Abstract
A naturally occurring plant of the ginger family,
References
Curcumin and oral mucosal disease: a review of the literature
From Volume 52, Issue 3, March 2025 | Pages 206-210
Article
Curcuma longa (turmeric) is a plant of the ginger family (zingiberaceae), originating in the tropical regions of south-east India. Curcumin is the component that is responsible for turmeric's familiar, characteristic golden colour. It has been used extensively as a culinary spice and dye, as well as to treat a wide variety of medical issues in Ayurvedic and Chinese traditional medicine for thousands of years.1 In the UK herbal remedy market, turmeric is predominately used as an anti-inflammatory agent and is typically found as a dietary supplement.2
Curcumin, chemically known as 1,7-bis(4-hydroxy-3-methoxyphenyl)-1, 6-heptadiene-3, 5-dione, is the main bioactive component found in the thick underground stems (rhizomes) of Curcuma longa. It is the principal curcuminoid found in the rhizome, alongside three others, namely demethoxycurcumin, bisdemethoxycurcumin and cyclocurcumin.2,3
Curcumin is regarded as having a ‘privileged structure’, owing to its potential to modulate different signalling pathways in the pathological processes of various diseases.4 Curcumin can play a crucial role in inflammation-mediated pro-inflammatory molecular pathways by interrupting nuclear factor-kappa B (NF-κB) signalling at multiple levels. Additionally, it exerts its anti-inflammatory properties by regulating inflammatory signalling pathways by downregulating the activity of cyclo-oxygenase-2 (COX-2) and lipo-oxygenase, and inhibiting the production of pro-inflammatory cytokines such as tumour necrosis factor-alpha (TNF-α) and interleukins -1, -2, -6, -8, and -12.5,6
Curcumin exerts its antioxidant properties by scavenging different forms of free radicals, such as reactive oxygen and nitrogen species, and by regulating the neutralization of free radicals by glutathione, catalase and superoxide dismutase.7
Studies have investigated the role of curcumin as a therapeutic adjunct in managing diseases where the pathogenesis is associated with higher inflammatory biomarkers. Over recent years, numerous clinical studies have demonstrated the safety, efficacy and tolerability of curcumin supplementation in various inflammatory diseases including coronary artery disease, rheumatoid arthritis, psoriasis and inflammatory bowel disease.8
However, the application of curcumin in managing oral disease remains to be explored. This article reviews the current literature to ascertain the effects of curcumin and its emerging role in the management of oral mucosal disease.
Materials and methods
Literature search
Studies were identified for this literature review by searching electronic databases. The search was applied to MEDLINE (via Ovid) (1946 to 24 January 2023) and Embase (via Ovid) (1974 to 24 January 2023). The search strategies are detailed in Table 1.
| turmeric.ab. or turmeric.ti. or turmeric.kw. |
| curcuma longa.ab. or curcuma longa.ti. or curcuma longa.kw. |
| curcumin.ab. or curcumin.ti. or curcumin.kw. |
| 1 or 2 or 3 |
| dental.ab. or dental.ti. or dental.kw. |
| tooth.ab. or tooth.ti. or tooth.kw. |
| teeth.ab. or teeth.ti. or teeth.kw. |
| mouth.ab. or mouth.ti. or mouth.kw. |
| oral.ab. or oral.ti. or oral.vkw. |
| facial.ab. or facial.ti. or facial.kw. |
| orofacial.ab. or orofacial.ti. or orofacial.kw. |
| maxillofacial.ab. or maxillofacial.ti. or maxillofacial.kw. |
| temporomandibular.ab. or temporomandibular.ti. or temporomandibular.kw. |
| 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13 |
| pain.ab. or pain.ti. or pain.kw. |
| inflam*.ab. or inflam*.ti. or inflam*.kw. |
| neuralgi*.ab. or neuralgi*.ti. or neuralgi*.kw. |
| neuropath*.ab. or neuropath*.ti. or neuropath*.kw. |
| analgesi*.ab. or analgesi*.ti. or analgesi*.kw. |
| 15 or 16 or 17 or 18 or 19 |
| 4 and 14 and 20 |
| limit 21 to (meta analysis or systematic review or randomized controlled trial) |
Inclusion and exclusion criteria
Studies investigating the effects of Curcuma longa or its derivatives on oral disease in humans were included in the review. The authors considered randomized controlled trials (RCTs), systematic reviews and meta-analyses. No language, publication date, publication status or other exclusion criteria were applied.
Results
The search of MEDLINE and Embase yielded 93 results. The studies were screened for eligibility and the relevant findings from the highest quality evidence are discussed.
Findings and discussion
Recurrent aphthous stomatitis
The review of the literature identified five research papers assessing the effect of curcumin in patients experiencing recurrent aphthous stomatitis (RAS). Two of these papers were systematic reviews and the other three were RCTs.9,10,11,12,13
The systematic review by Al-Maweri et al reported curcumin had good efficacy in reducing the healing time of recurrent apthous stomatitis, as reflected by a significant decrease in ulceration size.9
Another systematic review by Gharibpour et al found a reduction in the size and number of apthae, as well as in pain intensity and erythema. Four of the studies examined found curcumin to have similar favourable effects when compared with the standard medication, triamcinolone.10
Further to this, the RCT by Kia et al demonstrated that the treatment of RAS by topical 5% curcumin was as effective as 0.1% triamcinolone acetonide.11 It could therefore potentially be used as an effective alternative treatment for patients who are unable to use topical corticosteroids.
