Table 3.

Main studies in relation to thymoquinone (TQ) and Nigella sativa (NS) of interest in periodontal disease.

Compound	Study Type	Sample Studied, n	Adminitration (Dosage, Frecuency and Duration)	Main Effects	Reference
TQ	RCT	Systemic healthy periodontitis male and female patients with at least 2 periodontally involved sites (≥5 mm), n = 20	0.2% TQ topical (intra-pocket) oral gel; repeated every week beginning from baseline up to 4 weeks.	Significant decrease in PPD, GCF-ALP levels and rise in CAL Antibacterial effect of TQ against against P. gingivalis, A. actinomycetemcomitans and P. intermedia	[62]
TQ	RCT	Systemic healthy chronic periodontitis male and female patients (25–58 years) with at least 10 periodontally involved sites (≥5 mm), n = 48	0.1% TQ topical (intra-pocket) oral gel; immediately after accomplishment of SRP. The gel was applied again after 48 h and the gel applied sites were covered with a periodontal pack for 7 days. Results were recorded at baseline and at weeks 4 and 12 after treatment.	Significant improvement in PI, GI, PPD, CAL Significant improvement in the levels of IL-1β and TAOC	[63]
TQ	RCT	Systemic healthy chronic periodontitis male patients (35–56 years) with at least 4 periodontally involved sites (≥5 mm), n = 12	Biodegradable chitosan subgingival periodontal chip with integrated 0.25 mg TQ with second chip insertion at day 14. Results were recorded at day 14 and 60 of the trial.	Significant gains in CAL	[65]
TQ	Animal	Male Wistar rats with ligature-induced periodontal inflammation (300 ± 10 g), n = 8	Systemic intragastric (10 mg/kg, daily for 11 days)	Significant reduction of alveolar bone loss and inflammatory cell infiltration Maintenance of osteoblastic activity	[66]
TQ	Animal	Male Fisher rats (21 days old), n = 16	0.2% TQ topical oral gel and systemic administration in drinking water. The oral gel was applied daily over gingiva and the drinking water was changed 3 times a week. Outcomes were measured at day 1, 7 and 35.	Significant reduction in BOP, PI in rats that received TQ as oral gel or systemically Less evident signs of gingivitis and periodontitis histologically in TQ treated rats Antibacterial effect of TQ against subgingival bacteria	[64]
TQ	In vitro	Bacterial strains of Fusobacterium nucleatum ATCC25586 (FN), Actinomyces naeslundii X600 (AN) and Streptococcus mitis ATCC 903 (SM)	0.1%, 0.01% and 0.05% TQ reagents were added to bacterial formed biofilms and incubated for 24 h and for 30 min	Inhibitory effect of 0.1% TQ on FN-containing biofilm Significantly decreased biofilm formation of FN pretreated with 0.01% TQ Significant cleansing effect of 0.01% and 0.05% TQ on FN-containing biofilm	[67]
TQ	In vitro	Bacterial strains of Fusobacterium nucleatum ATCC 25586 (FN) and Porphyromonas gingivalis A7436 (PG)	10% TQ reagent was added to bacterial formed biofilms and incubated for 48 h	The minimum inhibitory concentration (MIC) of TQ was 12.5 and 1.56 μg/mL in FN and PG, respectively. Sub-MIC concentrations of TQ prevented biofilm formation, hemolysis activities and H2S generation of FN and PG and TQ disintegrated bacterial membranes and reduced the expression of virulence factors in FN and PG	[68]
NS	In vitro	Twelve gram-positive and eleven Gram-negative bacterial strains, including Staphylococcus aureus, Enterococcus faecalis, Staphylococcus epidermidis, Porphyromonas sp., Proteus sp., Streptococcus pneumoniae, Klebsiella pneumoniae, Acinetobacter baumannii/calcoaceticus and Veillonella sp., isolated from supra- and subgingival plaque of periodontal patients	Methanol and essential oil solutions of NS 2% ±0.35 dry extract were added to the isolated bacteria in microdilution test and Agar well diffusion assay	Antibacterial effect of the essential oil and less efficiency of the methanol against all tested bacteria	[69]

PPD: Probing pocket depth; GCF-ALP: Gingival crevicular fluid alkaline phosphatase; CAL: Clinical attachment level; SRP: Scaling and root planning; PI: Plaque index; GI: Gingival index; TAOC: Total antioxidant capacity; FN: Fusobacterium nucleatum; AN: Actinomyces naeslundii; PG: Porphyromonas gingivalis.