Interventions for managing oral submucous fibrosis.

BACKGROUND: Oral submucous fibrosis (OSF) is a chronic disease of the oral cavity that causes progressive constriction of the cheeks and mouth accompanied by severe pain and reduced mouth opening. OSF has a significant impact on eating and swallowing, affecting quality of life. There is an increased risk of oral malignancy in people with OSF. The main risk factor for OSF is areca nut chewing, and the mainstay of treatment has been behavioural interventions to support habit cessation. This review is an update of a version last published in 2008. OBJECTIVES: To evaluate the benefits and harms of interventions for the management of oral submucous fibrosis. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 5 September 2022. SELECTION CRITERIA: We considered randomised controlled trials (RCTs) of adults with a biopsy-confirmed diagnosis of OSF treated with systemic, locally delivered or topical drugs at any dosage, duration or delivery method compared against placebo or each other. We considered surgical procedures compared against other treatments or no active intervention. We also considered other interventions such as physiotherapy, ultrasound or alternative therapies. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. participant-reported resumption of normal eating, chewing and speech; 2. change or improvement in maximal mouth opening (interincisal distance); 3. improvement in range of jaw movement; 4. change in severity of oral/mucosal burning pain/sensation; 5. ADVERSE EFFECTS: Our secondary outcomes were 6. quality of life; 7. postoperative discomfort or pain as a result of the intervention; 8. participant satisfaction; 9. hospital admission; 10. direct costs of medication, hospital bed days and any associated inpatient costs for the surgical interventions. We used GRADE to assess certainty of evidence for each outcome. MAIN RESULTS: We included 30 RCTs (2176 participants) in this updated review. We assessed one study at low risk of bias, five studies at unclear risk of bias and 24 studies at high risk of bias. We found diverse interventions, which we categorised according to putative mechanism of action. We present below our main findings for the comparison 'any intervention compared with placebo or no active treatment' (though most trials included habit cessation for all participants). Results for head-to-head comparisons of active interventions are presented in full in the main review. Any intervention versus placebo or no active treatment Participant-reported resumption of normal eating, chewing and speech No studies reported this outcome. Interincisal distance Antioxidants may increase mouth opening (indicated by interincisal distance (mm)) when measured at less than three months (mean difference (MD) 3.11 mm, 95% confidence interval (CI) 0.46 to 5.77; 2 studies, 520 participants; low-certainty evidence), and probably increase mouth opening slightly at three to six months (MD 8.83 mm, 95% CI 8.22 to 9.45; 3 studies, 620 participants; moderate-certainty evidence). Antioxidants may make no difference to interincisal distance at six-month follow-up or greater (MD -1.41 mm, 95% CI -5.74 to 2.92; 1 study, 90 participants; low-certainty evidence). Pentoxifylline may increase mouth opening slightly (MD 1.80 mm, 95% CI 1.02 to 2.58; 1 study, 106 participants; low-certainty evidence). However, it should be noted that these results are all less than 10 mm, which could be considered the minimal change that is meaningful to someone with oral submucous fibrosis. The evidence was very uncertain for all other interventions compared to placebo or no active treatment (intralesional dexamethasone injections, pentoxifylline, hydrocortisone plus hyaluronidase, physiotherapy). Burning sensation Antioxidants probably reduce burning sensation visual analogue scale (VAS) scores at less than three months (MD -30.92 mm, 95% CI -31.57 to -30.27; 1 study, 400 participants; moderate-certainty evidence), at three to six months (MD -70.82 mm, 95% CI -94.39 to -47.25; 2 studies, 500 participants; moderate-certainty evidence) and at more than six months (MD -27.60 mm, 95% CI -36.21 to -18.99; 1 study, 90 participants; moderate-certainty evidence). The evidence was very uncertain for the other interventions that were compared to placebo and measured burning sensation (intralesional dexamethasone, vasodilators). Adverse effects Fifteen studies reported adverse effects as an outcome. Six of these studies found no adverse effects. One study evaluating abdominal dermal fat graft reported serious adverse effects resulting in prolonged hospital stay for 3/30 participants. There were mild and transient general adverse effects to systemic drugs, such as dyspepsia, abdominal pain and bloating, gastritis and nausea, in studies evaluating vasodilators and antioxidants in particular. AUTHORS' CONCLUSIONS: We found moderate-certainty evidence that antioxidants administered systemically probably improve mouth opening slightly at three to six months and improve burning sensation VAS scores up to and beyond six months. We found only low/very low-certainty evidence for all other comparisons and outcomes. There was insufficient evidence to make an informed judgement about potential adverse effects associated with any of these treatments. There was insufficient evidence to support or refute the effectiveness of the other interventions tested. High-quality, adequately powered intervention trials with a low risk of bias that compare biologically plausible treatments for OSF are needed. It is important that relevant participant-reported outcomes are evaluated.

