Abstract
Background:
Preparations of Nigella sativa and its major bioactive compound thymoquinone (TQ) possess antioxidant, antimicrobial, anti-inflammatory, and wound-healing properties. These characteristics suggest potential utility as adjuncts in the management of gingivitis, mucositis, periodontitis, and peri-implantitis.
Objective:
To critically evaluate the current clinical evidence regarding the use of Nigella sativa preparations and TQ in periodontal therapy.
Methods:
A systematic literature search following PRISMA guidelines was conducted in PubMed, Embase, Scopus, Web of Science, and Cochrane CENTRAL for English-language clinical studies published through July 2026. Eligible studies investigated preparations of Nigella sativa or TQ for periodontal inflammatory diseases. Hand-searching was performed to identify additional relevant publications.
Results:
Fourteen exploratory clinical trials were identified. Overall, adjunctive use of Nigella sativa preparations or TQ was associated with improvements in clinical periodontal outcome measures. However, interpretation is limited by small sample sizes, methodological heterogeneity, short follow-up periods, and insufficient characterization of the investigational products. Only one of the studies adequately reported the administered daily TQ dose.
Discussion:
Without knowledge of the administered TQ dose, neither dose–response relationships nor reliable sample-size calculations for confirmatory trials can be established. Experimental evidence nevertheless supports the biological plausibility of the observed clinical findings and provides a rationale for further clinical investigation.
Conclusions:
Current clinical evidence remains preliminary and hypothesis-generating despite encouraging findings. Future confirmatory randomized controlled trials should employ well-characterized, TQ-standardized preparations and report the administered TQ dose to enable reproducibility, dose–response assessment, and evidence-based study planning.
1 Introduction
Periodontal diseases are highly prevalent chronic inflammatory conditions associated with systemic disorders, including cardiovascular disease, metabolic syndrome, and neurodegenerative diseases (–). Disease initiation is driven by dysbiotic biofilms and a dysregulated host immune response, leading from reversible gingivitis to irreversible tissue destruction in periodontitis (–).
While effective oral hygiene prevents gingival inflammation, active periodontitis requires professional subgingival instrumentation and lifelong supportive care (, ). The EFP S3 clinical guideline recommends a stepwise approach including mechanical biofilm control, risk-factor management, subgingival instrumentation, surgical intervention when needed, and supportive maintenance (). The endpoint is pocket closure (≤ 4 mm probing depth and no bleeding on probing) ().
A central challenge in periodontal therapy lies in the persistence and tissue invasion of periodontitis-associated bacteria supporting biofilm formation (). Such biofilms show markedly enhanced tolerance—up to 1,000-fold—to antimicrobial agents compared with planktonic bacteria (, ). Consequently, adjunctive antimicrobial strategies have been explored. Systemic antibiotics (typically metronidazole + amoxicillin) are reserved for defined indications due to resistance concerns (), while topical antiseptics such as chlorhexidine (CHX) show only modest additional benefit () and can contribute to antimicrobial resistance and dysbiosis (, ).
These limitations have prompted interest in herbal medicines which combine affordability, high biocompatibility, and favorable safety (). Among the phytotherapeutics, Nigella sativa (black seed) and its leading compound thymoquinone (TQ) display potent antioxidant, antimicrobial, anti-inflammatory, and bone-regenerative actions (–). This systematic review summarizes and critically assesses the evidence for the clinical effectiveness of preparations from Nigella sativa in periodontal therapy.
2 Methods
Following peer-review, the original PubMed search was expanded to include Embase, Scopus, Web of Science and Cochrane Central Register of Controlled Trials (CENTRAL). The systematic review was subsequently conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses () statement using a rigorous methodology to minimize the risk of bias. Ethical approval was not required because all data were obtained from previously published studies.
The final search of all databases was completed on July 16, 2026; therefore, publications indexed after this date were not eligible for inclusion. The search strategy combined terms related to Nigella sativa and its active constituent TQ with terms describing gingivitis, oral mucositis, periodontitis, and peri-implantitis. The following search string was adapted for each database: (“Nigella sativa” OR “black cumin” OR “black cumin seed” OR “black seed” OR kalonji OR thymoquinone) AND (periodontitis OR gingivitis OR “oral mucositis” OR stomatitis OR “periodontal disease*” OR “oral disease*” OR “oral inflammation” OR “oral health”). Eligible studies included randomized controlled trials, randomized clinical trials, controlled clinical trials, and prospective clinical studies published in English and involving human participants. Exclusion criteria comprised in vitro studies, animal studies, narrative or systematic reviews, case reports or case series, studies investigating aggressive periodontitis (Grade C periodontitis) or multicomponent interventions in which the independent effect of Nigella sativa or TQ could not be determined, and studies outside the predefined disease spectrum of the present review.
Following the initial search, all the retrieved results were imported into Excel for extraction. All articles where a
Nigella sativapreparation was either used alone or compared to any other intervention for gingivitis/mucositis or peri-implantitis-periodontitis were included. Duplicates were removed before title and abstract screening. Two reviewers (SCH and AA) independently performed title/abstract screening and full-text assessment according to the predefined eligibility criteria. Discrepancies at the full-text stage were resolved through discussion and consultation with a third reviewer (JV). Data were extracted using a customized data extraction form. The PICO framework was used to structure the focus of this literature review, ensuring a comprehensive and systematic approach to evaluating clinical studies where Nigella sativa preparations were used to improve oral health. The PICO components were defined as follows:
P: Patients—The review included patients of all ages with gingivitis/mucositis and peri-implantitis/periodontitis.
