Luteolin alleviates cognitive impairment in Alzheimer's disease mouse model via inhibiting endoplasmic reticulum stress-dependent neuroinflammation
摘要Luteolin is a flavonoid in a variety of fruits,vegetables,and herbs,which has shown anti-inflammatory,antioxidant,and anti-cancer neuroprotective activities.In this study,we investigated the potential beneficial effects of luteolin on memory deficits and neuroinflammation in a triple-transgenic mouse model of Alzheimer's disease(AD)(3×Tg-AD).The mice were treated with luteolin(20,40 mg·kg-1·d-1,ip)for 3 weeks.We showed that luteolin treatment dose-dependently improved spatial learning,ameliorated memory deficits in 3×Tg-AD mice,accompanied by inhibiting astrocyte overactivation(GFAP)and neuroinflammation(TNF-α,IL-1 β,IL-6,NO,COX-2,and iNOS protein),and decreasing the expression of endoplasmic reticulum(ER)stress markers GRP78 and IRE1α in brain tissues.In rat C6 glioma cells,treatment with luteolin(1,10 μM)dose-dependently inhibited LPS-induced cell proliferation,excessive release of inflammatory cytokines,and increase of ER stress marker GRP78.In conclusion,luteolin is an effective agent in the treatment of learning and memory deficits in 3×Tg-AD mice,which may be attributable to the inhibition of ER stress in astrocytes and subsequent neuroinflammation.These results provide the experimental basis for further research and development of luteolin as a therapeutic agent for AD.
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