Formononetin alleviates LPS-induced neuroinflammation in mice by modulating inflammatory signaling pathways

Neuroinflammation is a pathological condition characterized by inflammatory re-sponses with the central nervous system. Formononetin (FOR) has well-documented an-ti-inflammatory properties, however its therapeutic potential and underlying mechanisms in neuroinflammation remain incompletely characterized. This study elucidated the therapeutic ef-fects of FOR on lipopolysaccharide (LPS)-induced neuroinflammation and its underlying mecha-nisms. In vitro experiments demonstrated that FOR improved the viability of LPS-stimulated BV2 microglia and reduced nitric oxide (NO) production, indicating its protective effect against neu-roinflammatory injury. In vivo, FOR-treated mice exhibited significantly improved learning and memory performance in the Morris water maze (MWM) test compared with LPS-treated mice. Furthermore, Nissl staining showed that FOR increased the number of normal neurons in the cerebral cortex and hippocampus. Immunohistochemistry that FOR reduced IL-6 levels. Network pharmacology analysis indicated that FOR alleviated neuroinflammation via the regulation of multiple pathways, including nitrogen metabolism, serotonergic synapse signaling, arachidonic acid metabolism, and tyrosine and phenylalanine metabolism. Collectively, our findings demon-strate that FOR effectively ameliorates LPS-induced neuroinflammation, highlighting its potential as a therapeutic agent for neuroinflammation-related disorders.