PMID- 33544469
OWN - NLM
STAT- MEDLINE
DCOM- 20210721
LR  - 20210721
IS  - 1437-4315 (Electronic)
IS  - 1431-6730 (Linking)
VI  - 402
IP  - 2
DP  - 2021 Jan 27
TI  - Myricetin protects pancreatic beta-cells from human islet amyloid polypeptide 
      (hIAPP) induced cytotoxicity and restores islet function.
PG  - 179-194
LID - 10.1515/hsz-2020-0176 [doi]
AB  - The aberrant misfolding and self-assembly of human islet amyloid polypeptide 
      (hIAPP)-a hormone that is co-secreted with insulin from pancreatic beta-cells-into 
      toxic oligomers, protofibrils and fibrils has been observed in type 2 diabetes 
      mellitus (T2DM). The formation of these insoluble aggregates has been linked with 
      the death and dysfunction of beta-cells. Therefore, hIAPP aggregation has been 
      identified as a therapeutic target for T2DM management. Several natural products 
      are now being investigated for their potential to inhibit hIAPP aggregation 
      and/or disaggregate preformed aggregates. In this study, we attempt to identify 
      the anti-amyloidogenic potential of Myricetin (MYR)- a polyphenolic flavanoid, 
      commonly found in fruits (like Syzygium cumini). Our results from biophysical 
      studies indicated that MYR supplementation inhibits hIAPP aggregation and 
      disaggregates preformed fibrils into non-toxic species. This protection was 
      accompanied by inhibition of oxidative stress, reduction in lipid peroxidation 
      and the associated membrane damage and restoration of mitochondrial membrane 
      potential in INS-1E cells. MYR supplementation also reversed the loss of 
      functionality in hIAPP exposed pancreatic islets via restoration of 
      glucose-stimulated insulin secretion. Molecular dynamics simulation studies 
      suggested that MYR molecules interact with the hIAPP pentameric fibril model at 
      the amyloidogenic core region and thus prevents aggregation and distort the 
      fibrils.
CI  - (c) 2020 Walter de Gruyter GmbH, Berlin/Boston.
FAU - Dubey, Richa
AU  - Dubey R
AD  - Department of Biosciences and Bioengineering, Indian Institute of Technology 
      Bombay, Powai, 400076Mumbai, Maharashtra, India.
FAU - Kulkarni, Shruti H
AU  - Kulkarni SH
AD  - Department of Biotechnology, Savitribai Phule Pune University (Formerly 
      University of Pune), Ganeshkhind, 411007Pune, Maharashtra, India.
FAU - Dantu, Sarath Chandra
AU  - Dantu SC
AD  - Department of Biosciences and Bioengineering, Indian Institute of Technology 
      Bombay, Powai, 400076Mumbai, Maharashtra, India.
AD  - Department of Computer Science, Brunel University London, UB83PHUxbridge, UK.
FAU - Panigrahi, Rajlaxmi
AU  - Panigrahi R
AD  - Department of Biosciences and Bioengineering, Indian Institute of Technology 
      Bombay, Powai, 400076Mumbai, Maharashtra, India.
FAU - Sardesai, Devika M
AU  - Sardesai DM
AD  - Department of Biotechnology, Savitribai Phule Pune University (Formerly 
      University of Pune), Ganeshkhind, 411007Pune, Maharashtra, India.
FAU - Malik, Nikita
AU  - Malik N
AD  - Department of Biosciences and Bioengineering, Indian Institute of Technology 
      Bombay, Powai, 400076Mumbai, Maharashtra, India.
FAU - Acharya, Jhankar D
AU  - Acharya JD
AD  - Department of Zoology, Savitribai Phule Pune University (Formerly University of 
      Pune), Ganeshkhind, 411007Pune, Maharashtra, India.
FAU - Chugh, Jeetender
AU  - Chugh J
AD  - Department of Chemistry, Indian Institute of Science Education and Research, Homi 
      Bhabha Road, Pashan, 411008Pune, India.
AD  - Department of Biology, Indian Institute of Science Education and Research, Homi 
      Bhabha Road, Pashan, 411008Pune, India.
FAU - Sharma, Shilpy
AU  - Sharma S
AUID- ORCID: 0000-0001-5900-3140
AD  - Department of Biotechnology, Savitribai Phule Pune University (Formerly 
      University of Pune), Ganeshkhind, 411007Pune, Maharashtra, India.
FAU - Kumar, Ashutosh
AU  - Kumar A
AUID- ORCID: 0000-0002-5061-8162
AD  - Department of Biosciences and Bioengineering, Indian Institute of Technology 
      Bombay, Powai, 400076Mumbai, Maharashtra, India.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200916
PL  - Germany
TA  - Biol Chem
JT  - Biological chemistry
JID - 9700112
RN  - 0 (Flavonoids)
RN  - 0 (Islet Amyloid Polypeptide)
RN  - 0 (Protective Agents)
RN  - 0 (Protein Aggregates)
RN  - 76XC01FTOJ (myricetin)
SB  - IM
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Flavonoids/chemistry/*pharmacology
MH  - Fruit/chemistry
MH  - Humans
MH  - Insulin-Secreting Cells/*drug effects/metabolism
MH  - Islet Amyloid Polypeptide/*antagonists & inhibitors/chemical synthesis/chemistry
MH  - Islets of Langerhans/*drug effects/metabolism
MH  - Molecular Dynamics Simulation
MH  - Protective Agents/chemical synthesis/chemistry/*pharmacology
MH  - Protein Aggregates/drug effects
MH  - Syzygium/chemistry
OTO - NOTNLM
OT  - INS-1E
OT  - amyloid
OT  - hIAPP
OT  - myricetin
OT  - pancreatic beta-cells
OT  - type 2 diabetes mellitus
EDAT- 2021/02/06 06:00
MHDA- 2021/07/22 06:00
CRDT- 2021/02/05 12:16
PHST- 2020/05/02 00:00 [received]
PHST- 2020/08/25 00:00 [accepted]
PHST- 2021/02/05 12:16 [entrez]
PHST- 2021/02/06 06:00 [pubmed]
PHST- 2021/07/22 06:00 [medline]
AID - hsz-2020-0176 [pii]
AID - 10.1515/hsz-2020-0176 [doi]
PST - epublish
SO  - Biol Chem. 2020 Sep 16;402(2):179-194. doi: 10.1515/hsz-2020-0176. Print 2021 Jan 
      27.