Deacetylforskolin ameliorates bleomycin-induced pulmonary fibrosis by suppressing inflammation and TGF-β1-induced epithelial-mesenchymal transition.

Pulmonary fibrosis (PF) is a chronic, progressive and irreversible inflammatory disease with limited therapeutic methods in clinic. Deacetylforskolin (DFSK), derived from the plant Coleus forskohlii, is a potent adenylyl cyclase activator with potential anti-inflammatory activity. Herein, we attempted to investigate the therapeutic potential and mechanisms of DFSK against PF in bleomycin (BLM)-induced mouse models and TGF-β1-induced A549 cells. Our results showed that DFSK treatment alleviated lung injury and reduced inflammatory cytokines in a mouse model of BLM-induced acute lung inflammation, an early stage of PF. In a BLM-induced PF mouse model, DFSK attenuated pathological lung injury and collagen deposition, decreased pro-inflammatory cytokines (TNF-α, IL-1β) and profibrotic mediators (TGF-β1, CTGF, hydroxyproline). Upregulation of the epithelial marker E-cadherin and downregulation of the mesenchymal marker α-SMA were observed following DFSK treatment. Furthermore, DFSK significantly restored the pulmonary function of PF mice with decreased Te, f, Penh and increased RT, TV. Mechanistically, DFSK suppressed the phosphorylation of JNK and p38 MAPK, and inhibited TGF-β1-induced epithelial-mesenchymal transition (EMT) in A549 cells. Collectively, our findings demonstrate that DFSK is an effective therapeutic agent against PF by suppressing inflammation and EMT.