I: Intervention—The interventions considered were preparations from Nigella sativa seed.
C: Comparison—Comparisons were made between the groups (placebo or active control).
O: Outcome—The primary outcome was improvement in gingival, mucosal, and periodontal health assessed using established outcome measures appropriate for the condition investigated, including clinical indices (e.g., PI, GI, BOP, PPD, CAL, OMAS, WHO mucositis grade), patient-reported outcomes (e.g., VAS pain and swallowing), and biochemical markers (e.g., IL-6, TNF-α, MMP-8, TAC, ALP). Data were extracted using a customized data extraction form. For the purpose of this review, the following information was extracted and tabulated for all the selected studies: title; first author's name; study design, publication year; study location, population description; intervention, frequency, mg TQ per dose, comparator, established outcome measure(s), follow-up period, and overall RoB. A meta-analysis was not performed due to the significant clinical and methodological heterogeneity between studies.
3 Clinical evidence
3.1 Overview of search
Figure 1 presents the PRISMA 2020 flow diagram of the study selection process. The detailed search strategies are presented in Supplementary Table S1. The literature search identified 237 records from PubMed, Embase, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) (see Supplementary Table S2a). After removal of 45 duplicate records (see Supplementary Table S2b), 192 titles and abstracts were screened according to the predefined eligibility criteria. Potentially relevant reports underwent full-text assessment by two independent reviewers. Reports were excluded if they investigated an inappropriate intervention, used an ineligible study design, addressed diseases outside the predefined scope of this review, or if the full text could not be retrieved.
Figure 1
The database searches yielded eight eligible published clinical studies (see Supplementary Table S3). An additional six eligible clinical studies were identified through hand searching, resulting in a total of 14 studies included in the qualitative synthesis (Tables 1, 2).
Table 1
| Author | Arab Farashahi | Singh | Ilangovan | Khan | Almehmadi | Hussain | Ameen |
|---|---|---|---|---|---|---|---|
| Study design | triple-blind, parallel-group randomized controlled trial | split-mouth clinical trial | double-blind, parallel-group randomized controlled trial | prospective, single-blind, simple randomized controlled trial | double-blind, parallel, randomized controlled trial | open-label controlled trial with two parallel arms | prospective open-label clinical trial |
| Year | 2026 | 2019 | 2021 | 2021 | 2024 | 2021 | 2019 |
| Country | Iran | India | India | USA | Saudi Arabia | Iraq | Iraq |
| Participants | 36 patients with gingivitis (19 F, 17 M) | 24 patients with moderate-to-severe gingivitis (25–45 years; NR) | 30 participants with gingivitis (18–28 years; NR) | 60 children with gingivitis (12–18 years; NR) | 63 participants with gingivitis (18–40 years; NR) | 52 patients with chemotherapy-induced oral mucositis (<25 to >45 years; 27 M, 25 F) | 40 patients with chemotherapy-induced oral mucositis (28 M, 12 F) |
| Intervention | 20% Nigella sativa mouthwash, 10 mL | Nigella sativa ethanolic extract (1:3, 1:1, 3:1 in glycerin), 1 mL | 20% Nigella sativa mouthwash, 10 mL | 0.1% Nigella sativa gel (pea-sized amount) | Standard care + 5% Nigella sativa gel | Commercial Nigella sativa oil mouthwash, 10 mL | Commercial Nigella sativa oil mouthwash, 10 mL |
| Frequency | twice daily | repeated for 3 consecutive days | twice daily | twice daily | twice daily | four times daily | five times daily |
| mg TQ/Dose | NR | NR | NR | NR | NR | NR | NR |
| Comparator | CHX 0.2% mothwash | SRP alone | CHX 0.12% mothwash | CHX 0.12% gel | SC + placebo gel, SC alone | moutwasha | moutwasha |
| Outcome | significant reductions in PI and PBI | significant reductions in PI and GI | significant reductions in PI and GI | significant reductions in PI and GI | significant reductions in PI and PBI | significant reductions in OMAS, VAS pain, VAS swallowing and salivary IL-6 | significant reductions in VRS mucositis severity and salivary Il-6 + TNFa |
| Follow-Up | 2 weeks | 28 days | 2 weeks | 28 days | 2 weeks | 28 days | 60 days |
| Overall RoB | some concerns | some concerns | some concerns | low risk | low risk | some concerns | some concerns |
Characteristics of the included studies and overall risk of bias assessment (RoB 2) for gingivitis/mucositis.
Ns, Nigella sativa; SRP, scaling and root planing; SC, standard protocol of scaling; PI, plaque index; PBI, papillary bleeding index; GI, gingival index; OMAS, oral mucositis assessment scale; VAS, visual analogue scale, IL-6 interleukin-6, TNF-a tumor necrosis factor-a, NR not reported.
nystatin 1,00,000 U tetracycline 0.02% lidocaine 0.5%, dexamethasone 0.5%.
