Diosgenin inhibits TGF-ß1/Smad signaling and regulates epithelial mesenchymal transition in experimental pulmonary fibrosis.

Idiopathic Pulmonary Fibrosis (IPF) is a grave disease characterized by abnormal wound healing associated with chronic, progressive, irreversible fatal lung disease, leading to persistent injuries to the alveolar epithelium. A consequent disturbance of fibroblast proliferation and apoptosis results in subsequent release of pro-inflammatory and pro-fibrotic mediators coupled with accumulation of extracellular matrix within the interstitium. Inexorable distortion of lung alveolar architecture leads to respiratory failure with a median survival rate of 3-5 years. Currently available drugs can only slowdown the progression of fibrosis and novel drugs are warranted to treat this disease. In this study, we demonstrate the fibro-protective effect of diosgenin in experimental lung fibrosis through regulation of Epithelial Mesenchymal Transition (EMT). A single dose of 3 U/kg body weight (b.wt) Bleomycin (BLM) was administered intratracheally in Wistar male albino rats and fibrotic animals were treated with diosgenin (100 mg/kg b.wt) orally for 28 days. BLM administered rat show histological alteration with increased mast cell and collagen accumulation. BLM induced abnormalities were significantly reduced upon treatment with diosgenin. Western blot analysis revealed an increased level of pro-inflammatory and pro-fibrotic molecules such as IL-1ß and TGF-ß in BLM induced rats. Rats supplemented with diosgenin showed a decreased expression of inflammatory and pro-fibrotic mediators. Markers of EMT molecules were evaluated by immunoblot. The results of immunoblot demonstrate that diosgenin regulated the expression of TGF-ß mediated EMT. Hence, from the overall study, administration of diosgenin prevents pulmonary fibrosis by restraint inflammation and EMT.