Abstract
Amyloid formation is associated with multiple amyloidosis diseases. Human calcitonin (hCT) is a typical amyloidogenic peptide, its aggregation is associated with medullary carcinoma of the thyroid (MTC), and also limits its clinical application. Magnolia officinalis is a traditional Chinese herbal medicine; its two major polyphenol components, magnolol (Mag) and honokiol (Hon), have displayed multiple functions. Polyphenols like flavonoids and their derivatives have been extensively studied as amyloid inhibitors. However, the anti-amyloidogenic property of a biphenyl backbone containing polyphenols such as Mag and Hon has not been reported. In this study, these two compounds were tested for their effects on hCT aggregation. We found that Mag and Hon both inhibited the amyloid formation of hCT, whereas Mag showed a stronger inhibitory effect; moreover, they both dose-dependently disassembled preformed hCT aggregates. Further immuno-dot blot and dynamic light scattering studies suggested Mag and Hon suppressed the aggregation of hCT both at the oligomerization and the fibrillation stages, while MTT-based and dye-leakage assays demonstrated that Mag and Hon effectively reduced cytotoxicity caused by hCT aggregates. Furthermore, isothermal titration calorimetry indicated Mag and Hon both interact with hCT. Together, our study suggested a potential anti-amyloidogenic property of these two compounds and their structure related derivatives.
Highlights
IntroductionPolyphenols, which have multiple aromatic phenolic rings, have been regarded as a class of potential amyloid inhibitors[47,48]
Great efforts have been made to identify inhibitors that suppress the aggregation of amyloidogenic proteins[17,29,30,31,32,33], among which, compounds derived from herbal medicines have been extensively reported[34,35]
Addition of an equimolar amount of epigallocatechin 3-gallate (EGCG) significantly inhibited the aggregation of hCT (Fig. 2A,B), which agrees with a previous report[55]
Summary
Polyphenols, which have multiple aromatic phenolic rings, have been regarded as a class of potential amyloid inhibitors[47,48] Flavonoids along with their derivatives are the most studied polyphenols, for example, (−)-epigallocatechin 3-gallate (EGCG), a derivative of flavanone, has been extensively studied for its anti-amyloidogenic activity on α -synuclein[49], SEVI50, islet amyloid polypeptide[51] and amyloid β 52,53, and is currently undergoing a phase II/III clinical study to treat Alzheimer’s disease[54]. Other polyphenols such as curcumin, caffeic acid, have been reported[17]. HCT was used as a model to test their anti-amyloid aggregation properties
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