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Aucubin Alleviates Bleomycin-Induced Pulmonary Fibrosis in a Mouse Model

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Abstract

Pulmonary fibrosis is a life-threatening disease characterized by progressive dyspnea and worsening of pulmonary function. No effective therapeutic strategy for pulmonary fibrosis has been established. Aucubin is a natural constituent with a monoterpene cyclic ring system. The potency of aucubin in protecting cellular components against inflammation, oxidative stress, and proliferation effects is well documented. In this study, we investigated the protective effect of aucubin against pulmonary fibrosis in mice. A mouse model of pulmonary fibrosis was established by intratracheal injection of bleomycin (BLM), and aucubin was administered for 21 days after BLM injection. We found that aucubin decreased the breathing frequency and increased the lung dynamic compliance of BLM-stimulated mice detected by Buxco pulmonary function testing system. Histological examination showed that aucubin alleviated BLM-induced lung parenchymal fibrotic changes. Aucubin also reduced the intrapulmonary collagen disposition and inflammatory injury induced by BLM. In addition, aucubin reduced the expression of pro-fibrotic protein transforming growth factor (TGF)-β1 and α-smooth muscle actin (α-SMA) of pulmonary fibrosis mice induced by BLM. Furthermore, the effect of aucubin on the proliferation and differentiation of fibroblast was investigated in vitro. Aucubin inhibited the mRNA and protein expression of Ki67 and proliferating cell nuclear antigen (PCNA) induced by TGF-β1 and reduced the cell proliferation in a murine fibroblast cell NIH3T3. Aucubin also reduced the collagen syntheses and α-SMA expression induced by TGF-β1 in fibroblast. Our results indicate that aucubin inhibits inflammation, fibroblast proliferation, and differentiation, exerting protective effects against BLM-induced pulmonary fibrosis in a mouse model. This study provides an evidence that aucubin may be a novel drug for pulmonary fibrosis.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (81500065, 81670014), Science and Technology Planning Project of Changsha, Hunan Province (K1308039-31), and Hunan Provincial Natural Science Foundation of China (14JJ2040).

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Authors and Affiliations

  1. Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, 410078, China

    Yong Zhou, Ping Li, Tian Liu, Xin-Xin Guan, Wen-Xiu Mei, Yong-Ping Liu, Guo-Ying Sun, Li Wan, Wen-Jing Zhong & Cha-Xiang Guan

  2. Department of Respiratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China

    Jia-Xi Duan

  3. Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, China

    Dong-Sheng Ouyang

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  1. Yong Zhou
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Contributions

Author Contributions

Conceived and designed the experiments: C.X.G. and Y.Z. Performed the experiments: P.L., Y.Z., J.X.D., L.T., X.X.G., W.X.M., L.W., and W.J.Z. Analyzed the data: Y.Z., Y.P.L., D.S.O.Y., and G.Y.S. Contributed reagents/materials/analysis tools: Y.Z. and C.X.G. Wrote the paper: Y.Z. and C.X.G. Critically reviewed the manuscript: C.X.G.

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Correspondence to Cha-Xiang Guan.

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Zhou, Y., Li, P., Duan, JX. et al. Aucubin Alleviates Bleomycin-Induced Pulmonary Fibrosis in a Mouse Model. Inflammation 40, 2062–2073 (2017). https://doi.org/10.1007/s10753-017-0646-x

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