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<p>This study assessed the wound-healing potential of <i>Heliotropium curassavicum </i>via a comparative metabolite profiling of its ethanol (HC-EtOH), ethyl acetate (HC-EtOAc), and <i>n</i>-butanol (HC-BuOH) extracts, alongside in vivo assessment. UHPLC-ESI-MS/MS analysis annotated 86 metabolites, including 13 pyrrolizidine alkaloids (4 of which, viz. uplandicine, uluganine, curassavine, and curassavine N-oxide are newly reported in the genus), 12 phenylpropanoids, and 8 fatty acid amides. Topical application of the extracts accelerated wound closure in a dose-dependent manner, with HC-BuOH exhibiting the strongest activity. HC-BuOH (200&#xa0;mg/kg) achieved near-complete closure by day 14 and improved healing by 39% compared with Intrasite Gel. This was accompanied by significant modulation of oxidative and inflammatory markers, including a 66% reduction in MDA, a 220% increase in GSH, a 94% reduction in TNF-α, and restoration of PGE-2 toward normal levels (<i>p</i> &lt; 0.05). Histopathology confirmed complete re-epithelialization, organized collagen deposition, and localized Ki-67 expression in HC-BuOH–treated wounds. Multivariate data and interaction analyses, supported by PLSR model demonstrated that the superior wound-healing activity of HC-BuOH is attributed for synergistic interactions among pyrrolizidine alkaloids, phenylpropanoids, and fatty acyl amides. These findings highlight <i>H. curassavicum</i>, particularly the HC-BuOH fraction, as a promising natural wound-healing agent. These effects are likely attributed to plant richness, in pyrrolizidine alkaloids, phenylpropanoids, and fatty acyl amides, highlighting its potential as a natural wound healing agent.</p>

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Synergistic wound healing mechanisms of Heliotropium curassavicum extracts via redox modulation, inflammation suppression, and tissue remodeling: linking phytochemical diversity to antioxidant and anti-inflammatory effects

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月16日

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  • Rania F. Ahmed,
  • Dalia M. Rasheed,
  • Noha A. Mowaad,
  • Rania Elgohary,
  • Eman H. Eltantawy,
  • Eman A. Negm,
  • Mohamed A. Farag,
  • Abdelsamed I. Elshamy

摘要

This study assessed the wound-healing potential of Heliotropium curassavicum via a comparative metabolite profiling of its ethanol (HC-EtOH), ethyl acetate (HC-EtOAc), and n-butanol (HC-BuOH) extracts, alongside in vivo assessment. UHPLC-ESI-MS/MS analysis annotated 86 metabolites, including 13 pyrrolizidine alkaloids (4 of which, viz. uplandicine, uluganine, curassavine, and curassavine N-oxide are newly reported in the genus), 12 phenylpropanoids, and 8 fatty acid amides. Topical application of the extracts accelerated wound closure in a dose-dependent manner, with HC-BuOH exhibiting the strongest activity. HC-BuOH (200 mg/kg) achieved near-complete closure by day 14 and improved healing by 39% compared with Intrasite Gel. This was accompanied by significant modulation of oxidative and inflammatory markers, including a 66% reduction in MDA, a 220% increase in GSH, a 94% reduction in TNF-α, and restoration of PGE-2 toward normal levels (p < 0.05). Histopathology confirmed complete re-epithelialization, organized collagen deposition, and localized Ki-67 expression in HC-BuOH–treated wounds. Multivariate data and interaction analyses, supported by PLSR model demonstrated that the superior wound-healing activity of HC-BuOH is attributed for synergistic interactions among pyrrolizidine alkaloids, phenylpropanoids, and fatty acyl amides. These findings highlight H. curassavicum, particularly the HC-BuOH fraction, as a promising natural wound-healing agent. These effects are likely attributed to plant richness, in pyrrolizidine alkaloids, phenylpropanoids, and fatty acyl amides, highlighting its potential as a natural wound healing agent.