Table 2
| Author | Thanasekaran | Kapil | Al-Bayaty | Khalil | Alaaeldin | Hassan | Nedumaran |
|---|---|---|---|---|---|---|---|
| Study design | prospective randomized controlled trial | prospective, randomized controlled trial | andomized, single-blind split-mouth clinical trial | prospective, controlled clinical trial | prospective, controlled clinical trial | triple-blind, parallel-arm, randomized controlled trial, | prospective, controlled clinical study |
| Year | 2025 | 2018 | 2013 | 2019 | 2017 | 2020 | 2026 |
| Country | India | India | Malaysia | Egypt | Egypt | Pakistan | India |
| Participants | 40 patients with peri-implantitis (25–60 years; NR) | 20 patients (40 periodontal sites) with chronic periodontitis (23–61 years; 15 M, 5 F) | 12 M with chronic periodontitis (180 periodontal pockets ≥5 mm) | 48 patients with moderate-to-severe chronic periodontitis (25–58 years) and 20 healthy controls | 48 patients with moderate-to-severe chronic periodontitis (25–58 years) and 20 healthy controls | 50 patients with chronic periodontitis (40 completed; NR) | 30 patients with Stage II Grade A periodontitis (20–55 years; NR) |
| Intervention | mechanical debridement + 0.2% TQ gel (single subgingival application) | SRP + 0.2% TQ gel (subgingival application) | SRP + TQ biodegradable chitosan chip (subgingival insertion) | SRP + 0.1% TQ chitosan gel (subgingival application) | SRP + 0.1% TQ carbopol-poloxamer gel (subgingival application) | SRP + Nigella sativa oil mouthwash | SRP + single application of 0.2% TQ gel |
| Frequency | single application at baseline | four applications (baseline, weeks 2, 3 and 4) | two chip insertions (baseline and day 14) | two applications (immediately after SRP and after 48 h) | two applications (immediately after SRP and after 48 h) | twice daily rinses | single application at baseline |
| TQ/Dose | NR | NR | 0.25 mg/chip | NR | NR | NR | NR |
| Comparator | mechanical debridement alone | SRP alone | SRP alone (control group), SRP + chitosan chip | SRP alone | SRP alone | SRP + normal saline | SRP alone |
| Outcomes | significant within group improvements in PI, GI, PPD and CAL after 3 months in both groups, with greater improvements in the TQ group | significant reductions in PPD, CAL and GCF-ALP levels compared with SRP alone; no significant intergroup differences for PI and GI; no adverse effects reported | significant improvements in PI, BOP, and PPD and CAL with greater improvements in the TQ group compared with the other groups | significant within-group improvements in PI, GI, PPD and CAL at 4 and 12 weeks. Statistical between-group comparison and additional clinical benefit of TQ gel over SRP alone unclear | significant improvements in PI, GI, PPD, CAL, reduced IL-1β levels, and increased TAOC levels in both groups, with superior improvements in the TQ group. | salivary MMP-8 levels decreased in both groups; adjunctive Nigella sativa mouthwash did not provide additional clinical benefit compared with saline. | compared to the control group, GI, PPD, and CAL were significantly more improved after 3 months, as were salivary TOS, TAOC and OSI |
| Follow-up | 3 months | 6 weeks | 60 days | 12 weeks | 12 weeks | 2 weeks | 3 months |
| Overall RoB | some concerns | some concerns | low risk | high risk | high risk | low risk | high risk |
Characteristics of the included studies and overall risk of bias assessment (RoB 2) for peri-implantitis/ periodontitis.
SRP, scaling and root planing; PPD, peri-implant/pocket probing depth; CAL, clinical attachment level; GCF, gingival crevicular fluid; ALP, alkaline phosphatase; OP, bleeding upon probing; TAOC, total antioxidant capacity; TOS, total oxidant status; OSI, oxidative stress index; TQ, thymoquinone; NR, not reported.
The CENTRAL search required particular consideration because it indexed both published articles and trial registry records. Twenty-five clinical records were identified, of which 18 were considered potentially relevant. These comprised five published full-text articles included in the review and 13 trial registry records referring to completed and published, ongoing, completed but unpublished, or otherwise unavailable studies. Seven records did not meet the predefined eligibility criteria. Registry records without an eligible published full-text article available by the final search date were not included in the qualitative synthesis.
3.2 In gingivitis/mucositis
The characteristics of the included clinical studies are summarized in Table 1. Detailed domain-specific RoB 2 assessments and the rationale for the overall judgements are presented in Supplementary Tables S4, S5.
In terms of study design, one of the five gingivitis studies was a triple-blind () and one () a double-blind, parallel-group randomized controlled trial. One study had a split-mouth design () and two studies were randomized (, ), one of them single-blind () (Table 1). All studies were exploratory and none was explicitly designed as a confirmatory efficacy trial. The two mucositis studies (, ) were open-label studies. Thus, considerable heterogeneity was observed in the study design, but also in the Nigella formulations, TQ concentrations, dosages, frequency of application and treatment duration. Four studies used a Nigella mouthwash, two a gel formulation that differed in their galenic and one study used an ethanolic extract in three dilutions with glycerin. The daily dose of TQ has not been reported in any of the studies. The overall risk of bias was some concerns in five of the seven studies, only two studies had a low risk of bias. Detailed domain-specific RoB 2 assessments and their justifications are presented in Supplementary Tables S4, S5. Overall, the evidence for the effectiveness of Nigella sativa preparations in gingivitis and oral mucositis remains limited.
