Curcumin in the treatment of oral submucous fibrosis: a systematic review and meta-analysis of randomized controlled trials.

The objective was to evaluate the efficacy of curcumin in improving mouth opening (MO), burning sensation (BS), and tongue protrusion (TP) symptoms in patients with oral submucous fibrosis (OSF). An electronic search up to November 2022 was conducted in the PubMed, Web of Science, Embase, EBSCO, ProQuest, and Cochrane Library databases to identify studies using curcumin in the treatment of OSF with comparison to control groups (drugs previously proven to be effective for OSF treatment) or placebo. Only randomized controlled trials (RCTs) were considered. RevMan 5.3 software was used for the meta-analysis. Thirteen RCTs met the eligibility criteria and were included in the analysis. The results showed no significant improvement in MO (in millimetres) for curcumin when compared to control at 1 month (P = 0.91), 2 months (P = 0.54), 3 months (P = 0.56), or 6 months (P = 0.17) of treatment. There was no significant difference in BS (assessed using a visual analogue scale) between curcumin and control after 1 month (P = 0.05), 2 months (P = 0.64), 3 months (P = 0.13), or 6 months (P = 0.56) of treatment. Compared with the control groups, treatment with curcumin for 1 month (P = 0.32), 2 months (P = 0.07), and 3 months (P = 0.14) did not significantly improve the TP (in millimetres) of patients. The administration of curcumin, whether topically applied or taken orally, did not confer statistically significant improvements in MO, BS, or TP in comparison to the control treatments, among patients with OSF. The results of this meta-analysis showed that compared to placebo, the application of curcumin for 6 months markedly alleviated BS (P < 0.001). Curcumin treatment in OSF reaches a clinically effective range, but more bioavailability-centred outcomes should be reported. Robust multicentre RCTs are warranted to elucidate the efficacy of curcumin in improving specific outcomes like MO, BS, and TP in patients with this condition. Defining the therapeutic role of this natural compound may provide an effective botanical alternative for managing OSF.

Drug treatment for oral submucous fibrosis: an update.

OBJECTIVE: The aim of this review is to evaluate the different medicinal interventions available for the management of oral submucous fibrosis (OSF). MATERIALS AND METHODS: We conducted a comprehensive electronic search on PubMed, Web of Science, and Cochrane Library databases for articles related to OSF patients treated with medications from December 2011 to September 2022. GRADE system was used to evaluate the evidence quality. The reporting of the systematic review is in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. The main outcomes were the improvement of maximum mouth opening, burning sensation, cheek flexibility, and tongue protrusion. RESULTS: Twenty-nine randomized controlled trials (RCTs), five clinical trials (CCTs) were included, and the use of drugs for OSF treatment were evaluated. Drugs like steroids, hyaluronidase, pentoxifylline, lycopene, curcumin, dpirulina, aloe vera, omega3, oxitard, allicin, colchicine have been used. It was found that drugs with evidence high quality were salvia miltiorrhiza combined with triamcinolone acetonide, lycopene, pentoxifylline, curcumin, and aloe vera, and those with evidence moderate quality were allicin, colchicine, omega 3, and oxitard. CONCLUSION: Based on the results of our comprehensive analysis, for long-term treatment, we found lycopene with low side effects, whereas for relieving the symptoms of severe burning sensation, aloe vera is the most effective. Although the recent review has made some progress, drug therapy for OSF remains unclear, and more high-quality RCTs are needed to identify better treatments for OSF.

Polyphenol-based targeted therapy for oral submucous fibrosis.

