PMID- 32569693
OWN - NLM
STAT- MEDLINE
DCOM- 20210416
LR  - 20211204
IS  - 1879-0003 (Electronic)
IS  - 0141-8130 (Linking)
VI  - 162
DP  - 2020 Nov 1
TI  - Inhibition of human islet amyloid polypeptide aggregation and cellular toxicity 
      by oleuropein and derivatives from olive oil.
PG  - 284-300
LID - S0141-8130(20)33612-6 [pii]
LID - 10.1016/j.ijbiomac.2020.06.170 [doi]
AB  - Loss of beta-cell function and beta-cell death is the key feature of type 2 diabetes 
      mellitus (T2DM). One hypothesis for the mechanism of this feature is amyloid 
      formation by the human islet amyloid polypeptide (hIAPP). Despite the global 
      prevalence of T2DM, there are no therapeutic strategies for the treatment of or 
      prevention of amylin amyloidosis. Clinical trials and population studies indicate 
      the healthy virtues of the Mediterranean diet, especially the extra virgin olive 
      oil (EVOO) found in this diet. This oil is enriched in phenolic compounds shown 
      to be effective against several aging and lifestyle diseases. Oleuropein (Ole), 
      one of the most abundant polyphenols in EVOO, has been reported to be 
      anti-diabetic. Some of Ole's main derivative have attracted our interest due to 
      their multi-targetted effects, including interference with amyloid aggregation 
      path. However, the structure-function relationship of Ole and its metabolites in 
      T2DM are not yet clear. We report here a broad biophysical approach and cell 
      biology techniques that enabled us to characterize the different molecular 
      mechanisms by which tyrosol (TYR), hydroxytyrosol (HT), oleuropein (Ole) and 
      oleuropein aglycone (OleA) modulate the hIAPP fibrillation in vitro and their 
      effects on cell cytotoxicity. The OleA formed by enolic acid and hydroxytyrosol 
      moiety was found to be more active than the Ole and HT at low micromolar 
      concentrations. We further demonstrated that OleA inhibit the cytotoxicity 
      induced by hIAPP aggregates by protecting more the cell membrane from 
      permeabilization and then from death. These findings highlight the benefits of 
      consuming EVOO and the great potential of its polyphenols, mainly OleA. Moreover, 
      they support the possibility to validate and optimize the possible 
      pharmacological use of EVOO polyphenols for T2DM prevention and therapy and also 
      for many other amyloid related diseases.
CI  - Copyright (c) 2020 The Author. Published by Elsevier B.V. All rights reserved.
FAU - Chaari, Ali
AU  - Chaari A
AD  - Premedical Department Weill Cornell Medicine, Qatar Foundation, Education City, 
      P.O. Box 24144, Doha, Qatar. Electronic address: alc2033@qatar-med.cornell.edu.
LA  - eng
PT  - Journal Article
DEP - 20200620
PL  - Netherlands
TA  - Int J Biol Macromol
JT  - International journal of biological macromolecules
JID - 7909578
RN  - 0 (Acetates)
RN  - 0 (Cyclopentane Monoterpenes)
RN  - 0 (Iridoid Glucosides)
RN  - 0 (Iridoids)
RN  - 0 (Islet Amyloid Polypeptide)
RN  - 0 (Olive Oil)
RN  - 0 (Phospholipids)
RN  - 0 (Pyrans)
RN  - 0 (oleuropein aglycone)
RN  - 10597-60-1 (3,4-dihydroxyphenylethanol)
RN  - 1AK4MU3SNX (4-hydroxyphenylethanol)
RN  - 2O4553545L (oleuropein)
RN  - ML9LGA7468 (Phenylethyl Alcohol)
SB  - IM
MH  - Acetates/pharmacology
MH  - Cell Survival/drug effects
MH  - Cyclopentane Monoterpenes/pharmacology
MH  - Diabetes Mellitus, Type 2/*drug therapy/metabolism/pathology
MH  - Diet, Mediterranean
MH  - Fluorescence
MH  - Humans
MH  - Inhibitory Concentration 50
MH  - Iridoid Glucosides
MH  - Iridoids/*pharmacology
MH  - Islet Amyloid Polypeptide/*metabolism/toxicity
MH  - Islets of Langerhans/cytology/*drug effects
MH  - Microscopy, Atomic Force
MH  - Olive Oil/*chemistry/*pharmacology
MH  - Phenylethyl Alcohol/analogs & derivatives/*pharmacology
MH  - Phospholipids/metabolism
MH  - Pyrans/pharmacology
MH  - Structure-Activity Relationship
OTO - NOTNLM
OT  - Amyloid inhibition
OT  - Hydroxytyrosol
OT  - Mediterranean diet
OT  - Oleuropein
OT  - Oleuropein aglycone
OT  - Polyphenols
OT  - Type 2 diabetes
OT  - Tyrosol
OT  - hIAPP
COIS- Declaration of competing interest The authors declare no conflict of interest.
EDAT- 2020/06/23 06:00
MHDA- 2021/04/17 06:00
CRDT- 2020/06/23 06:00
PHST- 2020/04/12 00:00 [received]
PHST- 2020/06/09 00:00 [revised]
PHST- 2020/06/17 00:00 [accepted]
PHST- 2020/06/23 06:00 [pubmed]
PHST- 2021/04/17 06:00 [medline]
PHST- 2020/06/23 06:00 [entrez]
AID - S0141-8130(20)33612-6 [pii]
AID - 10.1016/j.ijbiomac.2020.06.170 [doi]
PST - ppublish
SO  - Int J Biol Macromol. 2020 Nov 1;162:284-300. doi: 10.1016/j.ijbiomac.2020.06.170. 
      Epub 2020 Jun 20.