Curcumin shows promise in preventing and treating oral submucosal fibrosis

By Vijay Kumar MalesuReviewed by Benedette Cuffari, M.Sc.Oct 30 2024

Researchers examine curcumin's therapeutic power against oral submucosal fibrosis, revealing its potential to reduce inflammation, fibrosis, and cancer risks in this precancerous oral condition.

Study: Mechanism of curcumin in the prevention and treatment of oral submucosal fibrosis and progress in clinical application research. Image Credit: New Africa / Shutterstock.com

In a recent review published in the BDJ Open, researchers explore the mechanisms, therapeutic potential, and clinical applications of curcumin (CUR) in preventing and treating oral submucosal fibrosis (OSF).

What is OSF?

OSF is a chronic and precancerous condition that is characterized by progressive fibrosis of the oral mucosa. OSF remains highly prevalent in certain regions of the world, including parts of China with over five million cases reported worldwide.

OSF is primarily linked to the habit of betel nut chewing, especially in regions where this is a common cultural practice. The compound arecoline, which is found in betel nuts, induces inflammatory and fibrotic changes in the oral mucosa, thereby increasing the potential of OSF to progress toward oral cancer.

OSF pathogenesis involves several cellular mechanisms, including oxidative stress, inflammatory responses, and altered collagen metabolism, all of which lead to persistent fibrosis. OSF patients typically exhibit reduced levels of collagen-degrading enzymes, such as matrix metalloproteinases (MMPs), as well as elevated levels of tissue inhibitors of metalloproteinases (TIMPs), thereby leading to an accumulation of fibrous tissue in the oral submucosa.

Current treatments, including surgical and conservative options like glucocorticoid injections, often offer limited success in reversing fibrosis and are associated with high patient discomfort and compliance issues. Non-invasive alternative therapies like CUR, which is known for its anti-inflammatory and anti-fibrotic properties, are promising; however, additional research is needed to establish optimal protocols and improve patient outcomes.

Mechanisms of CUR against OSF

CUR, a polyphenol isolated from turmeric, is valued for its anti-tumor, anti-inflammatory, antioxidant, and anti-fibrotic properties. With low toxicity and multi-pathway action, CUR is a promising therapeutic that is 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 the fibroblast activity that contributes to the progression of OSF.

Autophagy

CUR influences cellular autophagy, by supporting tissue homeostasis and limiting fibrosis progression. In fibrosis models, CUR enhances autophagy, effectively manages fibrotic lesions, and inhibits epithelial-mesenchymal transition (EMT), a key factor in fibrosis.

In OSF, the modulation of autophagy by CUR in buccal fibroblasts prevents their transformation into fibrotic myofibroblasts, potentially reducing OSF pathology through autophagy-related protein regulation.

Inhibition of fibroblast activation

CUR also plays a crucial role in directly inhibiting the activation and proliferation of fibroblasts in OSF. Activated BMFs, the primary 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 impeding their proliferation.

CUR further disrupts the production of fibrosis-associated proteins, including α-smooth muscle actin, fibronectin, and types I and III collagen, all of which are integral to the development of fibrotic tissue. 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 and Streptococcus species. CUR disrupts the integrity of bacterial cell walls, 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 like signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and inhibiting vascular endothelial growth factor production.

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 can be attributed to its ability to neutralize free radicals, a process that reduces oxidative stress. Unlike synthetic antioxidants, CUR is considered safer, with no reported adverse effects related to its antioxidant activity. This property further enhances its appeal as a natural therapeutic agent against chronic conditions associated with oxidative damage, including OSF.

Clinical applications of CUR in OSF treatment

Systemic administration of CUR

The systemic administration of CUR is associated with favorable safety profiles, as no toxicity has been reported at doses as high as six grams daily for several weeks. Although systemic administration offers the advantage of non-invasive delivery, the low bioavailability of CUR due to its poor solubility and rapid metabolism poses challenges.

Novel 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 administration methods, including mouthwashes, gels, and mucoadhesive patches, have gained popularity in OSF treatment. These methods allow CUR to bypass first-pass metabolism, thereby delivering higher local concentrations with reduced systemic side effects.

Mucoadhesive patches and gels offer controlled release and, as a result, sustained therapeutic effects while improving symptoms such as restricted mouth opening and mucosal pain. Innovations in CUR-loaded nanoparticles further enhance the solubility of this compound, thus making it a versatile option for localized treatment in OSF.

Conclusions

CUR offers a promising and non-invasive approach for treating OSF due to its anti-inflammatory, antioxidant, and anti-fibrotic effects. By targeting cellular pathways involved in fibrosis, CUR reduces fibroblast activation and promotes autophagy, both of which are key to managing OSF.