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, H
2
O
2
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 IC
50
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.