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The oral cavity is considered to be a mirror of the body's health, as it reflects the manifestations of various systemic disorders. Most of the oral mucosa is derived embryologically from an invagination of ectoderm and thus, like other similar orifices, it may become involved in the disorders that are primarily associated with the skin. Oral submu...
Citations
... Flavonoids (tannins and catechins) inhibit the degradation of collagen by collagenase. Also, areca nut contains a high amount of copper which further increases the cross-linking of collagen fibers by enhancement of the lysyl oxidase pathway [9][10][11][12][13][14][15]. Numerous therapeutic strategies have been tried in the past and are mainly directed against the signs and symptoms of the OSMF disorder. ...
Oral submucous fibrosis (OSMF) has a high rate of malignant transformation and is an insidious chronic inflammatory disease. Though this disorder seems to be multifactorial in origin, betel quid chewing appears to be the main etiologic factor. Various treatment strategies have been attempted but none proven to cure the disorder because of its multimodal pathogenesis. Reactive oxygen species (ROS) appear to have a role in cancer formation. As OSMF is an oral premalignant disorder and found to be associated with carcinogens like areca nut and tobacco, it is believed to have some relationship with ROS. Tissue damage due to ROS along with other mechanisms may result in the complex pathophysiology of OSMF. The antioxidant system in the body helps to prevent damage caused by highly reactive ROS and helps in the repair of tissues. To study the levels of oxidative stress and antioxidant vitamins in OSMF condition, the present review was done. We carried out a thorough literature search to identify original reports and studies determining the status of oxidative stress and antioxidant vitamins in OSMF condition using several databases including Google Scholar, PubMed, and Scopus. Our review observed that the oxidative stress increased in the condition of OSMF as shown by an increase in malonaldehyde (MDA) and a decrease in antioxidant vitamins like vitamin A, vitamin C, and vitamin E. Also, after the intake of antioxidant vitamins, there was symptomatic improvement in OSMF patients. With the help of identifying oxidative stress and antioxidant status, we can assess the clinical stage of OSMF and can develop a comprehensive treatment plan.
... Therapeuti c potenti al of Sul foraphane: modul ati on of NRF2-medi ated PI3/AKT/mTOR pathway i n oral fi brosi s Adtani PN et al. Therapeutic potential of Sulforaphane: modulation of NRF2-mediated PI3/AKT/mTOR pathway in oral fibrosis bands is frequent [30]. Incorporating a potent phytomedicine-based supplementary therapy could improve the predictive results. ...
Oral Submucous Fibrosis is a potentially malignant disorder caused by habitual areca nut chewing, which contributes to the dispersion of active alkaloids into subepithelial tissues, stimulating excessive extracellular matrix deposition. Various treatment modalities are available; however, their efficacy in inhibiting fibrosis progression remains limited. Sulforaphane (SFN), an isothiocyanate found abundantly in cruciferous plants, is known to have effective antifibrotic properties. Objective: The present study investigated the antifibrotic effect of SFN via phosphatidylinositol 3 kinase (PI3K), Serine/Threonine Kinase 1 (AKT-1), mammalian target of rapamycin (mTOR) pathway in arecoline (AER) induced fibrosis in human gingival fibroblasts [HGFs]. Material and Methods: MTT assay determined the half-maximal inhibitory concentration of AER and SFN at 24h in the HGF cell line. Expression levels of transforming growth factor B1 (TGFB1), collagen type 1 alpha 2 (COL1A2), hydroxyproline (HYP), PI3, AKT, mTOR, and nuclear factor erythroid 2–related factor 2 (NRF2) were assessed post-AER and SFN treatment using qPCR and western blot analysis. Results: The findings of the study revealed that AER elicited a stimulatory effect, upregulating TGFB1, COL1A2, HYP, PI3K, AKT, and mTOR and downregulating NRF2 expression. Conversely, SFN treatment significantly upregulated NRF2, inhibiting TGFB1 mediated PI3/ AKT/mTOR pathway. Conclusion: These observations suggest that SFN can be used as a promising synergistic antifibrotic agent to combat fibrogenesis via the non-Smad pathway.
