Euphorbia cuneata Represses LPS-induced Acute Lung Injury in Mice via its Antioxidative and Anti-inflammatory Activities.

Amjad A. Elghamdi,Martin K. Safo,Dina S. El-Agamy,Hossam M. Abdallah,Gamal A. Mohamed,Sabrin R. M. Ibrahim,Wael M. Elsaed,Azizah M. Malebari

doi:10.3390/plants9111620

Abstract

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.

Highlights

Acute lung injury (ALI) associated with sepsis is a common clinical problem with a high morbidity rate [1,2]
The results showed the presence of 2R-naringenin-7-O-β-glucoside (1), kaempferol-7-O-β-glucoside (2), cuneatannin (3), quercetin (4), and 2R-naringenin (5) in concentrations of
LPS injection to mice resulted in elevation of lung W/D ratio and total protein content of Bronchoalveolar fluid (BALF)

Summary

Introduction

Acute lung injury (ALI) associated with sepsis is a common clinical problem with a high morbidity rate [1,2]. The pathogenesis of ALI involves disruption of epithelial integrity with massive infiltration of inflammatory cells into the lung tissue, leading to pulmonary edema and severe inflammation [3,4]. Infiltered inflammatory cells, mainly neutrophils and macrophages, release inflammatory mediators such as interleukins (ILs), tumor necrosis factor (TNF)-α, and nitric oxide (NO) [5,6]. Nuclear factor-κB (NF-κB) is a pro-inflammatory transcription factor that regulates and controls inflammatory response during ALI. NF-κB is present in the cytosol in inactive state due to linkage to its inhibitory protein (IκB). IκB rapidly degrades to liberate NF-κB, which migrates into the nucleus where it potentiates gene expression of inflammatory mediators, inducing inflammatory responses [7,8]

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