The Impact of Nigella sativa on Oral Health: A Scoping Review

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Abstract

Introduction:

Nigella sativa (NS) has been shown to improve periodontal health by reducing alveolar bone resorption and lowering periodontal indices and subgingival bacterial counts. However, public health and safety concerns are emerging, and there have been a few reported adverse effects associated with the use of NS. Thus , the current study aims to review clinical studies on the effectiveness NS for oral health conditions.

Methods:

The databases Pubmed and Google Scholar were used to search the literature ; t he year of publication was not restricted in the search. Studies conducted in animal models in laboratories , as well as those involving an intervention of NS in combination with other herbs , were excluded.

Results:

A total of thirteen human clinical studies that used NS as an intervention for treating different types of oral health conditions were included in this review. Improvement in clinical parameters was reported in all the included studies , although the statistical significance varied.

Conclusion:

Although the studies show that NS is beneficial in the treatment and management of oral health conditions, there is still a need for more rigorous research in this area, particularly in the application of NS in real-world clinical settings.

Keywords: Nigella sativa, Oral Health, Periodontal

Introduction

Specific to oral health, the application of TQ to oral tissues was found to control dental caries, retard the expansion of oral ulcers, induce bone formation in sockets of extracted teeth, promote apoptosis in human cancer cells, maintain pulp vitality, and stimulate healing and periodontal regeneration (10). Concerning the effect of NS on periodontal health, it has been shown to lessen alveolar bone resorption, and lower periodontal indices and sub-gingival bacterial counts (10).

exclusion criteria. Finally, 13 studies were included in this review. The complete process is outlined in the PRISMA flow diagram ( Figure 1 ).

A total of 13 clinical studies were identified that used NS as an intervention to treat various oral health conditions (19-31). Table 1 provides an overview of all these studies. The oral health conditions that were aimed to be treated included chronic periodontitis (22, 25-30), gingivitis (19, 23, 24), osseointegration of delayed implant (21), alveolar osteitis (31), and chemotherapy-induced oral mucositis (20).

Notwithstanding the benefits of herbal medicines, public health issues and safety concerns are also becoming evident in this regard (14), and there have been some reported adverse effects related to the use of NS. For instance, functional dyspeptic patients have reported nausea, bloating, and a burning sensation after taking NS oil, as well as a slight increase in liver and kidney enzyme markers after its consumption (15). This warrants the need for stringent clinical trials to assess the efficacy and safety of herbal medicinal products (16). Moreover, it is imperative to note that most of the studies related to the effects of NS on oral health have been conducted in animal models (17, 18). Recently, efforts have been made to study the effect of NS on

Improvement in clinical parameters was reported in all the included studies, although the statistical significance varied. The majority of the articles identified dealt with periodontitis (n=7). Elamrousy (28) evaluated the clinical, immunological, and mi the local crobiological effectiveness of

with grade C subjects gel in application of TQ periodontitis and found that at 8 weeks postoperative period, the treatment group showed a significant reduction in probing pocket depth, relative attachment level (RAL), matrix metallo- proteniease-8 (MMP- concentration 8) in gingival crevicular fluid, and Aggregatibacter actinomycetemcomitans count in subgingival plaque samples when compared with the placebo group (all p<0.05). Al-Bayaty et al. (26) investigated the effectiveness of a periodontal chip containing TQ in a chitosan base for the management of chronic periodontitis and reported a statistically significant improvement in plaque index (PI) and bleeding on probing (BOP) in both the TQ group and the group receiving chitosan chip (p<0.05). A the plain significant decrease in periodontal pockets compared with baseline was observed in all three groups (TQ, chitosan, control). Regarding clinical

the present human subjects; thus, study to aims review the clinical studies related to the effectiveness of using NS for oral health conditions.

Materials and Methods

The literature was searched using the PubMed and Google Scholar databases based on PICO clinical questions. There was no restriction on the year of publication. The search terms used were “oral health”, “dental health”, “Nigella sativa”, “thymoquinone”, “gingivitis”, “periodontitis”, “caries”, and “pulp treatment”.

