Glycyrrhizin attenuates the development of carrageenan-induced lung injury in mice.
Glycyrrhizin is a triterpene glycoside, a major active constituent of licorice (Glycyrrhiza glabra) root and numerous pharmacological effects like anti-inflammatory, anti-viral, anti-tumour and hepatoprotective activities has been attributed to it. In this study we evaluated the anti-inflammatory activities of glycyrrhizin in mice model of acute inflammation, carrageenan-induced pleurisy. We report here that glycyrrhizin (given at 10 mg/kg i.p. 5 min prior to carrageenan) exerts potent anti-inflammatory effects in this model. Injection of carrageenan into the pleural cavity of mice elicited an acute inflammatory response characterized by fluid accumulation in the pleural cavity which contained a large number of neutrophils (PMNs) as well as an infiltration of PMNs in lung tissues and subsequent lipid peroxidation (as determinated by thiobarbituric acid-reactant substances measurement) and increased production of tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta). All these parameters were attenuated by glycyrrhizin. Furthermore, carrageenan induced an upregulation of the expression of intercellular cell adhesion molecule (ICAM-1), P-selectin, as well as an increase in the amounts of nitrotyrosine and poly(ADP-ribose) (PAR), as determined by immunohistochemical analysis of lung tissues. The degree of staining for the ICAM-1, P-selectin, nitrotyrosine and PAR was significantly reduced by glycyrrhizin. Additionally, we demonstrate that these inflammatory events were associated with the activation of nuclear factor-kappaB (NF-kappaB) and signal transducer and activator transcription-3 (STAT-3) activation in the lung. NF-kappaB and STAT-3 activation were significantly reduced by glycyrrhizin treatment. Taken together, our results indicate that prevention of the activation of NF-kappaB and STAT-3 by glycyrrhizin reduces the development of acute inflammation.
Menegazzi
Marta
M
Biochemistry Division, Department of Neuroscience and Vision, University of Verona, Verona, Italy.
Di Paola
Rosanna
R
Mazzon
Emanuela
E
Genovese
Tiziana
T
Crisafulli
Concetta
C
Dal Bosco
Martina
M
Zou
Zhenzhen
Z
Suzuki
Hisanori
H
Cuzzocrea
Salvatore
S
D000208:Acute Disease; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002351:Carrageenan; D004789:Enzyme Activation; D019695:Glycyrrhizic Acid / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D053583:Interleukin-1beta / Q000096:biosynthesis; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D019007:P-Selectin / Q000096:biosynthesis; D030421:Peroxynitrous Acid / Q000378:metabolism; D010998:Pleurisy / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D053583:Interleukin-1beta; D016328:NF-kappa B; D019007:P-Selectin; D050796:STAT3 Transcription Factor; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D030421:Peroxynitrous Acid; D011064:Poly Adenosine Diphosphate Ribose; C002744:3-nitrotyrosine; D014443:Tyrosine; D019695:Glycyrrhizic Acid; D002351:Carrageenan