3.3 In peri-implantitis/periodontitis
The study characteristics are summarized in Table 2. Detailed domain-specific RoB 2 assessments and the rationale for the overall judgements are presented in Supplementary Tables S4, S5. One prospective randomized controlled clinical trial investigated patients suffering from peri-implantitis (). Four of the periodontitis studies were prospective controlled clinical trials (30–33) of which only one was randomized (30). One study had a randomized single-blind split-mouth clinical trial design (34) and one was a parallel-arm randomized controlled, triple-blinded trial (35). All studies were exploratory, none was adequately powered for efficacy confirmation. Considerable heterogeneity was observed in the study design, but also in the intervention, the frequency of application, the Nigella sativa preparation, comparator and evaluation period. Five studies used a gel with 0.2% (, 30, 33) or 0.1% (31, 32) of TQ. The galenic gel formulations were, however, not identical. One study inserted chips at baseline and day 14, each containing 0.25 mg of TQ (34) and one study used an uncharacterized Nigella sativa oil mouthwash (35) (Table 2). The daily TQ dose was reported in only one study.
The overall risk of bias in the peri-implantitis study was some concerns. A low risk of bias was found in only two of the periodontitis studies whereas it was worse in the others. Detailed domain-specific RoB 2 assessments and their justifications are presented in Supplementary Tables S4, S5. The evidence of effectiveness of preparations of N. sativa or its leading compound TQ in the treatment of peri-implantitis or periodontitis is currently limited.
4 Discussion
4.1 Clinical evidence current status
Clinical evidence for gingivitis/mucositis is limited to small exploratory trials investigating N. sativa mouthwashes, extract and gels. Across studies, improvements in plaque and gingival indices were observed, with some formulations demonstrating comparable or occasionally superior effects to chlorhexidine in short-term applications (–). However, these findings must be interpreted cautiously. Most earlier studies were characterized by methodological limitations including inadequate reporting of randomization procedures and lack of prospective sample-size calculations. In contrast, the recent trial by Arab Farashahi et al. addressed several of these methodological shortcomings through prospective registration, triple blinding, allocation concealment, intention-to-treat analysis, and an a priori sample-size calculation. Nevertheless, the short follow-up and exploratory sample size still limit definitive conclusions. Overall, the available evidence suggests potential short-term benefits but remains insufficient for clinical recommendations.
In the two gingivitis studies (, ) and the two mucositis studies (, ), Nigella sativa mouthwashes were used; however, none of the studies reported the TQ content in the daily administered dose. Although one group states that the extract was standardized to approximately 1.5% TQ, the analytical method described (Folin–Ciocalteu assay) determines total phenolic content rather than TQ specifically which is best determined by HPLC. Consequently, the reported TQ standardization cannot be independently verified and the actual TQ content of the administered mouthwash remains uncertain. Stating that the mouthwash was prepared from a 20% aqueous extract is insufficient to ensure reproducibility of the study, as the TQ content of Nigella sativa seeds can vary considerably (36), as can the TQ concentration in Ns oils, which we have previously demonstrated (37). The addition of honey and peppermint extract as flavouring agents may have introduced biological confounding, as both possess documented anti-inflammatory and antimicrobial activities (38, 39). The two mucositis studies undertaken by the same group used a commercial mouthwash preparation; however, the manufacturer's website could not be accessed (“Bandwidth Limit Exceeded”), preventing verification of its composition. However, reporting the TQ content of the administered daily dose is essential for planning adequately powered confirmatory studies. Without knowledge of the administered TQ dose, neither dose-response relationships nor clinically meaningful sample size calculations can be established. The remaining three gingivitis studies investigated different gel formulations: a 5% TQ gel incorporated into a novel liposomal drug delivery system (), an ethanolic N. sativa extract formulated with varying glycerin concentrations (), and a lipid-based gel containing 0.1% TQ (). None of these studies specified the amount of TQ delivered per application or per daily dose, limiting reproducibility and comparison across studies. Merely stating that a pea-sized amount () or 1 mL () of gel was administered is not enough. An inconsistency was noted in the publication by Almehmadi et al. (). The intervention was described as a “5% TQ gel”; however, the formulation details indicate a final concentration of 0.2% (20 mg TQ in 10 g gel). Consequently, the actual TQ concentration used in the study is internally inconsistent and the TQ dose per application remains unknown. Consequently, none of these studies provides an adequate basis for planning a confirmatory randomized controlled trial.
A limited number of exploratory clinical trials have investigated TQ as an adjunct to non-surgical periodontal therapy in the treatment of peri-implantitis/ periodontitis (–35). These studies generally report improvements in clinical parameters, including probing depth, plaque index, gingival index, and clinical attachment level. Despite consistent directional trends, considerable heterogeneity exists regarding study design, formulation, dosing regimens, and outcome assessment. For example, three periodontitis studies evaluated a gel containing 0.2% TQ in carbopol (, 30, 33) but did not report the amount of TQ applied per dose. Khalil investigated a TQ-loaded chitosan gel, Al-Bayaty used TQ-containing chitosan chips. Whereas Khalil did not provide the TQ content per gel application, the chips used by the Al-Bayaty group contained 0.25 mg TQ. This is the only study that provides sufficient information to permit independent replication. An important limitation of the study by Hassan et al. is the lack of characterization of the Nigella sativa oil. Neither TQ concentration nor any standardization or phytochemical analysis was reported. Since commercially available Nigella sativa oils may differ considerably in their TQ content (37), the administered dose of the presumed active constituent remains unknown, which limits interpretation and comparison with other studies.
