Polygalasaponin F has anti-neuroinflammatory activity, can inhibit the release of inflammatory cytokines TNF-α and NO induced by lipopolysaccharides (LPS) and reduce the expression of inducible nitric oxide synthases. Polygalasaponin F can significantly inhibit the cytotoxicity of conditioned medium prepared by LPS-stimulated BV-2 microglia (LPS conditioned media) to neuronal PC12 cells and improve cell viability. Polygalasaponin F can induce long-term potentiation in hippocampal dentate gyrus in anesthetized rats via NMDAR activation mediated by Ca(2+)/calmodulin-dependent kinase II, extracellular signal-regulated kinase and cAMP response element-binding protein signaling pathway. PS-F inhibits the secretions of neuroinflammatory cytokines by the regulation of the NF-kB-signaling pathway.