5-deoxy-rutaecarpine protects against LPS-induced acute lung injury via inhibiting NLRP3 inflammasome-related inflammation
Jinque Luo, Xin Li, Li Zhang, Meijing Deng, Jie Zhao, Jing Zhang, Wenyu Tang, Qinghua Guo, Lingling Wang
Abstract
Introduction Acute lung injury (ALI) induced by lipopolysaccharide (LPS) is a significant medical condition characterized by severe pulmonary inflammation and tissue damage. NLRP3 inflammasome-driven inflammation is essential in ALI pathogenesis, inspiring novel therapeutic strategies that focus on NLRP3 and inflammation. In this study, we investigated the therapeutic potential of 5-deoxy-rutaecarpine (5-DR), a rutaecarpine derivative, in attenuating LPS-induced ALI. Methods In this study, we evaluated the effects of 5-DR treatment in mice exposed to LPS, lung tissues, bronchoalveolar lavage fluid, and serum were collected for analysis. LPS-stimulated J774A.1 mouse macrophages were used to further investigate the anti-inflammatory effects of 5-DR in vitro . Various techniques including histopathology, Western blotting, and luciferase reporter assay were employed. Results 5-DR treatment significantly reduced lung edema, inflammatory cell infiltration in mice with LPS burden, and reduced the levels of inflammatory mediators like interleukin-1β in the mice and in LPS-stimulated J774A.1 mouse macrophages. Further western blotting analysis showed 5-DR decreased the levels of NLRP3, cleaved caspase-1, and mature IL-1β in mice and J774A.1 cells exposed to LPS. Additionally, NF-κB pathway activation significantly diminished the inhibition of the NLRP3 inflammasome by 5-DR. Discussion Our findings highlight the therapeutic potential of 5-DR as a promising candidate for treating LPS-induced ALI, offering insights into its underlying mechanism that targets NLRP3 inflammasome-mediated inflammation.