Shikonin alleviates asthmatic airway inflammation in mice through STAT3-dependent mechanism in airway epithelial cells

Shikonin showed good anti-inflammatory effects and was used in the treatment of several autoimmune diseases. However, the effects of shikonin on asthma and the underlied mechanisms have not fully understood. In this study, we firstly investigated whether shikonin could alleviated the airway inflammation and reduce airway reactivity in a mouse model of asthma. Then, the possible immunomodulatory effect of shikonin was evaluated by the expression of Th1/Th2/Th17 cytokines in bronchoalveolar lavage fluid (BALF). Moreover, whether STAT3-dependent mechanisms in airway epithelial cells play a pivotal role in the anti-inflammatory effects of shikonin was also analyzed. Our results showed that shikonin can protect mice against a range of allergic airway inflammatory pathologies, including the infiltration of inflammatory cells, mast cell degranulation and airway hyperreactivity partly via the recovery of imbalance of Th1/Th2 and Th17/Treg. Shikonin decreased the phosphorylation level of STAT3 and inhibited the transfer of p-STAT3 into the nucleus in airway epithelial cells, then down-regulated the expression of TNF-α, IL-1β, MMP9 and HIFα. In addition, STAT3 activator Colivelin could reverse the anti-inflammatory effects of shikonin. So, shikonin can suppress asthmatic airway inflammation via modulating airway epithelial STAT3 activity and may be a feasible, efficient therapy for asthma.