Sappanone A inhibits oxidative stress, inflammation and apoptosis in cigarette smoke-induced human bronchial epithelial cells through regulating Nrf2/HO-1 and TLR4/NF-κB signaling pathways

Chronic obstructive pulmonary disease (COPD) is a common respiratory disease associated with inflammation and oxidative stress. Sappanone A (SA) is a homoisoflavanone that has been proven to have anti-inflammatory and anti-oxidant effects. However, the role of SA in COPD remains unclear. Thus, the present study was aimed to evaluate the beneficial effect of SA on COPD in vitro. The human bronchial epithelial cells were exposed to 5% cigarette smoke extracts (CSE) to induce an in vitro model of COPD. Our results showed that SA treatment significantly attenuated the CSE-caused induction of ROS and reduction of SOD and GPx activities in 16HBE cells. In addition, SA inhibited the production of inflammatory cytokines IL-6, IFN-γ, and TNF-α in CSE-stimulated 16HBE cells. Moreover, the CSE-stimulated cell apoptosis of 16HBE cells were abrogated by SA. Furthermore, we observed that SA treatment greatly promoted the activation of Nrf2/HO-1 signaling pathway, as well as inhibited the activation of TLR4/NF-κB signaling pathway in CSE-stimulated 16HBE cells. Subsequent rescue assay revealed that the protective effects of SA on CSE-stimulated 16HBE cells were reversed by Nrf2 knockdown or TLR4 overexpression. Taken together, these findings demonstrated that SA inhibits oxidative stress, inflammation and apoptosis in CSE-induced human bronchial epithelial cells through regulating Nrf2/HO-1 and TLR4/NF-κB signaling pathways.