... The World Health Organization (WHO) described this condition as "a slowly progressing disease in which fibrous bands form in the oral mucosa, ultimately leading to the severe restriction of movement of the mouth including tongue" in 1978. 1 In 2019, More and Rao described it as "a debilitating, progressive, irreversible collagen metabolic disorder induced by chronic chewing of areca nut and its commercial preparations; affecting the oral mucosa and occasionally the pharynx and esophagus; leading to mucosal stiffness and functional morbidity, and has a potential risk of malignant transformation". 2,3 Prevalence According to estimates, 7-30% of oral submucous fibrosis (OSMF) cases will develop into oral squamous cell carcinoma (OSCC). ...
Background: Sushruta (600 B.C.) described a condition called "Vidari" linked with progressive narrowing of mouth, depigmentation of the oral mucosa, and pain on taking food, oral submucous fibrosis (OSMF). In 1952, Schwartz called this illness, which affected five Indian women existing in Kenya, "atrophica idiopathica mucosae oris." Pindborg and Sirsat coined the term "oral submucous fibrosis" in 1966, which is still in use today. With an overall Indian prevalence rate of between 0.2–0.5%, OSMF is primarily found in India and Southeast Asia, according to global estimations. Patients with OSMF need regular follow-ups and to maintain this follow-up it is not always possible for the patient to visit a dental clinic. Hence developing a smartphone-based application for the follow-up of OSMF will be of great value to the patients. The study aims to evaluate the effectiveness of a smartphone application on OSMF self-examination in the follow-up of patients.
Methods: There will be three phases of the research. The first phase will be the development of a smartphone-based application for the follow-up of patients with OSMF. The second phase will be distribution and training the patients regarding the usage of the application and the third phase will be evaluating the effectiveness of the smartphone application in maintaining the follow-up of the patients.
Expected results: The follow-up of patients with OSMF is expected to be better and feasible using a smartphone application as compared to regular Outpatient Department-based follow-up.
Conclusions: Designing a mobile application for the ease of users presents difficulties since it must take accessibility into account, which influences how well the application is received by users. The goal of OSMF examination awareness facilitation and intervention is to raise public knowledge. Educational activities significantly contribute to the advancement of information, convictions, and OSMF screening practice.
CTRI registration: CTRI/2023/06/054514 (registration pending)
... Wnt/-catenin signaling J o u r n a l P r e -p r o o f dysregulation exacerbates fibrosis by increasing myofibroblast differentiation [16]. Collagen cross-linking, increased extracellular matrix protein expression, and decreased collagenase activity all contribute to the fibrotic alterations in OSMF [19]. MiRNAs have emerged as important regulators of the molecular mechanisms that contribute to OSMF fibrosis. ...
... Betel quid chewing is a frequent risk factor in Southeast Asia, and consequently, this region has a high incidence of OSCC preceded OSF, which is an OPMD associated with such practice. 16 However, in some African countries, OSCC-dn seems to be the predominant presentation. 17 Furthermore, molecular progression models for oral carcinogenesis are mainly based on studies of OPMD and its subsequent MT. 18,19 Thus, there could be a subtype of OSCC unrelated to known OPMDs whose biomolecular progression is not embodied by current knowledge. ...
... Despite its well-documented association with these habits, the precise etiology of OSMF remains complex and multifactorial, involving genetic, immunologic, and environmental factors [4]. Current therapeutic approaches primarily focus on symptom management, with limited success in halting or reversing the fibrotic progression of the disease [3,5]. ...
Background: Oral submucous fibrosis (OSMF) is a chronic, potentially malignant disorder characterized by progressive fibrosis of the oral mucosa, leading to restricted mouth opening and discomfort. This study investigates the efficacy and safety of astaxanthin, a potent antioxidant and anti-inflammatory carotenoid, in the comprehensive management of OSMF.
Methods: A randomized, double-blind, placebo-controlled trial was conducted with 68 eligible participants diagnosed with OSMF. Participants were randomly assigned to the experimental group (astaxanthin capsules, 5 mg twice daily) or the control group (placebo capsules) for 12 weeks. Primary outcomes included changes in mouth opening and burning sensation assessed by Visual Analog Scale (VAS). Adverse events were monitored to evaluate safety.
Results: The experimental group demonstrated a statistically significant improvement in mouth opening compared to the control group over the 12-week intervention (p < 0.001). Additionally, the experimental group reported a significant reduction in burning sensation, as indicated by VAS scores (p < 0.001). Adverse
events were generally mild and comparable between groups.