All human clinical studies published in the English language that assessed the effects of NS or TQ, in any form, on oral health conditions were included. Review articles, studies conducted in laboratories in animal models, and those that consisted of an intervention of NS in combination with other herbs were excluded. Articles without a full text were also excluded.

showed group the TQ attachment levels, significantly greater improvement than the other groups (p<0.05). A study by Khalil and Alaaeldin (27) examined the effect of TQ gel on clinical periodontal parameters (PI, gingival index (GI), probing depth, and clinical attachment level) and reported a statistically significant improvement, compared with the baseline, in both group I,

After found. were A total of 1372 articles eliminating duplication, titles and abstracts were screened following the study’s inclusion and

Results

Figure. 1. PRISMA flow chart of included studies

(scaling and root planing (SRP) and TQ) and group II (SRP only) after weeks 4 and 12 (p<0.0001). Although group I showed more clinical improvement than group II, the difference was not statistically significant. Regarding biochemical parameters, significant improvement in group I was identified after 4 weeks compared with group II. Hassan and coworkers published three studies on this subject (22, 29, 30). The first examined the level of salivary MMP-8, and reported that the mean concentration of salivary MMP-8 in the NS treatment group decreased from 199.37 ± 300.75 ng/l to 114.17 ± 129.21 ng/l, although the reduction was statistically non-significant (22). The second article aimed to determine the change in salivary interleukin-1 β and found no significant change in the levels after the use of NS oil (30). The third study examined the effect of NS oil-based mouth- wash on clinical periodontal parameters such as periodontal pocket depth (PPD), clinical attachment loss (CAL), PI, and BOP, and reported a statistically significant difference in all the parameters, both in the NS oil mouthwash group and the control group, although the difference in improvement between the groups was not significant (29). Kapil et al. (25) reported a comparison between the treatment group that received 0.2% TQ along with SRP and the control group (SRP only). The former showed a significant reduction in PPD (p=0.018), GCF-ALP levels (p=0.048), and a rise in RAL (p=0.018) but no statistically significant differences were observed in PI and GI at 6 weeks.

day and 0–28th day, as well as to significantly lower GI (p=0.005) during the 0–14th day and the 0–28th day (p<0.001) as compared with CHX gel. The impact of NS gel on the osseointegration of delayed dental implants was evaluated by Ahmed et al. (21), who reported that in both treatment and control groups, there was a non-significant difference in the modified gingival index and

6 months follow up. at 3 and probing depth However, the treatment group showed a highly significant increase in bone density after 6 months in comparison with the control group.

One study, (31), al. et by Khan carried out

NS a evaluation of comparative conducted a

the Alvogyl in and oil mixture with powder treatment of alveolar osteitis, or dry sockets, in patients who had undergone tooth extraction and reported that the NS treatment group showed a significant difference in pain relief compared with the Alvogyl group (p=0.031) and the control group that was given a normal saline rinse (p=0.001).

The effect of NS on chemotherapy-induced oral mucositis (OM) was studied by Hussain et al. (20) who reported that, compared with the control formula, NS oil mouth rinse significantly decreased erythema and ulceration scores (AUC of total OMAS=11.4 vs. 85.9, p<0.001). Moreover, it significantly reduced salivary IL-6 (AUC=7376 vs. 16599, p<0.001), while the changes in TNF-α levels were not significant (AUC=676.9 vs. 885.2, p>0.05).

All the included studies were limited in being short-term (ranging between 7 days to 6 months) and having small sample sizes (ranging between 12- 60 participants). Double blinding was reported in only six studies (22, 23, 28-31), and only one study was multi-sited (25). One of the studies included only female participants (23) and another only male (26). Three studies reported a high loss of follow-up (22).

Concerning the treatment of gingivitis, Singh et al. (19) Demonstrated that topically applied ethanolic

3:1 significantly ratio of NS in the solution of reduced GI (p<0.001; F value 153.75) and PI (p<0.001, F value 30.40). Treatment at a ratio of 1:3 and 1:1 did not show a significant reduction. Rahman et al. (23) reported that both NS oil and the gold standard chlorhexidine (CHX) significantly reduced GI and PI scores (p<0.0001), as well as significantly decreasing colony-forming units (p<0.0001). However, compared with CHX, NS is better at lowering gingival IL-6 (p =0.0076 vs p=0.145), while neither CHX NS (p=0.284) nor (p=0.418) reduced IL-18 levels. Similarly, Khan and Ahmad (24) also confirmed the clinical efficacy of a thymoquinone gel to significantly reduce PI in comparison to CHX (p<0.001) during the 0–14th

The current review explored the potential impact of NS on oral health. Thirteen clinical studies involving human subjects were included. Generally

indicated a speaking, all studies potentially beneficial effect of NS in reducing symptoms related to the different oral health conditions under investigation; however, the statistical significance of the effect varied.

