A potential therapeutic effect of saikosaponin C as a novel dual-target anti-Alzheimer agent

被引：33

作者：

Lee, Tae Ho ^{[1
]}

Park, Sungha ^{[2
]}

You, Mi-Hyeon ^{[1
]}

Lim, Ji-Hong ^{[3
]}

Min, Sang-Hyun ^{[4
]}

Kim, Byeong Mo ^{[2
]}

机构：

[1] Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Med, Div Gerontol,Med Sch, Boston, MA 02215 USA

[2] Yonsei Univ, Coll Med, Severance Integrat Res Inst Cerebral & Cardiovasc, 50 Yonsei Ro, Seoul 120752, South Korea

[3] Konkuk Univ, Coll Biomed & Hlth Sci, Dept Biomed Chem, Chungju, South Korea

[4] DGMIF, New Drug Dev Ctr, Taegu, South Korea

来源：

JOURNAL OF NEUROCHEMISTRY | 2016年 / 136卷 / 06期

基金：

新加坡国家研究基金会;

关键词：

Alzheimer's disease; amyloid beta; tau; neurodegenerative diseases; saikosaponin C; therapeutic tool; AMYLOID PRECURSOR PROTEIN; ALPHA-SECRETASE CLEAVAGE; BLOOD-BRAIN-BARRIER; TAU-PHOSPHORYLATION; APOPTOTIC MECHANISM; NEURITE OUTGROWTH; SYNAPSE LOSS; A-BETA; DISEASE; AGGREGATION;

D O I：

10.1111/jnc.13515

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Alzheimer's disease (AD) is a chronic neurodegenerative disease and the risk of developing it increases with advancing age. In this study, we investigated the protective effects of saikosaponin C (SSc), one of the main bioactive components produced by the traditional Chinese herb, radix bupleuri, the root of Bupleurum falcatum, against AD in various neuronal models. Interestingly, we found that SSc has dual effects on AD by targeting amyloid beta (A) and tau, two key proteins in AD. SSc significantly suppressed the release of both A peptides 1-40 and 1-42 into cell culture supernatants, though it does not affect BACE1 activity and expression. SSc also inhibited abnormal tau phosphorylation at multiple AD-related residues. Moreover, SSc seems to have beneficial effects on cellular tau function; it accelerated nerve growth factor-mediated neurite outgrowth and increased the assembly of microtubules. In addition, SSc increased synaptic marker proteins such as synaptophysin and PSD-95. Considering its various biological activities, our results suggest that SSc might be a novel therapeutic tool for treating human AD and other neurodegenerative diseases.

引用

页码：1232 / 1245

页数：14

共 59 条

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