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In the current study, the anti-amyloidogenic potential of Azadirachtin (AZD)\u2014a secondary metabolite isolated from traditional medicinal plant Neem (Azadirachta indica)\u2014was 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 \u03b2-cells. Furthermore, AZD supplementation in pancreatic \u03b2-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-stimulated insulin secretion from pancreatic islets exposed to hIAPP. All-atom molecular dynamics simulation studies on full-length hIAPP pentamer with AZD suggested that AZD interacted with four possible binding sites in the amyloidogenic region of hIAPP. In summary, our results suggest AZD to be a promising candidate for combating T2DM and related amyloidogenic disorders.<\/jats:p>","DOI":"10.1042\/bcj20180820","type":"journal-article","created":{"date-parts":[[2019,2,27]],"date-time":"2019-02-27T18:06:15Z","timestamp":1551290775000},"page":"889-907","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Azadirachtin inhibits amyloid formation, disaggregates pre-formed fibrils and protects pancreatic \u03b2-cells from human islet amyloid polypeptide\/amylin-induced cytotoxicity"],"prefix":"10.1042","volume":"476","author":[{"given":"Richa","family":"Dubey","sequence":"first","affiliation":[{"name":"Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai, Maharashtra 400076, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ketaki","family":"Patil","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Savitribai Phule Pune University (Formerly University of Pune), Ganeshkhind, Pune, Maharashtra 411007, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarath C.","family":"Dantu","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai, Maharashtra 400076, India"},{"name":"Department of Computer Science-Synthetic Biology Theme, Brunel University London, Uxbridge UB83PH, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Devika M.","family":"Sardesai","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Savitribai Phule Pune University (Formerly University of Pune), Ganeshkhind, Pune, Maharashtra 411007, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Parnika","family":"Bhatia","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Savitribai Phule Pune University (Formerly University of Pune), Ganeshkhind, Pune, Maharashtra 411007, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikita","family":"Malik","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai, Maharashtra 400076, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jhankar D.","family":"Acharya","sequence":"additional","affiliation":[{"name":"Department of Zoology, Savitribai Phule Pune University (Formerly University of Pune), Ganeshkhind, Pune, Maharashtra 411007, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soham","family":"Sarkar","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai, Maharashtra 400076, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soumadwip","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai, Maharashtra 400076, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0785-1508","authenticated-orcid":false,"given":"Rajarshi","family":"Chakrabarti","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai, Maharashtra 400076, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shilpy","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Savitribai Phule Pune University (Formerly University of Pune), Ganeshkhind, Pune, Maharashtra 411007, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5061-8162","authenticated-orcid":false,"given":"Ashutosh","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai, Maharashtra 400076, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2019,3,15]]},"reference":[{"key":"2021112217562992800_BCJ-2018-0820C1","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1146\/annurev.biochem.75.101304.123901","article-title":"Protein misfolding, functional amyloid, and human disease","volume":"75","year":"2006","journal-title":"Annu. 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