Oral submucous fibrosis (OSF) is a chronic, progressive, and precancerous condition mainly caused by chewing areca nut. Currently, OSF therapy includes intralesional injection of corticosteroids with limited therapeutic success in disease management. Therefore, a combined approach of in silico, in vitro and in vivo drug development can be helpful. Polyphenols are relatively safer than other synthetic counterparts. We used selected polyphenols to shortlist the most suitable compound by in silico tools. Based on the in silico results, epigallocatechin-3-gallate (EGCG), quercetin (QUR), resveratrol, and curcumin had higher affinity and stability with the selected protein targets, transforming growth factor beta-1 (TGF-ß1), and lysyl oxidase (LOX). The efficacy of selected polyphenols was studied in primary buccal mucosal fibroblasts followed by in vivo areca nut extract induced rat OSF model. In in vitro studies, the induced fibroblast cells were treated with EGCG and QUR. EGCG was safer at higher concentrations and more efficient in reducing TGF-ß1, collagen type-1A2 and type-3A1 mRNA expression than QUR. In vivo studies confirmed that the EGCG hydrogel was efficient in improving the disease conditions compared to the standard treatment betamethasone injection with significant reduction in TGF-ß1 and collagen concentrations with increase in mouth opening. EGCG can be considered as a potential, safer and efficient phytomolecule for OSF therapy and its mucoadhesive topical formulation help in the improvement of patient compliance without any side effects. Highlights Potential polyphenols were shortlisted to treat oral submucous fibrosis (OSF) using in silico tools Epigallocatechin 3-gallate (EGCG) significantly reduced TGF-ß1 and collagen both in vitro and in vivo EGCG hydrogel enhanced antioxidant defense, modulated inflammation by reducing TGF-ß1 and improved mouth opening in OSF rat model.

Efficacy of Curcumin in Combination with Intralesional Dexamethasone with Hyaluronidase in the Treatment of Oral Submucous Fibrosis: A Randomized Controlled Trial.

OBJECTIVE: The objective of this study was to determine the efficacy of curcumin in combination with  intralesional dexamethasone with hyaluronidase in the treatment of oral submucous fibrosis (OSF). METHODS: This randomized, double blind, parallel design, clinical trial was conducted at B.P. Koirala Institute of Health Sciences, Nepal. Thirty-four patients with clinically diagnosed OSF were randomized into two groups (17 participants in each) with baseline treatment of intralesional dexamethasone with hyaluronidase for 6 weeks for the both. Curcumin (2gm/day) was provided to Group A (Test) and Group B (Control) received placebo. Interincisal mouth opening, tongue protrusion, cheek flexibility and visual analogue scale (VAS) scoring of burning sensation of oral mucosa was recorded at baseline, 6, 8 and 12 weeks follow-up and independent t-test was used to compare the improvements in two groups. RESULTS: On comparing the 6 weeks and baseline values, in Group A and B the mean difference in mouth opening was 8.82±1.33 mm and 5.53±1.17 mm respectively (p<0.001), in cheek flexibility was 2.94±1.02 mm and 1.94±1.24 mm respectively (p=0.02) and in tongue protrusion was 6.23±1.48 and 3.65±1.37 mm respectively (p<0.001). The findings were consistent in the 8 weeks follow-up. In 12 weeks follow-up, on comparing with the baseline values, in Group A and B, the mean difference in mouth opening was 8.71±1.16 mm and 5.35±1.22 mm respectively (<0.001), ), in cheek flexibility was 2.81±1.01 mm and 1.76±1.35 mm respectively (p=0.02) and in tongue protrusion was 6.06±1.48 and 3.35±1.50 mm respectively (p<0.001). Both the arms showed 100% improvement in burning sensation in 6, 8 and 12 weeks follow-up. CONCLUSION: Curcumin in combination with intralesional dexamethasone with hyaluronidase is efficacious in the treatment of OSF.

Clinical Assessment of Efficacy of Omega 3 in Oral Submucous Fibrosis Patients - A Randomized Controlled Trial.

