Ebeiedinone and peimisine inhibit cigarette smoke extract-induced oxidative stress injury and apoptosis in BEAS-2B cells

Abstract

Ebeiedinone and peimisine are the major active ingredients of Fritillariae Cirrhosae Bulbus. In this study, we looked at how these two forms of isosteroidal alkaloids protect human bronchial epithelial BEAS-2B cells from oxidative stress and apoptosis caused by cigarette smoke extract (CSE). First, the cytotoxicity was determined using the CCK8 assay, and an oxidative stress model was established. Then the antioxidative stress activity and mechanism were investigated by ELISA, flow cytometry, and Western blotting. By the CCK-8 assay, exposure to CSE (20%, 40%, and 100%) reduced the viability of BEAB-2S cells. The flow cytometry findings indicated that CSE-induced production of ROS (0.5% to maximum) and treatments with 10 μM ebeiedinone and 20 μM peimisine attenuated the production of ROS. The western blot assay results indicate that ebeiedinone and peimisine reduce CSE-induced oxidative stress, DNA damage, apoptosis, and autophagy dysregulation by inhibiting ROS, upregulating SOD and GSH/GSSG, and downregulating MDA, 4-HNE, and 8-OHdG through the NRF2/KEAP1 and JNK/MAPK-dependent pathways, thereby delaying the pathological progression of COPD caused by CS.Our data suggest that CSE causes oxidative stress, DNA damage, and apoptosis in BEAS-2B cells, as well as the progression of COPD. Ebeiedinone and peimisine fight CS-induced COPD by suppressing autophagy deregulation and apoptosis.