Bhatia M, Urolagin SS, Pentyala KB, Urolagin SB, Menaka KB, Bhoi S. Novel therapeutic approach for the treatment of periodontitis by curcumin. J Clin Diagn Res. 2014;8(12):ZC65-ZC69.
Randomized, controlled clinical trial
Twenty-five patients (15 men, 10 women) between 21 and 45 years of age participated in this trial and were randomized into 2 groups. All had been diagnosed with chronic periodontitis with periodontal pockets of a depth greater than 5 mm bilaterally. Patients who had undergone any form of nonsurgical or surgical periodontal therapy in the 6 months previous to the trial were excluded. In addition, patients with systemic disease, who had undergone antibiotic therapy within 3 months of the study, and who smoked were excluded.
Study Medication and Dosage
A split-mouth design (comparing changes in different quadrants of same patient) was employed to measure study parameters. Two sites of periodontitis in contralateral quadrants were chosen. Each had a probing pocket depth of greater than 5 mm at baseline. The test group periodontal sites received scaling and root planing along with 1% curcumin gel at baseline and 1-month, 3-month, and 6-month intervals. The control group periodontal sites received scaling and root planing only. Curcumin was inserted deep within the periodontal pockets, and sites were covered with periodontal dressings. The same procedure was followed at all intervals. Separately, the drug-release pattern of the curcumin gel was studied in vitro.
Periodontitis was assessed with use of clinical and microbiological measures taken at baseline and at 1-month, 3-month, and 6-month intervals. Clinical parameters included an examination of plaque index, bleeding index, probing pocket depth, and clinical attachment level. Microbiological parameters were assessed by taking samples at baseline and each interval. These included identifying the presence of 4 pathological pathogens: Porphyromonas gingivalis, Prevotella intermedia, Capnocytophaga genus, and Fusobacterium spp. All bacterial samples were cultured to enable subsequent species analysis.
According to intragroup analysis, the intervention and control group had significant improvements over time of most parameters, suggesting that scaling and root planing alone is therapeutically beneficial. However, the curcumin gel group yielded significant improvement over the control group when comparing them against one another via intergroup analysis at most intervals for almost all parameters measured. These results tended to gain in statistical significance in later time intervals, implying continued improvements over time and with multiple applications of curcumin gel.
In the past decade, several studies have substantiated curcumin’s effectiveness and supported its therapeutic potential as an armament to protect patients from the ravages of serious and chronic disease.
More specifically, the plaque index revealed significant intragroup reduction in scores from baseline to 1 month, 3 months, and 6 months while intergroup comparison revealed no significant reduction at baseline and 1-month readings. However, intergroup results were highly significant at 3-month and 6-month intervals (P=0.050, P=0.016).
On review of the bleeding index, both the test and control groups led to significant intragroup reduction in plaque scores from baseline to 1 month, 3 months, and 6 months. There was no significant difference of bleeding index at baseline between groups; however, at 1 month, 3 months, and 6 months, highly significant improvements were evident in the intervention group (P=<0.001).
Both the test and control groups had significant intragroup reduction in pocket depth at baseline and at 1-month, 3-month, and 6-month intervals. Intergroup comparison revealed no significant difference at baseline with highly significant improvement in the intervention group at 1 month, 3 months, and 6 months (P=<0.001).
Per the clinical attachment index, it was seen that both the test and control groups had improvements at 1 month, 3 months, and 6 months from baseline while intergroup analysis showed no significant reduction at baseline but highly significant results at 1 month, 3 months, and 6 months (P=0.001).
Additionally, microbiological culture analysis showed significant intragroup and intergroup reductions in those species identified. Both test and control groups saw significant intragroup reduction of P gingivalis from baseline and at 1-month, 3-month, and 6-month intervals. While intergroup comparison showed a baseline reading that was insignificant but a highly significant reduction readings at 1 month, 3 months, and 6 months (P=0.001), P intermedia was significantly reduced in intragroup parameters from baseline to 1-month, 3-month, and 6-month intervals. And although intergroup readings were insignificant at baseline, they were highly significant at 1-month, 3-month, and 6-month intervals (P=<0.001). This held true for Fusobacterium sp, as significant intragroup reductions were present at baseline to 1-month, 3-month, and 6-month intervals. Intergroup comparisons revealed insignificant reductions at baseline, and highly significant reductions were seen at 1-month, 3-month, and 6-month intervals (P=0.001).