BACKGROUND: Oral submucous fibrosis (OSMF) is a chronic, potentially malignant condition affecting the oral cavity. Omega 3 has shown innumerable health benefits in yesteryears. So, the aim of the study was to evaluate the efficacy of Omega 3 in the medical management of this disease. METHODS: A randomized controlled trial was designed and 48 clinically confirmed patients of OSMF (24 in each group) completed the study. Patients of both the groups were given biweekly intralesional injections of dexamethasone 1.5ml, hyaluronidase 1500 IU mixed with lignocaine for 6 weeks. Additionally, group A received a placebo (lactose capsule) for 3 months while group B received 1gm of omega 3 (flaxseed oil) three times daily continuously for 3 months. Patients were followed every month for 3 months and then, after 6 months and one year. RESULTS: During the first two months, improvement was observed in both the groups independently but intergroup comparison showed no significant difference. However, after 3 months statistically significant (p<0.05) improvement among all three clinical parameters i.e. inter-incisal distance (mean improvement in group A = 3.79±1.07mm and group B = 6.58±1.24mm, p=0.019), tongue protrusion (mean improvement in group A = 1.87±1.54mm and group B = 4.62±1.78mm, p=0.044) and cheek flexibility (mean improvement in group A = 2.08±1.38mm and group B = 3.50±1.84mm, p=0.035) was observed in group B when compared to group A. In contrast, statistically significant improvement in burning sensation was observed after one month itself in group B when compared to group A (mean drop in group A = 2.5±0.78 points and group B = 6.0±1.144 points, p<0.05). CONCLUSION: Omega 3 in conjunction with intralesional injections is an effective therapy when compared to intralesional injections alone in treatment of patients with OSMF (grade II and III) with no side effects.

Black Turmeric and Aloe Vera in the Management of Oral Submucous Fibrosis: A Prospective Clinical Study.

AIM: To determine the therapeutic efficacy of Kali haldi in the management of Oral submucous Fibrosis (OSMF) v/s steroid therapy. MATERIALS AND METHODS: A clinical prospective study was conducted on 42 patients of oral submucous fibrosis were equally divided into 2 groups. Group A patients were treated with a mixture of powdered Kali Haldi and aloe vera gel in equal ratio 3 times a day for 3 months. Group B patients were treated with intralesional injection of hydrocortisone and hyaluronidase for 6 weeks with oral antioxidant supplements for 3 months. Burning sensation, cheek flexibility, mouth opening, and tongue protrusion were evaluated before, during, and after treatment at an interval of 15 days, 1 month, 2, month and 3 months. RESULTS: Statistically significant results were obtained at the end of 3 months duration for both the groups (P < 0.001). The Symptomatic correction was more evident in the case of Group A patients than Group B. Response of the ayurvedic regimen was potentially better as compared to the regular steroid therapy. CONCLUSION: The study concludes that Combination therapy works wonders in the case of OSMF in stages I, II, III and can be a good option, comparatively safe and with negligible side effects, but potent and equally effective management of oral submucous fibrosis. Henceforth, it will be better to do such kinds of studies on a vast scale including larger samples and longer duration to check the efficacy and durability of this ancient ayurvedic regimen.

Prevalence and Pattern of Self-medication with Alternative Medicine: Treatment-switch Analysis in Oral Submucous Fibrosis Patients.

AIM: The aim of this study was to investigate prevalence and pattern of self-medication with alternative medicine (ALM) among oral submucous fibrosis (OSF) patients with emphasis on treatment-switch analysis. METHODS: A total of 115 OSF patients were recruited and subjected to scientifically validated questionnaire. Two groups were identified: S-ALM: patients who have previously received modern medicinal treatment but switched to ALM; and DN-ALM: patients who started ALM from De Novo. RESULTS: A total of 37 (32.18%) patients reported use of the ALM at some point of time. Twenty-five (67.56%) switched to ALM, whereas 12 (32.43%) patients used ALM from De Novo. The pattern of switching to ALM in short period was significantly prevalent in patients with advanced stages (stage III and IV) as compared to early stages (stage I and II) of OSF. Clarified butter, glycerin, and honey were the most commonly used ALM in both the groups. The most common reasons for switching to ALM were the cost of treatment (32.00%), longer duration of medicinal treatment (24.00%) and ineffectiveness of the medications (24.00%). CONCLUSIONS: ALM usage is common in OSMF patients with significant percentage of patient switched from modern medicine to ALM. Therapeutic efficacy of ALM in OSF needs exploration in future.

Turmeric in the management of oral submucous fibrosis: A systematic review and meta-analysis.

