PMID- 35797238
OWN - NLM
STAT- MEDLINE
DCOM- 20220721
LR  - 20220722
IS  - 1948-7193 (Electronic)
IS  - 1948-7193 (Linking)
VI  - 13
IP  - 14
DP  - 2022 Jul 20
TI  - Exploration of Isoquinoline Alkaloids as Potential Inhibitors against Human Islet 
      Amyloid Polypeptide.
PG  - 2164-2175
LID - 10.1021/acschemneuro.2c00206 [doi]
AB  - Type-2 diabetes mellitus (T2DM) is one of the most concerning public health 
      problems because of its high incidence, multiple complications, and difficult 
      treatment. Human islet amyloid polypeptide (hIAPP) is closely linked to T2DM 
      because its abnormal self-assembly causes membrane damage and cell dysfunction. 
      The development of potential inhibitors to prevent hIAPP fibrillation is a 
      promising strategy for the intervention and treatment of diabetes. Natural 
      isoquinoline alkaloids are used as effective medication that targets different 
      biomolecules. Although studies explored the efficacy of berberine, jatrorrhizine, 
      and chelerythrine in diabetes, the underlying mechanism remains unclear. Herein, 
      three isoquinoline alkaloids are selected to reveal their roles in hIAPP 
      aggregation, disaggregation, and cell protection. All three compounds displayed 
      good inhibitory effects on peptide fibrillation, scattered the preformed fibrils 
      into small oligomers and most monomers, and upregulated cell viability by 
      reducing hIAPP oligomerization. Moreover, combined biophysical analyses indicated 
      that the compounds affected the beta-sheet structure and hydrophobicity of 
      polypeptides significantly, and the benzo[c]phenanthridine structure of 
      chelerythrine was beneficial to the inhibition of hIAPP aggregation and their 
      hydrophobic interaction, compared with that of berberine and jatrorrhizine. Our 
      work elaborated the effects of these alkaloids on hIAPP fibrillation and reveals 
      a possible mechanism for these compounds against T2DM.
FAU - Wang, Yanan
AU  - Wang Y
AD  - Department of Chemistry, Renmin University of China, Beijing 100872, China.
FAU - Zheng, Ting
AU  - Zheng T
AD  - Department of Chemistry, Renmin University of China, Beijing 100872, China.
FAU - Huo, Yan
AU  - Huo Y
AD  - Department of Chemistry, Renmin University of China, Beijing 100872, China.
FAU - Du, Weihong
AU  - Du W
AUID- ORCID: 0000-0002-9976-4515
AD  - Department of Chemistry, Renmin University of China, Beijing 100872, China.
LA  - eng
PT  - Journal Article
DEP - 20220707
PL  - United States
TA  - ACS Chem Neurosci
JT  - ACS chemical neuroscience
JID - 101525337
RN  - 0 (Amyloid)
RN  - 0 (Islet Amyloid Polypeptide)
RN  - 0 (Isoquinolines)
RN  - 0I8Y3P32UF (Berberine)
SB  - IM
MH  - *Amyloid/pharmacology
MH  - *Berberine/pharmacology
MH  - *Diabetes Mellitus, Type 2/drug therapy
MH  - Humans
MH  - *Islet Amyloid Polypeptide/antagonists & inhibitors/chemistry
MH  - Isoquinolines/pharmacology/therapeutic use
MH  - Protein Conformation, beta-Strand
OTO - NOTNLM
OT  - fibrillation
OT  - hIAPP
OT  - inhibition
OT  - interaction
OT  - isoquinoline alkaloids
EDAT- 2022/07/08 06:00
MHDA- 2022/07/22 06:00
CRDT- 2022/07/07 13:22
PHST- 2022/07/08 06:00 [pubmed]
PHST- 2022/07/22 06:00 [medline]
PHST- 2022/07/07 13:22 [entrez]
AID - 10.1021/acschemneuro.2c00206 [doi]
PST - ppublish
SO  - ACS Chem Neurosci. 2022 Jul 20;13(14):2164-2175. doi: 
      10.1021/acschemneuro.2c00206. Epub 2022 Jul 7.