
==== Front
Clin Cosmet Investig Dent
Clin Cosmet Investig Dent
ccide
Clinical, Cosmetic and Investigational Dentistry
1179-1357
Dove

478181
10.2147/CCIDE.S478181
Review
Effectiveness of Lemon Verbena (Cymbopogon citratus) in Oral Candidiasis: A Systematic Review
Cuenca-León et al
Cuenca-León et al
Cuenca-León Katherine 1 2 3
Lima-Illescas Miriam 1 2
http://orcid.org/0000-0002-6168-3218
Pacheco-Quito Edisson-Mauricio 1 2
http://orcid.org/0000-0001-7002-9990
Vélez-León Eleonor 1 2
http://orcid.org/0000-0002-9169-4372
Zarzuelo-Castañeda Aránzazu 3
1 Universidad Católica de Cuenca, Facultad de Odontología, Cuenca, 010105, Ecuador
2 Grupo de Investigación: Innovación y Desarrollo Farmacéutico. Grupo de Investigación en Odontología, Facultad de Odontología, Jefatura de Investigación e Innovación, Universidad Católica de Cuenca, Cuenca, 010105, Ecuador
3 Pharmaceutical Sciences Department, University of Salamanca, Salamanca, 37007, Spain
Correspondence: Katherine Cuenca-León, Universidad Católica de Cuenca, Facultad de Odontología, Avenida de las Américas, Cuenca, 010105, Ecuador, Email kcuencal@ucacue.edu.ec
10 9 2024
2024
16 295305
14 5 2024
02 8 2024
© 2024 Cuenca-León et al.
2024
Cuenca-León et al.
https://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
Abstract

The rise of phytotherapy has enabled the utilization of various plant species for medicinal purposes, such as Cymbopogon citratus (C. citratus), providing solutions for oral pathologies, such as oral candidiasis. The PubMed, Web of Science, Scopus, and SciELO databases were searched. In vivo and in vitro studies on the action of C. citratus against oral candidiasis were included, and ROBINS-I was used to determine study quality and risk of bias. The search yielded 1922 articles, of which 10 met the inclusion criteria. Limited scientific evidence exists regarding the use of C. citratus for oral candidiasis. However, studies have indicated its potent antifungal effects. Further studies, preferably clinical trials, are necessary to confirm this effect and to enable its clinical use as a therapeutic option.

Keywords

systematic review
candidiasis
oral efficacy
phytotherapy
Universidad Católica de Cuenca Universidad Católica de Cuenca. Project: DISEÑO Y ELABORACIÓN DE UN ENJUAGUE BUCAL CON INGREDIENTES ACTIVOS NATURALES, PARA NEUTRALIZAR Y ELIMINAR HONGOS ORALES EN PACIENTES QUE PORTAN PRÓTESIS PARCIAL Y/O TOTAL, with code PICODS21- 21.
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pmcIntroduction

Oral candidiasis in adults with partial or total prostheses, also known as denture stomatitis, is a common fungal infection of the oral cavity primarily caused by Candida albicans. Patients using partial or total prostheses tend to have a higher risk of plaque accumulation and food debris under the prosthesis, favoring an environment conducive to the growth of C. albicans.1–7 Other risk factors include age, pre-existing immunosuppressive diseases, impaired salivary gland function, drug interactions, high-carbohydrate diets, and extreme living conditions.1,6,8–14

This study is of great interest in the dental field15,16 because the imbalance generated between this commensal fungus and its host (human) allows the development of opportunistic infections.17–20 In healthy populations, the presence of the microorganism C. albicans is between 2 and 7% and in hospitalized individuals between 13 and 76%. These data are alarming and represent health problems that must be addressed in a timely manner. Various therapeutic options exist as a solution to this pathology;21,22 in this study, we reviewed treatment using a phytotherapeutic approach, since the use of plant species with medicinal properties could have potential advantages over conventional pharmacological therapies23,24 Bioactive components of plant species act by damaging the cell walls of microorganisms, destabilizing the cell membrane and inhibiting ergosterol synthesis, modulation of the immune system and inhibition of adhesion and biofilm formation. The combination of these mechanisms may make plant-based therapies an effective and natural option for the treatment of Candida albicans infections.25,26

