Euphorbia cuneata (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 2R-naringenin-7-O-β-glucoside (1), kaempferol-7-O-β-glucoside (2), cuneatannin (3), quercetin (4), and 2R-naringenin (5) 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.

Phytochemical investigation of the aerial parts of Euphorbia cuneata Vahl. (Euphorbiaceae) revealed new cycloartane triterpenoid, cyclocuneatol (2) and new ellagitannin glycoside, cuneatannin (11), along with nine known metabolites: β‐sitosterol (1), 3β‐hydroxycycloart‐25‐ene‐24‐one (3), cycloart‐25‐ene‐3β,24β‐diol (4), cycloart‐23Z‐ene‐3β,25‐diol (5), 2R‐naringenin (6), β‐sitosterol‐3‐O‐β‐D‐glucopyranoside (7), quercetin (8), kaempferol‐7‐O‐β‐glucoside (9), and 2R‐naringenin‐7‐O‐β‐glucoside (10). Their chemical structures were identified by detailed analyses of physical, chemical, and spectral data as well as comparison with literature. Their cytotoxic activity was assessed towards HepG2, MCF7, and HCT116 cancer cell lines by sulphorhodamine B test (SRB). It is noteworthy that 3 and 4 demonstrated the most significant activity towards HepG2, MCF7, and HCT116 cells (IC50 2.6, 2.7, and 2.4 μM, respectively for 3 and 3.4, 4.1, and 5.3 μM, respectively for 4) in comparison with doxorubicin (IC50 0.18, 0.6, and 0.2 μM, respectively).