Therapeutic potential of sulforaphane: modulation of NRF2-mediated PI3/AKT/mTOR pathway in oral fibrosis

Pooja Narain Adtani 1, Rajasekaran Subbarayan 2, Rupendra Shrestha 3, Walid Elsayed 1
  1. Gulf Medical University, College of Dentistry, Department of Basic Medical and Dental Sciences. Ajman, United Arab Emirates.
  2. Chettinad Academy of Research and Education, Chettinad Hospital and Research Institute, Faculty of Allied Health Sciences, Center for Advanced Biotherapeutics and Regenerative Medicine. Chennai, India.
  3. Anka Analytica, Research and Collaboration. Melbourne, Victoria, Australia

Type: Original Article DOI: 10.4322/bds.2024.e4172

Abstract: 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 β1 (TGFβ1), 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 TGFβ1, COL1A2, HYP, PI3K, AKT, and mTOR and downregulating NRF2 expression. Conversely, SFN treatment significantly upregulated NRF2, inhibiting TGFβ1 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.