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Purpose <p><i>Phoenix dactylifera</i> L. seeds (PDS) are traditionally used to treat gastric ailments. This study evaluated the gastroprotective effects of PDS (Sewy variety) extracts polar (70% aqueous methanol) and non-polar (n-hexane)) against ethanol-induced gastric ulcers and characterized their chemical complexity using advanced metabolomics.</p> Methods <p>Thirty Wistar rats were allocated into five groups: normal, control (ethanol-treated rats), standard (Omeprazole, 20&#xa0;mg/kg, orally), polar PDS (30&#xa0;mg/kg, orally), and non-polar PDS (30&#xa0;mg/kg, orally). To induce gastric ulcer, 1mL/kg of ethanol was given orally at the 7th day to rats. The extracts and reference drug were pretreated for 7 consecutive days. Gastric tissue oxidative stress markers (catalase, nitric oxide, myeloperoxidase), inflammatory mediators (TLR4, p-NF-κBP65, TNFα), mucosal integrity markers (HSP70, PGE2, hydroxyproline, gastrin, EGF, BAX/BCL2 ratio), and mucus secretion were assessed. Untargeted metabolomic profiling was performed via LC-ESI-MS/MS (ESI<sup>+</sup>) integrated with GNPS2 molecular networking.</p> Results <p>Both polar and non-polar PDS extracts significantly reduced oxidative stress and inflammatory mediators, and improved mucosal integrity compared to the ethanol-control group (<i>p</i> &lt; 0.001 for HSP70 and PGE2). Hydroxyproline, gastrin, EGF, BAX/BCL2 levels, and mucus secretion were significantly enhanced. The non-polar extract exhibited superior activity. LC-MS/MS identified 44 metabolites, including phenolic acids, flavonoids, and glycerophospholipids. GNPS2 networking provided a structural map of the seed’s metabolites.</p> Conclusions <p>PDS extracts demonstrated a significant gastroprotection by modulating the oxido-inflammo-apoptotic response and enhancing mucosal healing. This activity is attributed to a rich chemical landscape of phenolics and phospholipids, supporting the traditional use of PDS as a therapeutic agent for gastric ulcers.</p> Graphical Abstract <p></p>

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Comparative Metabolomic Profiling and Gastroprotective Efficacy of Phoenix dactylifera L. Seed Extracts: Modulation of the Oxido-Inflammo-Apoptotic Axis in Gastric Ulcer Model

  • 期刊论文

  • 发表日期：

    2026年4月25日

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  • Zeinab A. El-Gendy,
  • Sara M. Baraka,
  • Shimaa Abdelazeem,
  • Gehad A. Abdel Jaleel,
  • Reda M. S. Korany,
  • Mona A. Raslan

摘要

Purpose

Phoenix dactylifera L. seeds (PDS) are traditionally used to treat gastric ailments. This study evaluated the gastroprotective effects of PDS (Sewy variety) extracts polar (70% aqueous methanol) and non-polar (n-hexane)) against ethanol-induced gastric ulcers and characterized their chemical complexity using advanced metabolomics.

Methods

Thirty Wistar rats were allocated into five groups: normal, control (ethanol-treated rats), standard (Omeprazole, 20 mg/kg, orally), polar PDS (30 mg/kg, orally), and non-polar PDS (30 mg/kg, orally). To induce gastric ulcer, 1mL/kg of ethanol was given orally at the 7th day to rats. The extracts and reference drug were pretreated for 7 consecutive days. Gastric tissue oxidative stress markers (catalase, nitric oxide, myeloperoxidase), inflammatory mediators (TLR4, p-NF-κBP65, TNFα), mucosal integrity markers (HSP70, PGE2, hydroxyproline, gastrin, EGF, BAX/BCL2 ratio), and mucus secretion were assessed. Untargeted metabolomic profiling was performed via LC-ESI-MS/MS (ESI+) integrated with GNPS2 molecular networking.

Results

Both polar and non-polar PDS extracts significantly reduced oxidative stress and inflammatory mediators, and improved mucosal integrity compared to the ethanol-control group (p < 0.001 for HSP70 and PGE2). Hydroxyproline, gastrin, EGF, BAX/BCL2 levels, and mucus secretion were significantly enhanced. The non-polar extract exhibited superior activity. LC-MS/MS identified 44 metabolites, including phenolic acids, flavonoids, and glycerophospholipids. GNPS2 networking provided a structural map of the seed’s metabolites.

Conclusions

PDS extracts demonstrated a significant gastroprotection by modulating the oxido-inflammo-apoptotic response and enhancing mucosal healing. This activity is attributed to a rich chemical landscape of phenolics and phospholipids, supporting the traditional use of PDS as a therapeutic agent for gastric ulcers.

Graphical Abstract