Protective Effect of Hydroxysafflor Yellow A against Chronic Mild Stress-induced Memory Impairments by Suppressing Tau Phosphorylation in Mice

• 作者: Ying WANG Qiang WANG Jun CHEN Li-he YAO Ni TANG Zhen-xiu JIANG Yu LUO
• 来源期刊: 当代医学科学（英文）
• 年，卷（期）: 2021,（3）
• 所属期刊栏目: ORIGINAL ARTICLES
• 页码范围: 555-564
• 页数: 10页
• 语种: 英文
• DOI: 10.1007/s11596-021-2369-3

摘要

Chronic stress plays a critical role in the etiology of sporadic Alzheimer's disease(AD).However,there are currently no effective drugs that can target chronic stress to prevent AD.In this study,we explored the neuroprotective effect of hydroxysafflor yellow A(HSYA)against chronic mild stress(CMS)-induced memory impairments in mice and the underlying mechanism.The Morris water maze test showed that HSYA significantly reduced CMS-induced learning and memory impairments in mice.HSYA increased the expression of brain-derived neurotrophic factor(BDNF)and activated downstream tropomyosin-related kinase B(TrkB)and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)signaling.HSYA decreased the expression of regulator of calcineurin 1-1L(RCAN1-1L)that could promote the activity of glycogen synthase kinase-3β(GSK-3β).HSYA also attenuated tau phosphorylation by inhibiting the activity of GSK-3β and cyclin-dependent kinase-5(Cdk5).Our data indicated that HSYA has protective effects against CMS-induced BDNF downregulation,tau phosphorylation and memory impairments.HSYA may be a promising therapeutic candidate for AD by targeting chronic stress.