Because the study medications were insufficiently characterized, six of the seven peri-implantitis/periodontitis trials cannot serve as an adequate basis for planning a confirmatory trial. The only trial using chips with 0.25 mg TQ can be considered a pilot study (34). Although no a priori sample size calculation was reported, a retrospective estimation suggests that the study was likely adequately powered to detect the relatively large difference observed between the TQ chip and SRP alone. However, it was probably underpowered to detect the smaller difference between the TQ and chitosan chips. Based on the observed CAL difference of 0.51 mm between the TQ chip and SRP alone, approximately 13 and 17 evaluable patients would have been required to achieve 80% and 90% power, respectively, assuming a standard deviation of the paired differences of 0.60 mm (two-sided α = 0.05). As the variance of the paired differences was not reported, these estimates should be interpreted with caution and no firm conclusions regarding sample-size requirements can be drawn. Thus, clinical evidence for peri-implantitis/periodontitis remains preliminary and does not allow firm conclusions regarding efficacy.
Taken together, based on current evidence, preparations of N. sativa or TQ cannot be recommended as replacements for established therapies of gingivitis, mucositis, peri-implantitis and periodontitis. Their use should currently be considered experimental, with potential as adjunctive agents pending further clinical validation.
4.2 Experimental and mechanistic evidence
A substantial body of preclinical research supports the biological plausibility of N. sativa and TQ in periodontal therapy.
4.2.1 Anti-inflammatory and wound-healing effects
Animal studies demonstrate that N. sativa and TQ reduce pro-inflammatory mediators, including TNF-α, PGE-2, and matrix metalloproteinases, in animal models of oral inflammation and mucosal injury (40–46). Additionally, enhanced epithelialization, reduced oxidative stress, and improved tissue repair have been reported.
4.2.2 Antimicrobial and antibiofilm activity
TQ exhibits inhibitory effects against key periodontal pathogens, including Porphyromonas gingivalis and Fusobacterium nucleatum, and significantly reduces biofilm formation in vitro (47–49). Broad-spectrum antimicrobial activity has been demonstrated against both bacterial and fungal species relevant to oral health (50, 51).
4.2.3 Modulation of microbial interactions and resistance mechanisms
Experimental evidence suggests that TQ interferes with microbial virulence factors and polymicrobial interactions, including bacterial–fungal synergism (52). Additional studies indicate potential antimicrobial resistance-modulating effects, including plasmid curing and restoration of antibiotic sensitivity (53).
4.2.4 Effects on bone metabolism
Preclinical studies further suggest that TQ may reduce alveolar bone loss in experimental periodontitis models, indicating potential modulation of host tissue responses (54–56).
5 Conclusions
The current evidence for the clinical efficacy of Nigella sativa and TQ in gingival and periodontal therapy remains insufficient despite encouraging preliminary findings. Experimental data consistently support plausible anti-inflammatory, antimicrobial, and regenerative effects.
Future confirmatory randomized controlled trials are needed to determine effect sizes, optimize TQ-standardized formulations, and assess long-term adjunctive utility in gingivitis, mucositis, peri-implantitis and periodontitis.
Statements
Author contributions
SC-H: Conceptualization, Writing – review & editing, Writing – original draft, Data curation. JV: Writing – review & editing, Data curation. MW: Writing – review & editing. FC: Writing – review & editing. AA-A: Supervision, Data curation, Writing – review & editing.
Funding
The author(s) declared that financial support was not received for this work and/or its publication.
Acknowledgments
The authors sincerely thank Kamila Winsauer (Bregenz, Austria) for her valuable contribution to the early development of this manuscript.
Conflict of interest
SC-H has received consultancy fees from Alpinamed (Switzerland) and Biolaviva (Germany). The preparation, conduct, and reporting of this systematic review were independent of these companies. Neither company influenced the design, analysis, interpretation, or conclusions of the review, nor will they derive any direct benefit from its findings.
The remaining author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
The author FC declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
Generative AI statement
The author(s) declared that generative AI was not used in the creation of this manuscript.
Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.
Publisher’s note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
Supplementary material
The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/froh.2026.1875959/full#supplementary-material
References
1.
GravesDTCorrêaJDSilvaTA. The oral microbiota is modified by systemic diseases. J Dent Res. (2019) 98(2):148–56. 10.1177/0022034518805739
2.
HajishengallisG. Interconnection of periodontal disease and comorbidities: evidence, mechanisms, and implications. Periodontol 2000. (2022) 89(1):9–18. 10.1111/prd.12430
3.
MaitreYMahalliRMicheneauPDelpierreAAmadorGDenisF. Evidence and therapeutic perspectives in the relationship between the oral microbiome and Alzheimer's Disease: a systematic review. Int J Environ Res Public Health. (2021) 18(21):11157. 10.3390/ijerph182111157
4.
