Panax notoginseng Saponins Alleviate OSF by Inhibiting Ferroptosis Through GPX4 Activation.

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

Oral submucous fibrosis (OSMF) is a potentially malignant disorder of the oral cavity. The surgical management of this condition involves excision of the fibrotic bands and interpositional grafts to retain the increased oral opening. Various procedures and graft material have been utilised with differing success rates. The present review aims to collate and analyze from world literature the different modalities utilized in the surgical management of OSMF. The reasons for the choice of a particular surgical procedure, the study protocol, the average follow-up period and the results were scrutinized. The PRISMA protocol was followed for the systematic review. Search engines and medical databases like Ovid, Medline, Pubgate, Researchgate, PubMed, Google etc. were tapped for information related to the subject. The search words "OSMF", "surgical interventions in OSMF", "flaps and grafts in treatment of OSMF" were employed for retrieval of data. An analysis of the treatment modalities, the reason for the selection of a particular modality, the organization of the sample selection and the follow-up periods including the proclaimed success rates was done. The review resulted in a total of 56 articles on the subject from the sources mentioned above. A total of 995 surgically treated cases were included in the analysis. Interestingly the review revealed very few controlled clinical trials, most being random trials on surgical procedures in small groups of patients with very short follow up periods. The choice of procedure seems to be determined entirely by the preference of the operator/s. There exist no definite protocols for the adoption of a particular treatment mode in OSMF. Adequate documentation and follow up need to be established to statistically analyse the results and proclaimed successes of various treatment modalities.

This narrative review provides an overview of the use of herbal formulations in the treatment of oral submucous fibrosis (OSMF). OSMF is a potentially malignant disorder characterized by progressive fibrosis of the oral mucosa, resulting in restricted mouth opening and other debilitating symptoms. Conventional treatment options for OSMF are limited, and their effectiveness varies. Herbal formulations have gained attention as alternative and complementary treatment options for OSMF due to their perceived natural origin, minimal side effects, and potential therapeutic effects. These formulations typically consist of plant-derived ingredients with bioactive compounds that possess anti-inflammatory, antioxidant, antifibrotic, and immunomodulatory properties. Various herbal ingredients, such as Aloe vera, curcumin, licorice, honey, and triphala, have been investigated for their potential efficacy in OSMF treatment. These ingredients have shown promise in targeting the underlying mechanisms involved in OSMF pathogenesis, including inflammation, fibrosis, oxidative stress, and immune dysregulation. Herbal formulations offer potential advantages in OSMF treatment. They may provide a holistic approach by addressing multiple aspects of the disease and promoting overall oral health. Herbal formulations also have the advantage of cultural acceptability and cost-effectiveness. To further advance our understanding of herbal formulations in OSMF treatment, well-designed clinical trials with standardized protocols and larger sample sizes are needed. In addition, the development of evidence-based guidelines for the use of herbal formulations in OSMF would aid health-care professionals in making informed treatment decisions. Herbal formulations have shown promise as potential treatment options for OSMF. While their efficacy and safety need further investigation, they offer a natural and holistic approach to OSMF management. Collaboration between researchers, clinicians, and regulatory bodies is essential to advance the research and ensure the safe and effective use of herbal formulations in OSMF treatment.

Oral submucous fibrosis (OSMF) is a potentially malignant disorder of the oral mucosa, mainly associated with the practice of chewing gutka and betel quid. The pathogenesis is obscure, and till date, no definitive therapy is available for the management of OSMF. Hence, this preliminary study was carried out to compare the efficacy of Aloe vera with antioxidants in the treatment for OSMF. Twenty study subjects with OSMF were included in the study. Patients were divided into two groups. There were 10 patients in each group; group A subjects received 5 mg of aloe vera gel to be applied topically three times daily for 3 months and group B subjects received antioxidant capsules twice daily for 3 months. The results were analyzed with paired 't' test and unpaired 't' test. Aloe vera responded better in all the parameters assessed and responded in all the clinicohistopathological stages particularly in those with mild-stage clinically and early-stage histopathologically. Aloe vera showed a statistically significant reduction in burning sensation (P = 0.008), improvement in mouth opening (P = 0.02), and cheek flexibility (P = 0.01) on comparing with the antioxidant group. Overall assessment of the parameters depicted that Aloe vera group showed a better treatment response compared to the antioxidants group. It reduces the burning sensation and improves mouth opening thereby enhanced the patients' compliance. It proves to be a relatively safe, can be applied topically, easily available, economical, noninvasive, and efficacious in the treatment for OSMF.

