1. Euphorbia factor L2 alleviates lipopolysaccharide-induced acute lung injury and inflammation in mice through the suppression of NF-κB activation
- Author
-
Cheng Xiaolan, Tao Weiwei, Shiyue Yi, Yuanyuan Zhang, Blackledge C. William, Chenyang Lu, Yubin Luo, Xue Cao, Yi Liu, Yi Zhao, Qiuping Zhang, and Shuai Zhu
- Subjects
Lipopolysaccharides ,Male ,0301 basic medicine ,MAPK/ERK pathway ,Lipopolysaccharide ,Acute Lung Injury ,Inflammation ,Lung injury ,Pharmacology ,Biochemistry ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Euphorbia ,Animals ,Medicine ,Dose-Response Relationship, Drug ,biology ,Plant Extracts ,business.industry ,NF-kappa B ,NF-κB ,Mice, Inbred C57BL ,IκBα ,RAW 264.7 Cells ,030104 developmental biology ,chemistry ,030220 oncology & carcinogenesis ,Myeloperoxidase ,biology.protein ,Tumor necrosis factor alpha ,medicine.symptom ,business - Abstract
Acute respiratory distress syndrome threatens public health with high morbidity and mortality due to ineffective intervention whereby lipopolysaccharide (LPS) induced acute lung injury (ALI) in mice provides a research model. The seeds of Euphorbia lathyris L. have a long history of usage in Traditional Chinese Medicine. Euphorbia factors L1-L11, extracted from this herb, have been reported to have anti-inflammation and anti-cancer effects. Here, we report the preventive and therapeutic potential of Euphorbia factor L2 (EFL2) on LPS-induced ALI in mice, where EFL2 attenuated pathological alterations in the lung and improved survival. Significant suppression of the recruitment and transmigration of inflammatory cells, specifically neutrophils, by 40 mg/kg of EFL2 was observed. EFL2 exerted potent anti-inflammatory effects by decreasing the levels of interleukin-1β (IL-1 β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF- α), interleukin-8 (IL-8) and myeloperoxidase (MPO) in the lung and bronchioalveolar lavage fluid. Consistent with the findings in vivo, EFL2 also showed robust inhibitory effects on the production of IL-1 β, IL-6, TNF- α and IL-8 released from LPS-stimulated RAW264.7 cells in vitro. Interestingly, this effect appeared to be mediated by EFL2’s inhibition of NF-κB signaling activation, but not the MAPK pathway. Not only phosphorylation of IKK α/β and IκBα was down-regulated, p65 translocation and its DNA-binding activity were also significantly suppressed by EFL2. Moreover, overexpression of p65 reversed the inhibitory effect of EFL2 in LPS-induced NF-κB activation and cytokines production. The observed anti-inflammatory bioactivity of EFL2 indicates its potential as a drug development candidate, particularly for LPS-mediated disorders of inflammation.
- Published
- 2018