Pulmonary fibrosis is a chronic lung disease characterized by abnormal accumulation of the extracellular matrix (ECM). Chronic damage of the alveolar epithelium leads to a process called "epithelial-mesenchymal transition" (EMT) and increases synthesis and deposition of ECM proteins. Therefore, inhibition of EMT might be a promising therapeutic approach for the treatment of pulmonary fibrosis. β-Sitosterol is one of the most abundant phytosterols in the plant kingdom and the major constituent in corn silk, which is derived from the stigma and style of maize (Zea mays). In this study, we elucidated that β-sitosterol inhibited transforming growth factor-β1 (TGF-β1)-induced EMT and consequently had an antifibrotic effect. β-Sitosterol (1-10 μg/mL) significantly downregulated the TGF-β1-induced fibrotic proteins, such as collagen, fibronectin, and α-smooth muscle actin in human alveolar epithelial cells (p < 0.01). After 24 h, relative wound density (RWD) was increased in TGF-β1 treated group (82.16 ± 5.70) compare to the control group (64.63 ± 2.21), but RWD was decreased in β-sitosterol cotreated group (10 μg/mL: 71.54 ± 7.39; 20 μg/mL: 65.69 ± 6.42). In addition, the changes of the TGF-β1-induced morphological shape and protein expression of EMT markers, N-cadherin, vimentin, and E-cadherin, were significantly blocked by β-sitosterol treatment (p < 0.01). The effects of β-sitosterol on EMT were found to be associated with the TGF-β1/Snail pathway, which is regulated by Smad and non-Smad signaling pathways. Taken together, these findings suggest that β-sitosterol can be used to attenuate pulmonary fibrosis through suppression of EMT by inhibiting the TGF-β1/Snail pathway.
Keywords: corn silk; epithelial−mesenchymal transition (EMT); human lung alveolar epithelial cell; pulmonary fibrosis; transforming growth factor-β1 (TGF-β1); β-sitosterol.