Turmeric exhibits a big promise as a therapeutic agent in the management of oral submucous fibrosis (OSMF). The primary aim of our study is to synthesize the evidence of the use of turmeric/curcumin in the management of OSMF. The secondary goal of this study is to assess the limitations of previous studies to identify gaps in evidence for future research and give an evidence-based recommendation regarding the usage of turmeric/curcumin for OSMF patients and outline the direction of research. A comprehensive search of PubMed, Web of Science, Scopus, Cochrane Library database, Google Scholar, clinical trial registries, and hand searching was conducted from inception until December 2018. This systematic review was conducted according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (guidelines). In this review, 11 articles were selected for qualitative analysis and 3 out of 11 were selected for meta-analysis. Of these 11 studies, involving 428 patients, 7 were randomized control trials (RCTs), 1 was a nonrandomized trial, and 3 were observational studies. Turmeric was found to be effective in reducing signs and symptoms of OSMF in all 11 studies. All the studies included in this review have reported improvement in mouth opening after treatment with turmeric formulations. This could also be concluded from the meta-analysis of three RCTs. Similar improvement in tongue protrusion, burning sensation, and cheek flexibility has been reported. The lack of reliable evidence for the effectiveness of turmeric for the management of OSMF is illustrated by the paucity and poor methodological quality of studies retrieved for this review. We recommend that RCTs are needed using larger sample size with longer duration follow-up with special attention to the recurrence of signs and symptoms.

[Efficacy of curcumin in the treatment of oral submucous fibrosis: a Meta-analysis].

OBJECTIVES: This study was performed to review the efficacy of curcumin in the treatment of oral submucous fibrosis systematically. METHODS: We searched seven databases, including Web of Science, PubMed, EBSCO, The Cochrane Library, CNKI, WanFang Data, and VIP, to obtain randomized controlled trials related to the treatment of oral submucous fibrosis by curcumin. Each database was searched from inception to 30 June 2019. RevMan 5.3 software was used for the meta-analysis. RESULTS: Six randomized controlled trials involving 350 patients were included in this study. Meta-analysis showed that curcumin can increase the maximal mouth opening and improve burning sensation compared with placebo treatment. Curcumin was not as effective as the controls in achieving maximal mouth opening after 1 month of treatment. However, no statistically significant difference was observed between the treatments from 2 months to 6 months. Curcumin significantly improved burning sensation compared with the controls after 3 months of treatment. No statistically significant diffe-rence in burning sensation was observed between the curcumin and control groups after 1, 2, and 6 months of treatment. CONCLUSIONS: The current evidence shows that curcumin is an effective treatment for improving maximal mouth opening and burning sensation in patients with oral submucous fibrosis. Given the limited number and low quality of the included studies, however, more high-quality studies are needed to verify these findings.

Multi-target pharmacological mechanisms of Salvia miltiorrhiza against oral submucous fibrosis: A network pharmacology approach.

OBJECTIVES: The herb Salvia miltiorrhiza is used to treat oral submucous fibrosis (OSF); however, the mechanism underlying its efficacy has not been elucidated. As such, a network pharmacology-based approach was applied to investigate the potential mechanisms of Salvia miltiorrhiza against OSF. MATERIALS AND METHODS: Potential targets of Salvia miltiorrhiza were collected by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine, and Swiss Target Prediction. Potential targets of OSF were collected from DisGeNET, GeneCards, and National Center for Biotechnology Information Gene database. Salvia miltiorrhiza against OSF targets protein-protein interaction and enrichment analyses network were constructed by Cytoscape and Metascape. RESULTS: Twelve active ingredients from Salvia miltiorrhiza and 57 potential OSF-related targets were identified. The constructed network predicted seven potential key targets of Salvia miltiorrhiza for the treatment of OSF. Functional enrichment analysis showed that biological processes such as cellular response to drugs and pathways such as bladder cancer were mainly regulated by the Salvia miltiorrhiza active ingredient targets. Furthermore, the protein-protein interaction network demonstrated that the molecular complex detection components were mainly related to the ErbB signaling pathway, cancer pathways and IL-17 signaling. CONCLUSIONS: A network approach was employed to document how Salvia miltiorrhiza active ingredients change various pathways against OSF. Salvia miltiorrhiza active ingredient targets against OSF involved CYP19A1, EGFR, PTPN11, ACHE, TERT, MAPK8 and PGR and were enriched in several signaling pathways.