Furthermore, Capnocytophaga was significantly reduced per intragroup readings at baseline and after 1 month, 3 months, and 6 months. On intergroup comparison, no significant reduction was noted at baseline while highly significant reductions were seen at 1 month (P=<0.001) and significant reductions were evident at 3-month and 6-month intervals (P=0.003, P=0.015).
The researchers found that approximately 16.30% of the curcumin was released from the gel at the end of day 1 and 69.44% at the end of the 7th day. This increased concentration of the curcumin gel over time may account for the apparent continued improvements in periodontitis parameters and microbiology over time in this study.
Periodontitis is a significant issue for approximately half of Americans aged 30 years and older with prevalence increasing to 70% in those adults 75 years and older.1 Periodontitis literally means “inflammation around the tooth.” As periodontitis progresses, the alveolar bone around the teeth is progressively lost, creating a breeding ground for pathogenic microorganisms. This in turn incites an increased immune response in the area. An overactive immune system may result in inflammation both locally and systemically. In fact, oral bacteria and inflammation, hallmarks of periodontitis, may result in greater systemic illness and susceptibility to various diseases like endocarditis, cardiovascular disease, premature labor and/or giving birth to babies with low birth-weight, diabetes, HIV/AIDs, osteoporosis, Alzheimer’s disease, and autoimmune conditions.2
Curcumin may offer a substantial tool for the management of periodontitis. In the past decade, several studies have substantiated its effectiveness and supported its therapeutic potential as an armament to protect patients from the ravages of serious and chronic disease. Its compelling nature lies in its ability to influence a vast range of molecular and intercellular targets. Its biological actions include but are not limited to the (1) antiinflammatory,3,4 (2) antioxidant,5,6 (3) antiallergic, (4) anticarcinogenic, (5) antimutagenic, (6) anticoagulant, (7) antidiabetic, (8) antifibrotic, (9) antiulcer, (10) antifungal, and (11) antibacterial.7-9 Its greatest antiinflammatory properties are due to its ability to inhibit nuclear factor-kappa B and specifically in its downregulation of the proinflammatory enzyme cyclooxygenase-2 (cox-2). Reduction in cox-2 results in reducing inflammatory mediators generated via the arachidonic acid pathway, which is why curcumin’s selective inhibition of prostaglandins gives it a substantial advantage over aspirin.3,10,11 Antimicrobial properties of curcumin are likely due to its ability to inhibit bacterial lipopolysaccharide‒induced cytokine expression and bacterial quorum sensing systems.9,12
The relatively safe nature of herbal extracts has prompted research and development in the dentistry field, though herbal therapies is still so new in dentistry that valuable studies are limited.
An in vitro and in vivo study from 2013 examined the effects of berberine on periodontal disease. Twelve animals were used and divided into 3 groups for the study: (1) nonligation, (2) ligation, and (3) ligation-plus-berberine (75 mg/kg berberine by gastric lavage daily). The effect of berberine on periodontal destruction was evaluated in the ligature-induced periodontitis in rats for 8 days by microcomputerized tomography, histology, and immunohistochemistry. Berberine demonstrated an in vitro inhibitory effect on P gingivalis lipopolysaccharide activities and macrophages and reduced in vivo gingival tissue degradation in periodontitic rats.13 It was proposed that berberine may slow periodontal degradation through the regulation of matrix metalloproteinases in periodontitis induced by bacterial plaque.
