Suhuang antitussive capsule inhibits NLRP3 inflammasome activation and ameliorates pulmonary dysfunction via suppression of endoplasmic reticulum stress in cough variant asthma

trafficking. Suhuang also inhibited NLRP3 inflammasome activation, as evidenced by disrupting the assembly of NLRP3 inflammasome and reducing the expression of cleaved caspase-1, and decreased IL-1β secretion. Besides, it's identified that TXNIP induction and RIP1-RIP3-Drp1 pathway were required for the inhibitory routes of Suhuang from ER stress to NLRP3 inflammasome activation. Consistent with the in vivo findings, Suhuang also attenuated ER stress/NLRP3 inflammasome activation, and thereby restored pulmonary homeostasis in vitro. Meantime, these functions were diminished by blocking ER stress, indicating that ER stress is essential for the effects of Suhuang on pulmonary function. A further in vivo analysis showed that Suhuang-driven pharmacological inactivation of NLRP3 inflammasome and amelioration of pulmonary dysfunction were reversed by an ER stress inducer tunicamycin, well confirming the beneficial effects of Suhuang on pulmonary function by regulation of ER stress. Collectively, these results indicated that Suhuang contributed to impairing NLRP3 inflammasome activation via inhibition of ER stress, which was responsible for the protection of pulmonary homeostasis. These findings may provide a pharmacological groundwork and important new experimental data regarding the clinical treatment of Suhuang in CVA patients.