Costunolide inhibits pulmonary fibrosis via regulating NF-kB and TGF-β1/Smad2/Nrf2-NOX4 signaling pathways

Specific study about the inhibitory effect of costunolide (CN) and relevant mechanism is of great significance for the treatment of pulmonary fibrosis. Here, the pharmacological activity of costunolide on the treatment of pulmonary fibrosis was investigated in vivo and in vitro. The in vivo mice study, mice were received intratracheal injection of bleomycin (BLM, 5 mg/kg) on 0 day to obtain BLM-induced pulmonary fibrosis firstly. From 2 day to 21 day, mice were orally administered with different dose of CN (low dose(CNL): 10 mg/kg, high dose(CNH): 20 mg/kg) and pirfenidone (PFD)(positive control, 50 mg/kg). The in vitro cells model, cells were incubated with recombinant human TGF-β1 for 24 h to get TGF-β1-induced pulmonary fibrosis. Cells were treated differently for 24 h and divided into five groups. Then, the activity of CN was evaluated by the expression level of related protein and the factors of oxidative stress in vivo and in vitro, and the mechanism was tested from the involved channel protein aspect. As a result, from the comparison of multiple factors (α-SMA, collagen type I/III, HYP, MDA, SOD) between pirfenidone group and CN group, it revealed the beneficial effects of CN against BLM-induced and TGF-β1-induced pulmonary fibrosis. In addition, our study also proved that CN exerted its effects through suppressing the NF-kB dependent inflammation and regulated TGF-β1/Smad2/ NOX4-Nrf2 signaling pathways. In conclusion, CN could be a potential theraputic candidate for the treatment pulmonary fibrosis in the future.