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Silymarin Attenuates Airway Inflammation Induced by Cigarette Smoke in Mice

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Abstract

Cigarette smoke (CS), which increases inflammation and oxidative stress, is a major risk factor for the development of COPD. In this study, we investigated the effects of silymarin, a polyphenolic flavonoid isolated from the seeds and fruits of milk thistle, on CS-induced airway inflammation and oxidative stress in mice and the possible mechanisms. BALB/c mice were exposed to CS for 2 h twice daily, 6 days per week for 4 weeks. Silymarin (25, 50 mg/kg · day) was administered intraperitoneally 1 h before CS exposure. Bronchoalveolar lavage fluid (BALF) was acquired for cell counting and the detection of pro-inflammatory cytokine levels. Lung tissue was collected for histological examination, myeloperoxidase (MPO) activity assay, superoxide dismutase (SOD) activities, and malondialdehyde (MDA) levels. The phosphorylation of ERK and p38 was evaluated by Western blotting. Pretreatment with silymarin significantly attenuated CS-induced thickening of the airway epithelium, peribronchial inflammatory cell infiltration, and lumen obstruction. The numbers of total cells, macrophages, and neutrophils, along with the MPO activity (a marker of neutrophil accumulation) in BALF, were remarkably decreased by silymarin in CS-exposed mice (all p < 0.05). In addition, silymarin pretreatment dampened the secretion of TNF-α, IL-1β, and IL-8 in BALF. High-dose silymarin (50 mg/kg · day) administration also prevented CS-induced elevation in MDA levels and decrease in SOD activities (p < 0.05). Furthermore, the CS-induced phosphorylation of ERK and p38 was also attenuated by silymarin (p < 0.05). These results suggest that silymarin attenuated inflammation and oxidative stress induced by cigarette smoke. The anti-inflammatory effect might partly act through the mitogen-activated protein kinases (MAPK) pathway.

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Acknowledgments

This study was supported by grants 31171103 and 81230001 from the National Natural Science Foundation of China and 06–834 from the China Medical Board of New York to Dr Fu-Qiang Wen.

Conflicts of Interest

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, Sichuan University, Chengdu, Sichuan, 610000, China

    Diandian Li, Dan Xu, Tao Wang, Yongchun Shen, Shujin Guo, Xue Zhang, Lingli Guo, Xiaoou Li, Lian Liu & Fuqiang Wen

  2. Department of Respiratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, 610041, China

    Diandian Li, Dan Xu, Tao Wang, Yongchun Shen, Shujin Guo, Xue Zhang, Lingli Guo, Xiaoou Li, Lian Liu & Fuqiang Wen

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  1. Diandian Li
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  2. Dan Xu
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  10. Fuqiang Wen
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Correspondence to Fuqiang Wen.

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Li, D., Xu, D., Wang, T. et al. Silymarin Attenuates Airway Inflammation Induced by Cigarette Smoke in Mice. Inflammation 38, 871–878 (2015). https://doi.org/10.1007/s10753-014-9996-9

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  • DOI: https://doi.org/10.1007/s10753-014-9996-9

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