Manifar 2012

Curcumin Gel in the Treatment of Minor Aphthous Ulcer: a
Randomized, Placebo- Controlled Trial
Manifar S (DDS), Obwaller A (Ph.D.), Gharehgozloo A (M.D.), Boorboor Shirazi Kordi HR
(M.D.), Akhondzadeh S (Ph.D.)
1- Oral Medicine Clinic, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran 2- Orphanidis Pharma Research GmbH, Vienna, Austria 3- Psychiatric Research Center, Tehran University of Medical Sciences, Tehran, Iran *Corresponding author: Psychiatric Research Center, Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences, South Kargar Street, Tehran 13337, Iran, Tel: +98-21-55412222, Fax: +98-21-55419113 Email: s.akhond@neda.net
Receive: 26 Dec 2011
Acceptance: 1 Feb. 2012
Abstract
Background: It has been reported that curcumin has anti inflammatory, antibacterial, anti
tumor and analgesic properties.
Objective: The purpose of this study was to investigate the efficacy of curcumin in the treatment
of minor aphthous stomatitis.
Methods: The study was a two week, randomized, double blind, placebo controlled of patients
with minor aphthous. Patients between 18 and 65 years old were included if they presented with
1–5 aphthous ulcers of less than 24 h duration. Twenty-eight patients were randomly allocated to
curcumin gel containing (2% curcumin) and 29 patients were allocated to placebo gel for a two
week, double-blind, placebo-controlled study. The patients used the medication using a swap
twice per day. After enrolment, the size of ulcers were measured by the investigator, and pain was
evaluated by the patients based on Perceived Pain Rating Scale before drug application (day 0)
and at days 4, 7, and 14. Patients overall satisfaction were assessed at the end of treatment.
Results: Curcimin gel significantly reduced pain intensity and size of aphthous ulcer compare to
placebo. Significant group differences appeared at the end of the trial regarding overall
satisfaction of the patients.
Conclusion: The results of present study provide evidence that curcumin gel is a well tolerated
effective treatment modality for minor aphthous stomatitis.
Keywords: Curcumin, Minor aphthous stomatitis, Pain
Volume 11, No. 41, Winter 2012
Introduction
also occur as widespread lesions in association with systemic diseases including Behcet’s Stomatitis (RAS), commonly referred to as syndrome, and gastrointestinal mal absorption canker sores, are inflammatory lesions of the disorders like Crohn's and Celiac diseases [1, 2, 5]. It is unclear whether these presentations involve the cheeks, gums, tongue, lips, and are manifestations of the underlying disease or roof or floor of the mouth. It is usually painful represent a separate oral disorder. Treatment and associated with redness, swelling, and for RAS is symptomatic; the goals being to occasional bleeding from the affected area (s) decrease pain, healing time, number and size [1, 2]. Manifestation of the disease can range of the ulcer, and to increase disease-free from mild to severe and, in extreme cases, periods. Current treatment options include even hinder a person’s ability to ingest foods, topical agents, systemic and topical steroids, thereby making the person susceptible to corticosteroids, cauterization and antibiotics, mouth rinses containing active enzymes, laser suspected including genetics, stress, nutritional The lack of predictability of the efficacy of deficiencies, diet, hormonal changes, and a particular treatment mirrors the mystery surrounding the etiology of the condition [4]. indeterminate etiology of the disease, it is Over the last decade evidence based herbal difficult to find a definitive cure and current medicine in the treatment of psychiatric treatments are aimed towards ameliorating the disorders and dermatological disease, has been symptoms [1, 3]. The less severe form of the considered [6-15]. There are some natural disease is often known as minor aphthous remedies that are being explored for the stomatitis while the less common but more treatment of aphthae [16, 17]. Herbal medicine severe type is major aphthous stomatitis [2, 4]. will relieve pain, reduce inflammation and Minor aphthous stomatitis is a very common prevent infection in the treatment of aphthae self-limiting, recurrent disease of unknown [17]. It has been reported that curcumin has cause. One or several painful ulcers appear on anti inflammatory, antibacterial, anti tumor the lining mucosa of the mouth [2]. The ulcers and analgesic properties [18-21]. Therefore, heal in 7-10 days with or without treatment. the objective of this study was to investigate Major aphthous stomatitis are larger recurrent the efficacy of curcumin in the treatment of ulcers of unknown cause appearing as deep, painful areas in the mouth that leave scars on healing. They last longer than minor aphthae [1 - 4]. The study was a randomized, double blind, common form of oral ulcerative diseases and placebo controlled of patients with minor affects an estimated 15-20% of the population aphthous ulcer referred to Oral Medicine prevalence has been documented as being as University of Medical Sciences, Tehran, Iran) high as 50-66%5 and it is especially common in North America [1 – 4]. These aphthae can Journal of Medicinal Plants, Volume 11,
