Flavonoids of Euphorbia hirta inhibit inflammatory mechanisms via Nrf2 and NF-κB pathways

Abstract Euphorbia hirta has anti-inflammatory effects in traditional medicine, but its anti-inflammatory mechanism has not been explored at the cellular and molecular levels. To this end, the main active components of the 65% and 95% ethanol extracts of Euphorbia hirta were first identified by UPLC-Q-TOF/MS. The potential targets and signaling pathway of Euphorbia hirta were identified through network pharmacology, followed by subsequent experimental validation using lipopolysaccharide (LPS)-induced inflammation model in RAW264.7 cells. The results showed that the main active components were flavonoids. Network pharmacology revealed 71 potential targets for anti-inflammation, with a protein-protein interaction (PPI) network highlighting 8 cores targets, including IL-6, TNF, et al. Furthermore, Euphorbia hirta exert anti-inflammation effects through pathways such as Nrf2 and NF-κB signaling pathway. In vitro experiment showed that the 65% ethanol extract of Euphorbia hirta (EE65) and quercetin (HPG) in it exerted anti-inflammatory activity by inhibiting the expression of inflammatory genes related to the NF-κB signaling pathway, whereas baicalein (HCS) suppressed cellular inflammation by promoting the expression of genes related to the Nrf2 antioxidant pathway and apoptosis of inflammatory cells. The results of the study suggest that Euphorbia hirta has potential for the development of anti-inflammatory drugs.