Characterization and anti-inflammatory investigation of sesquiterpene lactones from Ixeris chinensis

Ixeris chinensis is an edible and medicinal plant possessing anti-inflammatory activity. However, knowledge about the bioactive components of I. chinensis remains limited. Herein, comprehensive phytochemical study led to isolation and identification of 31 sesquiterpene lactones (SLs) from I. chinensis ethanol extract. Among them, 7 were previously undescribed guaianolides (1-4, 12-13, 24) and 16 were reported from this plant for the first time. Ixerisoside A (6) was proved to be the most predominant SL present in I. chinensis, and its content was determined as 0.34 ± 0.02% by HPLC-DAD method. Eleven SLs showed inhibition against NO production in LPS-induced RAW264.7 cells (IC₅₀ value ranging from 12.13 to 31.10 μM). Compounds 6 and 13 could suppress IL-6 and IL-1β release, and down-regulate gene expression levels of IL-6, IL-1β, and iNOS. Network pharmacology study identified MAPK among those of the core targets of SLs against inflammation, which was validated by molecular docking. Cellular study proved that SLs could suppress phosphorylation of ERK and p38. Our work highlights therapeutic potential of SLs against inflammatory diseases, and offers valuable insights for developing I. chinensis as functional food in the nutraceutical industry.