Experimental studies on the development and formulation of new oral phytotherapeutic treatments are still limited; hence, there is a need for therapeutic options aimed at reducing and eradicating pathogenic microorganisms such as C. albicans.24,27 Several studies have demonstrated the antifungal efficacy of C. citratus in the treatment of oral candidiasis;27–30 however, the evidence is inconsistent, highlighting the need for a systematic review that comprehensively evaluates these findings.31 This study aimed to systematically review the literature in order to critically and exhaustively evaluate the efficacy of C. citratus as an antifungal therapy for oral candidiasis.

Materials and Methods

This systematic review was conducted according to the PRISMA 2020 guidelines31,32 to determine whether the phytochemical components of C. citratus exhibit effective antifungal characteristics and thus provide evidence for new therapeutic options applicable to the dental field. The study protocol was registered in the PROSPERO database (CRD42023437844).

Search Strategy

A comprehensive literature search was conducted in MEDLINE (via PubMed), Scopus, Web of Science (WOS), and SciELO databases for articles published up to December 31, 2023, using variations of keywords such as “patients with oral candidiasis”, “anticandidal activity”, “lemon verbena”, “Cymbopogon citratus”, and “oral candidiasis”33 (see Table 1). Table 1 Search Strategy

Database	Search Strategy	Results	
PubMed	(((candidiasis oral) AND (prosthetic patients)) OR (lemon verbena)) OR (Cymbopogon citratus) AND “Cymbopogon”[Mesh]	5	
(((((oral candid*) AND (“candidiasis”[Mesh])) OR (oral thrush)) AND (sick person)) AND (lemon verbena)) OR (Cymbopogon citratus)	8	
(((((oral candidiasis) AND (“Patients”[Mesh])) AND (experimental)) AND (Cymbopogon citratus)) OR (lemon grass)) OR (lemon citratus)	21	
(((((oral thrush) OR (oral candidiasis)) AND (“Patients”[Mesh])) AND (oral prosthesis)) OR (lemon grass)) OR (lemon verbena) AND “Cymbopogon”[Mesh]	13	
(((“Candidiasis”[Mesh]) AND “Mouth”[Mesh]) AND “Antifungal Agents”[Mesh]) AND “Cymbopogon”[Mesh]	1	
((((((antifungal activity) OR (oral candidiasis)) AND (Cymbopogon citratus)) OR (lemon grasses)) AND (antifungal drugs)) OR (antifungals)) AND “Patients”[Mesh]	5	
Total	53	
Web of Science	ALL=((((candidiasis oral) AND (prosthetic patients)) OR (lemon verbena)) OR (Cymbopogon citratus) AND “Cymbopogon”[Mesh])	212	
ALL=(((((oral candid*) AND (“candidiasis”[Mesh])) OR (oral thrush)) AND (sick person)) AND (lemon verbena)) OR (Cymbopogon citratus)	408	
ALL=((((((oral candidiasis) AND (“Patients”[Mesh])) AND (experimental)) AND (Cymbopogon citratus)) OR (lemon grass)) OR (lemon citratus))	141	
ALL=(((((oral thrush) OR (oral candidiasis)) AND (“Patients”[Mesh])) AND (oral prosthesis)) OR (lemon grass)) OR (lemon verbena) AND “Cymbopogon”[Mesh]	132	
ALL=(((((prosthetic materials) AND (anti-candid*)) AND (lemon verbena)) OR (Cymbopogon citratus)) AND “Patients”)	7	
