|Year : 2021 | Volume
| Issue : 1 | Page : 25-30
Comparative evaluation of novel gel-containing curcumin, Aloe Vera, and honey with triamcinolone acetonide as an adjunct to oral physiotherapy in oral submucous fibrosis patients: A pilot study
Anagha P Bhelonde, Ajay R Bhoosreddy, Chetan J Bhadage, Priyanka R Giri, Shubhangi K Dhuldhule, Aishwarya M Kulkarni
Department of Oral Medicine and Radiology, MGV's KBH Dental College and Hospital, Nashik, Maharashtra, India
|Date of Web Publication||25-Feb-2021|
Ajay R Bhoosreddy
Department of Oral Medicine and Radiology, MGV's KBH Dental College and Hospital, Nashik, Maharashtra
Source of Support: None, Conflict of Interest: None
Background and Objective: Oral submucous fibrosis (OSMF) is a juxtraepithelial inflammatory reaction followed by fibro elastic change of lamina propria. Hence, the inflammation is a definite component of OSMF. Combinations of turmeric, Aloe vera, and honey have antioxidant and anti-inflammatory effects which may act synergistically to serve as beneficiary for treating OSMF disease. Hence, the present study aims to compare the efficacy of topical application of novel gel containing curcumin, Aloe vera, honey, and physiotherapy with 0.1% triamcinolone acetonide and physiotherapy in the reduction of clinical signs and symptoms of OSMF patients. Materials and Methods: A total of 20 clinically diagnosed OSMF patients were divided into two groups containing 10 patients each. Participants including in Group A were treated with topical application of novel gel-containing curcumin, Aloe vera, and honey along with physiotherapy. Group B patients were treated with the topical application of 0.1% triamcinolone acetonide along with physiotherapy. Participants were evaluated at baseline and at the 7th day, 14th day, and 21st day. They were evaluated for mouth opening (maximum interincisal distance) and burning sensation (Visual Analogue Scale). Results: The reduction in burning sensation and increase in mouth opening is observed in both the groups. Both groups showed no statistically significant difference. Thus, both are statistically equally effective. Reduction burning sensation at the 21st day was more in Group A than in Group B, but difference is not statistically significant. Conclusion: Novel gel is as effective as topical steroid triamcinolone acetonide in reducing the signs and symptoms of OSMF.
Keywords: Aloe vera, curcumin, honey, oral submucous fibrosis, triamcinolone acetonide
|How to cite this article:|
Bhelonde AP, Bhoosreddy AR, Bhadage CJ, Giri PR, Dhuldhule SK, Kulkarni AM. Comparative evaluation of novel gel-containing curcumin, Aloe Vera, and honey with triamcinolone acetonide as an adjunct to oral physiotherapy in oral submucous fibrosis patients: A pilot study. J Dent Res Rev 2021;8:25-30
|How to cite this URL:|
Bhelonde AP, Bhoosreddy AR, Bhadage CJ, Giri PR, Dhuldhule SK, Kulkarni AM. Comparative evaluation of novel gel-containing curcumin, Aloe Vera, and honey with triamcinolone acetonide as an adjunct to oral physiotherapy in oral submucous fibrosis patients: A pilot study. J Dent Res Rev [serial online] 2021 [cited 2021 Jun 20];8:25-30. Available from: https://www.jdrr.org/text.asp?2021/8/1/25/310194
| Introduction|| |
Oral submucous fibrosis (OSMF) is defined as “An insidious chronic disease affecting any part of oral cavity and sometimes the pharynx. Although occasionally preceded by and/or associated with vesicle formation, it is always associated with a juxta-epithelial inflammatory reaction followed by a fibroelastic change of the lamina propria, with epithelial atrophy leading to stiffness of the oral mucosa and causing trismus and inability to eat.”, The prevalence of OSMF is found to be 6.42 per 1000, and the male-to-female ratio, 4.9:1. OSMF has a multifactorial etiology. Chewing of the areca nut, use of tobacco, consumption of chilies, genetic susceptibility, autoimmunity, and nutritional deficiencies have been attributed to the pathogenesis of OSMF. Symptoms of OSMF include burning sensation of the oral mucosa, blanching of oral mucosa, and progressive reduction of mouth opening. The involvement of faucial pillars ranges from a slight submucosal accumulation of fibrous tissue in both pillars to a dense fibrosis extending deep into the pillar with strangulation of the tonsils. Thus, in OSMF, fibrosis is wide spread. It progressively involves buccal mucosa, labial mucosa, tongue, floor of mouth, and soft palate.
