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Microglial cells play a critical role in mediating central nervous systeminammatory processes. Activated microglial cells induced by proinflammatory factor,such as lipopolysaccharide (LPS), release many kinds of neurotoxic cytokines includingreactive oxygen species (ROS) which contributes to the pathogenesis of neurodegenerativediseases. Puerarin, extracted from kudzu root, possesses the characteristic ofneuroprotection, antioxidation and anticancer. In the present study, we observedthat LPS induced over-production of nitric oxide (NO) and increased the levelof intracellular ROS in N9 microglial cells, but it was inhibited by puerarin.Furthermore, treatment with puerarin on N9 cells suppressed the over-expressionof inducible nitric oxide synthase (iNOS) induced by LPS which is implicated inintracellular O-linked β-N-acetylglucosamine (O-GlcNAc) level, phosphorylationof mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) signalingpathway. We also observed that the enhanced phosphorylation of p38, JNK and ERK1/2in N9 cells induced by LPS were inhibited by puerarin, otherwise the down-regulationof O-GlcNAcylation level of protein in N9 cell induced by LPS was up-regulatedby pretreatment with puerarin. These results indicate that puerarin effectivelyinhibits microglia activation induced by LPS through inhibiting expression ofiNOS, production of NO and ROS which was mediated via regulating O-GlcNAcylation,phosphorylation of MAPK and NF-κB translocation.

international journal of oncology

Puerarin suppresses production of nitric oxide and inducible nitric oxide synthase in lipopolysaccharide-induced N9 microglial cells through regulating MAPK phosphorylation, O-GlcNAcylation and NF-κB translocation