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Ligustilide attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice via Nrf2 Pathway Activation

Jie Chao, Jing Wang, Tianqing Wang, Qiuchen Yu, Juan Yin, Jingyan Yong, Zexi Jiang, Jiangkai Yu, Yusi Cheng, Wei Luo, Xinxin Zhang

Idiopathic pulmonary fibrosis is a progressive interstitial lung disease without effective therapeutic strategies at present. Ligustilide (LIG) is a main bioactive component of angelica. The present study aimed to observe the effect of LIG on mice lung fibrosis at late stage of pulmonary fibrosis and to explore the underlying mechanism. After 14 days for a single BLM instillation, the mice were daily treated with LIG for 2 weeks. Then the effect of LIG on lung fibrosis was observed then. The pulmonary function measurement, Hematoxylin- eosin (H&E) and Masson’s trichrome staining,Immunofluorescence and Western blot were used to evaluate the effect of LIG on pulmonary fibrosis. We investigated the underlying mechanism after transforming growth factor-β1 (TGF-β1) treatment in vitro. The results showed LIG attenuated BLM-induced pulmonary fibrosis and improved pulmonary function. LIG reduced fibroblast activation and reactive oxygen species (ROS) production after TGF-β1 treatment. LIG regulated the activation of nuclear factor E2-related factor 2 (Nrf2) pathways in fibroblasts after TGF-β1 exposed, which might be related to the protective effect of LIG on fibroblasts. LIG reduced pulmonary fibrosis in mice after BLM infusion, which might be related to Nrf2pathway activation. LIG might be a promising drug for the treatment of pulmonary fibrosis.