Discussion

A significant decrease in the gingival index and plaque index was reported in two studies related to the treatment of gingivitis (19, 23) and two studies related to the treatment of periodontitis (26, 27). However, one study reported no significant difference in PI and GI on treatment with TQ in patients with periodontitis (25). Thus, further clinical studies are required to examine the role of NS in reducing PI and GI.

due to cisplatin-induced pro-inflammatory cytokines (35). Taken together, these findings underpin the potentially potent role of NS in preventing painful symptoms of chemotherapy-induced oral mucositis. Several recent studies have suggested a correlation between periodontitis and chronic systemic diseases such as type 2 diabetes mellitus and cardiovascular disease (36). Most of the clinical studies included in this review consisted of systemically healthy partic in the of NS effect ipants. Thus, the exact treatment with patients among of periodontitis chronic con and ditions such as diabetes cardiovascular disease remains unclear.

Interleukin (IL)- be levels were found to 6 in study participants significantly lowered with gingivitis (23) and chemotherapy-induced oral mucositis (20) on treatment with NS. This finding aligns with previous studies that established the anti-inflammatory property of TQ in hindering the production of IL 6 (32). Concerning IL-18, NS oil

It is worth mentioning that all the clinical studies included in this review were generally short- duration studies and had small sample sizes. It is recommended that future studies in this direction include robust methodology in terms of long-term follow-up, large sample size, and double blinding.

gingival produced no significant reduction in crevicular IL-18 levels in the clinical study by Rahman et al. (23). Since IL- 18 is known to have chemotactic, pro- angiogenic and inflammatory, may it play a role properties, in inflammation progression (33). Moreover, persistent gingival inflammation may be linked to IL- 18 accumulation in periodontal tissues (34). With regard to IL-1 β levels among patients with chronic periodontitis, no significant change in the levels of salivary IL-1 β in either the NS treatment group or the placebo group was reported by Hassan et al. (30). In contrast, Khalil and Alaaeldin (27) reported a significant reduction in IL-1 β levels from baseline to 4 weeks post-treatment (230.49± 24.73 (pg/μl) vs 153.26 ± 27.31 (pg/μl), respectively).

In conclusion, this review summarises the currently available research regarding the effect of NS on oral health. Although, in general, the studies indicate the beneficial role of NS in the treatment and management of oral health conditions such as gingivitis, periodontitis, osseointegration of de- layed implants, alveolar osteitis, and chemotherapy- induced oral mucositis, there remains a need for further vigorous studies in this area, particularly in relation to the application of NS in real-world clinical settings.

The use of NS oil for lowering chemotherapy- induced side effects such as oral mucositis in cancer patients has shown a significant reduction in erythema and ulceration scores (p<0.001) (20). This was confirmed earlier in an animal-model study that examined the effect of NS on cis- diamminedichloroplatinum (Cis) induced oral mucositis in rats (35). It was found that, compared with rats given only Cis (Group 1), rats fed Cis plus NS oil (Group 2) had less inflammatory cell infiltration, vascular dilatation, superficial erosion, and exudates. Additionally, Group 2 had similar results to the control groups (Groups 3 and 4). It was speculated that the anti-inflammatory, antioxidant and cytoprotective actions may be the mechanism by which NS oil prevents oral mucositis

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Table 1. Human-based studies related to the impact of Nigella sativa on oral health