In another berberine study (2008), experimental rats were randomized into different groups followed by oral treatment with berberine hydrochloride for 1 week, 2 weeks, 3 weeks, and 4 weeks. Berberine hydrochloride inhibited the expression of interleukin-1beta and tumor necrosis factor-alpha in periodontal tissues and promoted the regeneration of the periodontal tissues.14
Aloe vera has also been studied in the field of oral health due to its antimicrobial properties.15 A study from 2013 evaluated the antimicrobial effectiveness of 6 root canal–filling materials (some of which contained aloe vera) and a negative control agent against 18 strains of bacteria isolated from infected root canals of primary molar teeth using a diffusion assay. The combination of aloe vera and sterile water was found to have superior antimicrobial activity against most of the microorganisms as compared to zinc oxide and eugenol; zinc oxide eugenol with aloe vera; calcium hydroxide and sterile water; calcium hydroxide with sterile water and aloe vera; calcium hydroxide and iodoform; or petroleum jelly.16 The latter acted as the “control.” However, a study from 2012 evaluated the use of aloe vera toothpaste in the management of gingivitis (the precursor to periodontitis) and showed no additional effect on plaque and gingivitis compared to the “control” toothpaste.17 It is important to note that plaque itself is a biofilm of bacteria.
Tea tree oil, which possesses antimicrobial properties, has been evaluated for its use in periodontitis. For one study, 40 patients with moderate to severe chronic periodontitis were divided into 2 groups. Group I received scaling and root planing only while group II received scaling and root planing in addition to tea tree oil gel. Clinical parameters were recorded, and gingival fluid samples were collected from each subject and assessed for the inflammatory marker pentraxin-3 at baseline and at 1 month, 3 months, and 6 months after treatment.18 No significant difference was found between the tee tree oil group and the control group.
There is some evidence that Kampo formulas, standardized herbal mixtures that have been used for centuries in Japan, may have some action in the management of periodontitis. A 2013 study analyzed 27 Kampo formulas and their efficacy in the treatment of periodontitis. Seven of the 27 mixtures tested showed promise. On further review, Chinese rhubarb was found to be the common ingredient in all seven. In addition, those Kampo medications with rhubarb and purified anthraquinones exhibited the capacity to decrease the adherence of P gingivalis to oral epithelial cells and to reduce its proteinase activity. However, purified anthraquinones alone did not have the same effect.19 It follows that rhubarb and its anthraquinone derivatives may represent promising molecules for controlling periodontal diseases through their capacity to inhibit P gingivalis growth and adherent properties.
There are several consideration in the study reviewed here that strengthen its results. First, although the trial size was small, the results reached statistical significance. Second, control sites were effectively selected in same oral cavity as experimental sites. Third, although scaling and root planing did have a significant effect on the improvement of oral health, curcumin was shown to enhance that procedure significantly. Of course, a larger trial size is ideal, and the potency and the most effective frequency and dose of curcumin gel could be further explored. However, the nontoxicity of curcumin topically also gives a clinician more reason to consider its use even before such large interventions are finished.
Overall, we must always look for safe and effective means to treat disease—especially those diseases that may precipitate future ill health. Curcumin may offer potent assistance for the management of periodontitis. Studies regarding its use and benefits in the oral cavity have only begun within the past decade. If continued benefit of curcumin is witnessed in larger clinical trials, this may make a substantial impact not only on oral health but also on the onset of systemic disease and may ultimately have a substantial impact on overall health and well-being.20 Until then, we may want to discuss current options that include topical curcumin with our patients who have gingivitis or periodontitis.
- Centers for Disease Control and Prevention. Periodontal diseases. Available at: http://www.cdc.gov/oralhealth/periodontal_disease/. Accessed May 5, 2015.
- Genco RJ, Williams RC. Periodontal Disease and Overall Health: A Clinician’s Guide. 1st ed. Yardley, PA: Professional Audience Communications; 2010.
- Sajithlal GB, Chithra P, Chandrakasan G. Effect of curcumin on the advanced glycation and cross-linking of collagen in diabetic rats. Biochem Pharmacol. 1998;56(12):1607-1614
- Chainani-Wu N. Safety and anti-inflammatory activity of curcumin; a component of turmeric (Curcuma longa). J Altern Complement Med. 2003;9(1):161-168.