Herbal derivatives in the management of mouth opening in oral submucous fibrosis-A network meta-analysis.

OBJECTIVES: Oral submucous fibrosis is a potentially malignant disorder commonly seen in Asian countries. In this disease, the mucosa becomes stiff and patients have difficulty in mouth opening, thus affecting their quality of life. Recently, practitioners are focusing on herbal derivatives instead of commonly practiced intralesional steroids for the management of this disorder. Hence, we conducted a network meta-analysis of randomized clinical trials on herbal derivatives to identify the most effective treatment for oral submucous fibrosis. MATERIALS AND METHODS: Electronic search for articles published in various journals was undertaken through various search engines till January 2020. 14 articles were selected which had performed randomized control trials of herbal derivatives against control/placebo. Frequentist network meta-analysis was performed using R studio software, and effective treatment ranking was derived. RESULTS: The treatment ranking was generated, and relative to mouth opening, the most effective treatment was lycopene administered along with vitamin E and the second effective drug was aloe vera gel. CONCLUSION: This network meta-analysis highlights the efficacy of some of the drugs of herbal origin which can be implemented by the practitioners in the management of initial stages of oral submucous fibrosis.

Efficacy of curcumin in the treatment of oral submucous fibrosis: a Meta-analysis / 华西口腔医学杂志

OBJECTIVES@#This study was performed to review the efficacy of curcumin in the treatment of oral submucous fibrosis systematically.@*METHODS@#We searched seven databases, including Web of Science, PubMed, EBSCO, The Cochrane Library, CNKI, WanFang Data, and VIP, to obtain randomized controlled trials related to the treatment of oral submucous fibrosis by curcumin. Each database was searched from inception to 30 June 2019. RevMan 5.3 software was used for the meta-analysis.@*RESULTS@#Six randomized controlled trials involving 350 patients were included in this study. Meta-analysis showed that curcumin can increase the maximal mouth opening and improve burning sensation compared with placebo treatment. Curcumin was not as effective as the controls in achieving maximal mouth opening after 1 month of treatment. However, no statistically significant difference was observed between the treatments from 2 months to 6 months. Curcumin significantly improved burning sensation compared with the controls after 3 months of treatment. No statistically significant diffe-rence in burning sensation was observed between the curcumin and control groups after 1, 2, and 6 months of treatment.@*CONCLUSIONS@#The current evidence shows that curcumin is an effective treatment for improving maximal mouth opening and burning sensation in patients with oral submucous fibrosis. Given the limited number and low quality of the included studies, however, more high-quality studies are needed to verify these findings.

Efficacy of hyaluronidase combined with corticosteroids in treatment of oral submucous fibrosis: A meta-analysis of randomized controlled clinical trials.

OBJECTIVE: This meta-analysis was performed to systematically evaluate the efficacy of hyaluronidase combined with corticosteroids compared with other drugs in improving maximum mouth opening and alleviating the burning sensation in patients with oral submucous fibrosis (OSF). METHODS: PubMed, Embase, Web of Science and the Cochrane Library were searched. RevMan 5.3 software was used for the meta-analysis. RESULTS: Six studies involving 244 patients with OSF were analysed. No significant difference in improvement of maximum mouth opening was found between the hyaluronidase and control groups (lycopene, pentoxifylline, aloe vera, dexamethasone, Turmix [curcumin + piperine] and isoxsuprine) at 1 month (mean difference [MD]: 0.32, 95% confidence interval [CI]: -0.92-1.56, P = .61, I2  = 57%), 2 months (MD: 0.49, 95% CI: -0.14-1.12, P = .12, I2  = 41%) or 3 months (MD: 0.40, 95% CI: -1.08-1.87, P = .60, I2  = 92%). Additionally, no statistically significant difference was found in alleviation of the burning sensation between the two groups at 1 month (MD: 0.54, 95% CI: -0.62-1.71, P = .36, I2  = 0%), 2 months (MD: 0.53, 95% CI: -0.85-1.91, P = .45, I2  = 0%) or 3 months (MD: 0.64, 95% CI: -1.07 to 2.35, P = .46, I2  = 0%). CONCLUSIONS: According to this meta-analysis, weak evidence indicates that hyaluronidase combined with corticosteroids has no additional clinical benefit over control drugs (lycopene, pentoxifylline, aloe vera, dexamethasone, Turmix and isoxsuprine) in improving maximum mouth opening and alleviating the burning sensation in patients with OSF. Therefore, more high-quality, multi-centre randomized controlled trials with larger samples are needed to further assess the efficacy of hyaluronidase combined with corticosteroids in the treatment of OSF.

