Sophocarpine Alleviates Airway Epithelial Cell Inflammation in Asthma via Modulating the Cytokine- Cytokine Receptor and JAK2/STAT3 Signaling Pathways.

PURPOSE: Asthma is a complex, heterogeneous, and inflammatory disease with an increasing incidence worldwide. This study aimed to investigate the therapeutic mechanisms of sophocarpine in asthma systematically.

METHODS

A house dust mite (HDM)-induced mouse and cell model was built. The effects and mechanisms of sophocarpine on asthma were evaluated in vivo and in vitro.

RESULTS

In the mouse model, sophocarpine treatment reduced airway pathological damage, mucus secretion, levels of interleukin (IL)-4, IL-5, IL-17, immunoglobulin E (IgE), and splenic index, as well as eosinophil accumulation. Network pharmacology studies revealed that sophocarpine may target TLR4, STAT3, and TNF, and regulates the JAK-STAT, and Viral protein interaction with cytokine and cytokine receptor signaling pathway et al. Docking results showed that the binding energy of sophocarpine to major targets varied from -7.55 to -5.22 kcal/mol. Transcriptome analysis identified 436 DEGs, which were enriched in pathways consistent with the network pharmacology, such as the JAK-STAT signaling pathway. We further confirmed that sophocarpine downregulated the mRNA expression levels of CCL5, CCL7, CCL12, CXCL1, CXCL2, CXCL3, CCR2, CXCR2, CXCR3, JAK2, STAT3, and c-MYC, and protein expression of CXCR2, JAK2, STAT3, and c-MYC in the mouse model. Sophocarpine also inhibited HDM-induced BEAS-2B cell viability decrease, cell apoptosis, and ROS overproduction, which was associated with modulation of the cytokine-cytokine receptor and JAK-STAT signaling pathways. Further, similar to sophocarpine, STAT3 inhibitors and siRNA effectively reduced the levels of STAT3, MYC, and CXCR2.

CONCLUSION

These results indicate that sophocarpine effectively inhibits HDM-induced airway epithelial cell inflammation through regulating cytokine-cytokine receptor and JAK2/STAT3 signaling pathways.