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). 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. 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. 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. Curcumin role in the treatment of oral cancers and the precancer lesion is very promising.

Oral submucous fibrosis (OSF) is a premalignant and fibrosing disease, which is closely associated with the habit of chewing areca nut. Panax notoginseng Buck F. H. Chen is an often used antifibrotic and antitumor agent. To treat areca nut-induced OSF, we have developed a chewable tablet, in which one of the major medicines is total Panax notoginseng saponins (PNS). In this study, we have investigated the antifibrotic effect and mechanism of PNS on areca nut-induced OSF in vitro. Through human procollagen gene promoter luciferase reporter plasmid, hydroxyproline assay, gelatin zymography, qRT-PCR, ELISA, and Western blot, the influences of PNS on areca nut extract (ANE)-induced cell growth, collagen accumulation, procollagen gene transcription, MMP-2/-9 activity, MMP-1/-13 and TIMP-1/-2 expression, cytokine secretion, and the activation of PI3K/AKT, ERK/JNK/p38 MAPK, and TGFβ/Smads pathways were detected. Panax notoginseng saponins could inhibit the ANE-induced abnormal growth and collagen accumulation of oral mucosal fibroblasts in a concentration-dependent manner. PNS (25 μg/ml) could significantly inhibit the ANE-induced expression of Col1A1 and Col3A1, augment the ANE-induced decrease of MMP-2/-9 activity, inhibit the ANE-induced increase of TIMP-1/-2 expression, and decrease the ANE-induced transcription and release of CTGF, TGFβ1, IL-6, and TNFα. PNS (25 μg/ml) also significantly inhibited the ANE-induced activation of AKT and ERK/JNK/p38 MAPK pathways in oral mucosal fibroblasts and the ANE-induced activation of TGFβ/smad pathway in HaCaT cells. Panax notoginseng saponins possess excellent anti-OSF activity, and its mechanism may be related to its ability to inhibit the ANE-induced activation of PI3K/AKT, ERK/JNK/p38 MAPK, and TGFβ/smad pathways.

Oral submucous fibrosis is a disease of an Indian subcontinent with obscure aetiology and poorly treated with varying signs and symptoms. OSMF occurs at any age but is most commonly seen in teenagers and adults in the age ranging between 16 and 35years. A number of surgical treatments have been used for the treatment of oral submucous fibrosis with unpredictable results. In this study, 220 patients were randomly divided into two groups with mouth opening less than 16mm and evaluated with immediate and delayed aggressive physiotherapy with buccal fat pad interposition after fibrotomy. Group A (n=110) patients underwent aggressive mouth opening exercise from the next postoperative day while in group B (n=110), patients underwent physiotherapy 7th day postoperatively. Pain and discomfort, mucosalization, infection, flap dehiscence and necrosis were noted. Patients were followed for 1year on a regular interval basis. At the end of 1-year follow up, the post-operative mean mouth opening in group A was 38.63mm and 34.19mm in group B. In group A, the immediate physiotherapy results in mild to moderate pain and discomfort to the patients as compared to no apparent pain in the group B. The mean mucosalization time in group A and group B was 4.2 and 5.1weeks, respectively. Postoperatively, all patients achieve satisfactory mouth opening. Immediate aggressive physiotherapy yields a comparatively superior result than delayed physiotherapy with respect to mouth opening in 1year of follow-up.

