title: Hypericum perforatum attenuates the development of carrageenan-induced lung injury in mice.
abstract: Hypericum perforatum is a medicinal plant species containing many polyphenolic compounds, namely flavonoids and phenolic acids. Since polyphenolic compounds have a high antioxidant potential, in this study we evaluated the effect of H. perforatum in an animal model of acute inflammation, carrageenan-induced pleurisy. We report here that H. perforatum extract (given at 30 mg/kg orally, bolus prior to carrageenan) exerts potent anti-inflammatory effects in an animal model of acute inflammation. 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 determined by thiobarbituric acid-reactant substance measurement) and increased production of tumor necrosis factor-alpha, (TNF-alpha) and interleukin-1beta (IL-1 beta). All parameters of inflammation were attenuated by H. perforatum extract. Furthermore, carrageenan induced an upregulation of the expression of adhesion molecules ICAM-1, 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, nitrotyrosine, and PAR was significantly reduced by H. perforatum extract. 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-31) activation in the lung. NF-kappaB and STAT-3 activation were significantly inhibited by H. perforatum extract treatment. Taken together, our results indicate that prevention of the activation of NF-kappaB and STAT-3 by H. perforatum extract reduces the development of acute inflammation.
authors.affiliation: Biochemistry Division, Department of Neuroscience and Vision, University of Verona, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Menegazzi
authors.forename: Rosanna
authors.initials: R
authors.lastname: Di Paola
authors.forename: Emanuela
authors.initials: E
authors.lastname: Mazzon
authors.forename: Carmelo
authors.initials: C
authors.lastname: Muià
authors.forename: Tiziana
authors.initials: T
authors.lastname: Genovese
authors.forename: Concetta
authors.initials: C
authors.lastname: Crisafulli
authors.forename: Hisanori
authors.initials: H
authors.lastname: Suzuki
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
mesh_terms: D000818:Animals; D002351:Carrageenan / Q000633:toxicity; D020902:Hypericum / Q000737:chemistry*; D007375:Interleukin-1 / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000737:chemistry / Q000473:pathology; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D010936:Plant Extracts / Q000008:administration & dosage; D010998:Pleurisy / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D011014:Pneumonia / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D011064:Poly Adenosine Diphosphate Ribose / Q000032:analysis / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism
chemical_list: D007375:Interleukin-1; D016328:NF-kappa B; D010936:Plant Extracts; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D011064:Poly Adenosine Diphosphate Ribose; D002351:Carrageenan; D009195:Peroxidase