Another RCT, by Deshmukh and Bagewadi, compared the efficacy of 10 mg/g curcumin gel with triamcinolone acetonide gel when treating patients with RAS. Both groups showed a decrease in the size, pain, number and duration of ulcers, with no significant differences between the two groups.12
The RCT by Manifar et al investigated the efficacy of 2% curcumin gel in the treatment of minor RAS. The results showed that 2% curcumin gel produced a similar reduction as a placebo gel in ulceration size. The curcumin group showed significant reduction in pain intensity, with considerably less noted on day 4 onwards compared to the control group.13
Potentially malignant conditions
Oral lichen planus (OLP)
A meta-analysis by Ara et al and four systematic reviews were identified assessing the effect of curcumin in patients with OLP.14,15,16,17,18,19
The meta-analysis by Ara et al reviewed the role of curcumin in potentially malignant conditions.20 In the studies focusing on patients with OLP, one RCT was included. This study investigated curcumin's mechanism of action in pre-cancerous lesions based on serum and salivary markers of oxidative stress.20 The results demonstrated a significant reduction in patient-reported pain scores and lesion sizes, and increases in serum and salivary vitamins C and E. It was suggested that curcumin may mediate its anti-premalignant properties by increasing levels of vitamins C and E, preventing lipid peroxidation and DNA damage.
The most recent systematic review studied the safety and efficacy of ‘natural remedies’ in the management of OLP.15 Of the 12 studies assessed, only one RCT concerned the efficacy of curcumin. The RCT by Kia et al found topical 5% curcumin paste to be superior in reducing the size of OLP lesions compared to the control of 0.1% topical triamcinolone acetonide.16
A systematic review by Dharman et al investigated the role of curcumin in reducing the symptoms and clinical signs of OLP.17 Seven RCTs, two pilot clinical trials and three comparative studies were included in the review covering 315 patients. Four studies found that the use of topical curcumin had no statistically significant difference to corticosteroids. In three clinical trials, which compared treatment with placebo, one study showed a significant difference with an increased oral dosage of curcumin, while two were not statistically significant with a decreased oral dosage. Three studies with no controls showed statistical significance in reducing burning sensations and the clinical appearance of OLP lesions. The authors concluded that curcumin demonstrates promising effects in the treatment of symptomatic OLP, but there is insufficient evidence to draw definitive conclusions owing to insufficient sample sizes.
Another systematic review by White et al looked at the efficacy of curcumin in the treatment of OLP and compared it to topical corticosteroids.18 While it found topical curcumin to reduce pain, burning and clinical manifestations of OLP, the effects of topical curcumin were found to be similar or inferior to topical corticosteroids. Oral curcumin showed no significant differences when compared to placebo. The findings show promising preliminary results with the topical application of curcumin in treating OLP.
The final systematic review by Lv et al evaluated nine studies on the safety and efficacy of curcumin in the treatment of OLP.19 The review included 259 patients with OLP. Seven studies showed statistical significance in differences in pain severity and the clinical appearance of OLP lesions after treatment with curcumin. Three RCTs showed no statistical significance in pain severity and clinical appearance when comparing treatment with curcumin and corticosteroids. The authors found treatment with curcumin to be safe, and suggested it could be used as an adjunct to corticosteroids to reduce pain and burning symptoms and to improve the clinical appearance of OLP lesions.
Oral submucous fibrosis
Four papers were identified and are discussed assessing the effect of curcumin in patients experiencing oral submucous fibrosis (OSF). These papers comprise two meta-analyses, one combined meta-analysis and systematic review and one systematic review.14,21,22,23
A meta-analysis by Guo et al reviewed the efficacy of curcumin in the systemic treatment of OSF.21 A total of 350 patients were covered by this study, which included six RCTs. The results showed curcumin to increase maximal mouth opening and reduce burning pain when compared to placebo treatment. However, no statistically significant difference was noted between curcumin and controls after 2 months of treatment. Additionally, no statistically significant difference was found in alleviating burning sensations between curcumin and the control after 1, 2 and 6 months of treatment. The authors concluded that, given the limited number and quality of studies, more high-quality research is required to verify curcumin as an effective treatment for improving maximal mouth opening and burning sensations in patients with OSF.
Another meta-analysis reviewed the role of curcumin in potentially malignant conditions.14 Of the studies focusing on patients with OSF, six were interventional studies. In total, there were 73 patients with OSF. The results from all studies demonstrated a reduction in pain scores and lesion sizes.