Oral submucous fibrosis is chronic, insidious disease affecting the oral cavity and sometimes the pharynx and rarely the tongue. Oral Submucous fibrosis is a well known clinical entity since the time of “Sushruta” as ‘Vidari’. A 20-year-old patient with oral submucous fibrosis was treated with contact diode laser under local anesthesia and was followed up for six months. Oral submucous fibrosis is an established precancerous condition with increased prevalence in the Indian subcontinent. The treatment of oral submucous fibrosis is a challenging task for a clinician. Different authors have suggested variety of treatment modalities and have claimed success rates; still there is no universally acceptable protocol for the management of oral submucous fibrosis. In this case transection of bands was done by contact diode lasers under local anaesthesia and it offered good results. Diode lasers offered excellent results and had many advantages over conventional surgical treatment.

Oral submucous fibrosis is a habit associated insidious precancerous condition of the oral cavity commonly found in Asian countries. Many treatment modalities have been attempted in treating the condition apart from steroids which have been the main stay. Hence the present study was designed to assess the efficacy of spirulina and pentoxyfilline and also to compare them in oral submucous fibrosis. Fourty Patients with clinico-histological diagnosis of oral sub mucous fibrosis were selected and divided into two groups with 20 in each group by simple randomization method. Group I received Pentoxyfilline and Group II Spirulina for period of 3 months. The efficacy was assessed by parameters like mouth opening, burning sensation and tongue protrusion using vernier caliper, visual analog scale and a metric scale respectively along with the side effects. Student's t-test was applied to obtain the results. Both Pentoxyfilline and Spirulina groups showed statistically significant results (p=0.000) in all the three parameters namely mouth opening, burning sensation and tongue protrusion. On comparing both the drugs statistically insignificant results were obtained for mouth opening (p=0.35) and tongue protrusion (p=0.25) but statistically significant difference was seen in subjective parameter i.e burning sensation (p=0.04). Side effects like bloating of stomach, nausea and gastritis were noted in the pentoxyfilline group in contrast to Spirulina group. Newer drugs Pentoxyfilline and Spirulina showed promising results in treatment of Oral sub mucous fibrosis. Spirulina was used for the first time for treatment of Oral submucous fibrosis (OSMF) and it proved to be superior than pentoxyfilline as no side effects were observed. Also it was superior in reducing burning sensation and hence can be advised in OSMF patients suffering from severe subjective symptoms.

Oral Sub Mucous Fibrosis is a well- recognized clinical entity, known since the time of Sushruta. In the modern literature OSMF was first reported by Schwartz (1952), Joshi (1953) was the first person to describe this entity in India. Oral Sub Mucous Fibrosis (OSMF) is a potentially malignant disease that results in progressive juxtaepithelial fibrosis of the oral soft tissues, resulting in increasing loss of tissue mobility, marked rigidity and an eventual inability to open the mouth. The basic change is a fibroelastic transformation of the connective tissue in the lamina propria followed by vesicle formation. It is a well-known chronic insidious disease, precancerous condition, an autoimmune and collagen related disorder whose origin is multifactorial and is associated with chewing of betel quid. It is characterized by progressive hyalinization of the lamina propria. In the later stages the oral mucous membrane becomes very stiff and the patient suffers from trismus and hence difficulty in eating. Earlier OSMF had been confined to countries like India, Pakistan, Bangladesh, etc., but now it is being reported from western countries as well. Inspite of intensive research over the years, a single etiologic factor for OSMF cannot be pointed out with certainty. Patients suffering with OSMF are initially present with a blanched or marble‑like pale mucosa, vesiculations and also show intolerance to hot and spicy food. The treatment of oral submucous fibrosis includes iron, multivitamins including lycopene, spirulina, pentoxifyline, colchicine local submucosal injections of steroids, hyaluronidase and chylomicrons, and surgical excision of the fibrous bands. Keywords: Oral Sub Mucous Fibrosis, juxtaepithelial fibrosis, oral soft tissues, fibroelastic, lamina propria, collagen.

Efficacy of Lycopene in the Treatment of Oral Submucous Fibrosis: A Meta-analysis of Randomized Controlled Trials

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). 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. 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. Curcumin in combination with intralesional dexamethasone with hyaluronidase is efficacious in the treatment of OSF.

