The inhibition of lipopolysaccharide-induced macrophage inflammation by 4 compounds in Hypericum perforatum extract is partially dependent on the activation of SOCS3

► Hypericum perforatum and the 4 compound mixture inhibited inflammatory mediators in macrophages. ► The 4 compounds required SOCS3 activation to inhibit the inflammatory response. ► H. perforatum ethanol extract had SOCS3 independent anti-inflammatory activity. ► The 4 compounds inhibited LPS-induced cytokines without activating SOCS3.