Silibinin alleviates house dust mite induced allergic airway inflammation by inhibiting NLRC4 inflammasome and MMP-9 expression

Silibinin, a major compound of silymarin, has been reported to alleviate respiratory diseases including acute lung injury, asthma, chronic obstructive pulmonary disease, and pulmonary fibrosis through its antifibrotic, anti-inflammatory, and antioxidant properties. However, the specific mechanisms underlying its therapeutic effects, particularly in allergic asthma, are not fully understood. With the increasing prevalence and impact of allergic asthma, there is a need to elucidate the exact underlying mechanisms of its potential treatment effects. Herein, we investigated the therapeutic effects of silibinin on allergic asthma using house dust mite (HDM)-exposed mice and an HDM-stimulated human bronchial epithelium cell line, focusing on the roles of the NLR family CARD domain containing 4 (NLRC4) inflammasome and matrix metalloproteinase-9 (MMP-9). To induce airway inflammation, HDM extracts were instilled intranasally on days 0, 4, 8, and 12 to mice. Silibinin (20 and 40 mg/kg) was orally administered daily from days 0-12. The results showed that silibinin treatment attenuated allergic immune responses induced by HDM exposure, as evidenced by decreased airway hyperresponsiveness, reduced inflammatory cells and cytokines, lower immunoglobulin E levls, and decreased mucus production. Furthermore, silibinin treatment suppressed NLRC4 inflammasome activation and downregulated MMP-9 expression in the lungs. In HDM-stimulated cells, silibinin treatment decreased inflammatory cytokine levels and the expression of NLRC4 and interleukin-1β, indicating inhibition of NLRC4 inflammasome activation. Overall, our data demonstrated that silibinin alleviated allergic responses in HDM-induced asthmatic mice by inhibiting NLRC4 inflammasome activation and MMP-9 expression, underscoring its therapeutic potential in the treatment of asthma.