Conclusion: This study suggests that astaxanthin may have a positive impact on mouth opening and burning sensation in individuals with OSMF. The safety profile observed supports the feasibility of astaxanthin as a potential therapeutic adjunct in OSMF management. Further research with larger sample sizes and extended follow-up periods is warranted to validate these findings.
... OSF is characterized by hyalinization and epithelial atrophy of the oral mucosa, juxta-epithelial inflammation, excessive fibrosis in the lamina propria, and degenerative changes in the muscles. [1,2]. Areca nut chewing, which contains compounds such as arecoline and arecaidine, along with immunological and genetic factors, as well as nutritional deficiencies, is considered an etiological factor contributing to OSF [3,4]. ...
Oral submucous fibrosis (OSF) is a prevalent chronic condition, and understanding its pathogenesis is crucial for developing effective therapeutic strategies. This study explores the potential of adipose tissue-derived stromal cell-extracellular vesicles (ADSC-EVs) in mitigating OSF and investigates the underlying molecular mechanisms. OSF was induced in mice by arecoline feeding. Adipose tissue-derived stromal cells (ADSCs), fibrotic buccal mucosal fibroblasts (fBMFs) isolated from OSF mice, and ADSC-EVs were comprehensively characterized. The treatment effects of extracellular vesicles (EVs) and pcDNA3.1-IGF1R on fBMF proliferation, migration, and invasion were assessed using Cell Counting Kit-8 (CCK-8) assay, transwell assay, and flow cytometry assay. The expression levels of alpha smooth muscle actin (α-SMA), collagen I, collagen III, and insulin-like growth factor 1 receptor (IGF1R) were evaluated by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot. The interaction between miR-760-3p and IGF1R was investigated. In fBMFs and OSF mice treated with a miR-760-3p inhibitor and/or EVs, the expression patterns of miR-760-3p, IGF1R, and proteins related to the TGF-β1/Smad3 pathway were determined. ADSC-EVs demonstrated the ability to upregulate miR-760-3p, impede cell proliferation, migration, and invasion, and reduce α-SMA, collagen I, and collagen III levels in fBMFs. The expression of miR-760-3p was diminished in ADSC-EVs treated with a miR-760-3p inhibitor. However, silencing miR-760-3p or overexpressing IGF1R partially counteracted the beneficial effects of ADSC-EVs on fBMF fibrosis. miR-760-3p directly targets IGF1R. Significantly, ADSC-EVs exert their suppressive effects on the TGF-β1/Smad3 pathway through the miR-760-3p/IGF1R axis. In summary, ADSC-EVs, by transferring miR-760-3p and inhibiting IGF1R expression, effectively block the TGF-β1/Smad3 pathway, thereby alleviating fibrosis in fBMFs and preventing the progression of OSF.
... Increases lymph flow and metabolism. Ultrasound therapy reduces pain, hastens the healing process, and improves collagen fiber extensibility [22]. ...
One of the most poorly recognized and inadequately managed diseases, oral submucous fibrosis progresses over time. Betel nut eating is the foremost cause of oral submucous fibrosis. One such condition is oral submucous fibrosis, which is characterized by severe trismus, disability, and a higher risk of cancer. The mouth opening gradually decreases, which is related to difficulty eating, altered gustatory sensation, and mouth dryness, leading to decreased oral intake. The main and beginning signs include decreased mouth opening, pain, difficulty eating, dry mouth, and blanching of the buccal mucosa. This is treated first with medication, then with exercises for the mouth that a physiotherapist has recommended. However, the function of a physical therapist is not clearly defined. Physiotherapy may be used with other therapies to treat oral submucous fibrosis. Mouth-opening exercises, ultrasound, and other therapeutic interventions are available. This article tries to describe the kind of physical therapy that can be recommended for treating oral submucous fibrosis. It is crucial to understand pain management, physiotherapy management for grade III and IV oral submucous fibrosis various additional exercises, modalities and their ideal dose, and strategy for the long-term effect of the treatments to conduct further research.