No. 41, Winter 2012
Patients between 18 and 65 years old were patients were advised not to eat or drink for 1 included if they presented with 1–5 aphthous ulcers of less than 24 h duration. The ulcers Measurements
diameter was not greater than 6 mm and they did not suffer from acute or chronic diseases of After enrolment, the size of ulcers were the oral mucosa. Patients were excluded from measured by the investigator, and pain was the study if they had concurrent clinical evaluated by the subjects based on Perceived conditions including serious liver, kidney, and Pain Rating Scale before drug application (day heart dysfunctions or if they had ulcers as a 0) and at days 4, 7, and 14 as well as subject manifestation of a systemic disease process overall satisfaction score at the end of such as ulcerative colitis, Crohn’s disease, treatment on four-point description scale excellent=4) [22). Ulcer size was measured using a sterile calibrated dental probe with component of the study, the patients could not millimeter marking and the longest diameter have a history of alcohol or drug abuse nor was used as measurement. In addition, all could they be taking any narcotic analgesics. subjects were requested to immediately inform Patients were excluded if they had a history of investigators at any time for any side effect. Pregnant or lactating women and those of deviation (SD) for quantitative variables with contraception were also excluded. The trial descriptive statistics. To evaluate the efficacy the Mann-Whitney U test was used. committee at Tehran University of Medical All patients completed the study protocol. No adverse drug reaction to a treatment was entering into the study. This trial is registered reported as a reason for leaving the study. No with the Iranian Clinical Trials Registry significant difference was identified between patients randomly assigned to the group 1 or 2 condition with regard to basic demographic data including age, gender, level of education Efficacy based on Perceived Pain Rating
allocated to placebo gel for a two week, double-blind, placebo-controlled study. The At the study entry, the mean ulcer pain of patients used the medication using a swap the 2 groups matched well (ns), but it was later twice per day and the surface of lesions were significantly relieved in the turmeric group at covered by a thin layer of medications. The Table 1- Characteristics of the patients
Curcumin (n=28)
Placebo (n=29)
mean±SD Number of ulcers, median (range)
Efficacy based on global satisfaction:
antibiotics, mouth rinses containing active Significant group differences appeared at enzymes, laser treatments and combination satisfaction of the patients (P≤0.01; Table 2) Our findings suggest that curcimin gel can reduce pain intensity and size of aphthous Efficacy based on size of the ulcers:
ulcer. To our knowledge this is the first Although the ulcer size of the treatment group and the placebo group matched well at the study entry (p>0.05), significant group characteristics of the patients, such as sex, age differences appeared at the later visits (day 4 and type of aphthouse, did not differ between groups and cannot explain differences in the therapeutic outcome. So far, several studies Discussion
have shown positive effects of curcumin as anti inflammatory, anti tumor, antibacterial effective treatment for RAS that can efficiently and analgesic agent. Therefore, the results of reduce the signs and symptoms of the disease our study are in line with these studies [18-21]. at a low daily dose and with minimal effects In conclusion, the results of this study [1-4]. Treatment for RAS is symptomatic; the provide evidence that curcumin gel is a well goals being to decrease pain, healing time, tolerated and effective treatment modality for number and size of the ulcer, and to increase RAS. Additional studies with higher number disease-free periods. Current treatment options of patients and in the prevention of ulcer include topical agents, systemic and topical development if treatment is commenced at the prodromal stage may be needed to examine the Journal of Medicinal Plants, Volume 11,
No. 41, Winter 2012
role of curcumin in the treatment of RAS. Acknowledgment
This study was supported by a grant from References
1. Shashy RG, Ridley MB. Aphthous ulcers: a
difficult clinical entity. Am. J. Otolaryngol. 2000; Phytomedicine 2006; 13: 607 - 11. 10. Akhondzadeh Basti A, Moshiri E, Noorbala