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.

Molecular Mechanisms of Malignant Transformation of Oral Submucous Fibrosis by Different Betel Quid Constituents-Does Fibroblast Senescence Play a Role?

Betel quid (BQ) is a package of mixed constituents that is chewed by more than 600 million people worldwide, particularly in Asia. The formulation of BQ depends on a variety of factors but typically includes areca nut, betel leaf, and slaked lime and may or may not contain tobacco. BQ chewing is strongly associated with the development of potentially malignant and malignant diseases of the mouth such as oral submucous fibrosis (OSMF) and oral squamous cell carcinoma (OSCC), respectively. We have shown recently that the constituents of BQ vary geographically and that the capacity to induce disease reflects the distinct chemical composition of the BQ. In this review, we examined the diverse chemical constituents of BQ and their putative role in oral carcinogenesis. Four major areca alkaloids-arecoline, arecaidine, guvacoline and guvacine-together with the polyphenols, were identified as being potentially involved in oral carcinogenesis. Further, we propose that fibroblast senescence, which is induced by certain BQ components, may be a key driver of tumour progression in OSMF and OSCC. Our study emphasizes that the characterization of the detrimental or protective effects of specific BQ ingredients may facilitate the development of targeted BQ formulations to prevent and/or treat potentially malignant oral disorders and oral cancer in BQ users.

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.

A Comparative Study to Evaluate Efficacy of Curcumin and Aloe Vera Gel along with Oral Physiotherapy in the Management of Oral Submucous Fibrosis: A Randomized Clinical Trial.

Rationale (Hypothesis): The antioxidant,anti-inflammatory,immunomodulatory and anti-tumorigenic properties of natural plant's extracts like aloe Vera and curcumin  may produce beneficial therapeutic effects on OSMF patients and may lead to their symptomatic relief. Also, increase in the tissue elasticity with the help of oral physiotherapy excercises , would help in reinforcing increment in  mouth opening. AIM: The aim of the study is to compare the efficacy of Curcumin gel with Aloe Vera gel when both the gel are supplemented along with oral physiotherapy in the management of OSMF. MATERIALS AND METHODS: A study of parallel group trial design, using simple randomization technique, was conducted on confirmed cases of OSMF. Patients were divided into two groups, one group(30 patients) was given curcumin gel(Curenext) and other group (30 patients) aloe Vera gel (Aloe Vera 100% relief) and each group was asked to do same oral physiotherapy excercises supplementally. Follow-up was done for 6 weeks and patients were assessed on the basis of improvement in mouth opening and burning sensation at 2, 4, and 6 weeks. RESULTS: There was an improvement in both the parameters at subsequent visits, but the Aloe Vera gel showed better improvement than curcumin gel in burning sensation after 6 weeks of treatment which was highly statistically significant p < 0.01. CONCLUSION: Curcumin gel and Aloe Vera gel are effective in improving OSMF symptoms, but aloe Vera gel is more efficacious in burning sensation improvement without any side effects. Hence, we can advocate these drugs as adjuvant treatment in addition to the recommended treatment.