(((((((ALL=(antifungal activity)) OR ALL=(oral candidiasis)) AND ALL=(Cymbopogon citratus)) OR ALL=(lemon grasses)) AND ALL=(antifungal drugs)) OR ALL=(antifungals)) AND ALL=(Patients)) AND ALL=(Stomatitis)	46	
Total	946	
Scopus	(TITLE-ABS-KEY (candidiasis AND oral AND prosthetic AND patients OR lemon AND verbena) OR ALL (Cymbopogon AND citratus) AND ALL (“Cymbopogon”[mesh])) AND (LIMIT-TO (DOCTYPE, “ar”)) AND (LIMIT-TO (EXACTKEYWORD, ”Article”))	6	
TITLE-ABS-KEY ((((((oral AND candid*) AND (“candidiasis”mesh])) OR (oral AND thrush)) AND (sick AND person)) AND (lemon AND verbena)) OR (Cymbopogon AND citratus)) AND (LIMIT-TO (DOCTYPE, “ar”)) AND (LIMIT-TO (LANGUAGE, ”Chinese”))	12	
TITLE-ABS-KEY ((((candidiasis AND oral) AND (prosthetic AND patients)) OR (lemon AND verbena)) OR (Cymbopogon AND citratus) AND “Cymbopogon”[mesh]) AND (LIMIT-TO (DOCTYPE, ”ar”))	1	
TITLE-ABS-KEY ((((candidiasis AND oral) AND (prosthetic AND patients)) OR (lemon AND verbena)) OR (Cymbopogon AND citratus) AND “Cymbopogon”[mesh])	2	
TITLE-ABS-KEY (((((prosthetic AND materials) AND (anti-candid*)) AND (lemon AND verbena)) OR (Cymbopogon AND citratus)) AND “Patients”) AND (LIMIT-TO (DOCTYPE, “ar”)) AND (LIMIT-TO (EXACTKEYWORD, ”Article”))	73	
TITLE-ABS-KEY ((((“Candidiasis”) AND “Mouth”) AND “Antifungal Agents”) AND ”Cymbopogon”) AND (LIMIT-TO (DOCTYPE, ”ar”)) AND (LIMIT-TO (EXACTKEYWORD, ”Article”))	3	
TITLE-ABS-KEY (((((((antifungal AND activity) OR (oral AND candidiasis)) AND (Cymbopogon AND citratus)) OR (lemon AND grasses)) AND (antifungal AND drugs)) OR (antifungals)) AND “Patients”)) AND (LIMIT-TO (DOCTYPE, “ar”)) AND (LIMIT-TO (EXACTKEYWORD, “Article”)) AND (LIMIT-TO (LANGUAGE, ”Chinese”) OR LIMIT-TO (LANGUAGE, ”Japanese”))	694	
TITLE-ABS-KEY (((((((antifungal AND activity) OR (oral AND candidiasis)) AND (Cymbopogon AND citratus)) OR (“lemon grasses”)) AND (antifungal AND drugs)) OR (antifungals)) AND “Patients” AND “Stomatitis”)) AND (LIMIT-TO (DOCTYPE, “ar”)) AND (LIMIT-TO (EXACTKEYWORD, “Article”) OR (LIMIT-TO (EXACTKEYWORD, ”Antifungal Agent”)) OR (LIMIT-TO (EXACTKEYWORD, ”Humans”)) AND (LIMIT-TO (LANGUAGE, ”Chinese”)) OR (LIMIT-TO (LANGUAGE, ”Japanese”))	1	
Total	792	
SciELO	(((candidiasis oral) AND (prosthetic patients)) OR (lemon verbena)) OR (Cymbopogon citratus) AND “Cymbopogon”	133	
Total	133	
	Total number of articles	1924	

Inclusion Criteria

Articles in English and Spanish that reported in vivo and in vitro studies involving the presence of C. albicans, antimycotic efficacy of C. citratus, oral candidiasis, patients of any sex and age and patients using or not using oral prostheses were included.

Exclusion Criteria

Non-relevant studies and reviews, clinical case reports, studies with low-quality scientific evidence, studies in Chinese and Russian languages, studies without full text available, conferences, surveys, studies of other active components, letters, and editorial opinions were excluded.