Turmeric (Curcuma longa) is a medicinal plant extensively used in Ayurveda. Curcumin (principle curcuminoid of turmeric) is considered as safe, nontoxic, and effective alternative for many traditional drugs because of its therapeutic properties. Aloe vera (Aloe barbadensis miller and Indian Aloe) leaves have wound healing, anti-inflammatory, anticancer, immunomodulatory, and gastroprotective properties. Honey acts as permeability enhancer. Local drug delivery may provide a more targeted and efficient drug systemic delivery for the diseases of the oral mucosa.,, These properties could be collectively used in the management of OSMF. Earlier clinical studies reported safety and efficacy of curcumin, A. vera and honey individually and/or in combination in the management of OSMF patients.,,,,, However, very few researches have shown the efficacy of topical application of gel containing curcumin in combination with A. vera and honey as targeted local drug delivery in OSMF. In a study conducted by Syed et al., positive results were obtained with the use of mucoadhesive patch of curcumin in OSMF. In a study conducted by Yadav et al., intralesional dexamethasone and hyaluronidase were compared with curcumin tablet for 3 months in OSMF also obtained positive results. These studies were either invasive or uncomfortable for the patients. In a study conducted by Hazrey et al., efficacy of curcumin lozenges was compared with that of topical steroid clobetasol propionate 0.05%. It also showed positive results. None of the above-mentioned studies utilized the combination of herbal product which could act synergistically in the management of OSMF.
Hence, the study was planned aiming to evaluate the difference in the reduction of clinical signs and symptoms by the topical application of novel gel and physiotherapy with 0.1% triamcinolone acetonide and physiotherapy in OSMF patients.
| Materials and Methods|| |
This randomized clinical trial was conducted in a dental college and hospital situated in North Maharashtra, India. Approval was obtained by an Institutional Ethical Committee of dental College and Hospital as per the Maharashtra University of Health Sciences, Maharashtra, India (KBH/IEC/AL/028 Dated: 31/01/2020). A total of 20 clinically diagnosed patients with OSMF were selected randomly for the study.
Patients from 16 to 75 years of age who are willing to give informed written consent and participate in study with regular follow-up and diagnosed clinically with OSMF were included in the study. Patients undergoing any other treatment for OSMF or who has undergone any other treatment for OSMF within the period of 3 months, individuals with reduced mouth opening for other reason than OSMF and patients allergic to (turmeric extract) curcumin, A. vera, honey, and triamcinolone acetonide were excluded from the study.
The selected patients were asked to discontinue the habits of tobacco or areca-nut usage. Clinical grading of the OSMF patients was done as per in previous study by Hazarey VK and Priyadharshni B. et al. classification based on interincisal distance., A total of 20 OSMF patients included in the study. These patients were divided randomly into two groups: Group A and Group B containing 10 patients each, as shown in [Figure 1]. Group A patients received the topical application of Novel gel (The gel was prepared at the local Pharmacy College and contains curcumin, A. vera, and honey as main ingredients. 10 g of novel gel contains 0.1 g curcumin, 0.5 g honey, and 9.39 g A. vera, 0.003 g methyl paraben and 0.001 g propyl paraben as preservatives and 0.0001 g Butylated hydroxytoluene as antioxidant). This dose was very low to the safety limits for the herbal products. Patients were advised for mouth opening exercise and topical application of gel three times a day for 21 days. Group B patients were instructed for mouth opening exercise and topical application of 0.1% triamcinolone acetonide (commercially available as Kenacort 0.1% manufactured by Mepromax Lifesciences Pvt. Ltd. Marketing Authorization Holder: Abbott Healthcare Pvt.) three times a day for 21 days.
Instructions for topical application procedure for both groups-pea sized amount of gel to be taken and applied on mucosa where fibrous bands are palpable. Gel should be applied by massaging it on buccal mucosa. Patients were instructed to rinse mouth with water after 10–15 min and not to eat anything for about half an hour before and after the application of gel.
All the patients were advised for mouth opening exercise. To increase the extensibility of the buccal mucosa, they were advised blowing the mouth and tongue protrusion exercises, tongue blade exercise by placing ice cream sticks between the jaws and increasing one by one to provide stretch and maintaining for 3–5 min for three times a day with in tolerable pain limits. Patients in both the groups were evaluated at baseline and on the 7th, 14th, and 21st day after baseline for maximum mouth opening and burning sensation.
