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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
Correspondence Address:
Hong-Zhong Yang
State Key Laboratory of Safety Evaluation for New Drugs, Hangzhou Medical College, Hangzhou 310013
China
Wei-Hong Ge
Department of Pharmacology, College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053
China
 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
DOI: 10.4103/2221-1691.328055
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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. |