Study Design Duratio	Patient	Aim/Outcome Measure	Methods	Key Findings	Clinical Significance
& Setting n	of Group
Study
Clinical study 8 weeks	26 subjects	To evaluate the efficacy	Random assignment of	At the 8-week evaluation point,	TQ gel shows favourable outcomes
Kafrelsheikh,	with grade C	of local	the involved sites to	the TQ group showed a	when used as an adjunct to
Egypt	periodontitis	application of TQ gel.	either the TQ group (30	significant decrease in PPD,	nonsurgical periodontal therapy in
		The parameters	sites) or the placebo	RAL, MMP-8 levels in GCF,	subjects with grade C periodontitis.
		investigated included:	group (30 sites). In the	and A.a count in subgingival
		probing pocket depth	TQ group, sites were	plaque samples when compared
		(PPD), relative	treated with SRP	with the placebo group (all p
		attachment level (RAL),	followed by 0.2% TQ	values <0.05).
		matrix metallo-	topical (intra-pocket)
		proteinase-8 (MMP8)	gel, while in the
		concentration in	placebo group sites
		gingival crevicular fluid	were treated with SRP
		(GCF), and	followed by a placebo
		Aggregatibacter	topical (intra-pocket)
		actinomycetemcomitans	gel.
		(A.a) count in subgingival
		plaque.
et Randomised 2 months	12 male	To evaluate the	At day 0, all patients	Significant improvement in PI	Periodontal chips containing TQ
(26) single-blind	patients with	effectiveness of a	were treated with full-	and BOP and a reduction in	can be used as an adjunct to
split-mouth	chronic	biodegradable periodontal	mouth scaling and root	periodontal pockets from	conventional SRP in the
study	periodontitis	chip containing TQ for	planing (SRP).	baseline were observed in all	management of chronic
Shah Alam,		managing chronic	Periodontal pockets	three groups (p<0.05). Gains in	periodontitis.
Selangor,		periodontitis. Clinical	were divided into three	CAL were significantly higher
Malaysia		parameters recorded on	groups: Group I	(p<0.005) in the group
		day 0	consisted of 60 sites	receiving TQ chips compared
		and day 60 were: plaque	and received SRP alone	with other groups.
		index (PI), bleeding	(control group). Group
		on probing (BOP),	II: 60 sites; received
		clinical probing pocket	plain chitosan chips.
		depth (PPD)	Group III: 60 sites;
		and clinical attachment	received chips
		level (CAL).	containing TQ.
and Clinical study 12 weeks	68 subjects	To investigate the effect	Group I (24 patients)	When compared with the	Adjunctive use of TQ gel showed
Minia, Egypt	(including 48	of TQ gel on PI, GI,	received non-surgical	baseline, a statistically	significant improvement in
	with	probing depth (PD), and	periodontal therapy and	significant improvement in	biochemical parameters after 4
of Medicine, Law &	Public Health Vol	3, No 3. 2023
	moderate to	clinical attachment level	TQ gel (0.1 % w/w).	clinical parameters was found	weeks of treatment compared with
	severe	(CAL), as well as the	Group II (24 patients)	in both Group I and Group II	single non-surgical periodontal
	chronic	level of IL-1β and total	received only non-	after weeks 4 and 12	therapy.
	periodontitis)	antioxidant capacity	surgical periodontal	(p<0.0001). Although Group I
		levels in the gingival	therapy. Group III were	showed more clinical
		crevicular fluid.	20 healthy subjects	improvement than Group II, the
			(control group). The	difference was not statistically
			clinical parameters	significant. Regarding
			were recorded at	biochemical parameters,
			baseline (before	significant improvement in
			treatment) and at weeks	Group I was noted at 4 weeks
			4 and 12 after	as compared with group II.
			treatment.
al., Randomised 2 weeks	40 patients	To explore salivary	The treatment group	The mean concentration of	MMP-8 levels in patients with
controlled	with chronic	matrix metalloproteinase-	received NS oil and the	salivary MMP-8 in the NS	chronic periodontitis were slightly
trial	periodontitis	8 (MMP-8) levels after	control group received	group decreased from 199.37 ±	decreased with NS oil-based
Lahore,		NS oil-based mouthwash	simple normal saline.	300.75 ng/l to 114.17 ± 129.21	mouthwash after non-surgical
Pakistan		compared with placebo	Salivary samples for	ng/l, while in the normal saline	periodontal therapy, but this
		(normal saline) after non-	MMP-8 levels were	group, it decreased from 195.29	decrease was not statistically
		surgical periodontal	collected once before	± 175.89 ng/l to 147.35 ± 144.9	significant.
		therapy.	non-surgical	ng/l. This reduction was
			periodontal therapy and	statistically non-significant
