Researchers are examining the therapeutic potency of curcumin against oral submucosal fibrosis, revealing its potential to reduce inflammation, fibrosis and cancer risks in this precancerous oral disease.
Study: Mechanism of curcumin in the prevention and treatment of oral submucosal fibrosis and progress in clinical application research. Image credit: Nouvelle Afrique/Shutterstock.com
In a recent review published in the BDJ Open, Researchers are exploring the mechanisms, therapeutic potential and clinical applications of curcumin (CUR) in the prevention and treatment of oral submucosal fibrosis (OSF).
What is OSF?
OSF is a chronic, precancerous disease characterized by progressive fibrosis of the oral mucosa. FSO remains highly prevalent in some parts of the world, including parts of China, with more than five million cases reported worldwide.
OSF is mainly linked to the habit of chewing betel nut, especially in regions where it is a common cultural practice. The compound arecoline, present in betel nuts, induces inflammatory and fibrous changes in the oral mucosa, thereby increasing the potential for OSF to progress to oral cancer.
The pathogenesis of OSF involves several cellular mechanisms, including oxidative stress, inflammatory responses, and impaired collagen metabolism, all of which lead to persistent fibrosis. OSF patients typically have reduced levels of collagen-degrading enzymes, such as matrix metalloproteinases (MMPs), as well as elevated levels of tissue inhibitors of metalloproteinases (TIMPs), thus leading to accumulation of fibrous tissue in the subsurface. -oral mucosa.
Current treatments, including surgical and conservative options such as glucocorticoid injections, often offer limited success in reversing fibrosis and are associated with high patient discomfort and compliance issues. Non-invasive alternative therapies such as CUR, known for its anti-inflammatory and antifibrotic properties, are promising; however, additional research is needed to establish optimal protocols and improve patient outcomes.
CUR mechanisms against OSF
CUR, a polyphenol isolated from turmeric, is appreciated for its antitumor, anti-inflammatory, antioxidant and antifibrotic properties. With low toxicity and multi-pathway action, CUR is a promising therapy widely recognized in traditional and modern medicine for its broad therapeutic potential.
By interacting with various cytokines associated with inflammation, oxidative stress, and collagen metabolism, CUR can modulate fibroblast activity that contributes to the progression of OSF.
Autophagy
CUR influences cellular autophagy by promoting tissue homeostasis and limiting the progression of fibrosis. In fibrosis models, CUR enhances autophagy, effectively manages fibrotic lesions, and inhibits epithelial-mesenchymal transition (EMT), a key driver of fibrosis.
In OSF, modulation of autophagy by CUR in oral fibroblasts prevents their transformation into fibrous myofibroblasts, potentially reducing OSF pathology through regulation of autophagy-related proteins.
Inhibition of fibroblast activation
CUR also plays a crucial role in directly inhibiting fibroblast activation and proliferation in OSF. Activated BMFs, the main drivers of fibrosis in OSF, exhibit reduced growth and migration rates in the presence of CUR. At higher concentrations, CUR induces cytotoxic effects on these cells, thereby preventing their proliferation.
CUR further disrupts the production of proteins associated with fibrosis, including α-smooth muscle actin, fibronectin, and collagen types I and III, all of which are integral to fibrous tissue development. This targeted inhibition of fibroblast activation supports the potential of CUR as a non-invasive therapy to manage or prevent OSF.
Antibacterial properties
CUR is approved by the United States Food and Drug Administration (FDA) as a safe food additive with antibacterial properties against various pathogens, including Staphylococcus aureus et Streptococcus species. CUR disrupts bacterial cell wall integrity, which may be beneficial in managing secondary infections in OSF patients and reducing oral bacterial loads.
Anti-inflammatory and anti-tumor effects
The anti-inflammatory activity of CUR includes regulating proteins involved in inflammation and cell death, blocking key pathways such as signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa- light chain enhancer of activated B cells (NF-κB) and inhibit the production of vascular endothelial growth factors.
These effects are valuable for OSF, as inflammation is a key component of its pathology and may increase the risk of malignant transformation. By modulating these pathways, CUR alleviates OSF symptoms and reduces the risk of OSF progressing to oral cancer.
Antioxidant activity
The antioxidant effects of CUR may be attributed to its ability to neutralize free radicals, a process that reduces oxidative stress. Unlike synthetic antioxidants, CUR is considered safer and no adverse effects related to its antioxidant activity have been reported. This property further enhances its appeal as a natural therapeutic agent for chronic conditions associated with oxidative damage, including OSF.
Clinical applications of CUR in OSF treatment
Systemic administration of CUR
Systemic administration of CUR is associated with favorable safety profiles, since no toxicity has been reported at doses up to six grams per day for several weeks. Although systemic administration offers the advantage of non-invasive administration, the low bioavailability of CUR due to its low solubility and rapid metabolism poses problems.
New formulations such as Turmix, which combines CUR with piperine, improve the bioavailability of CUR and have demonstrated promising effects in managing OSF symptoms, including alleviating oral burning sensations.
Local oral administration of CUR
Localized CUR delivery methods, including mouthwashes, gels, and mucoadhesive patches, have gained popularity in the treatment of OSF. These methods allow CUR to bypass first-pass metabolism, thereby delivering higher local concentrations with reduced systemic side effects.
Mucoadhesive patches and gels provide controlled release and, therefore, long-lasting therapeutic effects while improving symptoms such as restricted mouth opening and mucosal pain. Innovations in CUR-loaded nanoparticles further improve the solubility of this compound, making it a versatile option for localized treatment of OSF.
Conclusions
CUR offers a promising, non-invasive approach to treating OSF due to its anti-inflammatory, antioxidant, and antifibrotic effects. By targeting cellular pathways involved in fibrosis, CUR reduces fibroblast activation and promotes autophagy, both essential for managing OSF.
