Senkyunolide A alleviates asthma by inhibiting TGF-β/Smad2/3 signaling pathway and NLRP3 inflammasome activation

Background: Asthma is a chronic disease characterized by airway remodeling, which results in a progressive decline in lung function. Senkyunolide A is one of the effective components of ligusticum chuanxiong Hort, it shows protective effects on many human diseases. However, the role of Senkyunolide A in asthma remains unclear.

Results: In our study, we established an asthma mouse model by ovalbumin (OVA) sensitization and challenge, and Senkyunolide A (20 mg/kg and 40 mg/kg) was given by intraperitoneal injection. For in vitro study, lung epithelial BEAS-2B cells were treated with TGF-β1 to induce epithelial mesenchymal transformation. Our study showed that Senkyunolide A (40 mg/kg) alleviated airway injury, inflammatory infiltration and airway remodeling induced by OVA in asthma mice. Meanwhile, Senkyunolide A (40 μM) recovered the high level of cell migration and profibrotic factors expression induced by TGF-β1. Mechanistically, Senkyunolide A abolished the effect of OVA or TGF-β1 on SMAD2/3 phosphorylation at site Ser^465/467/Ser^423/425 in mice or BEAS-2B cells and inhibited the activation of NLRP3 inflammasome induced by OVA.

Conclusions: In total, our study indicated that Senkyunolide A alleviated airway damage and airway remodeling in asthmatic mice and regulated the progress of asthma by inhibiting the TGF-β/SMAD2/3 signaling pathway and NLRP3 activation.

Airway remodeling; Asthma; Inflammation; Senkyunolide A; TGF-β/Smad2/3 signaling pathway.