Targeted Screening of Cyclooxygenase-2 Inhibitors from Dendropanax dentiger root Using Affinity Ultrafiltration Coupled with UHPLC-MS.

Cyclooxygenase-2 (COX-2) plays a critical role in the pathogenesis of rheumatoid arthritis (RA), while Dendropanax dentiger root (DDR) is a traditional Chinese medicine (TCM) used to treat RA. However, the specific bioactive ingredients responsible for its therapeutic effect remain unidentified. In this study, 10 phenylpropanoids, including neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, liriodendrin, isochlorogenic acid B, isochlorogenic acid A, eleutheroside E1, isochlorogenic acid C, 3,5-di-O-caffeoylquinic acid methyl ester, and 4,5-di-O-caffeoylquinic acid methyl ester, were identified as potential COX-2 inhibitors in DDR using affinity ultrafiltration coupled with ultra-high-performance liquid chromatography and mass spectrometry (AUF-LC-MS). Mass spectrometric fragmentation patterns of these compounds were analyzed, revealing consistent and logical fragmentation profiles. Molecular docking results revealed that all ten compounds exhibited strong binding affinities with COX-2, with binding energies ranging from -8.0 to -9.8 kcal/mol. Further experimental validation confirmed that these compounds exhibited potent COX-2 inhibitory activity, with IC50 values ranging from 5.2 to 10.3 µM. These compounds are likely to represent the primary anti-inflammatory components of DDR. Additionally, this study provides a systematic identification of chlorogenic acids within the Dendropanax genus and investigates their mass spectrometric fragmentation patterns. The findings contribute to the scientific basis for the clinical application of DDR.