Abstract
The hydroalcoholic extract of Punica granatum (pomegranate) leaves was previously demonstrated to be anti-inflammatory in a rat model of lipopolysaccharide- (LPS-) induced acute peritonitis. Here, we investigated the anti-inflammatory effects of the ethyl acetate fraction obtained from the pomegranate leaf hydroalcoholic extract (EAFPg) on the LPS-induced acute lung injury (ALI) mouse model. Male Swiss mice received either EAFPg at different doses or dexamethasone (per os) prior to LPS intranasal instillation. Vehicle-treated mice were used as controls. Animals were culled at 4 h after LPS challenge, and the bronchoalveolar lavage fluid (BALF) and lung samples were collected for analysis. EAFPg and kaempferol effects on NO and cytokine production by LPS-stimulated RAW 264.7 macrophages were also investigated. Pretreatment with EAFPg (100–300 mg/kg) markedly reduced cell accumulation (specially neutrophils) and collagen deposition in the lungs of ALI mice. The same animals presented with reduced lung and BALF TNF-α and IL-1β expression in comparison with vehicle controls (p < 0.05). Additionally, incubation with either EAFPg or kaempferol (100 μg/ml) reduced NO production and cytokine gene expression in cultured LPS-treated RAW 264.7 macrophages. Overall, these results demonstrate that the prophylactic treatment with EAFPg attenuates acute lung inflammation. We suggest this fraction may be useful in treating ALI.
Highlights
Acute lung injury (ALI) is a clinical condition that causes disruption of the lung endothelial tissue and epithelial barrier and loss of lung function [1, 2]
We recently demonstrated that the leaf hydroalcoholic extract obtained from pomegranate is anti-inflammatory as it inhibits TNF-α production and decreases neutrophil migration in a rat model of lipopolysaccharide- (LPS-) induced acute peritonitis [8]
The chemical constituents of EAFPg were analyzed in a high-performance liquid chromatography (HPLC) system (LC-10AD, Shimadzu) equipped with a photodiode array detector coupled to an Esquire 3000 Plus ion trap mass spectrometer (Bruker Daltonics, Bremen, Germany), using electrospray ionization (ESI) as previously described [10]
Summary
Acute lung injury (ALI) is a clinical condition that causes disruption of the lung endothelial tissue and epithelial barrier and loss of lung function [1, 2]. ALI is characterized by intense transepithelial leukocyte infiltration, exudate accumulation in the lungs, loss of integrity of the alveolar-capillary membrane, and tissue damage [4]. Journal of Immunology Research response has been suggested to be due to the increased production of inflammatory mediators including cytokines (TNF-α, IL-1β, and IL-6), especially by alveolar macrophages and neutrophils [5]. Due to its antiinflammatory activities, pomegranate is traditionally used to treat infections. In this context, we recently demonstrated that the leaf hydroalcoholic extract obtained from pomegranate is anti-inflammatory as it inhibits TNF-α production and decreases neutrophil migration in a rat model of lipopolysaccharide- (LPS-) induced acute peritonitis [8]. Haseeb et al showed that the pomegranate fruit extract attenuates IL-6 production, reactive oxygen species, IL-1βmediated phosphorylation of the inhibitor of nuclear factor kappa-B kinase subunit beta (IKKβ), expression of IKKβ mRNA, degradation of IκBα, and the activation and nuclear translocation of NF-κB/p65 in human chondrocytes [9]
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