(-)-Epicatechin ameliorates cigarette smoke-induced lung inflammation via inhibiting ROS/NLRP3 inflammasome pathway in rats with COPD

Chronic obstructive pulmonary disease (COPD) with increased morbidity and mortality is a worldwide healthcare challenge closely associated with cigarette smoking (CS). Currently, there is no effective therapeutic strategy to control inflammation in COPD patients. The present study tested the protective effects of (-)-Epicatechin (EC), a type of flavonoid, on CS-induced COPD and the underlying mechanism. Also, EC repressed the production of reactive oxygen species (ROS) and improved human bronchial epithelial cell viability after cigarette smoke extract (CSE) treatment. Further studies demonstrated that EC promotes ubiquitin-mediated Keap1 degradation by upregulating tripartite motif-containing protein 25 (TRIM25) expression and enhances the nuclear localization of Nrf2 protein. Also, EC dramatically inhibits the activation of NLRP3 inflammasome and reduces the CSE-induced pyroptosis, as indicated by decreasing lactate dehydrogenase release and the number of caspase-1-positive cells. Importantly, Nrf2 knockdown reversed the protective effect of EC on human bronchial epithelial cells, at least partially. Consistent with the results in vitro, EC inhibits the activation of NLRP3 inflammasome and relieves the CS-induced lung inflammation, as evident from decreased interleukin (IL)-1 beta and IL-18 secretion in a COPD rat model. In conclusion, this study revealed the protective effect of EC on experimental COPD rats and elucidated the mechanism of EC promoting Nrf2 activity, which might provide a novel therapeutic strategy for COPD.

Automated summary

This study demonstrated the protective effect of EC on experimental COPD rats and elucidated the mechanism of EC promoting Nrf2 activity, which might provide a novel therapeutic strategy for COPD.