{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T15:29:09Z","timestamp":1788276549756,"version":"build-2803163510"},"reference-count":94,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Chronic inflammation sustained by cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) underlies many human diseases, while the cardiovascular liabilities of coxibs have renewed interest in plant-derived alternatives. This study characterised the volatile composition of Corymbia citriodora essential oil under two distillation regimes and identified constituents able to inhibit human COX-2 and iNOS. Methods: Oils obtained by steam distillation (SD) and microwave-assisted steam distillation (MSD) were profiled by GC\u2013MS\/MS. All identified constituents were screened with SASA Vina against human COX-2 (PDB: 5KIR, 3LN1), ovine COX-1 (4COX) and human iNOS (3E7G), with native-ligand re-docking validating each protocol (RMSD 0.39\u20130.84 \u00c5). The lead compound underwent density functional theory (B3LYP\/3-21G\/CPCM), 100 ns all-atom molecular dynamics, MM\/GBSA and MM\/PBSA decomposition, and pkCSM ADMET prediction. Results: Sixty-three constituents were identified (99.85% SD; 99.97% MSD). MSD enriched oxygenated monoterpenes (93.23% versus 88.27%), citronellal rose from 38.24% to 48.41%. (Z,Z,Z)-1,5,9,9-Tetramethyl-1,4,7-cycloundecatriene ranked highest at COX-2 (\u22128.0 to \u22128.2 kcal\/mol) and also bound COX-1 (\u22128.8 kcal\/mol) and iNOS (\u22126.8 kcal\/mol). DFT indicated high kinetic stability (\u0394E = 6.12 eV; \u03b7 = 3.06 eV) and purely non-covalent hydrophobic binding. The COX-2 complex remained stable over 100 ns (C\u03b1 RMSD 0.17 \u00b1 0.02 nm), with MM\/GBSA and MM\/PBSA binding energies of \u221223.98 and \u221221.95 kcal\/mol and Val523 as the principal hotspot. ADMET prediction returned 96.61% human intestinal absorption and no mutagenicity, hepatotoxicity or hERG I blockade. Conclusions: MSD offers a faster route to a citronellal-enriched oil, and C. citriodora hydrocarbon sesquiterpenes emerge as chemically stable, multi-target COX-2\/iNOS scaffolds. Comparable binding at COX-1 indicates that isoform selectivity remains to be established; in vitro enzymatic and cell-based validation is therefore required.<\/jats:p>","DOI":"10.3390\/ph19091382","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T15:08:43Z","timestamp":1788275323000},"page":"1382","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Extraction, Phytochemical Profiling, and Computational Evaluation of Corymbia citriodora Essential Oil as a COX-2 Inhibitor: Steam vs. Microwave-Assisted Distillation, GC\u2013MS\/MS, Docking, DFT, and MD Simulations"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-3804-7330","authenticated-orcid":false,"given":"Sabrina","family":"Koribeche","sequence":"first","affiliation":[{"name":"Laboratory of Matter\u2019s Valorization and Recycling for Sustainable Development, Faculty of Mechanical and Process Engineering, University of Science and Technology Houari Boumediene (USTHB), Algiers 16111, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"given":"Sadjia","family":"Bertouche","sequence":"additional","affiliation":[{"name":"Laboratory of Matter\u2019s Valorization and Recycling for Sustainable Development, Faculty of Mechanical and Process Engineering, University of Science and Technology Houari Boumediene (USTHB), Algiers 16111, 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M.","family":"Al-dossari","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Toxicology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9100-8934","authenticated-orcid":false,"given":"Mohamed Said","family":"Kahaleras","sequence":"additional","affiliation":[{"name":"Laboratory of Energy Systems Technologies (LTSE), National Higher School of Technology and Engineering, Annaba 23005, 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