A Comparative Study on the Anti‐Inflammatory Activity of Kaempferol and Its O ‐Glycosides in LPS‐Induced RAW264.7 Cells

ABSTRACT Kaempferol and its O ‐glycosides are prevalent dietary flavonoids, yet their comparative anti‐inflammatory activities and underlying mechanisms remain poorly defined. This study evaluated the effects of kaempferol and three O ‐glycosides (K3G, K3R, K3S) on LPS‐induced inflammation in RAW264.7 macrophages. Compared with its O ‐glycosides, kaempferol exhibited markedly stronger anti‐inflammatory activity, shown by greater suppression of inflammatory mediators (NO, PGE 2 , IL‐6, TNF‐α) and ROS production. Mechanistically, kaempferol inhibited G0/G1 to S phase progression and attenuated MAPK/NF‐κB/IκBα signaling, reducing iNOS and COX‐2 expressions. Lipidomics analysis revealed that kaempferol restored LPS‐disrupted glycerophospholipid homeostasis and modulated key lipid metabolites. Collectively, these findings highlighted the superior in vitro anti‐inflammatory activity of kaempferol relative to its O ‐glycosides, supporting further investigation of its physiological relevance.