Solasodine inhibits the Th2 immune response and airway remodeling in asthmatic mice through the Runx3/NLRP3 pathway

To explore the therapeutic effects of Solasodine on Th2 immune responses and airway remodeling, and to assess whether its mechanism involves NLRP3 inflammasome inactivation mediated by Runx3.

We created an asthma model with wild-type and Runx3 knockout mice using ovalbumin (OVA). After oral administration of Solasodine, we assessed inflammatory and Th2 immune responses using HE staining, ELISA, and flow cytometry. Airway remodeling was assessed with Masson's trichrome staining and α-SMA and TGF-β immunohistochemistry. Mucus secretion was analyzed through MUC5AC immunohistochemistry, and expectoration assays. We studied NLRP3 inflammasome activation using immunohistochemistry and Western blot. We used western blotting and flow cytometry to evaluate how Solasodine regulates Runx3 protein levels.

Solasodine effectively inhibited the inflammatory response in OVA-induced asthmatic mice, evidenced by reducing inflammatory cell infiltration and lower IL-4, IL-5, and IL-13 levels, decreasing airway remodeling and mucus secretion. Solasodine reduced airway hyperresponsiveness, shown by a lower Penh value. Solasodine boosts Runx3 expression and suppresses NLRP3 inflammasome activation in asthmatic mice. We created an asthma model in Runx3 knockout mice and administered Solasodine at a consistent dose. Following OVA induction, Runx3 knockout mice showed greater inflammation, a Th2 immune response, airway remodeling, and mucus secretion than wild-type mice. Solasodine is less effective in Runx3 knockout asthmatic mice than in wild-type mice.

The anti-asthmatic effects of Solasodine are shown through the inhibition in the Th2 immune response, airway remodeling, hyperresponsiveness, and mucus secretion. The effectiveness may be linked to Runx3-mediated the NLRP3 inflammasomes.