Anti-inflammatory potential of dandelion polyphenols through modulation of AGE–RAGE signaling: key bioactive compounds and implications for functional foods

Dandelion, a widely used traditional medicinal and edible plant in China, is known for its anti-inflammatory properties, primarily attributed to polyphenols. Although the underlying mechanisms have yet to be fully clarified, in this study, a network pharmacology approach was combined with molecular docking to identify key bioactive polyphenols, followed by validation of their anti-inflammatory effects using cell-based assays, transcriptomics, proteomics profiling, quantitative polymerase chain reaction (qPCR), Western blot, and computational analysis. A total of 29 protein targets were identified for dandelion-derived polyphenols, among which quercetin and caffeic acid were found to regulate 11 key proteins within the advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE) signaling pathway, a central route linking dietary AGEs to chronic inflammation. Inflammatory cytokine assays showed that both 100% quercetin, and a combination of 50% quercetin + 50% caffeic acid exhibited the strongest inhibition of tumor necrosis factor-α (TNF-α), and interleukin-1 beta (IL-1β) expression. This effect was primarily associated with the downregulation of ICAM1, IL1B, and THBD, while caffeic acid reduced IL-1β secretion. Calculation results revealed that both compounds strongly bound to receptors for advanced glycation end products (RAGE) without competing with advanced glycation end products (AGEs), disrupting protein and receptor interactions, and impeding inflammatory signal transduction. Overall, quercetin and caffeic acid effectively regulate AGE-RAGE-mediated inflammation, with their combination showing enhanced anti-inflammatory potential, and supporting the development of dandelion-based functional foods aimed at mitigating diet-induced inflammation.