PMID- 37952497 OWN - NLM STAT- MEDLINE DCOM- 20231216 LR - 20240207 IS - 1873-4200 (Electronic) IS - 0301-4622 (Print) IS - 0301-4622 (Linking) VI - 304 DP - 2024 Jan TI - Pomegranate peel, chokeberry leaves and Ironwort extract as novel natural inhibitors of amylin aggregation and cellular toxicity in pancreatic beta cells. PG - 107130 LID - S0301-4622(23)00181-3 [pii] LID - 10.1016/j.bpc.2023.107130 [doi] AB - Impeding or reducing human amylin aggregation and/or its toxicity can be key to preventing pancreatic islet amyloidosis and beta-cell loss in patients with Type 2 Diabetes Mellitus (T2DM). Here, Punica granatum (pomegranate) peel, Sideritis raeseri (ironwort) and Aronia melanocarpa (chokeberry) leaf extracts, were tested for their novel anti-aggregative and antitoxic properties in human amylin (hIAPP) treated rat pancreatic insulinoma (INS) cells. The protein aggregation (Th-T) assay revealed an inhibitory trend of all three plant extracts against amylin aggregates. In agreement with this finding, pomegranate peel and ironwort extracts effectively prevented the transition of hIAPP from disordered, random coil structures into aggregation prone beta-sheet enriched molecular assemblies, revealed by CD spectroscopy. Consistent with their anti-aggregative action, all three extracts prevented, to various degrees, reactive oxygen species (ROS) accumulation, mitochondrial stress, and, ultimately, apoptosis of INS cells. Collectively, the results from this study demonstrate effectiveness of natural products to halt hIAPP aggregation, redox stress, and toxicity, which could be exploited as novel therapeutics against amylin-derived islet amyloidosis and beta-cell stress in T2DM. CI - Copyright (c) 2023. Published by Elsevier B.V. FAU - Rishisree, Achanta AU - Rishisree A AD - Department of Biological Sciences, The George Washington University, Washington, DC 20052, USA. FAU - Mallory, Brayer AU - Mallory B AD - Department of Biological Sciences, The George Washington University, Washington, DC 20052, USA. FAU - Elena, Karnaukhova AU - Elena K AD - Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA. FAU - Teodora, Jankovic AU - Teodora J AD - Institute for Medicinal Plant Research "Dr. Josif Pancic", 11000 Belgrade, Serbia. FAU - Gordana, Zdunic AU - Gordana Z AD - Institute for Medicinal Plant Research "Dr. Josif Pancic", 11000 Belgrade, Serbia. FAU - Katarina, Savikin AU - Katarina S AD - Institute for Medicinal Plant Research "Dr. Josif Pancic", 11000 Belgrade, Serbia. FAU - Aleksandar, Jeremic AU - Aleksandar J AD - Department of Biological Sciences, The George Washington University, Washington, DC 20052, USA. Electronic address: jerema@gwu.edu. LA - eng GR - R01 DK091845/DK/NIDDK NIH HHS/United States GR - R01 EB027648/EB/NIBIB NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20231031 PL - Netherlands TA - Biophys Chem JT - Biophysical chemistry JID - 0403171 RN - 0 (Islet Amyloid Polypeptide) RN - 0 (Plant Extracts) SB - IM MH - Humans MH - Rats MH - Animals MH - Islet Amyloid Polypeptide/chemistry MH - *Diabetes Mellitus, Type 2/metabolism MH - *Sideritis/metabolism MH - *Insulin-Secreting Cells MH - *Pomegranate/metabolism MH - *Amyloidosis/metabolism MH - Plant Extracts/pharmacology PMC - PMC10841580 MID - NIHMS1944534 OTO - NOTNLM OT - Amylin OT - Mitochondrial stress OT - Plant extracts OT - Protein aggregation OT - Proteotoxicity OT - Reactive oxygen species COIS- Declaration of Competing Interest Aleksandar Jeremic reports financial support was provided by National Institute of Health. EDAT- 2023/11/13 00:42 MHDA- 2023/12/17 09:44 PMCR- 2025/01/01 CRDT- 2023/11/12 18:12 PHST- 2023/07/01 00:00 [received] PHST- 2023/10/27 00:00 [revised] PHST- 2023/10/28 00:00 [accepted] PHST- 2025/01/01 00:00 [pmc-release] PHST- 2023/12/17 09:44 [medline] PHST- 2023/11/13 00:42 [pubmed] PHST- 2023/11/12 18:12 [entrez] AID - S0301-4622(23)00181-3 [pii] AID - 10.1016/j.bpc.2023.107130 [doi] PST - ppublish SO - Biophys Chem. 2024 Jan;304:107130. doi: 10.1016/j.bpc.2023.107130. Epub 2023 Oct 31.