ChappleILCVan der WeijdenFDoerferCHerreraDShapiraLPolakDet al. Primary prevention of periodontitis: managing gingivitis. J Clin Periodontol. (2015) 42:S71–6. 10.1111/jcpe.12366
5.
HerreraDTonettiMSChappleIKebschullMPapapanouPNSculeanAet al. Consensus report of the 20th European workshop on periodontology: contemporary and emerging technologies in periodontal diagnosis. J Clin Periodontol. (2025) 52:4–33. 10.1111/jcpe.14152
6.
LasserreJFBrecxMCTomaS. Oral microbes, biofilms and their role in periodontal and peri-implant diseases. Materials (Basel). (2018) 11(10):1802. 10.3390/ma11101802
7.
SanzMHerreraDKebschullMChappleIJepsenSBerglundhTet al. Treatment of stage I–III periodontitis—the EFP S3 level clinical practice guideline. J Clin Periodontol. (2020) 47:4–60. 10.1111/jcpe.13290
8.
SuvanJLeiraYMoreno SanchoFMGrazianiFDerksJTomasiC. Subgingival instrumentation for treatment of periodontitis. A systematic review. J Clin Periodontol. (2020) 47:155–75. 10.1111/jcpe.13245
9.
LoosBGNeedlemanI. Endpoints of active periodontal therapy. J Clin Periodontol. (2020) 47:61–71. 10.1111/jcpe.13253
10.
GebreyohannesGNyerereABiiCSbhatuDB. Challenges of intervention, treatment, and antibiotic resistance of biofilm-forming microorganisms. Heliyon. (2019) 5(8):e02192. 10.1016/j.heliyon.2019.e02192
11.
JakubovicsNSGoodmanSDMashburn-WarrenLStaffordGPCieplikF. The dental plaque biofilm matrix. Periodontol 2000. (2021) 86(1):32–56. 10.1111/prd.12361
12.
HaqueMMYerexKKelekis-CholakisADuanK. Advances in novel therapeutic approaches for periodontal diseases. BMC Oral Health. (2022) 22(1):492. 10.1186/s12903-022-02530-6
13.
da CostaLFNPAmaralCDSFBarbiratoDDSLeãoATTFogacciMF. Chlorhexidine mouthwash as an adjunct to mechanical therapy in chronic periodontitis: a meta-analysis. J Am Dent Assoc. (2017) 148(5):308–18. 10.1016/j.adaj.2017.01.021
14.
BartschSKohnertEKreutzCWoelberJPAndersonABurkhardtA-Set al. Chlorhexidine digluconate mouthwash alters the oral microbial composition and affects the prevalence of antimicrobial resistance genes. Front Microbiol. (2024) 15:1429692. 10.3389/fmicb.2024.1429692
15.
McCoyLCWehlerCJRichSEGarciaRIMillerDRJonesJA. Adverse events associated with chlorhexidine use: results from the department of veterans affairs dental diabetes study. J Am Dent Assoc. (2008) 139(2):178–83. 10.14219/jada.archive.2008.0134
16.
RaniNSinglaRKNarwalSTanushreeKumarNRahmanMM. Medicinal plants used as an alternative to treat gingivitis and periodontitis. Evid Based Complement Alternat Med. (2022) 2022:2327641–14. 10.1155/2022/2327641
17.
AbbasMGururaniMAAliABajwaSHassanRBatoolSWet al. Antimicrobial properties and therapeutic potential of bioactive compounds in Nigella sativa. A Review. Molecules. (2024) 29(20):4914. 10.3390/molecules29204914
18.
AlAttasSAFat'heyaMZTurkistanySA. Nigella sativa and its active constituent thymoquinone in oral health. Saudi Med J. (2016) 37(3):235–44. 10.15537/smj.2016.3.13006
19.
KurniaDPadilahRApriyantiEDharsonoHDA. Phytochemical analysis and anti-biofilm potential that cause dental caries from black cumin seeds (Nigella sativa Linn.). Drug Des Devel Ther. (2024) 18:1917–32. 10.2147/DDDT.S454217
20.
MekhemarMHassanYDörferC. Nigella sativa and thymoquinone: a natural blessing for periodontal therapy. Antioxidant. (2020) 9(12):1260. 10.3390/antiox9121260
21.
PageMJMcKenzieJEBossuytPMBoutronIHoffmannTCMulrowCDet al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Br Med J. (2021) 372:71. 10.1136/bmj.n71
22.
Arab FarashahiMVaziriFRamezaniVMoradiSZareshahiR. Comparative efficacy of Nigella sativa and chlorhexidine mouthwashes in the management of gingivitis: a randomized controlled trial. J Integr Complement Med. (2025):32:277–83. 10.1177/27683605251406898
23.
IlangovanSRajasekarA. Evaluation of efficacy of 20% nigella sativa on gingival health. J Pharm Res Int. (2021) 33(61A):354–63. 10.9734/jpri/2021/v33i61A35595
24.
SinghVGuptaAVermaUPMishraTPalM. An evaluation of the efficacy of ethanolic extract of Nigella sativa L.(Kalonji) on the clinical parameters of moderate-to-severe gingivitis: a split-mouth clinical study. AYU. (2019) 40(3):152–58. 10.4103/ayu.AYU_68_18
25.