Study Selection, Data Extraction, and Analysis

Study selection was performed by two independent reviewers who initially assessed the titles and abstracts of the identified articles and excluded those that did not meet the eligibility criteria. After the initial evaluation, all studies were imported into Mendeley Reference Manager software (version 2.72.0) to eliminate duplicates. Potentially eligible full-text articles were independently analyzed by the reviewers based on the inclusion/exclusion criteria, and any disagreement was resolved through consultation with a third author. The PRISMA flow diagram (Figure 1) shows the included and excluded studies. The information from each selected article was compiled into an evidence table (Tables 2 and 3) using Microsoft Office Excel, reporting data on in vivo and in vitro studies, year of publication, first author, study type, study unit, population characteristics, application, effects of C. citratus on oral health, control group, main findings, database, and journal names. Table 2 Characteristics of the Studies in Chronological Order, Describing the Main Author, Type of Design, Study Unit, Outcome, and Control

Year	First Author	Type of Study	Unit of Study	Outcome	Control	Reference	
2009	Wright	Clinical trial	82 patients	Positive antifungal effect	Not reported	[34]	
2010	Tyagi	In vitro	ATCC 10231 (C. albicans)	Positive antifungal effect	Not reported	[35]	
2010	Taguchi Yuuki	In vitro	TIMM 1768 and TIMM 2640 (C. albicans)	Positive antifungal effect	Not reported	[36]	
2013	Almeida	In vitro	C. albicans ATCC 18804 isolated from the oral cavity of healthy individuals	Positive antifungal effect	Sterile distilled water	[28]	
2014	Amornvit	In vitro	ATCC 10231 (C. albicans)	Positive antifungal effect	Nystatin	[37]	
2014	Boukhatem	Clinical trial/in vitro	60 male and female Swiss albino mice	Positive antifungal effect	Not reported	[24]	
2014	Bersan	In vitro	CBS 562 (C. albicans)	Positive antifungal effect	Nystatin	[38]	
2019	Pedroso	Clinical trial/in vitro	SC 5314 (C. albicans) and 20 worms	Positive antifungal effect	Amphotericin	[39]	
2022	Paiva	In vitro	292 pre-identified Candida strains from the oral cavity of oncologic patients (C. albicans ATCC 90028, C. dubliniensis CBS 7987, C. parapsilosis ATCC 22019, C. glabrata MYA 2950, C. krusei ATCC 6258, and C. utilis ATCC 9950)	Positive antifungal effect	Not reported	[27]	
2023	Revelo Motta	In vitro	ATCC 10231 (C. albicans)	Positive antifungal effect	Nystatin (+) Saline solution (–)	[31]	

Table 3 Study Characteristics According to Article Title, Study Location, Database, and Journal and Database

Article Title	Study Location	Database	Journal	Reference	
Treatment of oral thrush in HIV/AIDS patients with lemon juice and lemon grass (Cymbopogon citratus) and gentian violet.	South Africa	WOS, PubMed, Scopus	Phytomedicine Journal	[34]	
Liquid and vapour-phase antifungal activities of selected essential oils against Candida albicans: Microscopic observations and chemical characterization of Cymbopogon citratus.	Unspecified	PubMed, Scopus, Web of Science, Embase	BMC Complementary and Alternative Medicine	[35]	
Therapeutic Effects on Murine Oral Candidiasis by Oral Administration of Cassia (Cinnamomum cassia) Preparation	Japan	PubMed	Japanese Society for Medical Mycology	[36]	
Antimicrobial activity of the essential oil of Cymbopogon citratus (DC) Stapf. on Staphylococcus spp., Streptococcus mutans and Candida spp	Brazil	SciELO	Rev. Bras. Pl. Med., Campinas	[28]	
Lemongrass-incorporated tissue conditioner against Candida albicans culture	Unspecified	Scopus	Journal of Clinical and Diagnostic Research	[37]	
Lemon grass (Cymbopogon citratus) essential oil as a potent anti-inflammatory and antifungal drugs	Unspecified	Scopus-WOS-PubMed Central	Evidence-Based Complementary and Alternative Medicine	[24]	
Action of essential oils from Brazilian native and exotic medicinal species on oral biofilms.	Brazil	PubMed Central, Scopus	BMC Complementary and Alternative Medicine	[38]	
In vitro and in vivo Anti-Candida spp. Activity of plant-derived products	Unspecified	Scopus, PubMed, WOS	Plants	[39]	
Association of the essential oil of Cymbopogon citratus (DC) Stapf with nystatin against oral cavity yeasts	Brazil	SciELO	Anais da Academia Brasileira de Ciencias	[27]	
Evaluation of Ecuadorian lemongrass oil as an inhibitor of some oral pathogens.	Ecuador	Scopus, SciELO	Revista Cubana de Estomatología	[31]	