... Differences in this frequency can be partially explained by OPMD geographic variations, conditioned by the prevalence of different risk factors. For instance, areca nut chewing is a frequent condition in Southeast Asia, and consequently, this region shows a high incidence of OSCC arising from OSMF, an OPMD produced by this practice (Gupta & Jawanda, 2021). These differences in demographics and clinical-epidemiological factors of oral cancer in the world are strongly conditioned by the lifestyles and cultural behaviours of each of the geographical areas where the research is developed. ...
Objective
To determine the frequency of oral squamous cell carcinoma (OSCC) associated or not with oral potentially malignant disorders (OPMD), and the epidemiological profile and traditional risk factors in Latin America.
Methods
A retrospective observational study was conducted in 17 Latin American centres. There were included cases of OSCC, analysing age, gender, OSCC and their association with previous OPMD. Clinicopathological variables were retrieved. The condition of sequential‐OSCC versus OSCC‐de novo (OSCC‐dn) was analysed concerning the aforementioned variables. Quantitative variables were analysed using Student's t ‐test, and qualitative variables with chi‐square.
Results
In total, 2705 OSCC were included with a mean age of 62.8 years old. 55.8% were men. 53.75% of the patients were smokers and 38% were common drinkers. The lateral tongue border was the most affected site (24.65%). There were regional variations in OPMD, being leukoplakia the most frequent. Of the overall 2705 OSCC cases, 81.4% corresponded to OSCC‐dn, while s‐OSCC were 18.6%. Regarding lip vermillion SCC, 35.7% corresponded to de novo lip SCC and 64.3% were associated with previous OPMD.
Conclusions
In Latin America, OSCC‐dn seems to be more frequent with regional variations of some clinical and histopathological features. Further prospective studies are needed to analyse this phenomenon.
... OSF is one of the most common precancerous lesions of the oral mucosa, involving any part of the mouth, resulting in tissue scarring, difficulty swallowing, and muscle atrophy. 44 Histopathologically, OSF is characterized by epithelial atrophy, chronic inflammation, and hyalinization of the proximal epithelium, leading to submucosal tissue fibrosis. 45 α-SMA, Ki67, and CD105 were significantly increased in OSCC in the context of OSF compared to OSF and normal subjects. ...
Purpose
Arecoline is one of the main toxic components of arecoline to cause oral mucosal lesions or canceration, which seriously affects the survival and life quality of patients. This study analyzed the mechanism of Jiawei Danxuan Koukang (JDK) in alleviating arecoline induced oral mucosal lesions, to provide new insights for the treatment of oral submucosal fibrosis (OSF) or cancerosis.
Methods
Metabolomics was applied to analyze the composition of JDK and serum metabolites. The active ingredients of JDK were analyzed by the combined ultra-high performance liquid chromatography and mass spectrometry. The target network of JDK, metabolites and OSF was analyzed by network pharmacology, and molecular docking. Oral mucosal lesions and fibrosis were analyzed by HE and Masson staining. Cell differentiation, proliferation and apoptosis were detected. The expressions of α-SMA, Collagen I, Vimentin, Snail, E-cadherin, AR and NOTCH1 were detected by Western blot.
Results
Arecoline induced the gradual atrophy and thinning of rat oral mucosal, collagen accumulation, the increase expressions of fibrosis-related proteins and Th17/Treg ratio. JDK inhibited arecoline-induced oral mucosal lesions and inflammatory infiltration. Arecoline induced changes of serum metabolites in Aminoacyl-tRNA biosynthesis, Alanine, aspartate and glutamate metabolism and Arginine biosynthesis pathways, which were reversed by M-JDK. Quercetin and AR were the active ingredients and key targets of JDK, metabolites and OSF interaction. Arecoline promoted the expression of AR protein, and the proliferation of oral fibroblasts. Quercetin inhibited the effect of arecoline on oral fibroblasts, but was reversed by AR overexpression. Arecoline induced NOTCH1 expression in CAL27 and SCC-25 cells, and promoted cell proliferation, but was reversed by M-JDK or quercetin.
Conclusion
JDK improved the arecoline-induced OSF and serum metabolite functional pathway. Quercetin targeted AR protein to improve arecoline-induced OSF. JDK and quercetin inhibited arecoline-induced NOTCH1 protein expression in CAL27 and SCC-25 cells to play an anti-oral cancer role.
