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.

Jie-jian Kou;Jun-zhuo Shi;Yang-yang He;Jiao-jiao Hao;Hai-yu Zhang;Dong-mei Luo;Jun-ke Song;Yi Yan;Xin-mei Xie;Guan-hua Du;Xiao-bin Pang

School of Pharmacy,Henan University,Kaifeng 475004,China;State Key Laboratory of Bioactive Substances and Functions of Natural Medicines,Institute of Materia Medica,Chinese Academy of Medical Science and Peking Union Medical College,Beijing 100050,China;Beijing Key Laboratory of Drug Target Identification and Drug Screening,National Center for Pharmaceutical Screening,Institute of Materia Medica,Chinese Academy of Medical Science and Peking Union Medical College,Beijing 100050,China;Institute for Cardiovascular Prevention(IPEK),Ludwig-Maximilians-University Munich,Munich 80336,Germany;DZHK(German Centre for Cardiovascular Research),Partner Site Munich Heart Alliance,Munich 80336,Germany

中国药理学报（英文版）

[1]Jie-jian Kou;Jun-zhuo Shi;Yang-yang He;Jiao-jiao Hao;Hai-yu Zhang;Dong-mei Luo;Jun-ke Song;Yi Yan;Xin-mei Xie;Guan-hua Du;Xiao-bin Pang-.Luteolin alleviates cognitive impairment in Alzheimer's disease mouse model via inhibiting endoplasmic reticulum stress-dependent neuroinflammation)[J].中国药理学报（英文版）,2022(04):840-849

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