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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\u00a0mg\/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-\u03b1, and restoration of PGE-2 toward normal levels (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). Histopathology confirmed complete re-epithelialization, organized collagen deposition, and localized Ki-67 expression in HC-BuOH\u2013treated 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\n                    <jats:italic>H. curassavicum<\/jats:italic>\n                    , 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.\n                  <\/jats:p>","DOI":"10.1007\/s10787-025-02096-z","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T05:12:58Z","timestamp":1771218778000},"page":"1659-1682","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["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"],"prefix":"10.1007","volume":"34","author":[{"given":"Rania F.","family":"Ahmed","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalia M.","family":"Rasheed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noha A.","family":"Mowaad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rania","family":"Elgohary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman H.","family":"Eltantawy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman A.","family":"Negm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed A.","family":"Farag","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3302-3623","authenticated-orcid":false,"given":"Abdelsamed I.","family":"Elshamy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,16]]},"reference":[{"issue":"11","key":"2096_CR1","doi-asserted-by":"publisher","first-page":"482","DOI":"10.3390\/plants8110482","volume":"8","author":"AM Abd-ElGawad","year":"2019","unstructured":"Abd-ElGawad AM, Elshamy AI, Al-Rowaily SL, El-Amier YA (2019) Habitat affects the chemical profile, allelopathy, and antioxidant properties of essential oils and phenolic enriched extracts of the invasive plant Heliotropium curassavicum. 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