Interaction of natural compounds with biomembrane models: A biophysical approach for the Alzheimer’s disease therapy

• Published in: Colloids and surfaces, B, Biointerfaces B, Biointerfaces, 2019-08, Vol.180, p.83-92
• Main Authors: Andrade, Stephanie, Ramalho, Maria J., Loureiro, Joana A., Pereira, Maria Carmo
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - drug therapy; Caffeine - chemistry; Cholesterol - chemistry; Dimyristoylphosphatidylcholine - chemistry; Fluorescence quenching; Gallic Acid - chemistry; Humans; Lipid bilayer; Lipid Bilayers - chemistry; Liposome; Membrane Fluidity; Partition coefficient; Solutions; Tannins - chemistry; Unilamellar Liposomes - chemistry
• ISSN: 0927-7765; 1873-4367
• DOI: 10.1016/j.colsurfb.2019.04.019

[Display omitted] •Drug-membrane interactions are crucial to understand the mechanisms of Alzheimer’s.•Liposomes are suitable for the study of drug–membrane interactions.•Cholesterol hampers the interaction of natural compounds with membranes.•Tannic acid has a significant higher affinity than caffeine and gallic acid.•Tannic acid may interact with extracellular Aβ fibrils and intracellular oligomers. Natural compounds such as caffeine (CA), gallic acid (GA) and tannic acid (TA) have been reported to be useful for Alzheimer’s disease (AD) therapy. It was proved that some natural compounds inhibit the formation of senil plaques composed by beta-amyloid peptide (Aβ), a hallmark of AD. Evidences suggest that the therapeutic activity of compounds depends of their interaction with biological membranes. To understand why these compounds fail in vivo and in clinical trials, it is important to evaluate their pharmacokinetics properties. Thus, a biophysical approach to study drug-membrane interactions is essential to understand the mechanisms by which the drugs interact with the cellular membranes and affect the Aβ production, aggregation and clearance pathways. 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and cholesterol (chol) were used to mimic the biophysical properties of cell membranes and study their interactions with these compounds. The partition coefficient, influence on membrane fluidity and location within the bilayer of the drugs were studied by derivative spectrophotometry, dynamic light scattering and fluorescence quenching, respectively. The results suggest that TA exhibited a significant higher partition than CA and GA and a preferential location near to the polar head of bilayer. The obtained results may explain the therapeutic mechanisms reported for these natural compounds.