Therapeutic potential of sulforaphane: modulation of NRF2-mediated PI3/AKT/mTOR pathway in oral fibrosis
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 eff...
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| Language: | English |
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Universidade Estadual Paulista
2024-04-01
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| Series: | Brazilian Dental Science |
| Online Access: | https://ojs.ict.unesp.br/index.php/cob/article/view/4172 |
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| author | Pooja Narain Adtani Rajasekaran Subbarayan Rupendra Shrestha Walid Elsayed |
| author_facet | Pooja Narain Adtani Rajasekaran Subbarayan Rupendra Shrestha Walid Elsayed |
| author_sort | Pooja Narain Adtani |
| collection | DOAJ |
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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.
KEYWORDS
Arecoline; NRF2; Oral submucous fibrosis; PI3/AKT/mTOR; Sulforaphane.
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| format | Article |
| id | doaj-art-22baeceb78ce44eb9cbbcb53e5d9cd5c |
| institution | Kabale University |
| issn | 2178-6011 |
| language | English |
| publishDate | 2024-04-01 |
| publisher | Universidade Estadual Paulista |
| record_format | Article |
| series | Brazilian Dental Science |
| spelling | doaj-art-22baeceb78ce44eb9cbbcb53e5d9cd5c2025-08-22T14:49:15ZengUniversidade Estadual PaulistaBrazilian Dental Science2178-60112024-04-0127110.4322/bds.2024.e4172Therapeutic potential of sulforaphane: modulation of NRF2-mediated PI3/AKT/mTOR pathway in oral fibrosisPooja Narain Adtani0https://orcid.org/0000-0002-5320-271XRajasekaran Subbarayan 1https://orcid.org/0000-0001-5890-5273Rupendra Shrestha 2https://orcid.org/0000-0001-6804-6070Walid Elsayed 3https://orcid.org/0000-0002-6647-516XGulf Medical University, College of Dentistry, Department of Basic Medical and Dental Sciences. Ajman, United Arab Emirates.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.Anka Analytica, Research and Collaboration. Melbourne, Victoria, Australia.Gulf Medical University, College of Dentistry, Department of Basic Medical and Dental Sciences. Ajman, United Arab Emirates. 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. KEYWORDS Arecoline; NRF2; Oral submucous fibrosis; PI3/AKT/mTOR; Sulforaphane. https://ojs.ict.unesp.br/index.php/cob/article/view/4172 |
| spellingShingle | Pooja Narain Adtani Rajasekaran Subbarayan Rupendra Shrestha Walid Elsayed Therapeutic potential of sulforaphane: modulation of NRF2-mediated PI3/AKT/mTOR pathway in oral fibrosis Brazilian Dental Science |
| title | Therapeutic potential of sulforaphane: modulation of NRF2-mediated PI3/AKT/mTOR pathway in oral fibrosis |
| title_full | Therapeutic potential of sulforaphane: modulation of NRF2-mediated PI3/AKT/mTOR pathway in oral fibrosis |
| title_fullStr | Therapeutic potential of sulforaphane: modulation of NRF2-mediated PI3/AKT/mTOR pathway in oral fibrosis |
| title_full_unstemmed | Therapeutic potential of sulforaphane: modulation of NRF2-mediated PI3/AKT/mTOR pathway in oral fibrosis |
| title_short | Therapeutic potential of sulforaphane: modulation of NRF2-mediated PI3/AKT/mTOR pathway in oral fibrosis |
| title_sort | therapeutic potential of sulforaphane modulation of nrf2 mediated pi3 akt mtor pathway in oral fibrosis |
| url | https://ojs.ict.unesp.br/index.php/cob/article/view/4172 |
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