title: Effects of several quinones on insulin aggregation.
abstract: 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.
authors.affiliation: Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China430030.
authors.forename: Hao
authors.initials: H
authors.lastname: Gong
authors.affiliation: Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China430030.
authors.forename: Zihao
authors.initials: Z
authors.lastname: He
authors.affiliation: Department of Pharmacy, The Third Hospital of Wuhan, Wuhan, Hubei, P. R. China430060.
authors.forename: Anlin
authors.initials: A
authors.lastname: Peng
authors.affiliation: Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China430030.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China430030.
authors.forename: Biao
authors.initials: B
authors.lastname: Cheng
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan, Hubei, P. R. China430072.
authors.forename: Yue
authors.initials: Y
authors.lastname: Sun
authors.affiliation: College of Life Sciences, Wuhan University, Wuhan, Hubei, P. R. China430072.
authors.forename: Ling
authors.initials: L
authors.lastname: Zheng
authors.affiliation: 1] Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China430030 [2] Centre for Biomedicine Research, Wuhan Institute of Biotechnology, Wuhan, Hubei, P. R. China430075.
authors.forename: Kun
authors.initials: K
authors.lastname: Huang
mesh_terms: D000682:Amyloid / Q000378:metabolism; D000686:Amyloidosis / Q000188:drug therapy / Q000378:metabolism; D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D059808:Polyphenols / Q000494:pharmacology; D066263:Protein Aggregation, Pathological / Q000188:drug therapy* / Q000378:metabolism; D017510:Protein Folding / Q000187:drug effects*; D011809:Quinones / Q000494:pharmacology*; D012250:Rheum / Q000737:chemistry; D013552:Swine
chemical_list: D000682:Amyloid; D000880:Anthraquinones; D007328:Insulin; D059808:Polyphenols; D011809:Quinones