Alizarin and Purpurin from Rubia tinctorum L. Suppress Insulin Fibrillation and Reduce the Amyloid-Induced Cytotoxicity

Abstract

Alizarin (1,2-dihydroxy­anthraquinone) and purpurin (1,2,4-trihydroxy­anthraquinone), natural anthraquinone compounds from Rubia tinctorum L., are reported to have diverse biological effects including antibacterial, antitumor, antioxidation, and so on, but the inhibition activity against amyloid aggregation has been rarely reported. In this study, we used insulin as a model protein to explore the anti-amyloid effects of the two compounds. The results showed that alizarin and purpurin inhibited the formation of insulin fibrils in a dose-dependent manner and reduced insulin-induced cytotoxicity. Meanwhile, purpurin had a more significant inhibitory effect on insulin amyloid fibrils compared with alizarin. In addition, computer simulations indicated that the two compounds interacted mainly with the hydrophobic residues of insulin chain B and interfered with the binding of phenylalanine residues. The research indicated that natural anthraquinone compounds had potential effects in preventing protein misfolding diseases and could be further used to design effective antiamyloidosis compounds.

Alizarin as a New Activator of the Aryl Hydrocarbon Receptor Signaling Pathway

“…14 Moreover, alizarin inhibits insulin-induced fibrillation and amyloid-induced cytotoxicity. 15 On the basis of these, it was demonstrated that alizarin has several biological effects including antibacterial, antitumor, antioxidation, and anti-Alzheimer's disease.…”

Molecular Aspects of Insulin Aggregation and Various Therapeutic Interventions

“…Moreover, the degradation species, dehydroascorbic acid and diketogulonic acid, showed a much stronger disruptive effect on mature amyloid fibrils and exhibited less cytotoxicity. Wang et al reported the use of two naturally occurring anthraquinones, alizarin and purpurin, in the disintegration of mature insulin fibrils to shorter ones . TEM imaging and DLS analysis of the samples confirmed the shorter size of fibrils after small molecule treatment compared to untreated insulin aggregates, although the authors did not comment on the cytotoxicity of the degraded products.…”

In vitro retardation and modulation of human insulin amyloid fibrillation by Fe3+ and Cu2+ ions

“…There are very few known inhibitors of insulin aggregation, like cyclodextrins, 23 natural and synthetic polypeptides, 24–27 epigallocatechin-3-gallate, 28 quercetin, 29 quinones, 30 anthraquinones-alizarin and purpurin, 31 and ascorbic acid. 32 Fibrils once formed are very much stable thermodynamically.…”