Journal
BIOMEDICINE & PHARMACOTHERAPY
Volume 118, Issue -, Pages -Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2019.109188
Keywords
Suhuang antitussive capsule; Pulmonary dysfunction; Cough variant asthma; Endoplasmic reticulum stress; NLRP3; Inflammasome
Funding
- Fund of State Key Laboratory of Natural Medicines of China Pharmaceutical University [3144060028]
- Program for Innovative Research Team of Jiangsu Province
- National New Drug Innovation Major Project of the Ministry of Science and Technology of China [2017ZX09309027]
- Postgraduate Research and Practice Innovation Program of Jiangsu Province [KYCX19_0693]
- Graduate Student Innovative Foundation of Zhejiang Huahai Pharmaceutical Co., Ltd. [CX17S-010HH]
- Double First-Class University Project from China Pharmaceutical University [CPU2018GF05]
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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 PKC epsilon 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-1 beta 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.
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