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 × 1012/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.