Simvastatin Attenuates Areca Nut Extract-Induced Subdermal Fibrosis in Mice by Targeting TGF-β Signaling Pathways

Curr Issues Mol Biol. 2023 Oct 27;45(11):8622-8632. doi: 10.3390/cimb45110542.

Abstract

Oral submucous fibrosis (OSMF) is a chronic inflammatory disease and a potentially malignant oral disorder, characterized by fibrosis of the oral mucosa. TGF-β signaling pathways have been implicated in the development of OSMF, with areca nut extract (ANE) contributing to the disease progression. Simvastatin, a statin drug, has demonstrated anti-fibrotic properties in various fibrotic conditions. However, its therapeutic potential in treating OSMF remains unclear. In this study, 8-week-old male BALB/c mice were randomly divided into three groups based on different time points. Each mouse was then treated with four different drug formulations. Post-treatment, specimens were collected for histopathological examination and staining to assess skin thickness, fibrosis, and collagen deposition. ANE treatment alone significantly increased skin thickness and collagen deposition compared to the control group after the 4-week time point. The combined administration of ANE and simvastatin, resulted in a notable reduction in skin thickness and collagen deposition. Western blot analysis revealed that simvastatin effectively suppressed the expression of fibrosis-related proteins, including CTGF, and α-SMA, in ANE-induced subdermal fibrosis. These results suggest that simvastatin has potential therapeutic effects on ANE-induced subdermal fibrosis, providing a foundation for future studies and possible clinical applications.

Keywords: TGF-β signaling pathway; areca nut extract; collagen deposition; fibrosis; oral submucous fibrosis; simvastatin.

Grants and funding

This study was funded by the National Science and Technology Council of Taiwan (grant numbers (MOST104-2314-B-037-059-MY2) and the Regenerative Medicine and Cell Therapy Research Center of Kaohsiung Medical University (grant number KMU-TC112A02).