Crotalaria ferruginea extract attenuates lipopolysaccharide-induced acute lung injury in mice by inhibiting MAPK/NF-κB signaling pathways
Wei Pan1, Li-Ping Meng2, Jie Su3, Zheng-Biao Yang4, Wei-Feng Du3, Zhi-Wei Xu3, Yun-Xiang Chen4, Sheng Zhang4, Feng Xie4, Cong Xu4, Hong-Zhong Yang4, Wei-Hong Ge3
1 Department of Pharmacology, College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053; State Key Laboratory of Safety Evaluation for New Drugs, Hangzhou Medical College, Hangzhou 310013, China
2 Department of Surgical Nursing, The First Affiliated Hospital of Hainan Medical University, Haikou 570102, China
3 Department of Pharmacology, College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China
4 State Key Laboratory of Safety Evaluation for New Drugs, Hangzhou Medical College, Hangzhou 310013, China
State Key Laboratory of Safety Evaluation for New Drugs, Hangzhou Medical College, Hangzhou 310013
Department of Pharmacology, College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053
Source of Support: This work was supported by the Natural Science Foundation of Zhejiang province (Grant LQ19H280009); Special Projects of Zhejiang Academy of Medical Sciences (Grant CA1918D-04, CA1903Q-04); Medical Health Science and Technology Project of Zhejiang Provincial Health Commission (Grant 2020384536)., Conflict of Interest: None
Objective: To evaluate the anti-inflammatory activity of Crotalaria ferruginea extract (CFE) and its mechanism.
Methods: An intratracheal lipopolysaccharide (LPS) instillation-induced acute lung injury (ALI) model was used to study the anti-inflammatory activity of CFE in vivo. The LPS-induced shock model was used to analyze the effect of CFE on survival. LPS-stimulated RAW264.7 cell model was used to investigate the anti-inflammatory activity of CFE in vitro and the effects on mitogen-activated protein kinase (MAPK) or nuclear factor-κB (NF-κB) signaling pathways.
Results: CFE administration decreased the number of inflammatory cells, reduced the levels of tumor necrosis factor-α (TNF-a), monocyte chemotactic protein-1 (MCP-1), interleukin-6 (IL-6), and interferon-γ, and diminished protein content in the bronchoalveolar lavage fluid of mice. CFE also reduced lung wet-to-dry weight ratio, myeloperoxidase, and lung tissue pathological injury. CFE pre-administration improved the survival rate of mice challenged with a lethal dose of LPS. CFE reduced LPS-activated RAW264.7 cells to produce nitric oxide, TNF-α, MCP-1, and IL-6. Furthermore, CFE inhibited nuclear translocation and phosphorylation of NF-κB P65, extracellular signal-regulated kinase, c-Jun N-terminal kinases, and P38 MAPKs.
Conclusions: CFE exhibits potent anti-inflammatory activity in LPS-induced ALI mice, LPS-shock mice, and RAW264.7 cells, and its mechanism may be associated with the inhibition of NF-κB and MAPK signaling pathways. Crotalaria ferruginea may be a useful therapeutic drug for the treatment of ALI and other respiratory inflammations.