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Hui Qin,*,1,2 Hao-Tian Wen,*,1,3 Kai-Juan Gu,*,1 Xu-Dong Hu,1 Tao Yang,4 Xiao-Feng Yan,1 Ting-Jie Ye,1 Jin-Lin Huo,1 Jing Hu11Preclinical Medicine College, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, People’s Republic of China; 2Seventh People’s Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200137, People’s Republic of China; 3Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, People’s Republic of China; 4Department of Cardiology, Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, People’s Republic of ChinaCorrespondence: Jing HuPreclinical Medicine College, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Rd., Shanghai 201203, People’s Republic of ChinaEmail h6enter@hotmail.com*These authors contributed equally to this workPurpose: Pulmonary fibrosis (PF) is a common clinical disease, which results in serious respiratory impairment. Xin Jia Xuan Bai Cheng Qi Decoction (XJXBCQ) is a traditional prescription commonly used in treating lung diseases. We investigate the effect of XJXBCQ against PF and its mechanism via the regulation of TGF-β1/Smad in vitro and in vivo.Materials and methods: XJXBCQ was first extracted and probed for chemical characterization. An PF model in vitro and in vivo was established in rats and in MRC-5 cells. In bleomycin (BLM)-induced rats model, lung function such as peak expiratory flow (PEF), minute ventilation (MV) and hydroxyproline (HYP) were measured; histopathological changes of lung tissue and TGF-β1 in peripheral blood of rats were detected. TGF-β receptor, Smad2 and its phosphorylation expression were tested by Western blot assay in rats model. Then the effects of XJXBCQ on TGF-β1/Smad signal pathway were assessed by Western blot analysis in vitro, and IL-17A and IL-25 levels were evaluated by ELISA in vivo.Results: Our results showed that XJXBCQ significantly enhanced the lung functions, such as PEF, MV and HYP, by reducing the expression level of lung inflammatory cytokine and the content and fibrosis of lung collagen. Moreover, XJXBCQ effectively inhibited TGF-β1, Smad2 and its phosphorylation expression, and the activation of Smad7 in vitro and in vivo. Furthermore, XJXBCQ had an inhibitory effect on the α-smooth muscle actin (α-SMA) and fibronectin (Fn) in vitro and downregulated IL-17A and IL-25 by inhibiting the activation of TGF-β1/Smad signaling pathway in vitro and in vivo. Further, XJXBCQ effectively inhibitied ventilation volume and peak expiratory content remodeling and hydroxyproline content through inhibition of TGF-βRⅡ, Smad2 and its phosphorylation expression, and activation of Smad7 in vivo.Conclusion: XJXBCQ extract had an anti-PF effect in vitro and in vivo, which could be attributed to the inhibition of the expression of p-Smad2 and increase in the expression of Smad7 by regulating the TGF-β1/Smad activity.Keywords: pulmonary fibrosis, lung inflammatory cytokines, transforming growth factor beta family, Smads family, Xin Jia Xuan Bai Cheng Qi decoction