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.