Pulmonary dysfunction is tightly associated with
cough variant asthma (CVA), a respiratory damage disease. Suhuang
antitussive capsule (Suhuang), one of traditional Chinese
patent medicines, plays a crucial role in the treatment and complication of CVA in the long clinical application. In this study, we aimed to investigate the protective effects and underlying
antitussive mechanisms of Suhuang on pulmonary function in
ovalbumin (OVA)-induced CVA rats. Administration (i.g.) of Suhuang significantly alleviated pulmonary damage and dysfunction. Suhuang improved ER stress and PKCε translocation via regulation of Ca2+ 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.