<p class="first" id="d871844e152">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.
</p>