Protective effect of Arbutus unedo aqueous extract in carrageenan-induced lung inflammation in mice.
In the present study, we show that an aqueous extract of Arbutus unedo L. (AuE), a Mediterranean endemic plant widely employed as an astringent, diuretic and urinary anti-septic, in vitro down-regulates the expression of some inflammatory genes, such as those encoding inducible nitric oxide synthase (iNOS) and intracellular adhesion molecule-(ICAM)-1, exerting a inhibitory action on both IFN-gamma-elicited STAT1 activation and IL-6-elicited STAT3 activation. To evaluate further the effect of AuE in animal models of acute inflammation, we examined whether AuE administration attenuates inflammatory response of murine induced by intrapleural injection of carrageenan. For this purpose we studied: (1) STAT1/3 activation, (2) TNF-alpha, IL-1beta and IL-6 production in pleural exudate, (3) lung iNOS, COX-2 and ICAM-1 expression, (4) neutrophil infiltration, (5) the nitration of cellular proteins by peroxynitrite, (6) lipid peroxidation, (7) prostaglandin E2 and nitrite/nitrate levels and (8) lung injury. We show that AuE strongly down-regulates STAT3 activation induced in the lung by carrageenan with concomitant attenuation of all parameters examined associated with inflammation, suggesting that STAT3 should be a new molecular target for anti-inflammatory treatment. This study demonstrates that acute lung inflammation is significantly attenuated by the treatment with AuE.
Mariotto
Sofia
S
Biochemistry Division, Department of Neuroscience and Vision, University of Verona, Verona, Italy.
Esposito
Emanuela
E
Di Paola
Rosanna
R
Ciampa
Anna
A
Mazzon
Emanuela
E
de Prati
Alessandra Carcereri
AC
Darra
Elena
E
Vincenzi
Simone
S
Cucinotta
Giovanni
G
Caminiti
Rocco
R
Suzuki
Hisanori
H
Cuzzocrea
Salvatore
S
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002351:Carrageenan; D002460:Cell Line; D015232:Dinoprostone / Q000378:metabolism; D029791:Ericaceae / Q000737:chemistry*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010936:Plant Extracts / Q000627:therapeutic use; D018515:Plant Leaves / Q000737:chemistry; D010998:Pleurisy / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D011014:Pneumonia / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014443:Tyrosine / Q000031:analogs & derivatives / Q000096:biosynthesis
D000893:Anti-Inflammatory Agents; D015850:Interleukin-6; D010936:Plant Extracts; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D007371:Interferon-gamma; D002351:Carrageenan; D052247:Nitric Oxide Synthase Type II; D015232:Dinoprostone