Anti‐Inflammatory Activity of Cotula cinerea Essential Oil: Integrated Chemical, In Vivo, Histological, and Computational Evaluation

The anti‐inflammatory activity of Cotula cinerea essential oil (EO) was evaluated using integrated chemical, in vivo, histological, and computational approaches. Gas chromatography–mass spectrometry (GC–MS) identified trans‐thujone (51.86%), santolina triene (10.60%), and sabinene (6.17%) as the most abundant constituents. In benzylthiouracil (BTU)‐treated Wistar rats, EO administration reduced the liver and kidney indices from 4.36% to 2.70% and from 0.65% to 0.52%, respectively; red blood cell count increased from 4.90 to 7.17 × 10 12 /L and hemoglobin from 9.40 to 15.40 g/dL. Aspartate aminotransferase decreased from 226.06 to 111.10 U/L and alanine aminotransferase from 116.00 to 71.56 U/L. C‐reactive protein and renal markers also moved toward control values, and histological examination showed improved liver and kidney architecture. Computational analyses were used as hypothesis‐generating complements to the experimental findings. Molecular docking predicted the most favorable cyclooxygenase‐2 (COX‐2) scores for cis‐verbenyl acetate (CVA; −7.01 kcal/mol) and camphor (CAM; −6.66 kcal/mol). Molecular dynamics (MD) trajectories and molecular mechanics/Poisson–Boltzmann surface area (MM‐PBSA) estimates indicated persistent simulated interactions, with COX‐2 binding free energies of −43.67 ± 3.80 and −39.93 ± 2.59 kcal/mol, respectively. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) outputs were favorable for CVA and CAM but remain predictive.