2. Preeti L, Magesh K, Rajkumar K, Karthik R.
AA, Jamshidi AH, Abbasi SH, Akhondzadeh S. Recurrent aphthous stomatitis. J. Oral Maxillofac Comparison of petal of Crocus sativus L. and 3. Akintoye SO, Greenberg MS. Recurrent
outpatients: a pilot double-blind randomized trial. aphthous stomatitis. Dent. Clin. North Am. 2005; Prog Neuropsychopharmacol. Biol. Psychiatry 4. Madrid C, Jaques B, Bouferrrache K, Broome
11. Akhondzadeh S, Abbasi SH. Herbal medicine
in the treatment of Alzheimer's disease. Am. J. stomatitis]. Rev. Med. Suisse 2010; 6: 1871 – 2. Alzheimers Dis Other Demen 2006; 21: 113 - 8. 5. Oh SH, Han EC, Lee JH, Bang D. Comparison
12. Agha-Hosseini M, Kashani L, Aleyaseen A,
of the clinical features of recurrent aphthous Ghoreishi A, Rahmanpour H, Zarrinara AR, stomatitis and Behçet's disease. Clin. Exp. Akhondzadeh S. Crocus sativus L. (saffron) in the treatment of premenstrual syndrome: a double- 6. Akhondzadeh S, Fallah-Pour H, Afkham K,
blind, randomised and placebo-controlled trial. Jamshidi AH, Khalighi-Cigaroudi F. Comparison of Crocus sativus L. and imipramine in the 13. Corazza M, Borghi A, Lauriola MM, Virgili
treatment of mild to moderate depression: a pilot A. Use of topical herbal remedies and cosmetics: a questionnaire-based investigation in dermatology [ISRCTN45683816]. BMC Complement Altern out-patients. J. Eur. Acad Dermatol. Venereol. 7. Akhondzadeh S, Tahmacebi-Pour N, Noorbala
14. Akhondzadeh S, Sabet MS, Harirchian MH,
AA, Amini H, Fallah-Pour H, Jamshidi AH, Khani Togha M, Cheraghmakani H, Razeghi S, Hejazi M. Crocus sativus L. in the treatment of mild to SSh, Yousefi MH, Alimardani R, Jamshidi A, Zare moderate depression: a double-blind, randomized F, Moradi A. Saffron in the treatment of patients and placebo-controlled trial. Phytother. Res. 2005; with mild to moderate Alzheimer's disease: a 16- week, randomized and placebo-controlled trial. J. 8. Noorbala AA, Akhondzadeh S, Tahmacebi-
Clin. Pharm. Ther. 2010; 35: 581 - 8. Pour N, Jamshidi AH. Hydro-alcoholic extract of 15. Akhondzadeh S, Shafiee Sabet M, Harirchian
Crocus sativus L. versus fluoxetine in the treatment MH, Togha M, Cheraghmakani H, Razeghi S, of mild to moderate depression: a double-blind, Hejazi SS, Yousefi MH, Alimardani R, Jamshidi randomized pilot trial. J. Ethnopharmacol. 2005; A, Rezazadeh SA, Yousefi A, Zare F, Moradi A, 9. Moshiri E, Basti AA, Noorbala AA, Jamshidi
randomized, double-blind controlled trial of Crocus sativus in the treatment of mild-to- Crocus sativus L. (petal) in the treatment of mild- moderate Alzheimer's disease. Psychopharmacol. 16. Hoseinpour H, Peel SA, Rakhshandeh H,
Spolidorio LC, Kirkwood KL, Rossa C Jr. Potent Forouzanfar A, Taheri M, Rajabi O, Saljoghinejad M, Sohrabi K. Evaluation of Rosa damascena administered curcumin modulate periodontal mouthwash in the treatment of recurrent aphthous disease in vivo. J. Periodontal. Res. 2011; 46: 269 stomatitis: a randomized, double-blinded, placebo- controlled clinical trial. Quintessence Int. 2011; 42: 20. Haukvik T, Bruzell E, Kristensen S, Tønnesen
HH. A screening of curcumin derivatives for 17. Zheng LW, Hua H, Cheung LK. Traditional
Chinese medicine and oral diseases: today and curcumin and curcuminoids. XLIII. Pharmazie tomorrow. Oral Dis. 2011; 17: 7 - 12. 18. Cheng AL, Hsu CH, Lin JK, Hsu MM, Ho
21. Han YK, Lee SH, Jeong HJ, Kim MS, Yoon
YF, Shen TS, Ko JY, Lin JT, Lin BR, Ming- MH, Kim WM. Analgesic effects of intrathecal Shiang W, Yu HS, Jee SH, Chen GS, Chen TM, curcumin in the rat formalin test. Korean J. Pain. Chen CA, Lai MK, Pu YS, Pan MH, Wang YJ, Tsai CC, Hsieh CY. Phase I clinical trial of 22. Barker G, Loftus L, Cuddy P, Barker B. The
curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer diphenhydramine syrup plus kaolin-pectin on radiotherapy-induced mucositis. Oral Surg Oral 19. Guimarães MR, Coimbra LS, de Aquino SG,
Med. Oral Pathol. 1991; 71: 288 - 93. Journal of Medicinal Plants, Volume 10,
No. 39, Summer 2011

Source: http://www.curcuminfluid.at/tl_files/media/Manifar_2012.pdf