Theranostics 2017; 7(17):4255-4275. doi:10.7150/thno.20270 This issue Cite

Research Paper

Dioscin Exerts Protective Effects Against Crystalline Silica-induced Pulmonary Fibrosis in Mice

Chao Li1, Yiping Lu1, Sitong Du1, Siyi Li1, Yiting Zhang1, Fangwei Liu1, Ying Chen1, Dong Weng1, 2✉, Jie Chen1✉

1. Division of Pneumoconiosis, School of Public Health, China Medical University, Shenyang, PR China;
2. Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, PR China.

Citation:
Li C, Lu Y, Du S, Li S, Zhang Y, Liu F, Chen Y, Weng D, Chen J. Dioscin Exerts Protective Effects Against Crystalline Silica-induced Pulmonary Fibrosis in Mice. Theranostics 2017; 7(17):4255-4275. doi:10.7150/thno.20270. https://www.thno.org/v07p4255.htm
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Abstract

Graphic abstract

Inhalation of crystalline silica particles leads to pulmonary fibrosis, eventually resulting in respiratory failure and death. There are few effective drugs that can delay the progression of this disease; thus, patients with silicosis are usually only offered supportive care. Dioscin, a steroidal saponin, exhibits many biological activities and health benefits including its protective effects against hepatic fibrosis. However, the effect of dioscin on silicosis is unknown.

Methods: We employed experimental mouse mode of silicosis. Different doses of dioscin were gavaged to the animals 1 day after crystalline silica instillation to see the effect of dioscin on crystalline silica induced pulmonary fibrosis. Also, we used RAW264.7 and NIH-3T3 cell lines to explore dioscin effects on macrophages and fibroblasts. Dioscin was also oral treatment but 10 days after crystalline silica instillation to see its effect on established pulmonary fibrosis.

Results: Dioscin treatment reduced pro-inflammation and pro-fibrotic cytokine secretion by modulating innate and adaptive immune responses. It also reduced the recruitment of fibrocytes, protected epithelial cells from crystalline silica injury, inhibited transforming growth factor beta/Smad3 signaling and fibroblast activation. Together, these effects delayed the progression of crystalline silica-induced pulmonary fibrosis. The mechanism by which dioscin treatment alleviated CS-induced inflammation appeared to be via the reduction of macrophage, B lymphocyte, and T lymphocte infiltration into lung. Dioscin inhibits macrophages and fibroblasts from secreting pro-inflammatory cytokines and may also function as a modulator of T helper cells responses, concurrent with attenuated phosphorylation of the apoptosis signal-regulating kinase 1-p38/c-Jun N-terminal kinase pathway. Also, dioscin could block the phosphorylation of Smad3 in fibroblast. Oral treatment of dioscin could also effectively postpone the progression of established silicosis.

Conclusion: Oral treatment dioscin delays crystalline silica-induced pulmonary fibrosis and exerts pulmonary protective effects in mice. Dioscin may be a novel and potent candidate for protection against crystalline silica-induced pulmonary fibrosis.

Keywords: Crystalline silica, Pulmonary fibrosis, Dioscin, Immune response, Fibrocytes, Epithelial cells, Natural products therapy.


Citation styles

APA
Li, C., Lu, Y., Du, S., Li, S., Zhang, Y., Liu, F., Chen, Y., Weng, D., Chen, J. (2017). Dioscin Exerts Protective Effects Against Crystalline Silica-induced Pulmonary Fibrosis in Mice. Theranostics, 7(17), 4255-4275. https://doi.org/10.7150/thno.20270.

ACS
Li, C.; Lu, Y.; Du, S.; Li, S.; Zhang, Y.; Liu, F.; Chen, Y.; Weng, D.; Chen, J. Dioscin Exerts Protective Effects Against Crystalline Silica-induced Pulmonary Fibrosis in Mice. Theranostics 2017, 7 (17), 4255-4275. DOI: 10.7150/thno.20270.

NLM
Li C, Lu Y, Du S, Li S, Zhang Y, Liu F, Chen Y, Weng D, Chen J. Dioscin Exerts Protective Effects Against Crystalline Silica-induced Pulmonary Fibrosis in Mice. Theranostics 2017; 7(17):4255-4275. doi:10.7150/thno.20270. https://www.thno.org/v07p4255.htm

CSE
Li C, Lu Y, Du S, Li S, Zhang Y, Liu F, Chen Y, Weng D, Chen J. 2017. Dioscin Exerts Protective Effects Against Crystalline Silica-induced Pulmonary Fibrosis in Mice. Theranostics. 7(17):4255-4275.

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