Baicalin suppresses type 2 immunity through breaking off the interplay between mast cell and airway epithelial cell

Ethnopharmacological relevance: The traditional Japanese herbal medicine Shin'iseihaito was reported to ameliorate the airway type 2 inflammatory response in clinical and experimental studies. Airway type 2 inflammatory diseases, including bronchial asthma and eosinophilic chronic rhinosinusitis (ECRS), often coexist and interact with each other. However, it is still unclear how Shin'iseihaito exerts its pharmacological effects on cells involved in airway mucosa. Aim of the study: This study aims to examine the direct effect of baicalin, a representative bioactive compound of Shin'iseihaito, on type 2 immune responses in human airway epithelial cells and mast cells. Material and methods: We measured the plasma pharmacokinetics of flavonoids derived from Shin'iseihaito and investigated the effects of baicalin on type 2 immune responses in human airway epithelial cells and human mast cells. Results: Baicalin, wogonin, and wogonoside were detected in the plasma. The maximum plasma concentration of baicalin was highest at 1610 ng/ml (3.6 mu M). In the normal human bronchial epithelial cells treated with baicalin, with or without stimulation by IFN-gamma, the IL-33 expression was significantly downregulated. However, baicalin treatment did not affect the levels of thymic stromal lymphopoietin and IL-25. We noted that IL-33-dependent expression of tryptase mRNA in mast cells was significantly inhibited by baicalin. Also, the expression of IL-5 in mast cells enhanced by stimulation with TSLP plus IL-1 beta was significantly downregulated by baicalin treatment. Moreover, the enhancement of IL-13 expression in mast cells by IL-33 simulation was also significantly inhibited by baicalin. Conclusions: Our results prove that by breaking off the vicious circle of mast cells and airway epithelial cells, baicalin may be an effective alternative therapeutic option for the treatment of type 2 inflammatory diseases, such as ECRS and comorbid asthma.

Automated summary

The traditional Japanese herbal medicine Shin'iseihaito, specifically its bioactive compound baicalin, has been found to have a direct effect on type 2 immune responses in human airway epithelial cells and mast cells. By inhibiting IL-33-dependent gene expression and downregulating IL-5 and IL-13 levels, baicalin shows potential as an effective alternative therapeutic option for type 2 inflammatory diseases like ECRS and asthma.