The Inhibitory Effect of Natural Products on Protein Fibrillation May Be Caused by Degradation Products – A Study Using Aloin and Insulin

Research output: Contribution to journalJournal articlepeer-review

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The Inhibitory Effect of Natural Products on Protein Fibrillation May Be Caused by Degradation Products – A Study Using Aloin and Insulin. / Lobbens, Eva Stephanie; Foderà, Vito; Nyberg, Nils; Andersen, Kirsten; Jäger, Anna K; Jørgensen, Lene; van de Weert, Marco.

In: PloS one, Vol. 11, No. 2, e0149148, 16.02.2016, p. 1-16.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Lobbens, ES, Foderà, V, Nyberg, N, Andersen, K, Jäger, AK, Jørgensen, L & van de Weert, M 2016, 'The Inhibitory Effect of Natural Products on Protein Fibrillation May Be Caused by Degradation Products – A Study Using Aloin and Insulin', PloS one, vol. 11, no. 2, e0149148, pp. 1-16. https://doi.org/10.1371/journal.pone.0149148

APA

Lobbens, E. S., Foderà, V., Nyberg, N., Andersen, K., Jäger, A. K., Jørgensen, L., & van de Weert, M. (2016). The Inhibitory Effect of Natural Products on Protein Fibrillation May Be Caused by Degradation Products – A Study Using Aloin and Insulin. PloS one, 11(2), 1-16. [e0149148]. https://doi.org/10.1371/journal.pone.0149148

Vancouver

Lobbens ES, Foderà V, Nyberg N, Andersen K, Jäger AK, Jørgensen L et al. The Inhibitory Effect of Natural Products on Protein Fibrillation May Be Caused by Degradation Products – A Study Using Aloin and Insulin. PloS one. 2016 Feb 16;11(2):1-16. e0149148. https://doi.org/10.1371/journal.pone.0149148

Author

Lobbens, Eva Stephanie ; Foderà, Vito ; Nyberg, Nils ; Andersen, Kirsten ; Jäger, Anna K ; Jørgensen, Lene ; van de Weert, Marco. / The Inhibitory Effect of Natural Products on Protein Fibrillation May Be Caused by Degradation Products – A Study Using Aloin and Insulin. In: PloS one. 2016 ; Vol. 11, No. 2. pp. 1-16.

Bibtex

@article{c5e2bb6401d24fb8b996037781966cb4,
title = "The Inhibitory Effect of Natural Products on Protein Fibrillation May Be Caused by Degradation Products – A Study Using Aloin and Insulin",
abstract = "Protein fibrillation is the pathological hallmark of several neurodegenerative diseases and also complicates the manufacturing and use of protein drugs. As a case study, the inhibitory activity of the natural compound aloin against insulin fibrillation was investigated. Based on Thioflavin T assays, high-performance liquid chromatography and transmission electron microscopy it was found that a degradation product of aloin, formed over weeks of storage, was able to significantly inhibit insulin fibrillation. The activity of the stored aloin was significantly reduced in the presence of small amounts of sodium azide or ascorbic acid, suggesting the active compound to be an oxidation product. A high-performance liquid chromatography method and a liquid chromatography-mass spectrometry method were developed to investigate the degradation products in the aged aloin solution. We found that the major compounds in the solution were aloin A and aloin B. In addition, 10-hydroxy aloin and elgonica dimers were detected in smaller amounts. The identified compounds were isolated and tested for activity by means of Thioflavin T assays, but no activity was observed. Thus, the actual fibrillation inhibitor is an as yet unidentified and potentially metastable degradation product of aloin. These results suggest that degradation products, and in particular oxidation products, are to be considered thoroughly when natural products are investigated for activity against protein fibrillation.",
author = "Lobbens, {Eva Stephanie} and Vito Foder{\`a} and Nils Nyberg and Kirsten Andersen and J{\"a}ger, {Anna K} and Lene J{\o}rgensen and {van de Weert}, Marco",
year = "2016",
month = feb,
day = "16",
doi = "10.1371/journal.pone.0149148",
language = "English",
volume = "11",
pages = "1--16",
journal = "PLoS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "2",

}

RIS

TY - JOUR

T1 - The Inhibitory Effect of Natural Products on Protein Fibrillation May Be Caused by Degradation Products – A Study Using Aloin and Insulin

AU - Lobbens, Eva Stephanie

AU - Foderà, Vito

AU - Nyberg, Nils

AU - Andersen, Kirsten

AU - Jäger, Anna K

AU - Jørgensen, Lene

AU - van de Weert, Marco

PY - 2016/2/16

Y1 - 2016/2/16

N2 - Protein fibrillation is the pathological hallmark of several neurodegenerative diseases and also complicates the manufacturing and use of protein drugs. As a case study, the inhibitory activity of the natural compound aloin against insulin fibrillation was investigated. Based on Thioflavin T assays, high-performance liquid chromatography and transmission electron microscopy it was found that a degradation product of aloin, formed over weeks of storage, was able to significantly inhibit insulin fibrillation. The activity of the stored aloin was significantly reduced in the presence of small amounts of sodium azide or ascorbic acid, suggesting the active compound to be an oxidation product. A high-performance liquid chromatography method and a liquid chromatography-mass spectrometry method were developed to investigate the degradation products in the aged aloin solution. We found that the major compounds in the solution were aloin A and aloin B. In addition, 10-hydroxy aloin and elgonica dimers were detected in smaller amounts. The identified compounds were isolated and tested for activity by means of Thioflavin T assays, but no activity was observed. Thus, the actual fibrillation inhibitor is an as yet unidentified and potentially metastable degradation product of aloin. These results suggest that degradation products, and in particular oxidation products, are to be considered thoroughly when natural products are investigated for activity against protein fibrillation.

AB - Protein fibrillation is the pathological hallmark of several neurodegenerative diseases and also complicates the manufacturing and use of protein drugs. As a case study, the inhibitory activity of the natural compound aloin against insulin fibrillation was investigated. Based on Thioflavin T assays, high-performance liquid chromatography and transmission electron microscopy it was found that a degradation product of aloin, formed over weeks of storage, was able to significantly inhibit insulin fibrillation. The activity of the stored aloin was significantly reduced in the presence of small amounts of sodium azide or ascorbic acid, suggesting the active compound to be an oxidation product. A high-performance liquid chromatography method and a liquid chromatography-mass spectrometry method were developed to investigate the degradation products in the aged aloin solution. We found that the major compounds in the solution were aloin A and aloin B. In addition, 10-hydroxy aloin and elgonica dimers were detected in smaller amounts. The identified compounds were isolated and tested for activity by means of Thioflavin T assays, but no activity was observed. Thus, the actual fibrillation inhibitor is an as yet unidentified and potentially metastable degradation product of aloin. These results suggest that degradation products, and in particular oxidation products, are to be considered thoroughly when natural products are investigated for activity against protein fibrillation.

U2 - 10.1371/journal.pone.0149148

DO - 10.1371/journal.pone.0149148

M3 - Journal article

C2 - 26882071

VL - 11

SP - 1

EP - 16

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 2

M1 - e0149148

ER -

ID: 161001416