			again after 2 weeks of	both within and between the
			rinsing.	study groups.
al., Parallel-arm 2 weeks	40 patients	To determine the change	Patients in the control	No statistically significant	Treatment with NS oil in chronic
triple-blind	with chronic	in salivary interleukin	group were given	change was found in the	periodontitis patients following
placebo-	periodontitis	(IL)-1β levels after the	normal saline (placebo),	salivary IL-1β levels, either in	scaling and root planing showed no
based		use of NS oil.	while those in the	the control or the treatment	significant change in before and
randomised			intervention group	group.	after IL-1β levels.
clinical trial			received NS oil. All
Lahore,			participants underwent
Pakistan			scaling and root planing
			before the start of the
			trial. Salivary samples
			were collected on day 0
			and day 15 and IL-1β
			levels were examined
			using ELISA.
al., Parallel-arm 2 weeks	40 patients	To analyse the effects of	Both the control group	A statistically significant	PI, CAL, PPD and BOP parameters
randomised	with chronic	NS oil mouthwash after	and the treatment group	difference was found in the pre-	improved following non-surgical
controlled	periodontitis	non-surgical therapy. The	underwent scaling and	treatment and post-treatment	periodontal therapy
trial		parameters evaluated	root planing, and were	values of PI, CAL, PPD and	in both the group using NS oil-
L h		i l d i d t l	i th h f	BOP i b th th Th	b d th h d th t i
of Medicine, Law &	Public Health Vol	3, No 3. 2023
Pakistan		pocket depth (PPD),	either normal saline	difference in improvement	normal saline-based mouthwash.
		clinical attachment loss	solution or NS oil,	between the treatment and	Thus, both types of mouthwash
		(CAL), PI, BOP.	respectively, to be used	control groups	showed a beneficial effect.
			daily for 2 weeks.	was not statistically significant.
al., Clinical study 6 weeks	40 subjects	To evaluate the benefit of	Subjects in Group I	There was a significantly high	Using 0.2% TQ intracrevicularly as
India	with chronic	local application of TQ	were administered with	reduction in PI, GI, PPD, gain	an adjunct to SRP could be
	periodontitis	gel as an adjunctive to	0.2% TQ along with	in RAL, and GCF ALP	beneficial in treating chronic
		scaling and root planing	SRP, while the control	(p=0.001) in both the groups at	periodontitis.
		(SRP) in subjects with	(Group II) consisted of	6 weeks from baseline.
		chronic periodontitis.	subjects who only	In a comparison between Group
		Clinical parameters	received SRP.	I and Group II, the former
		recorded were: plaque		showed a significant reduction
		index (PI), gingival index		in PPD, GCF-ALP levels and
		(GI), probing pocket		rise in RAL, but no statistically
		depth (PPD), and relative		significant differences were
		attachment level (RAL).		observed in PI and GI at 6
				weeks.
al., Split‑mouth 28 days	24 patients	To explore the clinical	Individuals were	Intergroup comparison of GI	The NS extract showed better
clinical study	with	efficacy of different	divided into group I1,	showed a significant difference	wound healing potential, and can be
Lucknow,	moderate to	ethanolic solutions of NS	group II1 and group III1	on the 14th and 28th day from	used in conjunction with scaling and
India	severe	in moderate‐to‐severe	(scaling and root	baseline between I1 & I2, at	root planing and during periodontal
	gingivitis	gingivitis patients.	planing; i.e., control)	only the 28th day between II1 &	flap surgery procedures to speed up
		The clinical parameters,	and group I2, group II2	II2, and a non-significant	periodontal wound healing.
		i.e., gingival index (GI)	and group III2	difference between III1 & III2 at
		and plaque index (PI),	(experimental). Three	all time intervals from baseline.
		were recorded at baseline,	doses of solution 1	On intragroup comparison,
		14 days, and 28 days in	(1:3), solution 2 (1:1),	a significant reduction in GI
		all the individuals.	and solution 3 (3:1)	was found in all groups from
			were administered to	baseline until 28 days, but
			the experimental groups	among the experimental
			for 3 consecutive days.	groups, the best result was seen
				in group III2 (p<0.001; F value
				153.75). Regarding the PI,
				comparison between different
				groups showed significant
				differences from baseline to the
				14th and 28th days between all
				groups; i.e, I1 & I2, II1 & II2, and
				III1 & III2. On intragroup
				comparison, a significant
				d ti i PI t d i ll