After clinical observations, the collected data were tabulated and then subjected to statistical analytical tests using the produced by IBM in Armonk, New York, United states of America. The unpaired t-test was applied to compare maximum mouth opening in both the groups at baseline and at regular interval at 18 degrees of freedom and 95% confidence level. Moreover, similarly, compared for burning sensation. The pretreatment and post treatment values in both the groups were compared using the paired t-test at 9 degrees of freedom and 95% confidence level separately. P ≤ 0.05 was considered statistically significant.
| Results|| |
All OSMF patients included in the study were males, in the age group of 20–40 years. There were 7 patients having tobacco chewing and smoking habit, 6 were tobacco chewer, 4 were tobacco and betel quid chewer, and 3 were tobacco smokers out of 20 OSMF patients. [Table 1] summarizes the demographic data.
To compare improvement in burning sensation and mouth opening in both groups, they are evaluated at baseline (T0), at the 7th day (T1), 14th day (T2), and at 21st day (T3). The recorded parameters for both the groups are compared separately at the end of every time interval using the unpaired t-test at 18 degrees of freedom and 95% confidence level. [Table 2] shows the results obtained for the same.
The comparison of burning sensation in both the groups at baseline (T0) (P = 0.05726) after 1 week (T1) (P = 0.2513), after 2 weeks (T2) (P = 0.3326) and at the end of treatment (T3) (P = 0.2626) showed no statistically significant difference (P = 0.057), as shown in [Table 2]. Thus, the treatment regimens in both the groups are statistically either equally effective or ineffective in reducing burning sensation.
Similarly, the mouth opening in both the groups at T0 (P = 0.25) T1 (P = 0.25), T2 (P = 0.25) and T3 (P = 0.250) shows no statistically significant difference. It means both the groups produces similar effects on mouth opening, as shown in [Table 2].
It can be observed that there is no significant difference in the average value of Visual Analog Scale score as well as average interincisal distance in the groups treated with two different medicines. Thus, it can be concluded that both medicines along with physiotherapy are either equally effective or ineffective in reducing burning sensation and increasing mouth opening in OSMF patients, as depicted in [Figure 2] and [Figure 3].
|Figure 3: Comparison between group A and group B for interincisal distance|
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Furthermore, both the groups were evaluated for pretreatment and posttreatment improvement in OSMF patients, as shown in [Table 3].
|Table 3: Within group comparison for novel gel and 0.1% triamcinolone acetonide|
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In Group A participants, burning sensation at T0 (6.3 ± 1.345) and T3 (3.6 ± 1.019) shows P ≤ 0.05 which showed statistically significant reduction in burning sensation. For maximum mouth opening at T0 (28.5 ± 5.12) and at T3 (28.8 ± 5.3) also showed significant P ≤ 0.05. Thus, Group A receiving novel gel along with physiotherapy showed improvement in reducing the sign and symptoms in OSMF patients.
In Group B, burning sensation at T0 (5.4 ± 0.91) and T3 (3.9 ± 0.94) shows P ≤ 0.05, showed and for maximum mouth opening at T0 (26.6 ± 6.28) and T3 (27 ± 6.496) shows P ≤ 0.05. Thus, 0.1% triamcinolone acetonide along with physiotherapy also showed effectiveness in OSMF Group B participants.
Thus, both the treatment medicines are effective in the improvement of burning sensation and increasing mouth opening. All the patients included in the study showed good compliance with gel and only positive results were obtained which improved OSMF condition at the 21st day, as shown in [Figure 4] and [Figure 5].
| Discussion|| |
In the present study, novel gel along with physiotherapy showed improvement in sign (mouth opening) and symptom (burning sensation) as similar as topical steroid therapy with 0.1% triamcinolone acetonide along with physiotherapy. Group A and Group B showed greater reduction in burning sensation at the 7th day of follow-up which was then further reduced at the end of the treatment. The reduction occurred in Group A was slightly more than Group B, though it is not statistically significant (P > 0.05). At the middle of the 7th and 14th day, the effect of both treatments was similar, but at the 21st day, burning sensation in Group A participants (3.6 ± 1.019) was lesser than Group B participants (3.9 ± 0.943), but their difference is not significant, as depicted in [Figure 2]. The anti-inflammatory and antioxidant activity of curcumin could be one of the reasons for significant reduction of burning sensation.,
In between group comparison for maximum mouth opening, initially, the curve is flat till the 7th day of treatment [Figure 2]. However rises after the 7th day and show statistically significant results (P ≤ 0.05). [Figure 4] shows the effects of novel gel in OSMF patients. The area denoting burning sensation sharply reduces as duration very close to attain zero. Simultaneously, the area of mouth opening increases with the duration. Similarly, [Figure 5] shows the effects of triamcinolone acetonide. Since the area of burning sensation reduces significantly with time, conversely increasing area of mouth opening is seen. Hence, within group comparison for both groups individually shows improvement in reducing the signs and symptoms of OSMF.