Figure 1 The PRISMA flow diagram.

Quality Assessment

The “Risk of Bias in Non-randomized Studies – of Interventions” (ROBINS I) tool was used to determine the methodological quality and risk of bias of the studies identified. This tool has been used in non-randomized interventional studies. The response options of this tool allow for the assessment of low, moderate, serious, and critical risks based on the individual evaluation of each article, resulting in a color-coded graphical representation. The quality assessment was conducted by the reviewers (K.C.-L. and M.L.-I). In cases of disagreement, a third reviewer (E.P.-Q.) assessed the articles, and consensus was reached through discussion.

Results

The total number of publications initially identified was 1,922, of which 53 were from PubMed, 792 from Scopus, 946 from the Web of Science, and 133 from SciELO. After removing duplicates, 1,299 articles were reviewed, and 1,289 were excluded based on the eligibility criteria. Ten articles were evaluated based on the full-text inclusion criteria, including in vitro studies and/or clinical trials (see Table 2).

Characteristics of the Included Studies in Chronological Order

In a randomized controlled trial, Wright investigated the use of lemon juice and C. citratus for the treatment of oral candidiasis in patients with HIV.34

In 2010, Tyagi reported that the minimum inhibitory concentration (MIC) of C. citratus essential oil in the liquid phase was higher than that in the vapor phase, and a 4-hour exposure to the vapor phase was sufficient to cause a 100% loss in the viability of C. albicans cells. Chemical analysis revealed that C. citratus essential oil is dominated by oxygenated monoterpenes, particularly α-citral or geranial and β-citral or neral. This study suggests that the use of C. citratus essential oil in the vapor phase may be an effective method for controlling C. albicans growth.35

In an in vitro study, Taguchi et al reported that C. citratus has antifungal activity against C. albicans strains TIMM 1768 and TIMM 2640.36

In 2013, Almeida et al showed that the essential oil of C. citratus reduced the colony-forming units (CFU/mL) of S. aureus, S. mutans, and C. albicans, both individually and in combination, thereby demonstrating the efficacy of the active components of C. citratus.28

In an in vitro study, Amornvit et al demonstrated that C. citratus has potent antifungal activity against C. albicans ATCC 10231, with a minimum inhibitory concentration (MIC) of 0.06% (v/v).37

Boukhatem et al reported significant results and stated that C. citratus essential oil (LGEO) has potent antifungal effects. LGEO was administered orally and topically and showed promising antifungal activity against C. albicans, C. tropicalis, and Aspergillus niger, with C. albicans being the most important species. This study had a mixed design (both in vitro and clinical trials).24

In 2014, Bersan et al evaluated the antifungal activity of essential oils from various medicinal plants, including C. citratus, against oral pathogens (C. albicans) and their effects on biofilm formation.38

The efficacy of several essential oils obtained from different plants, including C. citratus, was demonstrated by Pedroso in an in vitro/clinical test study on worms contaminated with C. albicans, showing the antifungal efficacy of this plant.39

