Aucubin Alleviates Bleomycin-Induced Pulmonary Fibrosis in a Mouse Model

• Published in: Inflammation 2017-12, Vol.40 (6), p.2062-2073
• Main Authors: Zhou, Yong, Li, Ping, Duan, Jia-Xi, Liu, Tian, Guan, Xin-Xin, Mei, Wen-Xiu, Liu, Yong-Ping, Sun, Guo-Ying, Wan, Li, Zhong, Wen-Jing, Ouyang, Dong-Sheng, Guan, Cha-Xiang
• Format: Article
• Language: English
• Subjects: Actin; Animals; Biomedical and Life Sciences; Biomedicine; Bleomycin; Bleomycin - toxicity; Cell Differentiation - drug effects; Cell proliferation; Collagen; Disease Models, Animal; Dyspnea; Fibroblasts; Fibroblasts - drug effects; Fibroblasts - pathology; Fibrosis; Gene expression; Immunology; Inflammation; Inflammation - drug therapy; Inflammation - prevention & control; Injection; Internal Medicine; Iridoid Glucosides - pharmacology; Lung diseases; Mice; mRNA; Original Article; Oxidative stress; Pathology; Pharmacology/Toxicology; Proliferating cell nuclear antigen; Pulmonary fibrosis; Pulmonary Fibrosis - chemically induced; Pulmonary Fibrosis - drug therapy; Pulmonary Fibrosis - prevention & control; Respiration; Respiratory function; Rheumatology; Rodents; Smooth muscle; Trachea; Transforming growth factor; Transforming growth factor-b1
• ISSN: 0360-3997; 1573-2576
• DOI: 10.1007/s10753-017-0646-x

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.