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Human-based studies related to the impact of Nigella sativa on oral health Author, Study Design Duratio Patient Aim/Outcome Measure Methods Key Findings Clinical Significance Year & Setting n of Study Group Elamrousy, 2018 (
Clinical study 8 weeks 26 subjects with grade C periodontitis To evaluate the efficacy of local application of TQ gel. The parameters investigated included: probing pocket depth (PPD), relative attachment level (RAL), matrix metallo- proteinase-8 (MMP8) concentration in gingival crevicular fluid (GCF), and Aggregatibacter actinomycetemcomitans (A.a) count in subgingival plaque. Kafrelsheikh, Egypt Al-Bayaty et al., 2013 (26) Randomised single-blind split-mouth study Shah Alam, Selangor, Malaysia 2 months 12 male patients with To evaluate the effectiveness of a biodegradable periodontal chip containing TQ for managing chronic periodontitis. Clinical parameters recorded on day 0 and day 60 were: plaque index (PI), bleeding on probing (BOP), clinical probing pocket depth (PPD) and clinical attachment level (CAL). chronic periodontitis Khalil and Clinical study Minia, Egypt 12 weeks 68 subjects (including 48 To investigate the effect of TQ gel on PI, GI, probing depth (PD), and Alaaeldin, 2019 (27) with Random assignment of the involved sites to either the TQ group (30 sites) or the placebo group (30 sites). In the TQ group, sites were treated with SRP followed by 0.2% TQ topical (intra-pocket) gel, while in the placebo group sites were treated with SRP followed by a placebo topical (intra-pocket) gel. At the 8-week evaluation point, the TQ group showed a significant decrease in PPD, RAL, MMP-8 levels in GCF, and A.a count in subgingival plaque samples when compared with the placebo group (all p values <0.05). TQ gel shows favourable outcomes when used as an adjunct to nonsurgical periodontal therapy in subjects with grade C periodontitis. At day 0, all patients were treated with full- mouth scaling and root planing (SRP). Periodontal pockets were divided into three groups: Group I consisted of 60 sites and received SRP alone (control group). Group II: 60 sites; received plain chitosan chips. Group III: 60 sites; received chips containing TQ. Significant improvement in PI and BOP and a reduction in periodontal pockets from baseline were observed in all three groups (p<0.05). Gains in CAL were significantly higher (p<0.005) in the group receiving TQ chips compared with other groups. Periodontal chips containing TQ can be used as an adjunct to conventional SRP in the management of chronic periodontitis. Group I (24 patients) received non-surgical periodontal therapy and When compared with the baseline, a statistically significant improvement in Adjunctive use of TQ gel showed significant improvement in biochemical parameters after 4 moderate to clinical attachment level (CAL), as well as the level of IL-1β and total antioxidant capacity levels in the gingival crevicular fluid. severe chronic periodontitis) Hassan et al., 2020 (
Randomised controlled trial Lahore, Pakistan 2 weeks 40 patients with chronic periodontitis To explore salivary matrix metalloproteinase- 8 (MMP-8) levels after NS oil-based mouthwash compared with placebo (normal saline) after non- surgical periodontal therapy. Hassan et al., 2020 (
Parallel-arm triple-blind placebo- based randomised clinical trial Lahore, Pakistan 2 weeks 40 patients with chronic periodontitis To determine the change in salivary interleukin (IL)-1β levels after the use of NS oil. Hassan et al., 2021 (
Parallel-arm randomised controlled trial Lahore, 2 weeks 40 patients with chronic periodontitis To analyse the effects of NS oil mouthwash after non-surgical therapy. The parameters evaluated include: periodontal TQ gel (0.1 % w/w). Group II (24 patients) received only non- surgical periodontal therapy. Group III were 20 healthy subjects (control group). The clinical parameters were recorded at baseline (before treatment) and at weeks 4 and 12 after treatment. clinical parameters was found in both Group I and Group II after weeks 4 and 12 (p<0.0001). Although Group I showed more clinical improvement than Group II, the difference was not statistically significant. Regarding biochemical parameters, significant improvement in Group I was noted at 4 weeks as compared with group II. weeks of treatment compared with single non-surgical periodontal therapy. The treatment group received NS oil and the control group received simple normal saline. Salivary samples for MMP-8 levels were collected once before non-surgical periodontal therapy and again after 2 weeks of rinsing. The mean concentration of salivary MMP-8 in the NS group decreased from 199.37 ± 300.75 ng/l to 114.17 ± 129.21 ng/l, while in the normal saline group, it decreased from 195.29 ± 175.89 ng/l to 147.35 ± 144.9 ng/l. This reduction was statistically non-significant both within and between the study groups. MMP-8 levels in patients with chronic periodontitis