Piperlongumine activates Sirtuin1 and improves cognitive function in a murine model of Alzheimer's disease

被引:21
作者
Go, Jun [1 ,2 ]
Ha, Thi-Kim-Quy [3 ]
Seo, Ji Yeon [3 ]
Park, Tae-Shin [1 ]
Ryu, Young-Kyoung [1 ]
Park, Hye-Yeon [1 ]
Noh, Jung-Ran [1 ]
Kim, Yong-Hoon [1 ,4 ]
Hwang, Jung Hwan [1 ,4 ]
Choi, Dong-Hee [1 ]
Hwang, Dae Youn [2 ]
Kim, Sanghee [3 ]
Lee, Chul-Ho [1 ,4 ]
Oh, Won Keun [3 ]
Kim, Kyoung-Shim [1 ,4 ]
机构
[1] KRIBB, Lab Anim Resource Ctr, 125 Gwahak Ro, Daejeon 34141, South Korea
[2] Pusan Natl Univ, Dept Biomat Sci, Coll Nat Resources & Life Sci, Life & Ind Convergence Res Inst, Miryang 50463, South Korea
[3] Seoul Natl Univ, Korea Bioact Nat Mat Bank, Pharmaceut Sci Res Inst, Coll Pharm, Seoul 08826, South Korea
[4] Univ Sci & Technol, Dept Funct Genom, Daejeon 34113, South Korea
基金
新加坡国家研究基金会;
关键词
Alzheimer's disease; Cognition; Sirtuin; 1; Piperlongumine; SIRT1; PIPLARTINE; STRESS; MEMORY; INFLAMMATION; MICROGLIA; ALKALOIDS; PROTECTS; ANALOGS; FRUITS;
D O I
10.1016/j.jff.2018.02.002
中图分类号
TS2 [食品工业];
学科分类号
0832 ;
摘要
Sirtuinl (Sirt1) is an unusual target for aging and aging-associated diseases. During the screening for Sirt1 activators from natural compounds, piperlongumine (PL), one of the major constituents of Piper longum, potently activated the deacetylase ability of Sirt1 in vitro. Treatment with PL, which regulated the gene transcription of antioxidant response element in hippocampal neurons, attenuated the cytotoxicity induced by intraneuronal A beta(1-42) expression. The oral administration of PL, at a dose of 50 mg/kg/day for 2.5 months, significantly reduced the occupied area of beta-amyloid in parietal cortex of APP/PS1 mice. Novel object recognition and working memory impairment also markedly improved. Moreover, activated microglia and astrocytes in the cortex notably decreased, indicating the anti-inflammatory activity of PL. Finally, vesicular glutamate transporter 1 significantly increased in the hippocampus of APP/PS1 mice following PL treatment. These results suggested the beneficial effects PL and its therapeutic potential to ameliorate AD-like pathology.
引用
收藏
页码:103 / 111
页数:9
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