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.

Zwitterionic Polymer Design that Inhibits Aggregation and Facilitates Insulin Refolding: Mechanistic Insights and Importance of Hydrophobicity

“…These results confirm that hydrophobic derivatives of poly‐SPB arrest the growth and formation of toxic fibrils. They exhibit higher efficiencies than reported in previous studies using quinones and osmolytes . Compared to our previous report, where 15% polymer concentration was used for aggregation inhibition, these polymers yield significantly higher efficiency at both 1% and 1.5% concentration, indicating tenfold increase in the efficiency with these hydrophobic sulfobetaines.…”

Biophysical insight into the anti-amyloidogenic behavior of taurine

“…Delay in lag time in the presence of taurine attributed to stabilization of the native form as reported earlier [35,36]. Quinones and carnosine act in the same way and prolong the lag phase of insulin and lysozyme aggregation pathway, respectively [37,38]. Fig.…”

Inhibition effects of tanshinone on the aggregation of α-synuclein

“…14 TAN I and TAN IIA ( Fig. 15 In addition, TAN I and TAN IIA share similar structures with curcumin by having two ketone groups and aromatic groups, which has been reported to inhibit α-synuclein aggregation both in vitro and in a Drosophila PD model. We have recently shown that phenanthrenequinone can inhibit insulin aggregation.…”

“…Samples were detected by using a JASCO-810 circular dichroism spectropolarimeter (JASCO, Japan) under continuous N 2 flow. 15 Densitometry analysis was performed using the software Quantity One 4.6.2 (Bio-Rad, Hercules, USA). All results were repeated three times.…”