Introduction: Oral submucous fibrosis (OSMF) is a chronic insidious and a well-recognized potentially malignant disorder of the oral cavity. Due to its high morbidity and malignant transformation rate, relentless efforts have been made to improve effective management, despite not much improvement in the prognosis. Omega 3 polyunsaturated fatty acids have been reported to have anti-inflammatory properties. With its antioxidant, anti-inflammatory, and immunomodulating properties, Spirulina has shown promising results in the management of OSMF. This present study was conducted to compare the effectiveness of Omega-3 fatty acids and Spirulina in the management of OSMF. Aims and Objectives: To find out and compare the effectiveness of Omega-3 fatty acids and spirulina in the management of OSMF. Methods and Material: 40 OSMF patients with clinically diagnosed OSMF were selected and divided into two groups. Group A was given biweekly intralesional injections of 1.5 ml Dexamethasone in 4 mg/1 ml and Hyaluronidase 1500 IU mixed with Lignocaine 0.5 ml for six weeks and with omega-3 fatty acid capsules 1 gm three times daily for three months. Group B received similar intralesional injections but with spirulina 500 mg twice daily for three months. All the patients were followed up every month for 3 months and then after six months. Results: Both groups improved mouth opening, cheek flexibility, and VAS burning sensation except tongue protrusion (p &lt; 0.05). When the efficacy was compared between two drugs, statistically insignificant results were found for mouth opening, tongue protrusion, cheek flexibility, and burning sensation. Conclusion: Omega 3 and Spirulina can be effective adjunctive treatment options in patients with OSMF to reduce subjective symptoms. Statistically, significant improvement was seen in both groups.

Oral submucous fibrosis (OSMF) is a well-recognized, chronic debilitating and potentially malignant disease of the aerodigestive tract, with initial inflammation followed by progressive fibrosis of the underlying connective tissues which can be treated by stem cell therapy. Aims and objectives: To assess the effectiveness of stem cell therapy in the treatment of OSMF by evaluating the improvement in function and to assess the sustainability of the result with 5 years follow-up. This study also assessed the safety of stem cell therapy for OSMF. Materials and methods: Seven patients with OSMF were selected. Out of seven patients, three were treated with stem cells obtained by Ficoll method and four patients were treated with stem cells obtained by point of care delivery system. Posttreatment improvement in the clinical presentation was assessed and confirmed by histopathological features. The range of follow-up of cases is from 6 months to 5 years. Results: Reduction in blanching, improved/better suppleness of the mucosa, decrease in the burning sensation while consuming spicy food, increase in the mouth opening was observed. The above mentioned results were found to be sustained in the follow-up period. Conclusion: From the results obtained, it is evident that the stem cell therapy has played a role in the improvement of the signs and symptoms probably through neoangiogenesis, antiinflammatory effects and antifibrinolytic effect. However, as this is only a preliminary attempt to assess the safety of stem cell therapy in OSMF, further randomized control trials with larger sample size are required for using this as a possible alternative therapeutic approach.

Context:Oral submucous fibrosis (OSMF) is chronic, scarring disease of the oral cavity. Cytokines and growth factors produced by inflammatory cells play a major role in its pathogenesis. Low-level laser therapy (LLLT) application, which has an anti-inflammatory, was used to determine the improvement in mouth opening.Aims:The aim of the study is to evaluate the effectiveness of laser photobiomodulation (PBM) in OSMF treatment.Materials and Methods:Thirty patients who were diagnosed with OSMF after obtaining consent form and ethical clearance were included. LLLT was applied for 4 cycles for 15 s each in the left and right buccal mucosa. Therapy was done on day 0, 3, 7, and 15 and measurements were done immediately after each LLLT application. Patients were recalled after 1, 3, and 6 months from the commencement of the therapy for follow-up measurements.Results:The mean increase in mouth opening following application of LLLT from day 0 to day 15 was 9.91 ± 3.34, and day 1–6 months was 14.29 ± 6.82, which was statistically significant.Conclusions:The study shows significant improvements in the mouth opening of the OSMF patient during treatment and postoperatively. Thus, our study confirms LLLT can be used as one of the modality in OSMF management.