Azadirachtin inhibits amyloid formation, disaggregates pre-formed fibrils and protects pancreatic β-cells from human islet amyloid polypeptide/amylin-induced cytotoxicity

The Biochemical Journal
Richa DubeyAshutosh Kumar

Abstract

The human islet amyloid polypeptide (hIAPP) or amylin is the major constituent of amyloidogenic aggregates found in pancreatic islets of type 2 diabetic patients that have been associated with β-cell dysfunction and/or death associated with type 2 diabetes mellitus (T2DM). Therefore, developing and/or identifying inhibitors of hIAPP aggregation pathway and/or compound that can mediate disaggregation of preformed aggregates holds promise as a medical intervention for T2DM management. In the current study, the anti-amyloidogenic potential of Azadirachtin (AZD)-a secondary metabolite isolated from traditional medicinal plant Neem (Azadirachta indica)-was investigated by using a combination of biophysical and cellular assays. Our results indicate that AZD supplementation not only inhibits hIAPP aggregation but also disaggregates pre-existing hIAPP fibrils by forming amorphous aggregates that are non-toxic to pancreatic β-cells. Furthermore, AZD supplementation in pancreatic β-cells (INS-1E) resulted in inhibition of oxidative stress; along with restoration of the DNA damage, lipid peroxidation and the associated membrane damage, endoplasmic reticulum stress and mitochondrial membrane potential. AZD treatment also restored glucose-s...Continue Reading

References

Jan 1, 1991·Acta Oncologica·M Stridsberg, E Wilander
Dec 4, 2001·Biochimica Et Biophysica Acta·E T Jaikaran, A Clark
Sep 7, 2002·Toxicological Sciences : an Official Journal of the Society of Toxicology·Liuji ChenBaolu Zhao
Apr 3, 2003·Experimental Gerontology·Lucy MarzbanC Bruce Verchere
Jun 8, 2006·Annual Review of Biochemistry·Fabrizio Chiti, Christopher M Dobson
Nov 25, 2006·Protein Science : a Publication of the Protein Society·Jessica A Williamson, Andrew D Miranker
Jan 11, 2007·The Journal of Chemical Physics·Giovanni BussiMichele Parrinello
Jun 28, 2007·International Journal of Clinical Practice. Supplement·M Hanefeld
Aug 19, 2007·Biochimica Et Biophysica Acta·Andreas Barth
Mar 21, 2008·Journal of Computational Chemistry·Sunhwan JoWonpil Im
Nov 29, 2008·Journal of Molecular Biology·Matthew BiancalanaShohei Koide
Dec 30, 2008·Bioorganic & Medicinal Chemistry·E David Morgan
Jan 24, 2009·Chembiochem : a European Journal of Chemical Biology·Rajesh MishraRoland Winter
Apr 25, 2009·Evidence-based Complementary and Alternative Medicine : ECAM·Menakshi BhatBimba N Joshi
Nov 4, 2009·Biophysical Journal·Innocent B Bekard, Dave E Dunstan
Mar 13, 2010·Expert Review of Cardiovascular Therapy·Christina L Aquilante
Apr 20, 2010·Biochimica Et Biophysica Acta·Matthew Biancalana, Shohei Koide
Jun 12, 2010·Journal of the American Chemical Society·Jeffrey R BrenderAyyalusamy Ramamoorthy
Jul 12, 2011·Physiological Reviews·Per WestermarkGunilla T Westermark
Sep 20, 2011·Nucleic Acids Research·Shilpy SharmaChristine E Canman
Nov 15, 2011·Diabetes Research and Clinical Practice·David R WhitingJonathan Shaw
Jan 13, 2012·Protein Science : a Publication of the Protein Society·Harris NoorDaniel P Raleigh
Mar 1, 2012·Biochemical and Biophysical Research Communications·Biao ChengKun Huang
May 15, 2012·Biochemical and Biophysical Research Communications·Samuel SparksNoel D Lazo
May 16, 2012·Clinical Research in Cardiology : Official Journal of the German Cardiac Society·Arnt V KristenHugo A Katus
Feb 6, 2013·FEBS Letters·Ping CaoDaniel P Raleigh
Feb 20, 2013·The Analyst·Fiona T S ChanClemens F Kaminski
Feb 26, 2013·Chemical Communications : Chem Comm·Aseem MishraVirander Singh Chauhan
Mar 19, 2013·Chemical Communications : Chem Comm·Jeffrey R BrenderAyyalusamy Ramamoorthy
Sep 24, 2013·Metallomics : Integrated Biometal Science·Lei HeWeihong Du
Nov 13, 2013·Proceedings of the National Academy of Sciences of the United States of America·Lauren E BuchananMartin T Zanni
May 23, 2014·Journal of Chemical Information and Modeling·Rashmi KumariAndrew Lynn

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Mar 19, 2020·International Journal of Endocrinology·Wei XuJun Liang
Oct 13, 2021·Journal of Cellular Physiology·Carine MarmentiniMirian A Kurauti

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