Dehydrozingerone alleviates pulmonary fibrosis via inhibition of inflammation and epithelial-mesenchymal transition by regulating the Wnt/β-catenin pathway

In idiopathic pulmonary fibrosis (IPF), excessive collagen deposition predisposes to irreversible lung function decline, respiratory failure, and ultimately death. Due to the limited therapeutic efficacy of FDA-approved medications, novel drugs are warranted for better treatment outcomes. Dehydrozingerone (DHZ) is an analogue of curcumin that has been investigated against pulmonary fibrosis using a bleomycin-induced pulmonary fibrosis model in rats. In in vitro, TGF-β-induced differentiation models (using NHLF, LL29, DHLF and A549 cells) were adopted to assess fibrotic markers expression and explored the mechanism of action. DHZ administration attenuated the bleomycin-induced elevation of lung index, inflammatory cell infiltrations, and hydroxyproline levels in lung tissues. Furthermore, treatment with DHZ mitigated the bleomycin-mediated elevation of extracellular matrix (ECM), epithelial-to-mesenchymal-transition (EMT), and collagen deposition markers and improved lung mechanics. In addition, treatment with DHZ significantly suppressed the BLM-induced apoptosis and rescued the BLM-induced pathological abnormalities in lung tissues. In vitro assays revealed that DHZ suppressed the expression of TGF-β-elevated collagen deposition, EMT and ECM markers in both mRNA/protein levels. Our findings showed that DHZ has anti-fibrotic effect against pulmonary fibrosis by modulating Wnt/β-catenin signaling, suggesting that DHZ may serve as a potential treatment option for IPF.