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<p>Medicinal plants have long been recognized as reservoirs of bioactive compounds, and <i>Haloxylon articulatum</i>, a halophyte adapted to arid environments, has traditional medicinal relevance. In this study, we systematically investigated the chemical composition, antioxidant activity, and anticancer potential of Iraqi <i>H. articulatum</i> extracts through both experimental assays and computational modeling. LC–ESI–MS/MS profiling identified diverse alkaloids, flavonoids, and phenolic acids. Antioxidant assays demonstrated that aerial parts exhibited stronger radical scavenging activity than roots, with IC₅₀ values comparable to the reference antioxidant BHT. Cytotoxicity assays revealed that <i>n</i>-caffeoyltyramine (n-CLA) and sinapoyltyramine (SLA) showed moderate anticancer activity against gastric cancer cells, with IC₅₀ values of 14.55 and 23.10&#xa0;µg/mL in AGS and 19.10 and 26.68&#xa0;µg/mL in NCI-N87, respectively. Importantly, in AGS cells both compounds markedly potentiated the effects of cisplatin, lowering the IC₅₀ to 4–5&#xa0;µg/mL (CI &lt; 1), confirming synergism. Docking simulations suggested strong interactions with EGFR kinase, consistent with a possible non-classical binding mode, while ADMET predictions indicated favorable drug-like and low-toxicity profiles. To our knowledge, this is the first report demonstrating that Iraqi <i>H. articulatum</i> represents a sustainable source of bioactive phenolic amides with both antioxidant and synergistic anticancer activity. These findings provide a foundation for developing plant-based therapeutic agents with improved efficacy and safety.</p>

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Exploring Haloxylon articulatum: a Sustainable Source of Allosteric EGFR Inhibitors with Promising Anticancer Activity

  • 期刊论文

  • 发表日期：

    2026年2月2日

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  • Reyadh R. AL-Rashidi,
  • Amira ZAÏRI

摘要

Medicinal plants have long been recognized as reservoirs of bioactive compounds, and Haloxylon articulatum, a halophyte adapted to arid environments, has traditional medicinal relevance. In this study, we systematically investigated the chemical composition, antioxidant activity, and anticancer potential of Iraqi H. articulatum extracts through both experimental assays and computational modeling. LC–ESI–MS/MS profiling identified diverse alkaloids, flavonoids, and phenolic acids. Antioxidant assays demonstrated that aerial parts exhibited stronger radical scavenging activity than roots, with IC₅₀ values comparable to the reference antioxidant BHT. Cytotoxicity assays revealed that n-caffeoyltyramine (n-CLA) and sinapoyltyramine (SLA) showed moderate anticancer activity against gastric cancer cells, with IC₅₀ values of 14.55 and 23.10 µg/mL in AGS and 19.10 and 26.68 µg/mL in NCI-N87, respectively. Importantly, in AGS cells both compounds markedly potentiated the effects of cisplatin, lowering the IC₅₀ to 4–5 µg/mL (CI < 1), confirming synergism. Docking simulations suggested strong interactions with EGFR kinase, consistent with a possible non-classical binding mode, while ADMET predictions indicated favorable drug-like and low-toxicity profiles. To our knowledge, this is the first report demonstrating that Iraqi H. articulatum represents a sustainable source of bioactive phenolic amides with both antioxidant and synergistic anticancer activity. These findings provide a foundation for developing plant-based therapeutic agents with improved efficacy and safety.