The meta-analysis and systematic review by Rai et al investigated the effectiveness of turmeric treatment for the relief of the signs and symptoms of OSF.22 A total of 11 studies covering 428 patients were included in the review. All studies reported improved mouth opening after treatment with turmeric, which was also concluded in a meta-analysis of three studies. Four studies that measured tongue protrusion reported an increase after a minimum of 3 months of treatment with turmeric, with one study specifying a greater improvement seen with topical turmeric versus systemic treatment. Two studies that measured cheek flexibility both reported an increase after a minimum of 3 months of treatment. Burning sensations were assessed in 10 studies. Two studies reported burning sensations being eliminated after turmeric treatment, while the others showed a reduction.
A systematic review explored the effects of turmeric on OSF in four studies.23 This included a total of 159 patients over 1–3 months of turmeric treatment. All studies reported a reduction in burning sensations after the use of turmeric treatment regardless of the mode of administration.
Leukoplakia
The review of the literature found one meta-analysis assessing the effects of curcumin in patients with oral leukoplakia.14
The meta-analysis reviewed the role of curcumin in potentially malignant conditions. Of the studies focused on patients with leukoplakia, two were interventional. The samples from the studies included a total of 32 patients with leukoplakia. The results from all studies demonstrate a reduction in pain scores and lesion sizes following oral curcumin treatment.14
Oral cancer
An RCT by Basak et al that investigated the inhibitory effect on cytokines and tumour-associated microbes in patients diagnosed with oral cancer was identified.24 The study included 25 patients, 12 of whom had a diagnosis of oral cancer and 13 in whom oral cancer was absent. Curcumin was delivered in botanical lozenges. The results show statistically significant reductions in the concentration of bacteroides species and inflammatory cytokine concentrations of Il-8, Il-1β and TNF-α in salivary cells among patients treated with curcumin compared to placebo. There was no statistical difference between patients with or without oral cancer.
Pre- and post-treatment tumour samples from the cancer patients treated with the curcumin demonstrated T cell recruitment and inhibition of xenograft tumour cell growth. Non-cancerous tissue samples did not demonstrate immune cell infiltration. The authors suggested that curcumin could suppress tumour cell sequence by reducing concentrations of inflammatory cytokines driven by NF-κB.24
Mucositis
The literature search yielded two meta-analyses assessing the effects of curcumin in patients experiencing oral mucositis.25,26
The more recent meta-analysis evaluated the efficacy of curcumin in head and neck cancer patients experiencing oral mucositis from radiotherapy and/or chemotherapy.25 The paper included six RCTs involving 266 patients with differing administration methods and dosages of curcumin. Findings showed curcumin did not reduce the total number of incidences of oral mucositis. However, when used preventively, curcumin reduced the severity and symptoms experienced by patients. Additionally, the results revealed curcumin reduced weight loss associated with oral mucositis. The authors posited this to be linked to the reduction of oral mucositis severity and consequent increase in oral intake.
Zhang et al carried out a Bayesian network meta-analysis comparing the effect of 10 types of mouthwash in preventing oral mucositis.26 This included nine RCTs on curcumin mouthwash, corresponding to a total of 392 patients. The results of this study concluded that the use of mouthwashes containing curcumin in cancer patients was statistically significant in the prevention of intolerable oral mucositis. Curcumin was ranked the third most effective mouthwash, with chamomile mouthwash ranking most effective and sucralfate ranking least effective.
Denture stomatitis
Two RCTs were identified assessing the effect of curcumin in patients with denture stomatitis.27,28
The RCT by Labban et al compared the efficacy of rose bengal- and curcumin-mediated photodynamic therapy (PDT) with nystatin therapy in the treatment of denture stomatitis.27 The findings demonstrated that curcumin-mediated PDT showed comparable clinical efficacy to nystatin therapy in the treatment of denture stomatitis. Rose bengal-mediated PDT, curcumin-mediated PDT and nystatin therapy demonstrated clinical efficacy rates of 53%, 51% and 49%, respectively. The authors suggested that the findings on PDT in regard to reducing fungal count might not be adequate without mechanical cleaning of the denture surfaces, so concluded that PDT should be considered primarily a treatment adjunct.
The other RCT investigated the effectiveness of curcuminoid mouthwash compared with chlorhexidine mouthwash in managing denture stomatitis.28 Thirty patients were randomly assigned to three equal groups, 10 using chitosan-curcuminoid mouthwash, 10 using 0.2% chlorhexidine mouthwash and the remaining 10 using a vehicle formulation of chitosan and PEG 400. Of patients using the chitosan-curcuminoid mouthwash, 80% had complete resolution of their erythematous denture stomatitis lesion after completing the 2-week treatment course. In comparison, only 30% of the chlorhexidine mouthwash group and 10% of the vehicle formulation group had resolution in this time frame. Chitosan-curcuminoid mouthwash and chlorhexidine mouthwash groups produced comparable reductions in the number of candida colonies on the denture fitting surface.
Conclusion
The use of curcumin has demonstrated promising results in the management of a range of oral conditions. The evidence suggests curcumin may have the most potential as a therapeutic agent in managing potentially malignant conditions, mucositis and RAS. Where it does not provide better results than established medications, a comparable effect has often been demonstrated, which may be of clinical benefit when certain drugs are contraindicated or adjuncts are required.
Further research with larger sample sizes, standardized study designs and uniformity in preparations and dosages is warranted to substantiate its use in the clinical setting and role as a ‘cure-cumin’.