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.
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.
Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, China; School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.
Jing
J
Yao
Di
D
Pan
Yue
Y
Zhao
Li
L
Zhao
Jie
J
Sun
Yu
Y
Wang
Qi-Dong
QD
You
Tao
T
Xi
Qing-Long
QL
Guo
Na
N
Lu
D055371:Acute Lung Injury / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D044950:Flavanones / Q000494:pharmacology*; D005786:Gene Expression Regulation; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D047495:PPAR gamma / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D011014:Pneumonia / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D014162:Transfection
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D044950:Flavanones; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D047495:PPAR gamma; C482199:lipopolysaccharide, E coli O55-B5; C085514:wogonin
acute lung injury; lipopolysaccharide; nuclear factor-κB; peroxisome proliferator-activated receptor γ; wogonin