title: Coffee components inhibit amyloid formation of human islet amyloid polypeptide in vitro: possible link between coffee consumption and diabetes mellitus.
abstract: Global epidemic studies have suggested that coffee consumption is reversely correlated with the incidence of type 2 diabetes mellitus (T2DM), a metabolic disease. The misfolding of human islet amyloid polypeptide (hIAPP) is regarded as one of the causative factors of T2DM. Coffee extracts have three major active components: caffeine, caffeic acid (CA), and chlorogenic acid (CGA). In this study, the effects of these major coffee components, as well as dihydrocaffeic acid (DHCA) (a major metabolite of CGA and CA), on the amyloidogenicity of hIAPP were investigated by thioflavin-T based fluorescence emission, transmission electronic microscopy, circular dichroism, light-induced cross-linking, dynamic light scattering, and MTT-based cell viability assays. The results suggest that all components show varied inhibitory effects on the formation of toxic hIAPP amyloids, in which CA shows the highest potency in delaying the conformational transition of the hIAPP molecule with the most prolonged lag time, whereas caffeine shows the lowest potency. At a 5-fold excess molar ratio of compound to hIAPP, all coffee-derived compounds affect the secondary structures of incubated hIAPP as suggested by the circular dichroism spectra and CDPro deconvolution analysis. Further photoinduced cross-linking based oligomerization and dynamic light scattering studies suggested CA and CGA significantly suppressed the formation of hIAPP oligomers, whereas caffeine showed no significant effect on oligomerization. Cell protection effects were also observed for all three compounds, with the protection efficiency being greatest for CA and least for CGA. These findings suggest that the beneficial effects of coffee consumption on T2DM may be partly due to the ability of the major coffee components and metabolites to inhibit the toxic aggregation of hIAPP.
authors: Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, Hubei 430030, People's Republic of China.
authors: Biao
authors: B
authors: Cheng
authors: Xinran
authors: X
authors: Liu
authors: Hao
authors: H
authors: Gong
authors: Lianqi
authors: L
authors: Huang
authors: Hong
authors: H
authors: Chen
authors: Xin
authors: X
authors: Zhang
authors: Chuanzhou
authors: C
authors: Li
authors: Muyang
authors: M
authors: Yang
authors: Bingjun
authors: B
authors: Ma
authors: Lihua
authors: L
authors: Jiao
authors: Ling
authors: L
authors: Zheng
authors: Kun
authors: K
authors: Huang
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000037:antagonists & inhibitors* / Q000737:chemistry; D002109:Caffeic Acids / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002726:Chlorogenic Acid / Q000494:pharmacology; D003069:Coffee / Q000737:chemistry*; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000517:prevention & control*; D006801:Humans; D058228:Islet Amyloid Polypeptide / Q000737:chemistry*; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D017510:Protein Folding; D017433:Protein Structure, Secondary
chemical_list: D000682:Amyloid; D002109:Caffeic Acids; D003069:Coffee; D058228:Islet Amyloid Polypeptide; D002726:Chlorogenic Acid; D002110:Caffeine; C040048:caffeic acid