Tanshinone IIA + Osthole alleviates ferroptosis in LPS-induced acute lung injury by Keap1-Nrf2/HO-1 pathway

作者：Jin F, Yujuan Li, Lei Pan, Qi Zhao, Huanqing Xiong, Xiaoan Fang, Jian Chen, Xian Guo, Yongheng Gao, Ying Wang, Xiaorong Su, Pan Liu · 年份：2024 · DOI：10.22541/au.172451512.26871295/v1 · 研究领域：Cancer-related molecular mechanisms research、Ferroptosis and cancer prognosis、Circular RNAs in diseases

Background: Acute lung injury (ALI) is associated with a high mortality rate and requires effective treatment. Tanshinone IIA (T) and Osthole (O) exhibit anti-inflammatory effects and have been used to protect against lipopolysaccharide (LPS)-induced lung injury in mice. However, the combined effects of T and O on lung injury protection and their potential protective mechanisms have not been studied. Objective: To assess the protective effects of TO on LPS-induced ALI in mice and BEAS-2B cell injury and to investigate the potential mechanisms. Methods: An animal model of LPS-induced ALI and a BEAS-2B cell injury model were established. The assessment encompassed the viability of BEAS-2B cells, cell count, myeloperoxidase (MPO) activity, protein content, as well as IL-6 and TNF-a levels in bronchoalveolar lavage fluid (BALF). Additionally, malondialdehyde (MDA), reactive oxygen species (ROS), and glutathione (GSH) levels in mouse lung tissue were measured. The effects of TO were assessed using immunofluorescence (IF), immunohistochemistry (IHC), Western Blot (WB), RT-PCR, and ELISA. Statistical analysis involved one-way ANOVA and t-test. Results: TO administration led to a significant reduction in lung edema (W/D), MDA, ROS, GSH, and superoxide dismutase (SOD) levels compared to the individual T or O groups, alleviating LPS-induced ALI. TO also significantly attenuated lung tissue damage, reduced inflammatory response, decreased Fe2+ and 4-HNE levels, and increased GPX4, SLC7A...