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Antifibrotic effect of silymarin on arecoline-induced fibrosis in primary human buccal fibroblasts: an in silico and
Divyambika Catakapatri Venugopal1, Paramesh Viswanathan2, Soundharya Ravindran3
1Department of Oral Medicine and Radiology, Sri Ramachandra Dental College & Hospital, Sri Ramachandra Institute of Higher Education and Research (DU), Porur, Chennai, 600 116, India. cvdivyambika@sriramachandra.edu.in.
Silymarin shows promise in treating oral submucous fibrosis (OSMF). This study found silymarin inhibits fibroblast proliferation and downregulates key genes linked to cancer and epithelial-mesenchymal transition (EMT) in vitro.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Oral submucous fibrosis (OSMF) is a potentially malignant condition.
- Arecoline is a key etiological factor in OSMF development.
- Silymarin is a natural compound with potential therapeutic properties.
Purpose of the Study:
- To evaluate silymarin's anticancer and antifibrotic effects.
- To investigate silymarin's impact on arecoline-induced fibrosis in human buccal fibroblasts (HBF).
- To explore silymarin as a potential therapeutic agent for OSMF.
Main Methods:
- In silico analysis using iGEMDOCK and molecular dynamics simulations.
- In vitro induction of fibrosis in HBF using arecoline.
- Cytotoxicity assessment via MTT assay and gene expression analysis using qPCR.
Main Results:
- Silymarin exhibited high target affinity and stable interaction with Transforming Growth Factor Beta.
- Silymarin demonstrated a determined IC50 of 143µM in HBF cells.
- Silymarin significantly downregulated collagen, EMT, stem cell, hypoxia, angiogenesis, and stress markers.
Conclusions:
- Silymarin effectively inhibited fibroblast proliferation in an in vitro OSMF model.
- Silymarin downregulated genes associated with cancer progression and EMT.
- This study highlights silymarin's potential as a novel therapeutic agent for OSMF.
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