Efficacy of Salvia miltiorrhiza injection combined with steroids in the treatment of oral submucous fibrosis: A meta-analysis of randomized controlled trials.

BACKGROUND: This study was performed to systematically review the efficacy of Salvia miltiorrhiza injection combined with steroids in the treatment of oral submucous fibrosis. METHODS: We searched 9 databases: Web of Science, PubMed, Medline, EBSCO, Embase, The Cochrane Library, WanFang Data, the China National Knowledge Infrastructure (CNKI), and Chinese Scientific Journals Full-text Database (VIP). Randomized controlled trials were collected to study the treatment of oral submucous fibrosis by S miltiorrhiza injection combined with steroids. Each database was searched from inception to November 2018. RevMan 5.3 software was used for the meta-analysis. RESULTS: In total, 13 randomized controlled trials involving 1190 patients were included. The results of the meta-analysis showed that compared with conventional treatment, S miltiorrhiza injection combined with steroids could significantly increase the maximal mouth opening [mean difference (MD), 0.23; 95% confidence interval (CI), 0.16-0.30; P <.0001], decrease the oral mucosal lesion area (MD, -1.35; 95% CI, -2.46 to -0.25; P = .02), improve the subjective symptom burning sensation (MD, -0.77; 95% CI, -1.38 to -0.16; P = .01), and reduce adverse drug reactions (risk ratio, 0.27; 95% CI, 0.14-0.49; P <.0001). CONCLUSIONS: The results of this meta-analysis from current evidence showed that compared with conventional treatment, S miltiorrhiza injection combined with steroid could significantly improve the maximal mouth opening and the subjective symptom burning sensation as well as decrease the oral mucosal lesion area without increasing adverse effects.

Comparison of therapeutic response of lycopene and curcumin in oral submucous fibrosis: A randomized controlled trial.

OBJECTIVES: To evaluate and compare the therapeutic response of lycopene and curcumin with placebo in patients suffering from oral submucous fibrosis (OSMF) and to correlate the habit variables of smoked and smokeless tobacco products in OSMF. METHODS: A randomized placebo-controlled parallel clinical study was conducted on ninety OSMF patients, who were divided into three treatment groups using computer-generated randomization. Group A patients (n = 30) were given curcumin tablet (300 mg) twice daily, Group B patients (n = 30) received lycopene capsules (8 mg) twice daily, and for Group C (n = 30), placebo capsules were given once daily for a period of six months. Both the participant and outcome assessor were blinded. Pre- and post-treatment comparison of mouth opening, burning sensation, tongue protrusion, and cheek flexibility was analyzed at periodic follow-up of 9 months. RESULTS: The overall improvement in mouth opening, burning sensation, tongue protrusion, and cheek flexibility was 3.9 ± 4.9 mm, 4.8 ± 2.6, 5.0 ± 7.2 mm, & 0.36 ± 0.71 mm, respectively, for curcumin and 4.1 ± 4.2 mm, 5.0 ± 2.3, 2.4 ± 3.5 mm, & 0.66 ± 0.80 mm, respectively, for lycopene with the p value <0.05. CONCLUSION: Statistically significant improvement in clinical findings was observed in both curcumin and lycopene treatment groups in comparison with placebo. However, the therapeutic efficacy of curcumin and lycopene was found to be almost equal in OSMF patients.

Aloe vera in treatment of oral submucous fibrosis: A systematic review and meta-analysis.

