Refined Supercritical CO ₂ Extract of Roman Chamomile Exhibits Enhanced Anti‐Inflammatory Potential: A Comparative Chemical and Network Pharmacology Study

Roman chamomile essential oil is valued in aromatherapy for its sedative and anti‐inflammatory effects, yet systematic comparisons of extracts obtained by different methods are limited. To compare the volatile profiles of Roman chamomile obtained by headspace solid‐phase microextraction (HS‐SPME), steam distillation (SD) and refined supercritical CO 2 extraction (SFE‐CO 2 ), and to investigate the anti‐inflammatory mechanisms of the refined SFE‐CO 2 extract via network pharmacology. Volatile constituents were analysed by GC–MS. Multivariate statistics identified core differential compounds. Skin permeability was predicted using SwissADME. Network pharmacology was employed to explore anti‐inflammatory mechanisms. A total of 122 compounds were identified. HS‐SPME and SD extracts were dominated by esters and terpenes, whereas refined SFE‐CO 2 extract was enriched in aldehydes, fatty acids, alkanes and a phthalide derivative. Twenty‐one core differential compounds were identified; 15 enriched in SFE‐CO 2 exhibited favourable predicted skin permeability. These 15 compounds targeted 15 skin inflammation‐associated proteins, forming a network centred on adhesion molecules (ICAM1, VCAM1, selectins) and signalling mediators (STAT3, TLR2), with enrichment in leukocyte adhesion, AGE‐RAGE and lipid metabolism pathways. SD‐enriched compounds yielded only four skin‐inflammation targets with minimal network connectivity. Extraction method dictates chemical composition and predicted therapeutic potential. Refined SFE‐CO 2 extract possesses enhanced anti‐inflammatory properties suitable for topical applications, providing a scientific basis for precision aromatherapy.