Anti-Fibrosis Effects of Magnesium Lithospermate B in Experimental Pulmonary Fibrosis: By Inhibiting TGF-βRI/Smad Signaling |
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Authors: | Xin Luo Qiangqiang Deng Yaru Xue Tianwei Zhang Zhitao Wu Huige Peng Lijiang Xuan Guoyu Pan |
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Affiliation: | 1.State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Science, 501 Haike Road, Shanghai 201203, China; (X.L.); (Q.D.); (Y.X.); (T.Z.); (H.P.);2.School of Pharmacy, University of Chinese Academy of Sciences, Beijing 100049, China;3.School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210033, China; |
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Abstract: | Pulmonary fibrosis is a severe and irreversible interstitial pulmonary disease with high mortality and few treatments. Magnesium lithospermate B (MLB) is a hydrosoluble component of Salvia miltiorrhiza and has been reported to have antifibrotic effects in other forms of tissue fibrosis. In this research, we studied the effects of MLB on pulmonary fibrosis and the underlying mechanisms. Our results indicated that MLB treatment (50 mg/kg) for seven days could attenuate bleomycin (BLM)-induced pulmonary fibrosis by reducing the alveolar structure disruption and collagen deposition in the C57 mouse model. MLB was also found to inhibit transforming growth factor-beta (TGF-β)-stimulated myofibroblastic transdifferentiation of human lung fibroblast cell line (MRC-5) cells and collagen production by human type II alveolar epithelial cell line (A549) cells, mainly by decreasing the expression of TGF-β receptor I (TGF-βRI) and regulating the TGF-β/Smad pathway. Further studies confirmed that the molecular mechanisms of MLB in BLM-induced pulmonary fibrosis mice were similar to those observed in vitro. In summary, our results demonstrated that MLB could alleviate experimental pulmonary fibrosis both in vivo and in vitro, suggesting that MLB has great potential for pulmonary fibrosis treatment. |
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Keywords: | pulmonary fibrosis bleomycin magnesium lithospermate B transforming growth factor-beta Smad signaling |
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