Effects of several quinones on insulin aggregation

被引:115
作者
Gong, Hao [1 ]
He, Zihao [1 ]
Peng, Anlin [2 ]
Zhang, Xin [1 ]
Cheng, Biao [1 ]
Sun, Yue [3 ]
Zheng, Ling [3 ]
Huang, Kun [1 ,4 ]
机构
[1] Huazhong Univ Sci & Technol, Tongji Sch Pharm, Wuhan 430030, Hubei, Peoples R China
[2] Third Hosp Wuhan, Dept Pharm, Wuhan 430060, Hubei, Peoples R China
[3] Wuhan Univ, Coll Life Sci, Wuhan 430072, Hubei, Peoples R China
[4] Wuhan Inst Biotechnol, Ctr Biomed Res, Wuhan 430075, Hubei, Peoples R China
来源
SCIENTIFIC REPORTS | 2014年 / 4卷
关键词
BIOPHYSICAL CHEMISTRY; MOLECULAR BIOPHYSICS; ISLET AMYLOID POLYPEPTIDE; BETA-AGGREGATION; FIBRIL FORMATION; ALPHA-SYNUCLEIN; ANTIAMYLOIDOGENIC PROPERTIES; THERAPEUTIC STRATEGY; TOXIC AGGREGATION; BOVINE INSULIN; IN-VITRO; A-BETA;
D O I
10.1038/srep05648
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Protein misfolding and aggregation are associated with more than twenty diseases, such as neurodegenerative diseases and metabolic diseases. The amyloid oligomers and fibrils may induce cell membrane disruption and lead to cell apoptosis. A great number of studies have focused on discovery of amyloid inhibitors which may prevent or treat amyloidosis diseases. Polyphenols have been extensively studied as a class of amyloid inhibitors, with several polyphenols under clinical trials as anti-neurodegenerative drugs. As oxidative intermediates of natural polyphenols, quinones widely exist in medicinal plants or food. In this study, we used insulin as an amyloid model to test the anti-amyloid effects of four simple quinones and four natural anthraquinone derivatives from rhubarb, a traditional herbal medicine used for treating Alzheimer's disease. Our results demonstrated that all eight quinones show inhibitory effects to different extent on insulin oligomerization, especially for 1,4-benzoquinone and 1,4-naphthoquinone. Significantly attenuated oligomerization, reduced amount of amyloid fibrils and reduced hemolysis levels were found after quinones treatments, indicating quinones may inhibit insulin from forming toxic oligomeric species. The results suggest a potential action of native anthraquinone derivatives in preventing protein misfolding diseases, the quinone skeleton may thus be further explored for designing effective anti-amyloidosis compounds.
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页数:8
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