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Microglial activation and resultant neuroinflammatory response are implicated in various brain diseases including Alzheimer\'s disease and Parkinson\'s disease.Treatment with anti-neuroinflammatory agents could provide therapeutic benefits for such disorders.Protosappanin A (PTA) is a major bioactive ingredient isolated from Caesalpinia sappan L..In this work,the anti-neuroinflammatory effects of PTA on LPS-stimulated BV2 cells were investigated and the underlying mechanisms were explored.Results showed that PTA significantly inhibited the production of TNF-a and IL-1β in LPS-activated BV2 microglia.Moreover,the mRNA expressions of IL-6,IL-1β,and MCP-1 were reduced by PTA in a dose-dependent manner.Furthermore,PTA suppressed JAK2/STAT3-dependent inflammation pathway through down-regulating the phosphorylation of JAK2 and STAT3,as well as STAT3 nuclear translocation against LPS treatment.These observations suggested a novel role for PTA in regulating LPS-induced neuroinflammatory injuries.