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Sci Rep. 2016 Dec 22;6:38846. doi: 10.1038/srep38846.

Investigating the Neuroprotective Effects of Turmeric Extract: Structural Interactions of β-Amyloid Peptide with Single Curcuminoids.

Author information

1
Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084-Fisciano-Italy.
2
Department of Pharmacy, University of Naples "Federico II", Via D. Montesano, 49, 80131-Naples-Italy.
3
Department of Chemical Sciences, University of Naples "Federico II", Via Cinthia, 80126-Naples-Italy.
4
Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro, 2, 53100-Siena-Italy.
5
R&D Department, Indena, Viale Ortles, 12, 20139-Milan-Italy.
6
Innovation &Development Fresenius-Kabi, Piazza Maestri del Lavoro, 7, 20063-Cernusco sul Naviglio Milan-Italy.

Abstract

A broad biophysical analysis was performed to investigate the molecular basis of the neuroprotective action of Curcuma longa extracts in Alzheimer's disease. By combining circular dichroism and electron paramagnetic resonance experiments with molecular modeling calculations, the minor components of Curcuma longa extracts, such as demethoxycurcumin (2, DMC), bisdemethoxycurcumin (3, BDMC) and cyclocurcumin (4, CYC), were analyzed in a membrane environment mimicking the phospholipid bilayer. Our study provides the first evidence on the relative role of single curcuminoids interacting with Aβ-peptide. When the CYC and curcumin metabolite tetrahydrocurcumin (5, THC) were inserted into an anionic lipid solution, a significant modification of the Aβ CD curves was detected. These data were implemented by EPR experiments, demonstrating that CYC reaches the inner part of the bilayer, while the other curcuminoids are localized close to the membrane interface. Computational studies provided a model for the curcuminoid-Aβ interaction, highlighting the importance of a constrained "semi-folded" conformation to interact with Aβ analogously to the pattern observed in α-helical coiled-coil peptide structures. This combined approach led to a better understanding of the intriguing in vitro and in vivo activity of curcuminoids as anti-Alzheimer agents, paving a new path for the rational design of optimized druggable analogues.

PMID:
28004737
PMCID:
PMC5177957
DOI:
10.1038/srep38846
[Indexed for MEDLINE]
Free PMC Article

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