Identification and Integrative Discovery of Anti-Inflammatory Compounds Isolated from Eclipta prostrata (L.) L. by...

Background/Objective: Eclipta prostrata (L.) L. is a traditional medicinal herb utilized throughout Asia that is widely used for hepatoprotective activity, wound healing, and blood cooling/bleeding disorders. This work aimed to identify bioactive constituents from E. prostrata collected in Vietnam, and clarify their anti-inflammatory capacity of the extract and active fraction. Method: Extraction and isolation of compounds from the extract of E. prostrata were performed. The extract, fractions, and isolated compounds were evaluated for inflammatory cytokines in LPS-stimulated RAW264.7 cells. Isolates showed inflammatory potential by in silico approaches. Results: Thirteen compounds, comprising a first isolated compound (diosmin), flavonoids, and phenolic derivatives, were separated and identified. The protein-protein interaction (PPI) network demonstrated TNF, IL6, AKT1, NFKB1, EGFR, and PTGS2 as central targets, highlighting their significance in inflammatory signaling. Gene Ontology and KEGG pathway enrichment underscored substantial participation in TNF and IL-17 cytokine signaling pathways. Molecular docking demonstrated robust interactions between several flavonoids and core targets, indicating their function as essential regulators. Experimental validation in LPS-stimulated RAW264.7 macrophages revealed that wedelolactone, luteolin, apigenin, and quercetin significantly inhibited TNF-α and IL-6 production. Conclusions: The results proposed that E. prostrata demonstrates its anti-inflammatory efficacy via a multi-target, poly-pharmacological strategy that encompasses central cytokine pathways and upstream receptor-mediated signaling. Our findings offer new mechanistic evidence that supports the ethnomedicinal application of E. prostrata and indicates its potential as a valuable natural resource for treating anti-inflammatory diseases.