Aqueous Extract of Paeonia lactiflora and Paeoniflorin as Aggregation Reducers Targeting Chaperones in Cell Models of Spinocerebellar Ataxia 3

作者：Chang Kuo Hsuan; Chen Wan Ling; Lee Li Ching; Lin Chih Hsin; Kung Pin Jui; Lin Te Hsien; Wu Yi Ci; Wu Yih Ru; Chen Yi Chun; Lee Chen Guey Jen^*; Chen Chiung Mei

来源：Evidence-Based Complementary and Alternative Medicine, 2013, 2013: 471659.

DOI：10.1155/2013/471659

Spinocerebellar ataxia (SCA) types 1, 2, 3, 6, 7, and 17 as well as Huntington%26apos;s disease are a group of neurodegenerative disorders caused by expanded CAG repeats encoding a long polyglutamine (polyQ) tract in the respective proteins. Evidence has shown that the accumulation of intranuclear and cytoplasmic misfolded polyQ proteins leads to apoptosis and cell death. Thus suppression of aggregate formation is expected to inhibit a wide range of downstream pathogenic events in polyQ diseases. In this study, we established a high-throughput aggregation screening system using 293 ATXN3/Q(75)-GFP cells and applied this system to test the aqueous extract of Paeonia lactiflora (P. lactiflora) and its constituents. We found that the aggregation can be significantly prohibited by P. lactiflora and its active compound paeoniflorin. Meanwhile, P. lactiflora and paeoniflorin upregulated HSF1 and HSP70 chaperones in the same cell models. Both of them further reduced the aggregation in neuronal differentiated SH-SY5YATXN3/Q(75)-GFP cells. Our results demonstrate how P. lactiflora and paeoniflorin are likely to work on polyQ-aggregation reduction and provide insight into the possible working mechanism of P. lactiflora in SCA3. We anticipate our paper to be a starting point for screening more potential herbs for the treatment of SCA3 and other polyQ diseases.

• 出版日期2013
• 单位长春大学