory and antimicrobial activities.These properties help reduce gingival inflammation and control microbial populations in the oral cavity, effectively combating dental plaque and periodontal pathogens.Another study showed that the addition of fluoride dentifrice enhances its ability to prevent dental caries, making this formulation effective for maintaining oral hygiene in orthodontic and orthognathic patients [55].
Matricaria chamomilla L., commonly known as chamomile, was another natural compound that was tested in a clinical trial and found to be effective.It can be utilized in the form of a mouthwash and has shown promising results in reducing plaque accumulation and gingival bleeding [56].Chamomile contains bisabolol, chamazulene, and flavonoids, which are compounds with potent anti-inflammatory and antiseptic properties [57].These components help soothe irritated mucous membranes and reduce bacterial activity, thus preventing inflammation and plaque buildup.Its use as a mouthwash in orthodontic patients provides a soothing, therapeutic effect, complementing traditional mechanical plaque control methods [58].
Overall, the most recent studies offer significant insights into the use of natural products and novel materials in dentistry, emphasizing their efficacy and potential applications.Eskandari et al. [59] demonstrated that elastomeric ligature ties coated with kombuchaderived bacterial nanocellulose maintain their mechanical properties while providing sustained antibacterial activity, which is crucial for preventing carious lesions in orthodontic patients.Another study [60] highlighted the broad therapeutic potential of Cissus extracts in dentistry, noting their antibacterial, anti-inflammatory, and tissue-regenerative properties, which could modernize dental practices.It is also worth mentioning the latest views on phytotherapy, which revealed that herbal treatments, such as mouthwashes, significantly enhance oral health-related quality of life, are cost-effective, and improve healthcare access [61].Lastly, Pedrinha's study on propolis and copaiba oil-resin showed these natural antimicrobials promote proliferation in human periodontal ligament fibroblasts without cytotoxic effects, suggesting their safe use in endodontic and other medical applications to manage inflammation and infection [62].These studies collectively underline the transformative potential of natural and innovative materials in enhancing dental care outcomes.

Limitations
While this systematic review employs a comprehensive approach to assess the efficacy of natural products in orthodontic care, several limitations are inherent to its design and scope.Firstly, the variability in natural products and their application methods poses a challenge in drawing generalized conclusions, as different studies may use distinct formulations, concentrations, and application protocols, potentially leading to heterogeneous results.Secondly, the review's reliance on randomized controlled trials published its breadth, potentially excluding relevant studies conducted in other languages or significant findings published in other types of research articles.Moreover, the inclusion criteria might omit studies involving broader demographic characteristics or varying orthodontic conditions that could influence the generalizability of the findings.Additionally, the specific focus on anti-inflammatory, antibacterial, and antioxidant effects may overlook other relevant biological or clinical impacts of natural products.Lastly, the extraction and synthesis of data from different studies require assumptions and interpretations that may introduce bias, particularly when comparing studies with diverse methodologies or outcome measures.

Conclusions
This systematic review confirms that natural products significantly enhance orthodontic treatment outcomes by reducing inflammation and bacterial levels, attributable to their active chemical compounds.For instance, Aloe vera's effectiveness in reducing gingival inflammation may be linked to compounds such as aloin and barbaloin, which exhibit anti-inflammatory and antibacterial properties.Similarly, the antibacterial action of honey, particularly against Streptococcus mutans, can be attributed to its natural peroxide content.Resveratrol's reduction in gingival indices is supported by its antioxidant properties that modulate inflammatory pathways.These findings suggest that natural products not only serve as viable alternatives to traditional treatments but also offer a potential for integration into routine orthodontic care, promising fewer side effects and enhanced patient outcomes.It is, therefore, recommended that natural products such as Aloe vera, resveratrol, Brazilian red propolis, and Matricaria chamomile should be introduced in routine practice for orthodontic and orthognathic patients in association with anti-inflammatory and anti-bacterial agents such as chlorhexidine or alike.Further research is recommended to standardize these treatments for broader clinical applications.

Table 2 .
Characteristics of study groups.
NR-Not Reported; * The intervention group was defined as patients that have received the natural product from the experiment vs. the control group (patients with the same dental procedures that have not received the natural dental product of the study); MTC-Matricaria chamomile.

Table 4 .
Assessment of outcomes.