The management of oral submucous fibrosis (OSF) is quite challenging, and as yet, no effective therapy is available for its management. The present systematic review and meta-analysis sought to assess the effectiveness of aloe vera in alleviating pain and clinical signs of OSF. A comprehensive search in PubMed/Medline, Scopus, and Web of Science databases was conducted to identify the relevant randomized clinical trials. RevMan 5.3 software was used for data analysis. Six randomized controlled trials fulfilled the inclusion criteria. The results of meta-analysis showed statistically significant differences between aloe vera and control groups in alleviating pain/burning sensation at the end of the first and second month, in favor of aloe vera, but no significant differences were found at the end of the third month. With regard to objective clinical outcomes, no statistically significant differences were found between the groups. Aloe vera has a promising effect in reducing pain/burning sensation and clinical improvement in patients with OSF. However, owing to the marked heterogeneity of the included studies, conducting well-designed trials with long follow-up periods, standardized outcome measures and adequate sample sizes are warranted.

A comparative study to evaluate the efficacy of lycopene and curcumin in oral submucous fibrosis patients: A randomized clinical trial.

BACKGROUND: : Oral submucous fibrosis (OSMF) is a most prevalent potentially malignant disorder associated with betel quid chewing frequently observed in the Indian population. The present study conducted is much of a keen interest because there is much new information, both in the press and the medical literature, about the benefits of fresh fruits and vegetables and antioxidants (such as lycopene and curcumin) for both prevention and treatment of diseases. As clinicians, we often prescribe medications with significant adverse effects, and certainly, if armed with evidence to support using such antioxidants as safer therapeutic alternatives for treatment of OSMF. AIMS AND OBJECTIVE: The aim of the study was to compare and evaluate the efficacy of lycopene and curcumin given orally in clinically diagnosed OSMF patients. MATERIALS AND METHODS: Sixty patients were divided randomly into two groups Group A and Group B. After fulfilling the eligibility criteria, sixty patients were randomly allotted based on fishbowl method into thirty each. This technique eliminated the selection bias arising in the study. Group A individuals were treated with 4 mg of lycopene and Group B individuals were given 300 mg of curcumin thrice daily for 3 months. Both the groups were assessed in terms of mouth opening and burning sensation. The statistical analysis was done using SPSS Version 16.0 statistical Analysis Software. RESULTS: In Group A, the initial burning sensation was 65.83 ± 3.98%, and in Group B, it was 62.33 ± 5.22% (visual analog scale). After 3 months, there was complete cessation of burning sensation in both the groups. Burning sensation between the groups was statistically nonsignificant (P > 0.05). In Group A, mean mouth opening at baseline (1st visit) observed was 3.17 ± 0.08 cm which improved to 3.52 ± 0.07 cm after 3 months of the treatment period. In Group B, mean mouth opening at baseline (1st visit) observed was 3.32 ± 0.07 cm which improved to 3.52 ± 0.08 cm after 3 months of the treatment period. On comparing intergroup, the difference was statistically nonsignificant (P > 0.05). However, on comparing intergroup, average percent change in mean mouth opening from 1st visit to subsequent time intervals across the time period was found to be statistically significant (P < 0.05). Group A showed 11.1 ± 1.0% improvement in mean mouth opening and Group B showed 6.2 ± 0.4% improvement in the mean mouth opening from the 1st visit till the posttreatment period. The change in the mean mouth opening from 1st visit till posttreatment in Group A was 0.35 ± 0.14, and in Group B, it was 0.20 ± 0.09. CONCLUSION: Lycopene showed better results than curcumin in improving mouth opening; both the drugs were equally effective in decreasing burning sensation in OSMF patients.

[Clinical effectiveness of salvianolic acid B and triamcinolone acetonide in treatment of oral submucous fibrosis].

