Wogonin prevents lipopolysaccharide-induced acute lung injury and inflammation in mice via peroxisome proliferator-activated receptor gamma-mediated attenuation of the nuclear factor-kappaB pathway.

Abstract

Acute lung injury (ALI) from a variety of clinical disorders, characterized by diffuse inflammation, is a cause of acute respiratory failure that develops in patients of all ages. Previous studies reported that wogonin, a flavonoid-like chemical compound which was found in Scutellaria baicalensis, has anti-inflammatory effects in several inflammation models, but not in ALI. Here, the in vivo protective effect of wogonin in the amelioration of lipopolysaccharide (LPS) -induced lung injury and inflammation was assessed. In addition, the in vitro effects and mechanisms of wogonin were studied in the mouse macrophage cell lines Ana-1 and RAW264.7. In vivo results indicated that wogonin attenuated LPS-induced histological alterations. Peripheral blood leucocytes decreased in the LPS-induced group, which was ameliorated by wogonin. In addition, wogonin inhibited the production of several inflammatory cytokines, including tumour necrosis factor-α, interleukin-1β (IL-1β) and IL-6, in the bronchoalveolar lavage fluid and lung tissues after LPS challenge, while the peroxisome proliferator-activated receptor γ (PPARγ) inhibitor GW9662 reversed these effects. In vitro results indicated that wogonin significantly decreased the secretion of IL-6, IL-1β and tumour necrosis factor-α in Ana-1 and RAW264.7 cells, which was suppressed by transfection of PPARγ small interfering RNA and GW9662 treatment. Moreover, wogonin activated PPARγ, induced PPARγ-mediated attenuation of the nuclear translocation and the DNA-binding activity of nuclear factor-κB in vivo and in vitro. In conclusion, all of these results showed that wogonin may serve as a promising agent for the attenuation of ALI-associated inflammation and pathology by regulating the PPARγ-involved nuclear factor-κB pathway.

• Authors: Jing Yao, Di Pan, Yue Zhao, Li Zhao, Jie Sun, Yu Wang, Qi-Dong You, Tao Xi, Qing-Long Guo, Na Lu
• Journal: Immunology (Immunology) Vol. 143 Issue 2 Pg. 241-57 (Oct 2014) ISSN: 1365-2567 [Electronic] England
• PMID: 24766487 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 John Wiley & Sons Ltd.

Chemical References

• Anti-Inflammatory Agents
• Cytokines
• Flavanones
• Inflammation Mediators
• Lipopolysaccharides
• NF-kappa B
• PPAR gamma
• lipopolysaccharide, E coli O55-B5
• wogonin

Topics

• Acute Lung Injury (chemically induced, genetics, immunology, metabolism, prevention & control)
• Animals
• Anti-Inflammatory Agents (pharmacology)
• Cell Line
• Cytokines (metabolism)
• Disease Models, Animal
• Female
• Flavanones (pharmacology)
• Gene Expression Regulation
• Inflammation Mediators (metabolism)
• Lipopolysaccharides
• Lung (drug effects, immunology, metabolism)
• Macrophages (drug effects, immunology, metabolism)
• Mice
• Mice, Inbred C57BL
• NF-kappa B (metabolism)
• PPAR gamma (drug effects, genetics, metabolism)
• Pneumonia (chemically induced, genetics, immunology, metabolism, prevention & control)
• RNA Interference
• Signal Transduction (drug effects)
• Time Factors
• Transfection