In 2020, Paiva reported that C. citratus essential oils inhibit and eradicate yeast from the oral cavity, including Candida spp., which are the main causative agents of oral candidiasis and thrush. The use of C. citratus essential oil in combination with nystatin may constitute a possible alternative to conventional pharmacological treatments for oral fungal infections, particularly in cases where microorganisms are resistant to commonly used drugs.27

An in vitro study conducted by Revelo aimed to define the possible preventive and therapeutic effects of essential oils in the treatment of oral diseases, resulting in the selection of C. citratus for its antibacterial, antifungal, antioxidant, antiproliferative, antiviral, and anti-inflammatory properties and reported significant antifungal activity.30

Methodological Quality and Risk of Bias

Most studies have reported a reduction in fungal burden after treatment with C. citratus. However, the methodological quality of the studies varied and some showed limitations in terms of design and execution. Therefore, each study was evaluated in seven domains (D): D1: Bias due to confounding; D2: Bias in the selection of participants; D3: Bias in the classification of interventions; D4: Bias due to deviations from intended interventions; D5: Bias due to missing data; D6: Bias in the measurement of outcomes; and D7: Bias in the selection of reported results. Based on these domains, judgment was made regarding the quality and risk of bias of each study. In general, most studies had a moderate risk, with one showing a serious risk owing to significant design problems (Figure 2). Figure 2 Risk of bias domains.

The results of these domains are presented here. D1: Most studies showed moderate risk, except for one that showed critical risk; the latter had multiple issues to be used as evidence. D2: All studies presented a moderate risk because of the absence of randomization. D3: Most studies presented a moderate risk, with only one publication classified as having serious risk. D4: Almost all studies presented low risk, one had moderate risk, and one had critical risk. D5: All studies had moderate risk, except for one that presented serious risk. D6: All studies presented a moderate risk. D7: All studies presented low risk, as they were comparable to randomized trials.

Discussion

Over the past few decades, increased antimicrobial resistance has become a significant threat to the global public health. This phenomenon diminishes the effectiveness of conventional treatments, elevates the morbidity and mortality associated with common infections, and complicates routine medical procedures, such as surgeries or organ transplants. The escalation of antimicrobial resistance is correlated with increased healthcare expenses, prolonged illness duration, and elevated mortality rates.40–42 Factors contributing to this phenomenon often stem from the inappropriate and indiscriminate use of antimicrobials, inaccurate diagnoses, inappropriate treatments, therapeutic non-adherence, or adverse effects of conventional medications.41–43 For example, prosthetic stomatitis is often managed with systemic or local medications, which may not be consistently effective because of inadequate therapeutic strategies or treatment discontinuation owing to adverse effects, potentially fostering antimicrobial resistance. Hence, several studies have explored the use of active components derived from medicinal plants (phytotherapeutics) for the treatment of oral diseases such as stomatitis induced by C. albicans.44–46

This systematic review aimed to evaluate scientific evidence regarding the efficacy of the active components of C. citratus as an antifungal therapy for oral candidiasis. Ten studies, including both in vitro and clinical trials, were reviewed, which revealed a limited number of studies, particularly clinical trials.47,48

Clinical Trial

All studies have reported the antifungal efficacy of the active components of C. citratus. Of these, six studies were exclusively in vitro trials, three were hybrid in vitro and clinical trials, and one was solely a clinical trial. Exclusive in vitro studies have investigated the essential oil of C. citratus against C. albicans strains, exhibiting promising antifungal effects that are comparable to those of conventional therapies. Despite the variability in quantitative results and units of measurement, all cases underscored the effectiveness of phytotherapy, as corroborated by previous studies.21,22,46,49 Additionally, these studies have reported efficacy against other microbial species and demonstrated bacteriostatic and microbicidal effects against Staphylococcus spp. and S. mutans strains.28 The bioactive efficacy of lemongrass was elucidated through chemical analysis, highlighting its high oxygenated monoterpene content, notably α-citral, geranial, and β-citral, which confer antimicrobial properties.35 However, the reviewed in vitro studies often yield heterogeneous results, focusing only on C. albicans or assessing the antimicrobial, anti-inflammatory, and antiproliferative effects of diverse bacterial strains.