- Ramsewak RS, Dewitt DL, Nair MG. Cytotoxicity, antioxidant and anti-inflammatory activities of curcumins I-III from Curcuma longa. Phytomedicine. 2000;7(4):303-308.
- Osawa T, Sugiyama, Inayoshi M, Kawakishi S. Antioxidative activity of the tetrahydrocurcuminoids. Biosci Biotechnol Biochem. 1995;59(9):1609-1612.
- Siddiqui AM, Cui X, Wu R, et al. The anti-inflammatory effect of curcumin in an experimental model of sepsis is mediated by upregulation of peroxisome proliferator-activated receptor-gamma. Crit Care Med. 2006;34(7):1874-1882
- Somparn P, Phisalaphong C, Nakornchai S, Unchern S, Morales NP. Comparative antioxidant activities of curcumin and its demethoxy and hydrogenated derivatives. Biol Pharm Bull. 2007;30(1):74-78.
- De R, Kundu P, Swarnakar S, et al. Antimicrobial activity of curcumin against Helicobacter pylori isolates from India and during infections in mice. Antimicrob Agents Chemother. 2009;53(4):1592-1597.
- Plummer SM, Holloway KA, Manson MM, et al. Inhibition of cyclo-oxygenase 2 expression in colon cells by the chemopreventive agent curcumin involves inhibition of the NF-kappaβ activation via the NIK/IKK signaling complex. Oncogene. 1999;18(44):6013-6020.
- Chen H, Zhang ZS, Zhang YL, Zhou DY. Curcumin inhibits cell proliferation by interfering with the cell cycle and inducing apoptosis in colon carcinomacells. Anticancer Res. 1999;19(5A):3675-3680.
- Packiavathy IA, Priya S, Pandian SK, Ravi AV. Inhibition of biofilm development of uropathogens by curcumin—an anti-quorum sensing agent from Curcuma longa. Food Chem. 2014 Apr 1;148:453-460.
- Tu HP, Fu MM, Kuo PJ, et al. Berberine’s effect on periodontal tissue degradation by matrix metalloproteinases: an in vitro and in vivo experiment. Phytomedicine. 2013;20(13):1203-1210.
- Yu ZH, Zhang GY, Zhang XH, Du JD, Yang Q, He FD. Effect of berberine hydrochloride on the expression of interleukin-1beta and tumor necrosis factor-alpha in periodontal tissues in rats [article in Chinese]. Hua Xi Kou Qiang Yi Xue Za Zhi. 2008;26(1):82-86.
- Varoni EM, Lodi G, Sardella A, Carrassi A, Iriti M. Plant polyphenols and oral health: old phytochemicals for new fields. Curr Med Chem. 2012;19(11):1706-1720.
- Kriplani R, Thosar N, Baliga MS, Kulkarni P, Shah N, Yeluri R. Comparative evaluation of antimicrobial efficacy of various root canal filling materials along with aloevera used in primary teeth: a microbiological study. J Clin Pediatr Dent. 2013;37(3):257-262.
- Namiranian H, Serino G.The effect of a toothpaste containing aloe vera on established gingivitis. Swed Dent J. 2012;36(4):179-185.
- Elgendy EA, Ali SA, Zineldeen DH. Effect of local application of tea tree (Melaleuca alternifolia) oil gel on long pentraxin level used as an adjunctive treatment of chronic periodontitis: A randomized controlled clinical study. J Indian Soc Periodontol. 2013;17(4):444-448.
- Liao J, Zhao L, Yoshioka M, Hinode D, Grenier D. Effects of Japanese traditional herbal medicines (Kampo) on growth and virulence properties of Porphyromonas gingivalis and viability of oral epithelial cells. Pharm Biol. 2013;51(12):1538-1544.
- Mayo Clinic. Patient care & health info: Diseases and conditions: Periodontitis. Available at: http://www.mayoclinic.org/diseases-conditions/periodontitis/basics/definition/con-20021679. Accessed May 5, 2015.