The Impact of Nigella sativa on Oral Health: A Scoping Reviewأثر الحبة السوداء (Nigella sativa) في صحة الفم: مراجعة نطاقية

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INTRODUCTION

Worldwide, approximately 3.5 billion individuals suffer from oral diseases such as dental caries, periodontal disease, and oral cancers, which have profound implications on their health and quality of life (1, 2). Oral diseases are closely related to socioeconomic status, with a disproportionate impact observed among the poor and marginalised groups (2). Moreover, the current model of dentistry, which is high-technology and treatment-oriented, is unaffordable in many low- and middle-income countries (3).

The World Health Organization estimates that nearly 88% of all countries rely on different forms of traditional medicine, including herbal medicine, for the treatment of various ailments (4). The rise in popularity of herbal medicine is driven largely by its affordability, consonance with the patient’s beliefs, and fewer side effects compared with modern synthetic medicines (5). Among the most commonly used herbal medicines globally is Nigella sativa (NS), a member of the Ranunculaceae family that grows annually in southwest Asia (6). This plant is also known as black cumin, black seed, and Habbatul- Barakah (7).

The Unani and Ayurvedic systems of medicine utilise this ancient herb extensively to treat an array of ailments, including headaches, nasal congestion, intestinal worms, conjunctivitis, and asthma (8, 9). The seeds are composed of 28-36% fixed oils, proteins, alkaloids, and saponins, and 0.4-2.5% essential oils (10). The key active ingredient of NS is thymoquinone (TQ), which promotes the action of CD8 T cells and displays a variety of biological effects such as anti-diabetic, anti-hypertensive, anticancer, antioxidant, hepatoprotective, neuroprotec, gastroprotective, immunomodulator, antimicrobial, anti-inflammatory, analgesic, and spasmolytic activities (11-13).

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).

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 human subjects; thus, the present study aims to 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.

A total of 1372 articles were found. After eliminating duplication, titles and abstracts were screened following the study’s inclusion and exclusion criteria. Finally, 13 studies were included in this review. The complete process is outlined in the PRISMA flow diagram (Figure 1).

RESULTS

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).

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 microbiological effectiveness of the local application of TQ gel in subjects with grade C 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 metalloproteniease-8 (MMP-8) concentration 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 the plain chitosan chip (p<0.05). A significant decrease in periodontal pockets compared with baseline was observed in all three groups (TQ, chitosan, control). Regarding clinical attachment levels, the TQ group showed 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, (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 mouthwash 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.

Concerning the treatment of gingivitis, Singh et al. (19) Demonstrated that topically applied ethanolic solution of NS in the ratio of 3:1 significantly 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 NS (p=0.284) nor CHX (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 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 probing depth at 3 and 6 months follow up. However, the treatment group showed a highly significant increase in bone density after 6 months in comparison with the control group.

One study, carried out by Khan et al. (31), conducted a comparative evaluation of a NS powder and oil mixture with Alvogyl in the 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).

DISCUSSION

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

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.

Interleukin (IL)-6 levels were found to be significantly lowered in study participants 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 produced no significant reduction in gingival crevicular IL-18 levels in the clinical study by Rahman et al. (23). Since IL- 18 is known to have chemotactic, pro-inflammatory, and angiogenic properties, it may play a role 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).

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 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 participants. Thus, the exact effect of NS in the treatment of periodontitis among patients with chronic conditions such as diabetes and cardiovascular disease remains unclear.

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.

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 delayed 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.

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