Abstract

Gastric ulceration is among the most serious humanpublic health problems. Olea europea L. cv. Arbequina is one of the numerous olive varieties which have scarcely been studied. The reported antioxidant and anti-inflammatory potential of the olive plant make it a potential prophylactic natural product against gastric ulcers. Consequently, the main goal of this study is to investigate the gastroprotective effect of Olea europea L. cv. Arbequina leaf extract. LC-HRMS-based metabolic profiling of the alcoholic extract of Olea europea L. cv. Arbequina led to the dereplication of 18 putative compounds (1–18). In vivo indomethacin-induced gastric ulcer in a rat model was established and the Olea europea extract was tested at a dose of 300 mg kg−1 compared to cimetidine (100 mg kg−1). The assessment of gastric mucosal lesions and histopathology of gastric tissue was done. It has been proved that Olea europea significantly decreased the ulcer index and protected the mucosa from lesions. The antioxidant potential of the extract was evaluated using three in vitro assays, H2O2 scavenging, xanthine oxidase inhibitory, and superoxide radical scavenging activities and showed promising activities. Moreover, an in silico based study was performed on the putatively dereplicated compounds, which highlighted that 3-hydroxy tyrosol (4) and oleacein (18) can target the 5-lipoxygenase enzyme (5-LOX) as a protective mechanism against the pathogenesis of ulceration. Upon experimental validation, both compounds 3-hydroxy tyrosol (HT) and oleacein (OC) (4 and 18, respectively) exhibited a significant in vitro 5-LOX inhibitory activity with IC50 values of 8.6 and 5.8 µg/mL, respectively. The present study suggested a possible implication of O. europea leaves as a potential candidate having gastroprotective, antioxidant, and 5-LOX inhibitory activity for the management of gastric ulcers.

Highlights

  • Mediterranean people frequently used olive leaf trees in the treatment of several diseases [1]

  • Among the retrieved hits for each compound, we found that the 5-lipoxygenase enzyme (5-LOX) is the more molecular target relevant to peptic ulcer pathogenesis

  • The LC-HRMS-based chemical profiling of OLE revealed the abundance of many phenolic putative compounds that can exert a profound antioxidant activity, which in turn can accelerate the ulcer healing process

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Summary

Introduction

Mediterranean people frequently used olive leaf trees in the treatment of several diseases [1]. Several biological applications were exhibited by Olea europea such as its effect as a diuretic, laxative, antiviral, and hypotensive agent [3]. It has been reported for the management of intestinal and stomach diseases, as well as diabetes [3,4,5]. Dekanski et al [6] have been reported that the Olea europea leaf extract was effective in the reduction of gastric lipid peroxidation and in maintaining the natural antioxidative enzyme activity. These results have indicated that the Olea europea leaf extract has a promising gastroprotective potential against ethanol-induced gastric lesions in rats

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