Safflower yellow ameliorates cognition deficits and reduces tau phosphorylation in APP/PS1 transgenic mice.
Alzheimer's disease (AD), the most common cause of dementia worldwide, is mainly characterized by the aggregated β-amyloid (Aβ) and hyperphosphorylated tau. Safflower yellow (SY) is a novel water extract of natural safflower and has been suggested to ameliorate memory deficits in several animal models of dementia. In this study, we aimed to investigate the effect and mechanism of SY on deficits of learning and memory and hyperphosphorylation of tau in APP/PS1 double transgenic mice. APP/PS1 mice were administered with SY (10, 30, 100 mg/kg) by oral gavage for three months at the age of six months. The ability of learning and memory was investigated using the step-down test and Morris water maze test, and protein level in the brain was evaluated using western blot. Here, we found that SY treatment can improve spatial learning and memory ability, and reduce tau hyperphosphorylation at Ser199, Thr205, Ser396, Ser404 sites in APP/PS1 mice. In addition, the activity the of cyclin-dependent kinase 5 (CDK-5) and glycogen synthase kinase 3β (GSK-3β), major kinases involved in tau phosphorylation, was siginificantly decreased in APP/PS1 mice by SY treatment. These results support SY can serve as a promising multitarget neuronal therapeutic agent for the treatment of AD.
Key Laboratory of Xinjiang Endemic Phytomedicine Resources of Ministry Pharmacy, Shihezi University, Bei'er Road, Shihezi, Xinjiang, 832000, China.
Ying-Ying
YY
Ruan
Key Laboratory of Xinjiang Endemic Phytomedicine Resources of Ministry Pharmacy, Shihezi University, Bei'er Road, Shihezi, Xinjiang, 832000, China.
Wei
W
Zhai
Key Laboratory of Xinjiang Endemic Phytomedicine Resources of Ministry Pharmacy, Shihezi University, Bei'er Road, Shihezi, Xinjiang, 832000, China.
Xiao-Meng
XM
Shi
Key Laboratory of Xinjiang Endemic Phytomedicine Resources of Ministry Pharmacy, Shihezi University, Bei'er Road, Shihezi, Xinjiang, 832000, China.
Lu
L
Zhang
Department of Pharmacology, College of Pharmaceutical Science, Shihezi University, Shihezi, Xinjiang, 832000, China. wzx330@163.com.
Yan-Li
YL
Hu
D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D003072:Cognition Disorders / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D053764:Presenilin-1 / Q000235:genetics*; D016875:tau Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*
D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1; C580804:presenilin 1, mouse; D016875:tau Proteins; C076422:safflower yellow; D002599:Chalcone
APP/PS1 transgenic mice; Alzheimer’s disease; Safflower yellow; Tau phosphorylation