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 Oil Pulling in the Management of Oral Submucous Fibrosis: A Preliminary Study

ABSTRACT Objective: To evaluate the effectiveness of oil pulling in the management of oral submucous fibrosis (OSMF). Material and Methods: A total of 62 patients clinically and histopathologically diagnosed as OSMF were incorporated in the present study. The subjects are randomly divided equally into two groups, Group A (oil pulling group) and Group B (placebo group). Subjects in Group A were asked to perform OP with sesame oil on an empty stomach in the morning for 3 months and Group B was given placebo capsules for 3 months. Assessment of various clinical parameters was done regularly, and data were analyzed using the Chi-square test. Results: Eighty-two percent had a habit of betel nut chewing, while 18% of the patients had tobacco chewing habits, which were among the main causative factors for OSMF. Clinical improvements in mouth opening, tongue protrusion, difficulty in speech and deglutition, and burning sensation were significant in the Group A. None of the patients reported any discomfort or side effects. The symptoms were not severe in nature and resolved in few days without stopping the therapy. Conclusion: Oil pulling can bring about significant clinical improvements in the symptoms like a mouth opening and tongue protrusion.

Photobiomodulation therapy inhibits oral submucous fibrosis in mice.

OBJECTIVES: Oral submucous fibrosis (OSMF) is a chronic inflammatory disease and a potentially malignant oral disorder. However, the best therapeutic treatment for OSMF remains uncertain. Our previous study showed that photobiomodulation (PBM) therapy and forskolin could reduce arecoline-induced fibrosis reactions via the cAMP pathway. The present study aimed to establish an animal model of areca nut extract (ANE)-induced OSMF and to evaluate the therapeutic potential of PBM and forskolin for ANE-induced OSMF. SUBJECTS AND METHODS: The mice were divided into five groups. The buccal tissues were harvested for histomorphological analysis and immunoblotting. RESULTS: Our results showed that PBM significantly reduced the development of ANE-induced OSMF, quantified by changes in submucosal layer thickness and collagen deposition. Additionally, PBM could extensively reduce the protein expression of the fibrotic marker genes alpha-smooth muscle actin (α-SMA) and connective tissue growth factor (CTGF) in buccal submucous lesions. However, forskolin treatment significantly decreased the protein expression of fibrotic marker genes but slightly decreased the observed histomorphological changes. CONCLUSIONS: We established an ANE-induced OSMF mouse model, which also provided a model for the development of a therapeutic treatment for OSMF. The anti-fibrotic effects of PBM and forskolin may be useful for clinical interventions.

Comparison of Efficacy of Topical Curcumin Gel with Triamcinolone-hyaluronidase Gel Individually and in Combination in the Treatment of Oral Submucous Fibrosis.

AIM: To study the efficacy of topical curcumin mucoadhesive semisolid gel, triamcinolone acetonide/hyaluronidase mucoadhesive semisolid gel, and a combination of both in the treatment of oral submucous fibrosis (OSMF). MATERIALS AND METHODS: One hundred and twenty patients diagnosed with OSMF were randomly divided into groups I, II, and III. Each patients in groups I, II, and III was given professionally prepared mucoadhesive semisolid gel of curcumin, a combination of triamcinolone acetonide and hyaluronidase mucoadhesive semisolid gel, and a combination of all three, respectively. Patients were instructed to apply the gel thrice daily for 6 weeks on buccal mucosa bilaterally using the tip of index finger. Three parameters were evaluated at the end of each week, namely, mouth opening, burning on visual analog scale (VAS), and the color of oral mucosa on the binary scale. The results were subjected to statistical analysis. RESULTS: It was observed that the group administered the three drug combinations achieved the greatest mouth opening (mean increase 4.05 mm) as compared to the other two groups. It was observed that triamcinolone and hyaluronidase group reported reduction in burning sensation on VAS (mean difference 6) as compared to the other two groups. It was observed that group III (1% curcumin, 1% hyaluronidase and 0.1% triamcinolone acetonide combined) drug therapy showed better change in mucosa color as compared to groups I (1% curcumin) and II. CONCLUSION: Thus, we can conclude that curcumin has a therapeutic effect on patients diagnosed with OSMF. Maximum utilization and enhanced drug delivery were achieved with the help of a combination other two active drugs, namely, triamcinolone and hyaluronidase. CLINICAL SIGNIFICANCE: Curcumin role in the treatment of oral cancers and the precancer lesion is very promising.

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.