Promising anti-<i>Helicobacter</i> <i>pylori</i> and anti-inflammatory metabolites from unused parts of <i>Phoenix dactylifera</i> CV 'Zaghloul': <i>in vitro</i> and <i>in silico</i> study.

Abstract

<h4>Context</h4>Date palm waste is an agricultural waste that accumulates in massive amounts causing serious pollution and environmental problems.<h4>Objectives</h4>Date palm trees, <i>Phoenix dactylifera</i> Linn CV 'Zaghloul' (Arecaceae) grown in Egypt, leave behind waste products that were investigated to produce compounds with anti-<i>Helicobacter pylori</i> and anti-inflammatory activities.<h4>Materials and methods</h4>Chromatographic workup of <i>P. dactylifera</i> aqueous methanol extract derived from fibrous mesh and fruit bunch (without fruit) afforded a new sesquiterpene lactone derivative, phodactolide A (<b>1</b>), along with ten known compounds (<b>2-11</b>), primarily identified as polyphenols. Chemical structures were unambiguously elucidated based on mass and 1D/2D NMR spectroscopy. All isolated compounds were assessed for their activities against <i>H. pylori</i> using broth micro-well dilution method and clarithromycin as a positive control. The anti-inflammatory response of isolated compounds was evaluated by inhibiting cyclooxygenase-2 enzyme using TMPD Assay followed by an <i>in silico</i> study to validate their mechanism of action using celecoxib as a standard drug.<h4>Results</h4>Compounds <b>4</b>, <b>6</b> and <b>8-10</b> exhibited potent anti-<i>H. pylori</i> activity with MIC values ranging from 0.48 to 1.95 µg/mL that were comparable to or more potent than clarithromycin. For COX-2 inhibitory assay, <b>4</b>, <b>7</b> and <b>8</b> revealed promising activities with IC₅₀ values of 1.04, 0.65 and 0.45 μg/mL, respectively. These results were verified by molecular docking studies, where <b>4</b>, <b>7</b> and <b>8</b> showed the best interactions with key amino acid residues of COX-2 active site.<h4>Conclusion</h4>The present study characterizes a new sesquiterpene lactone and recommends <b>4</b> and <b>8</b> for future <i>in vivo</i> studies as plausible anti-ulcer remedies.