KhanSYAhmadI. Clinical efficacy of a novel lipid-based thymoquinone gel: a two-arm, single-blinded, and randomized study. J Int Soc Prev Community Dent. (2021) 11(4):376–81. 10.4103/jispcd.JISPCD_49_21
26.
AlmehmadiAHAljohaniK. An assessment of the clinical efficacy of a topical application of 5% thymoquinone gel for plaque-induced gingivitis patients: a randomized controlled clinical trial. Healthcare (Basel). (2024) 12(18):1898. 10.3390/healthcare12181898
27.
AmeenHMohammedMOAhmedKMAliRSaeedKAHussainSA. Anti-inflammatory effect of Nigella sativa oil on chemoradiation-induced oral mucositis in patients with head and neck cancers. Int J Curr Pharm Res. (2019) 11(5):58–64. 10.22159/ijcpr.2019v11i5.35704
28.
HussainSAMohammed AmeenHAMohammedMOAhmedKMHama-Gareb AliRSafarBMet al. Nigella sativa oil mouth rinse improves chemotherapy-induced oral mucositis in patients with acute myeloid leukemia. Biomed Res Int. (2019) 2019:3619357–10. 10.1155/2019/3619357
29.
ThanasekaranARajasekarA. Therapeutic potential of thymoquinone in conjunction with mechanical debridement for peri-implantitis: a prospective clinical evaluation. J Long Term Eff Med Implants. (2025) 35(3):37–43. 10.1615/JLongTermEffMedImplants.2025058363
30.
KapilHSureshDBathlaSCAroraKS. Assessment of clinical efficacy of locally delivered 0.2% thymoquinone gel in the treatment of periodontitis. Saudi Dent J. (2018) 30(4):348–54. 10.1016/j.sdentj.2018.06.001
31.
KhalilAAlaaeldinE. Clinical and biochemical evaluation of thymoquinone gel in the treatment of chronic periodontitis. Int J Adv Res. (2019) 7(4):83–93. 10.21474/IJAR01/8794
32.
AlaaedinEGomaaMDEltewacyNKAliAKhalilA. Formulation and characterization of thymoquinone bioadhesive gel for treatment of chronic gum inflammation. Int J Sci Basic Appl Res. (2017) 31(2):321–30. Available online at: https://gssrr.org/JournalOfBasicAndApplied/article/view/10554
33.
NedumaranNRajasekarA. Therapeutic potential of thymoquinone gel in stage II grade A periodontitis: a prospective clinical and biochemical evaluation. Dental J. (Majalah Kedokteran Gigi). (2026) 59(2):172–7. 10.20473/j.djmkg.v59.i2.p172-177
34.
Al-BayatyFHKamaruddinAAIsmailMAAbdullaMA. Formulation and evaluation of a new biodegradable periodontal chip containing thymoquinone in a chitosan base for the management of chronic periodontitis. J Nanomater. (2013) 2013(1):397308. 10.1155/2013/397308
35.
HassanGGhafoorSChaudhrySKhanZA. Salivary interleukin-1 levels in chronic periodontitis patients after use of Nigella sativa (Kalonji) oil. J Pak Dent Assoc. (2020) 29(4):205–8. 10.25301/JPDA.294.205
36.
RaviYVethamoniIPSaxenaSNVelmuruganSSantanakrishnanVPRaveendranMet al. Guesstimate of thymoquinone diversity in Nigella sativa L. genotypes and elite varieties collected from Indian states using HPTLC technique. Open Life Sci. (2023) 18(1):20220536. 10.1515/biol-2022-0536
37.
KhaikinEChrubasik-HausmannSKayaSZimmermannBF. Screening of thymoquinone content in commercial Nigella sativa products to identify a promising and safe study medication. Nutrients. (2022) 14(17):3501. 10.3390/nu14173501
38.
StavropoulouEIeronymakiEDimitrouliaEConstantinidisTCVrioniGTsatsanisCet al. Anti-Inflammatory and antibacterial effects and mode of action of Greek arbutus, chestnut, and fir honey in mouse models of inflammation and sepsis. Microorganisms. (2022) 10(12):2374. 10.3390/microorganisms10122374
39.
ZhaoHRenSYangHTangSGuoCLiuMet al. Peppermint essential oil: its phytochemistry, biological activity, pharmacological effect and application. Biomed Pharmacother. (2022) 154:113559. 10.1016/j.biopha.2022.113559
40.
LotfyAZayedM. Immunohistochemical study of the effect of Nigella sativa L extract on chemotherapy induced oral mucositis in albino rats. Cairo Dent J. (2009) 25(2):159–66.
41.
Al-DouriASAl-kazazSGA. The effect of Nigella sativa oil (black seed) on the healing of chemically in-duced oral ulcer in rabbit (experimental study). Al-Rafidain Dent J. (2010) 10(1):151–57. 10.33899/rden.2010.45402
42.
KazemiSMoghadamniaAASaebnouriHRoudsariSHTAfrazES. Effect of intraperitoneal injection of Nigella sativa oil on 5-fluorouracil-induced oral mucositis in rats. J Biol Stud. (2022) 5(01):1–13. 10.62400/jbs.v5i1.6365
43.