Earlier studies reported that various different types of treatment modalities have been tried for OSMF, but no definitive therapy has been defined for the management of OSMF.,
Reported studies suggested Curcumin and A. vera as effective modalities in managing OSMF without any side effects.,,, Moreover, the effectiveness of steroids in treating OSMF is already evident from huge previous literature. However, there are very few evidences on efficacy of curcumin in combination with A. vera and honey as targeted local drug delivery in OSMF subjects. Hence, the present study compares the efficacy of novel gel to well-known topical steroid treatment for OSMF participants to reduce their chief signs and symptoms.
In a study conducted by Hazrey et al., efficacy of curcumin lozenges was compared with that of topical steroid clobetasol propionate 0.05% along with physiotherapy in OSMF patients and showed statistically significant results after 3 months in the improvement of burning sensation and mouth opening. Aich R. et al. conducted study to evaluate the efficacy of novel herbal mouth rinse containing Curcumin, Triphala, and Honey and found out it as effective in relieving symptoms associated with OSMF after 60 days. The results obtained in the present study were consistent with the previous studies, but the duration is much shorter. In the present study, significant reduction in burning sensation and mouth opening was obtained at the 21st day with the topical application of both medicaments. Similarly, positive results were obtained in study on mucoadhesive patch of curcumin in OSMF conducted by Syed et al.; however, they have used mucoadhesive patch that could be very uncomfortable for patients so lack of patient compliance is a major disadvantage. Alam et al. evaluated the efficacy of Aloe vera gel as adjuvant therapy in OSMF patients and concluded Aloe vera gel as an adjuvant to intralesional steroids and surgical procedure in the management of OSMF. In a study conducted by Yadav et al., intralesional dexamethasone and hyaluronidase were compared with curcumin tablet for 3 months in OSMF, they found out curcumin tablet were more efficient in reducing burning sensation. However, improvement in mouth opening was approximately equal in both the groups. Whereas, OSMF participants in our study were treated with noninvasive, comfortable, and easy local drug delivery method to obtain the nearly similar results.
Local drug delivery reduces the drug concentration needed for and increases bioavailability locally, hence low level of drug in blood. Which ultimately reduces systemic concentration thus minimising systemic toxicity. Furthermore reduces the risk of emergence of resistance, prolong duration of action, and better patient compliance. Hence, local drug delivery system can be preferred choice while considering for the management of OSMF., It has been reported in a study that curcumin inhibits cell proliferation in fibroblasts and myofibroblasts., Curcumin has a scavenging effect of on superoxide radicals, hydroxyl radicals and lipid peroxidation. Hence, the effect of curcumin could be brought about by synergism of their anti-inflammatory and antioxidant properties. This anti-inflammatory and antioxidant activity of curcumin would have been responsible for significant reduction of burning sensation., A. vera is an emollient resin and a mannoprotein containing many amino acids that have been called “wound-healing hormones.” The polysaccharides in the A. vera gel of the leaves have wound healing, anti-inflammatory properties. The effect of honey on infection is not only related to antibacterial agents but also to its effect on the immune system by stimulating the antibodies in the primary and secondary immune response., The positive outcome observed in the OSMF patients might be due to the synergistic mechanism of action of the ingredients of the Novel gel along with physiotherapy in the management of OSMF. However, the positive effects could also be due to use of antioxidant Butylated Hydroxyl Toluene in the preparation of gel; this could be limitation of our study. Other limitations are smaller sample size and duration of treatment also we could not evaluate the long-term effects of treatment.
Thus, further studies are needed to evaluate long-term effects with large sample size.
This research did not receive any financial support or sponsorship from funding agencies in public or commercial sectors.
| Conclusion|| |
Thus, it can be concluded that combination modality such as stoppage of habits, physiotherapy, and topical application of novel gel and steroid are effective in case of OSMF. Novel gel-containing curcumin, A. vera, and honey are effective in the symptomatic treatment of OSMF. Topical application of herbal products shows similar effects as steroids which can reduce several adverse effects of the topical application of steroids. It is evident from the present study that in the short span combination of curcumin, A. vera, honey along with physiotherapy holds good promise in case of OSMF.
The authors extend their sincere thanks to MGV'S pharmacy college Nashik for assisting us in preparation of novel gel-containing Curcumin, Aloe vera, and Honey.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2], [Table 3]