were slightly decreased with NS oil-based mouthwash after non-surgical periodontal therapy, but this decrease was not statistically significant. Patients in the control group were given normal saline (placebo), while those in the intervention group received NS oil. All participants underwent scaling and root planing before the start of the trial. Salivary samples were collected on day 0 and day 15 and IL-1β levels were examined using ELISA. No statistically significant change was found in the salivary IL-1β levels, either in the control or the treatment group. Treatment with NS oil in chronic periodontitis patients following scaling and root planing showed no significant change in before and after IL-1β levels. Both the control group and the treatment group underwent scaling and root planing, and were given a mouthwash of A statistically significant difference was found in the pre- treatment and post-treatment values of PI, CAL, PPD and BOP, in both the groups. The PI, CAL, PPD and BOP parameters improved following non-surgical periodontal therapy in both the group using NS oil- based mouthwash and that using Pakistan pocket depth (PPD), clinical attachment loss (CAL), PI, BOP. Kapil et al., 2019 (
Clinical study India 6 weeks 40 subjects with chronic periodontitis To evaluate the benefit of local application of TQ gel as an adjunctive to scaling and root planing (SRP) in subjects with chronic periodontitis. Clinical parameters recorded were: plaque index (PI), gingival index (GI), probing pocket depth (PPD), and relative attachment level (RAL). Singh et al., 2019 (19) Split‐mouth clinical study Lucknow, India 28 days 24 patients with moderate to severe gingivitis To explore the clinical efficacy of different ethanolic solutions of NS in moderate‐to‐severe gingivitis patients. The clinical parameters, i.e., gingival index (GI) and plaque index (PI), were recorded at baseline, 14 days, and 28 days in all the individuals. either normal saline solution or NS oil, respectively, to be used daily for 2 weeks. difference in improvement between the treatment and control groups was not statistically significant. normal saline-based mouthwash. Thus, both types of mouthwash showed a beneficial effect. Subjects in Group I were administered with 0.2% TQ along with SRP, while the control (Group II) consisted of subjects who only received SRP. There was a significantly high reduction in PI, GI, PPD, gain in RAL, and GCF ALP (p=0.001) in both the groups at 6 weeks from baseline. In a comparison between Group I and Group II, the former showed a significant reduction in PPD, GCF-ALP levels and rise in RAL, but no statistically significant differences were observed in PI and GI at 6 weeks. Using 0.2% TQ intracrevicularly as an adjunct to SRP could be beneficial in treating chronic periodontitis. Individuals were divided into group I 1 , group II 1 and group III 1 (scaling and root planing; i.e., control) and group I 2 , group II 2 and group III 2 (experimental). Three doses of solution 1 (1:3), solution 2 (1:1), and solution 3 (3:1) were administered to the experimental groups for 3 consecutive days. Intergroup comparison of GI showed a significant difference on the 14th and 28th day from baseline between I 1 & I 2 , at only the 28th day between II 1 & II 2 , and a non-significant difference between III 1 & III 2 at all time intervals from baseline. On intragroup comparison, a significant reduction in GI was found in all groups from baseline until 28 days, but among the experimental groups, the best result was seen in group III 2 (p<0.001; F value 153.75). Regarding the PI, comparison between different groups showed significant differences from baseline to the 14th and 28th days between all groups; i.e, I 1 & I 2 , II 1 & II 2, and III 1 & III 2 . On intragroup comparison, a significant reduction in PI was noted in all The NS extract showed better wound healing potential, and can be used in conjunction with scaling and root planing and during periodontal flap surgery procedures to speed up periodontal wound healing. control groups; i.e, I 1 , II 1 & III 1 , but among the experimental groups, only group III 2 showed a significant reduction (p<0.001, F value 30.40). Rahman et al., 2022 (Preprint) (23) Double-blind randomised clinical trial Riyadh, Saudi Arabia 2 weeks 40 systemically healthy participants, aged between 20 to 40 years, with chronic generalised gingivitis To investigate the clinical anti-inflammatory and antimicrobial efficacy of NS oil compared with chlorhexidine (CHX) in patients with gingivitis. Primary outcomes were gingival and plaque indices and levels of gingival crevicular IL-6 and IL-