BakhtiariSMashhadiabbasFKalaniFRoudsariSSTAfrazES. Histopathological efficacy of Nigella sativa oil for prevention of 5-fluorouracil-induced mucositis in rats. J Pharm Negat Results. (2023) 14(02):274–85. 10.47750/pnr.2023.14.02.34
44.
EğilmezOKKöktenNKalcıoğluMTEkiciAIDŞeriflerSYeşiladaE. Investigation of the protective effect of Nigella sativa oil in cisplatin-induced oral mucositis: an experimental study. Turk Arch Otorhinolaryngol. (2020) 58(1):10–5. 10.5152/tao.2020.4733
45.
MadaniFKazemiSShirafkanFLotfiMHosseiniSMMoghadamniaAA. Thymoquinone protects against 5-fluorouracil-induced mucositis by NF-κβ and HIF-1 mechanisms in mice. J Biochem Mol Toxicol. (2023) 37(9):e23405. 10.1002/jbt.23405
46.
TabaruARüzgarS. Efficacy of topical Nigella sativa oil for oral wound healing in rats. Laryngoscope Investig Otolaryngol. (2025) 10(3):e70153. 10.1002/lio2.70153
47.
TadaANakayama-ImaohjiHYamasakiHElahiMNagaoTYagiHet al. Effect of thymoquinone on Fusobacterium nucleatum-associated biofilm and inflammation. Mol Med Rep. (2020) 22(2):643–50. 10.3892/mmr.2020.11136
48.
MaduratnaESariDSRahayuRPMasyaRNAdinarN. The anti-inflammatory effect of Nigella sativa toothpaste on porphyromonas gingiv.alis Bacteria through decreased TNF-α, MMP-9, PGE-2 expression in Wistar rats. Eur J Dent. (2024) 18(3):808–14. 10.1055/s-0043-1772700
49.
TawfigA. The effect of Nigella sativa extracts against Porphyromonas gingivalis isolated from periodontitis patients. Eur Rev Med Pharmacol Sci. (2023) (21):27.
50.
BhavikattiSKZainuddinSLARamliRBNadafSJDandgePBKhalateMet al. Insights into the antioxidant, anti-inflammatory and anti-microbial potential of Nigella sativa essential oil against oral pathogens. Sci Rep. (2024) 14(1):11878. 10.1038/s41598-024-62915-1
51.
KiariFZMeddahBMeddahATT. In vitro study on the activity of essential oil and methanolic extract from Algerian Nigella sativa L. Seeds on the growth kinetics of micro-organisms isolated from the buccal cavities of periodontal patients. Saudi Med J. (2018) 30(4):312–23. 10.1016/j.sdentj.2018.05.011
52.
TantivitayakulPKaypetchRMuadchiengkaT. Thymoquinone inhibits biofilm formation and virulence properties of periodontal bacteria. Arch Oral Biol. (2020) 115:104744. 10.1016/j.archoralbio.2020.104744
53.
AhmadAAMAbdelwahabAMOFawzyEKhamisTAbdelmoneimMEl-HamidAet al. Novel plasmid curing mediated restoration of antimicrobial sensitivity by Nigella sativa extract against multidrug resistant Staphylococcus aureus. Sci Rep. (2026) 16(1):2611. 10.1038/s41598-025-33667-3
54.
OzdemirHKaraMErciyasKOzerHAyS. Preventive effects of thymoquinone in a rat periodontitis model: a morphometric and histopathological study. J Periodontal Res. (2012) 47(1):74–80. 10.1111/j.1600-0765.2011.01406.x
55.
SetiawatieEMGaniMARahayuRPUlfahNKurniaSAugustinaEFet al. Nigella sativa toothpaste promotes anti-inflammatory and anti-destructive effects in a rat model of periodontitis. Arch Oral Biol. (2022) 137:105396. 10.1016/j.archoralbio.2022.105396
56.
ThummuriDJeengarMKShrivastavaSNemaniHRamavatRNChaudhariPet al. Thymoquinone prevents RANKL-induced osteoclastogenesis activation and osteolysis in an in vivo model of inflammation by suppressing NF-KB and MAPK signalling. Pharmacol Res. (2015) 99:63–73. 10.1016/j.phrs.2015.05.006
Summary
Keywords
adjunctive therapy, black seed, evidence of effectiveness, gingivitis, Nigella sativa, oral diseases, peri-implantitis, periodontitis
Citation
Chrubasik-Hausmann S, Vlachojannis J, Wolf M, Cieplik F and Al-Ahmad A (2026) Preliminary evidence of effectiveness of preparations from Nigella sativa and its leading compound thymoquinone in periodontal therapy. Front. Oral Health 7:1875959. doi: 10.3389/froh.2026.1875959
Received
08 May 2026
Revised
07 August 2026
Accepted
17 August 2026
Published
28 August 2026
Volume
7 - 2026
Edited by
Muhammad Saad Shaikh, Jinnah Sindh Medical University, Pakistan
Reviewed by
Sebastián Castro Saavedra, University of Santiago, Chile
Zarrin Sarhadynejad, Kerman University of Medical Sciences, Iran
Updates
Copyright
© 2026 Chrubasik-Hausmann, Vlachojannis, Wolf, Cieplik and Al-Ahmad.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Sigrun Chrubasik-Hausmann sigrun.chrubasik@klinikum.uni-freiburg.de
Disclaimer
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.