Objective: To evaluate the clinical effectiveness of salvianolic acid B (SA-B) and triamcinolone acetonide (TA) by means of combined intralesional injection in the treatment of oral submucous fibrosis (OSF). Methods: According to clinical findings and symptoms, TA combined with SA-B were consecutively applied intralesionally 1 time weekly for 30 times. Mouth opening degree, color change of the buccal mucosae and numeral increase of the capillary vessels were determined by degree Ⅰ-Ⅳ visual analog scale were evaluated at 12, 24, and 36 months, respectively. Results: One hundred and fourteen subjects fulfilled the study without obvious adverse reactions. After treatment for 1 year, the net gain in mouth opening of the early stage group was (5.5 ± 1.5) mm at 12 months, (8.8 ± 1.6) mm at 24 months and (12.0±1.2) mm at 36 months. The net gain in mouth opening of the middle stage group were (5.3±1.7) mm at 12 months, (10.5±1.5) mm at 24 months and (14.5±2.4) mm at 36 months. The net gain in mouth opening of the advanced stage group were (5.7±1.3) mm at 12 months, (13.7±1.3) mm at 24 months and (15.5±1.5) mm at 36 months. The effective rates of color change of the buccal mucosae and numeral increase of the capillary vessels after treatment for 36 months were 100% in early stage group, 93% (51/55) in middle stage group and 90% (36/40) in advanced stage group. Conclusions: TA and SA-B combined intralesional injection in the treatment of oral submucous fibrosis is effective.

Omega 3: a novel treatment agent in oral submucous fibrosis: a pilot study.

BACKGROUND: Oral submucous fibrosis (OSF) is a chronic debilitating disease and a premalignant condition of the oral cavity. It is well known for its impervious nature to medical therapy. Omega-3 polyunsaturated fatty acids have been reported to have anti-inflammatory properties. However, its role in OSF is still not known. This preliminary study assessed the efficacy of systemic omega 3 in this disease. METHODS: A randomized single-blinded controlled trial was designed, and a total of 10 clinically confirmed adult patients with OSF were included in the study. Group A was given biweekly intralesional injections of dexamethasone 1.5 ml and hyaluronidase 1500 IU mixed with lignocaine for 6 weeks and a placebo for 3 months. Group B was also given similar intralesional injections but with 1 gm of omega 3 three times daily continuously for 3 months. Patients were followed every month for 3 months and then after 6 months. RESULTS: Significant improvement was noted among all clinical parameters (interincisal distance, tongue protrusion, cheek flexibility, and visual analogue scale) in both the groups. Intergroup comparison showed significant reduction in burning sensation in group B; that is, P value was 0.005, while improvement in rest of the three clinical features was not statistically significant. CONCLUSION: Omega 3 can be used as an adjunctive treatment option in patients with OSF to reduce subjective symptoms. More studies should be conducted with a larger sample size to study the effect of omega 3 in patients with OSF.

Antifibrotic effect of Centella asiatica Linn and asiatic acid on arecoline-induced fibrosis in human buccal fibroblasts.

AIM: The aim of the present study was to investigate the in vitro antifibrogenic effects of Centella asiatica Linn (CA) and its bioactive triterpene aglycone asiatic acid (AA) on arecoline-induced fibrosis in primary human buccal fibroblasts (HBF). METHODS: An ethanolic extract of CA was prepared, and AA was purchased commercially. High-performance thin-layer chromatography (HPTLC) was performed to quantify AA in the CA extract; colorimetric assay (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) was performed to determine an half-maximal inhibitory concentration. HBF were cultured and stimulated with arecoline. The inhibitory effects of CA and AA at different concentrations were assessed using gene-expression studies on fibrosis-related markers: transforming growth factor-ß1, collagen 1 type 2, and collagen 3 type 1. The stimulatory effect of arecoline and the inhibitory effect of AA on fibroblast morphology and extracellular matrix were assessed qualitatively using Masson trichrome stain. RESULTS: The HPTLC analysis determined 1.2% AA per 100 g of CA extract. Arecoline produced a concentration-dependent increase in the fibrotic markers, treatment with CA significantly downregulated fibrotic markers at higher concentrations, and AA downregulated at lower concentrations. Arecoline altered fibroblast morphology and stained strongly positive for collagen, and AA treatment regained fibroblast morphology with faint collagen staining. CONCLUSION: CA and AA can be used as antifibrotic agents.