| Summary: | <i>Euphorbia cuneata</i> (EC; Euphorbiaceae), which widely grows in Saudi Arabia and Yemen, is used traditionally to treat pain and inflammation. This study aimed to evaluate the protective anti-inflammatory effect of a standardized extract of EC against lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and the possible underlying mechanism(s) of this pharmacologic activity. ALI was induced in male Balb/c mice using intraperitoneal injection of LPS. A standardized total methanol extract of EC or dexamethasone was administered 5 days prior to LPS challenge. Bronchoalveolar fluid (BALF) and lung samples were collected for analysis. The results demonstrated the protective anti-inflammatory effect of EC against LPS-induced ALI in mice. Standardized EC contained 2<i>R</i>-naringenin-7-<i>O</i>-<i>β</i>-glucoside (<b>1</b>), kaempferol-7-<i>O</i>-<i>β</i>-glucoside (<b>2</b>), cuneatannin (<b>3</b>), quercetin (<b>4</b>), and 2<i>R</i>-naringenin (<b>5</b>) in concentrations of 6.16, 4.80, 51.05, 13.20, and 50.00 mg/g of extract, respectively. EC showed a protective effect against LPS-induced pulmonary damage. EC reduced lung wet/dry weight (W/D) ratio and total protein content in BALF, indicating attenuation of the pulmonary edema. Total and differential cell counts were decreased in EC-treated animals. Histopathological examination confirmed the protective effect of EC, as indicated by an amelioration of LPS-induced lesions in lung tissue. EC also showed a potent anti-oxidative property as it decreased lipid peroxidation and increased the antioxidants in lung tissue. Finally, the anti-inflammatory activity of EC was obvious through its ability to suppress the activation of nuclear factor-κB (NF-κB), and hence its reduction of the levels of downstream inflammatory mediators. In conclusion, these results demonstrate the protective effects of EC against LPS-induced lung injury in mice, which may be due to its antioxidative and anti-inflammatory activities.
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