Mixed Trials (in vitro / Clinical)

Two hybrid in vitro and clinical trials have been conducted. Both studies conducted microbiological evaluations of Candida spp. strains, followed by an assessment of the antifungal and anti-inflammatory properties of lemongrass in mice and demonstrated its effectiveness against C. albicans, C. tropicalis, and Aspergillus niger. In another study, the antifungal efficacy was assessed in worms. Notwithstanding the reported effectiveness, these findings warrant additional studies on the toxicity and adverse effects.

A mixed study was conducted to evaluate various plant species, including lemon balm (Melissa officinalis), thyme (Thymus vulgaris), rosemary (Rosmarinus officinalis), roselle (Hibiscus sabdariffa), green tea (Camellia sinensis), and cassia (Cinnamomum cassia). This study revealed that the anti-Candida activities of C. citratus, green tea, and cassia surpassed those of the other herbs tested, with cassia exhibiting the most favorable results, which is consistent with previous studies.50,51

Randomized Clinical Trial

The last included study was a randomized clinical trial that assessed the safety and efficacy of lemon juice and C. citratus in the treatment of oral candidiasis in HIV/AIDS patients. Lemon juice and C. citratus exhibited superior efficacy compared with the control (gentian violet) in the treatment of oral candidiasis. Notably, adverse effects were more frequent in the control group than in the lemon juice and C. citratus groups, suggesting that phytotherapy might mitigate the adverse effects associated with conventional treatments. However, this study was limited by its small sample size (90), which underscores the necessity for future studies to strengthen the existing evidence.22

The findings of this systematic review are expected to have a significant impact on clinical dental practice, particularly in settings with restricted access to conventional antifungals. Despite the absence of comprehensive pharmacological studies verifying its safety, toxicity, and adverse effects, these findings are promising for clinical application. If the efficacy and safety of C. citratus in the treatment of oral candidiasis are substantiated, it could emerge as an alternative or adjunct therapeutic option. Nonetheless, potential limitations such as variability in plant quality, product preparation based on active components, and study heterogeneity must be addressed. Further studies, particularly clinical trials, are required to validate the initial findings of this review and to establish clear clinical guidelines for C. citratus in oral candidiasis treatment with the aim of mitigating adverse effects and combating antimicrobial resistance.21,22,48,52,53

Lastly, we mention that this study used ROBINS I, a powerful tool that helped to evaluate the risk of bias in the estimation of harm or benefit of interventional studies that did not use randomization, obtaining objective results, as expected, and according to this study, its use is recommended in medical areas, justifying it due to the scarcity of ECCAS.53

Study Limitations

Owing to limited information and limited clinical trials, the review of the effects of C. citratus needs to be expanded to include in vitro studies involving both healthy and diseased individuals. The dearth of clinical trials that could provide more insights into the efficacy of C. citratus against C. albicans in vivo means that a precise definition of its therapeutic role requires further research.

Conclusion

This systematic review of the antifungal efficacy of C. citratus against oral candidiasis revealed a promising set of studies supporting its potential as an alternative or complementary therapy. Despite the variability in methodological quality and study design among the analyzed studies, the findings consistently suggested a significant antifungal effect of C. citratus against C. albicans. These results are encouraging and highlight the need for further research, particularly well-designed clinical trials, to validate and expand our understanding of the therapeutic benefits of C. citratus in the treatment of oral candidiasis, thereby contributing to improved clinical care and patient quality-of-life.

Acknowledgments

The authors thank the Universidad Católica de Cuenca for their constant and timely support.

Disclosure

The authors have declared that there are no conflicts of interest in this work.
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