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The phytochemical profile was characterized using high\u2010performance liquid chromatography coupled with a diode\u2010array detector (HPLC\u2010DAD), identifying 10 major bioactive constituents in all extracts. The leaf extract exhibited significant antioxidant activity (DPPH: IC\n                    <jats:sub>50<\/jats:sub>\n                    = 165.96\u00a0\u00b5g\/mL; ferric reducing antioxidant power [FRAP] = 1.045\u00a0\u00b5M BHT\/g DW). To decipher the molecular interactions with the CPR enzyme, a rigorous in silico workflow was applied, utilizing deep learning\u2010based molecular docking (GNINA 1.3) followed by duplicate 50\u00a0ns molecular dynamics (MD) simulations. A refined MM\/PBSA binding free energy analysis, focused on the thermodynamic equilibrium plateau (30\u201350\u00a0ns), revealed distinct binding strategies. Indeed, the glycosylated flavonoid rutin acted as a potent structural anchor (\u0394\n                    <jats:italic>H<\/jats:italic>\n                    \u2248 \u221219.6\u00a0kcal\/mol), leveraging an extensive eight\u2010residue contact footprint to rigidify the protein backbone, whereas the aglycone (+)\u2010catechin exhibited a \u201clock\u2010and\u2010key\u201d binding mode characterized by thermodynamic efficiency (\u0394\n                    <jats:italic>G<\/jats:italic>\n                    \u2248 \u22123.6\u00a0kcal\/mol) and a minimal entropic penalty. These findings provide structural evidence that\n                    <jats:italic>T. algeriensis<\/jats:italic>\n                    metabolites can target CPR via complementary enthalpic and entropic mechanisms, highlighting the dual bioactivity of the species and suggesting these flavonoids as promising bioactive scaffolds.\n                  <\/jats:p>","DOI":"10.1002\/cbdv.202503099","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T07:01:07Z","timestamp":1774508467000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Phytochemical Profiling and Computational Unveiling of\n                    <i>Thymus algeriensis<\/i>\n                    Boiss. Et Reut. Bioactive Metabolites as Dual\u2010Mechanism Inhibitors of NADPH\u2010Cytochrome P450 Reductase"],"prefix":"10.1002","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0204-925X","authenticated-orcid":false,"given":"Maher","family":"Boukhris","sequence":"first","affiliation":[{"name":"Laboratory of Plant Biotechnology LR01ES21, Sciences Faculty of Sfax University of Sfax Sfax Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3261-7884","authenticated-orcid":false,"given":"Fakher","family":"Frikha","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Screening Processes Centre of Biotechnology of Sfax  Sfax Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wissal","family":"Ayouni","sequence":"additional","affiliation":[{"name":"Laboratory of Organic Chemistry LR17ES08, Sciences Faculty of Sfax University of Sfax  Sfax 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