Effective suppression of the modified PHF6 peptide/1N4R Tau amyloid aggregation by intact curcumin, not its degradation products: Another evidence for the pigment as preventive/therapeutic "functional food"
Authors: Farhad Golmohammadi
Sajad Moradi
Vali Akbari
Reza Khodarahmi
Saeed Balalaie
Hadi Adibi
Nooshin Bijari
Journal: International journal of biological macromolecules (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: 1N4R Tau isoform; Amyloid aggregation; Curcumin; Degradation products.
Affiliations: Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran., Peptide Chemistry Research Center, K. N. Toosi University of Technology, P.O. Box 15875-4416, Tehran, Iran; Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran., Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran; Department of Biology, Faculty of Science, Razi University, Kermanshah, Iran., Peptide Chemistry Research Center, K. N. Toosi University of Technology, P.O. Box 15875-4416, Tehran, Iran., Nano Drug delivery Research Center, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran., Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran., Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran; Department of Pharmacognosy and Biotechnology, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address: .

Abstract:  Curcumin is a natural product with multiple biological activities and numerous potential therapeutic applications. In present study, the influence of curcumin and its degradation products (DPs) on the amyloid aggregation of Tau protein and the related PHF6 peptide were investigated. We provided experimental/theoretical evidence for suppressing effects of the compounds on the amyloid formation using far-UV CD as well as AFM, XRD and docking techniques and showed that the parent curcumin displayed stronger inhibition effect against Tau fibril aggregation. The obtained results suggest that the curcumin/DPs binding sites on the Tau molecule are likely to be the same, and provide a good structural basis to explain the efficient aggregation suppressing behavior of the curcumin, compared to the DPs. So, developing more stable curcumin nanoparticle formulations with improved curcumin bioavailability are of great importance. Curcumin's multi-functionality is also highly significant for the therapeutic application of this natural compound against various human diseases. 

Retracted: No

PubPeer comments:
 Why did the authors consider curcumin as Functional food? This spice could not be considered as a nutritive element. Simply, phenolic compounds are plant secondary metabolites biologically showed some potential benefits for the human body. This statement that curcumin is a functional food is absolutely not true. Curcumin also could not reach CNS milieu because of its low bioavailability and pharmacokinetics poorness. I am of the opinion that these results don t highlight significant achievements for curcumin, therefore, the data are scientifically problematic. Authors are responsible to share such troubling results. I seek to hear authors answers in response to my queries. , 
 Dear Authors and Pubpeer admins, According to the American Dietary Reference guide, polyphenols are not generally categorized as dietary food ingredients because these metabolites function as reactive substances whenever enter the human body. From this perspective that you assigned the name of  functional food for curcumin, the mentioned reference could not support your claim, therefore given discussion herein is not accurate. In agreement with F. Haghighi that shared the former comment, it is worth to mention curcumin is neither a functional food or drug-like polyphenol. Less bioavailable curcumin will disappear from the bloodstream 2.5 minutes after its consumption. So, neither its by-product metabolites or itself alone could not reach CNS to modulate something true herein. This flaw you made within your paper only misleads researchers to spend more grants on this worthless phenolic compound. The reader of your paper should be aware of this conspicuous mistake while they want to cite this paper. I kindly ask Pubpeer administrators to send a copy of these comments to the Editor in chief of the International Journal of Biological MacroMolecules to make a decision on this occurred error. Sieversia Pentapetala, Clinical Nutritionist, Cyprus. , 
 In agreement with two stated comments, it should be added to the discussion this point that curcumin-riched foods may consider as functional foods but curcumin alone is not a food and more particularly functional food. To confirm this claim, I refer to the ** international guideline for dietary agents ** that do not classify curcumin or similar phenolic compounds as a valuable edible ingredient to be considered as functional foods. Therefore, the authors may want to amend the title or discussion of this paper according to available standards. ,