Secondary outcomes were overall bacterial load and assessment of alpha- haemolytic plaque- causing bacteria. Khan and Ahmad, 2021 (24) Randomised clinical trial Aligarh, India 28 days 60 children with gingivitis To evaluate the clinical efficacy of topical 0.1% lipid-based thymoquinone (TQ) gel as an anti-plaque and anti- gingivitis agent. Clinical parameters recorded included the plaque index and the gingival index. Ahmed et al., 2020 (21) Randomised clinical trial Cairo, Egypt 6 months 12 healthy patients with delayed implant insertion To evaluate the effect of topically applied NS on osseointegration of delayed dental implants. Modified gingival index (MGI), probing depth (PD), and cone beam computed tomography Patients were randomly assigned to Group 1: NS oil (n = 18), or Group 2: CHX (n = 19). Both CHX and NS reduced PI and GI scores (p<0.0001). NS was better than CHX (p=0.145) at reducing gingival IL-6 (p= 0.0076). Neither NS (p=0.284) nor CHX (p=0.418) reduced IL- 18 levels. There was no difference in post-intervention PI and GI scores and inflammatory cytokine levels between treatments. Both NS and CHX caused a significant reduction in CFU (p<0.0001) and a reduction in pathogenic bacteria S. mitis, S. oralis, S. sanguinis , and S. parasanguinis in 50% of CHX patients (p=0.1031) and 20% of NS patients (p= 0.7395). There were clinically comparable results between NS oil and CHX for reducing gingival and plaque indices and lowering antimicrobial resistance. Clinicians can consider NS oil as a natural antimicrobial and anti-inflammatory mouthwash alternative without artificial flavours, colours, or preservatives. Group A (n=30) applied a peanut-sized amount of CHX gel, twice a day for 2 minutes. Group B (n=30) did the same, but with a 0.1% lipid- based TQ gel. The TQ significantly reduced the PI as compared with CHX (p<0.001) from day 0–14 and day 0–
Moreover, it produced a significant reduction in gingival index (p=0.005) from day 0–14 and day 0–28 (p<0.001), as compared with CHX gel. It may be possible to consider TQ- based gels as alternatives to CHX gels. The test group applied topical NS gel after preparation of the osteotomy site and before implant placement, while the control group did not. A non-statistically significant difference was recorded in clinical parameters (MGI, PD) after three and six months of follow-up in both groups. The test group showed a highly significant increase in bone density after six months in In delayed dental implants, NS gel may improve bone quality around implants by increasing bone density, resulting in better osseointegration of the implants and thus a better long-term outcome. (CBCT) to record bone density were recorded for each patient at 3 months and 6 months after implant placement. Khan et al., 2022 (
Comparative randomised double-blind controlled clinical trial Sakaka, Saudi Arabia 7 days 60 patients who underwent tooth extraction and were clinically diagnosed with dry socket or alveolar osteitis To evaluate and compare the effects of Alvogyl and a mixture of NS powder and oil in the treatment of dry sockets. Pain scores were assessed on a visual analogue pain scale. Hussain et al., 2019 (20) Randomised open-label controlled study Sulaimani City, Iraq 28 days 54 acute myeloid leukaemia (AML) patients receiving “3 + 7” chemotherapy protocol (3 days of 60- 90mg/m 2 daunorubicin and 7 days of 100 - 200mg/m 2 cytarabine) To evaluate the effects of NS oil as a mouth rinse against chemotherapy (CT)-induced oral mucositis (OM) in patients with AML. The primary outcome was the incidence and severity of CT-induced OM (erythema and ulcer). Secondary outcomes were pain severity score, swallowing function, and salivary concentrations of interleukin-6 (IL-6) and tumour necrosis factor- alpha (TNF-α). comparison with the control group. Patients were allocated randomly to one of three groups. Group 1 received Alvogyl; Group 2 received a mixture of NS powder and oil; Group 3 was the control and received normal saline rinse. Pain relief and socket healing were assessed. The group given NS powder and oil showed a significant difference in pain relief compared with the Alvogyl group (p=0.031) and the control group (p=0.001). Moreover, the NS group required A mixture of NS powder and oil dressings than the Alvogyl group. NS oil mixture can be used successfully in patients suffering from alveolar osteitis, since it demonstrated immediate pain relief and was shown to be more effective than Alvogyl or normal saline rinse. Patients in the test group received NS oil mouth rinse during their 28-day CT, while the control group received a “magic mouthwash” formula. NS oil mouth rinse attenuated the progression of CT-induced OM compared with the control formula (AUC=5.9 vs. 38.4, p<0.05) and significantly decreased the erythema and ulceration scores (AUC of total OMAS=11.4 vs. 85.9, p<0 . 001) compared with the magic mouthwash formula. It also reduced the pain score and enabled all the participants of this group to consume normal food during treatment. It significantly decreased salivary IL-6 (AUC =7376 vs. 16599, p<0.001), while the changes in TNF- α levels were not significant (AUC=676.9 vs. 885.2, p>0 . 05). In AML patients suffering from CT- induced OM, NS oil mouth rinse reduces pain and improves swallowing function.