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Neuroinflammation is recognized as an important pathogenic factor for aging and related cognitive disorders.Mitogen-activated protein kinase and nuclear factor kappa B signaling pathways may mediate neuroinflammation.Saponins from Panaxjaponicus are the most abundant and bioactive members in rhizomes of Panax japonicus,and show anti-inflammatory activity.However,it is not known whether saponin from Panaxjaponicus has an anti-inflammatory effect in the aging brain,and likewise its underlying mechanisms.Sprague-Dawley rats were divided into control groups (3-,9-,15-,and 24-month-old groups) and saponins from Panax japonicus-treated groups.Saponins from Panax japonicus-treated groups were orally administrated saponins from Panax japonicus at three doses of 10,30,and 60 mg/kg once daily for 6 months until the rats were 24 months old.Immunohistochemical staining and west blot assay results demonstrated that many microglia were activated in 24-month-old rats compared with 3-and 9-month-old rats.Expression of interleukin-1β,tumor necrosis factor-α,cydooxygenase-2,and inducible nitric oxide synthase increased.Each dose of saponins from Panax japonicus visibly suppressed microglial activation in the aging rat brain,and inhibited expression levels of the above factors.Each dose of saponins from Panaxjaponicus markedly diminished levels of nuclear factor kappa B,IκBα,extracellular signal-regulated kinase,c-Jun N-terminal kinase,and p38.These results confirm that saponins from Panax japonicus can mitigate neuroinflammation in the aging rat brain by inhibition of the mitogen-activated protein kinase and nuclear factor kappa B signaling pathways.