Cardamine komarovii flower extract reduces lipopolysaccharide-induced acute lung injury by inhibiting MyD88/TRIF signaling pathways.

Abstract

In the present study, we investigated anti-inflammatory effect of Cardamine komarovii flower (CKF) on lipopolysaccharide (LPS)-induced acute lung injury (ALI). We determined the effect of CKF methanolic extracts on LPS-induced pro-inflammatory mediators NO and prostaglandin E2 (PGE2), production of pro-inflammatory cytokines (IL-1β, TNF-α, and IL-6), and related protein expression levels of MyD88/TRIF signaling pathways in peritoneal macrophages (PMs). Nuclear translocation of NF-κB-p65 was analyzed by immunofluorescence. For the in vivo experiments, an ALI model was established to detect the number of inflammatory cells and inflammatory factors (IL-1β, TNF-α, and IL-6) in bronchoalveolar lavage fluid (BALF) of mice. The pathological damage in lung tissues was evaluated through H&E staining. Our results showed that CKF can decrease the production of inflammatory mediators, such as NO and PGE2, by inhibiting their synthesis-related enzymes iNOS and COX-2 in LPS-induced PMs. In addition, CKF can downregulate the mRNA levels of IL-1β, TNF-α, and IL-6 to inhibit the production of inflammatory factors. Mechanism studies indicated that CKF possesses a fine anti-inflammatory effect by regulating MyD88/TRIF dependent signaling pathways. Immunocytochemistry staining showed that the CKF extract attenuates the LPS-induced translocation of NF-kB p65 subunit in the nucleus from the cytoplasm. In vivo experiments revealed that the number of inflammatory cells and IL-1β in BALF of mice decrease after CKF treatment. Histopathological observation of lung tissues showed that CKF can remarkably improve alveolar clearance and infiltration of interstitial and alveolar cells after LPS stimulation. In conclusion, our results suggest that CKF inhibits LPS-induced inflammatory response by inhibiting the MyD88/TRIF signaling pathways, thereby protecting mice from LPS-induced ALI.

• Authors: Qi Chen, Ke-Xin Zhang, Tai-Yuan Li, Xuan-Mei Piao, Mei-Lan Lian, Ren-Bo An, Jun Jiang
• Journal: Chinese journal of natural medicines (Chin J Nat Med) Vol. 17 Issue 6 Pg. 461-468 (Jun 2019) ISSN: 1875-5364 [Electronic] China
• PMID: 31262458 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Chemical References

• Adaptor Proteins, Vesicular Transport
• Anti-Inflammatory Agents
• Lipopolysaccharides
• Myeloid Differentiation Factor 88
• NF-kappa B
• Plant Extracts
• TICAM-1 protein, mouse
• Tumor Necrosis Factor-alpha
• Nitric Oxide Synthase Type II
• Cyclooxygenase 2

Topics

• Acute Lung Injury (chemically induced, drug therapy, genetics, metabolism)
• Adaptor Proteins, Vesicular Transport (genetics, metabolism)
• Animals
• Anti-Inflammatory Agents (administration & dosage, chemistry)
• Cardamine (chemistry)
• Cyclooxygenase 2 (genetics, metabolism)
• Female
• Flowers (chemistry)
• Humans
• Lipopolysaccharides (adverse effects)
• Male
• Mice
• Myeloid Differentiation Factor 88 (genetics, metabolism)
• NF-kappa B (genetics, metabolism)
• Nitric Oxide Synthase Type II (genetics, metabolism)
• Plant Extracts (administration & dosage, chemistry)
• Signal Transduction (drug effects)
• Tumor Necrosis Factor-alpha (genetics, metabolism)