Inhibitory effects of flavonoids extracted from licorice on lipopolysaccharide-induced acute pulmonary inflammation in mice.
Airway inflammation plays important roles in the pathogenesis of acute respiratory distress syndrome (ARDS), asthma and chronic obstructive pulmonary disease (COPD), and anti-inflammatory treatment effectively improves the symptoms of these diseases. To develop the potentially therapeutic compounds for the treatment of pulmonary inflammation, we investigated the effects of licorice flavonoids (LF) extracted from the roots of Glycyrrhiza uralensis (licorice) on lipopolysaccharide (LPS)-induced acute pulmonary inflammation in mice. Acute pulmonary inflammation was induced by intracheal instillation with LPS, treatment with LF at dosages of 3, 10 and 30 mg/kg significantly reduced the LPS-induced inflammatory cells, including neutrophils, macrophages and lymphocytes accumulation in bronchoalveolar lavage fluids (BALF), among these inflammatory cells, LF predominately inhibited neutrophil infiltration, and the maximal effect (30 mg/kg) was as comparable as dexamethasone treatment at 1 mg/kg. Consistent with its effects on neutrophil infiltration, LF treatment significantly increased LPS-induced BALF superoxide dismutase activity, and significantly decreased lung myeloperoxidase activity as well. Furthermore, treatment with LF at 30 mg/kg significantly reduced LPS-induced lung TNFalpha and IL-1beta mRNA expression at 6 h and 24 h after LPS instillation, respectively. Finally, LF at different dosages not only significantly decreased the elevation of lung water content, but also markedly attenuated LPS-induced histological alteration. Therefore, we suggest that LF effectively attenuates LPS-induced pulmonary inflammation through inhibition of inflammatory cells infiltration and inflammatory mediator release which subsequently reduces neutrophil recruitment into lung and neutrophil-mediated oxidative injury, and this study provides with the potential rationale for development of anti-inflammatory compounds from flavonoid extracts of licorice.
Xie
Yi-Cheng
YC
Zhejing Respiratory Drugs Research Laboratory of State Food and Drugs Administration of China, Zhejiang University, Hangzhou 310058, China.
Dong
Xin-Wei
XW
Wu
Xi-Mei
XM
Yan
Xiao-Feng
XF
Xie
Qiang-Min
QM
D000208:Acute Disease; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D006035:Glycyrrhiza / Q000737:chemistry*; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000276:immunology*; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D009195:Peroxidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D011014:Pneumonia / Q000188:drug therapy* / Q000276:immunology; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005419:Flavonoids; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase; D013482:Superoxide Dismutase