PMID- 32012427 OWN - NLM STAT- MEDLINE DCOM- 20210621 LR - 20210621 IS - 1613-4133 (Electronic) IS - 1613-4125 (Linking) VI - 64 IP - 8 DP - 2020 Apr TI - Aspalathin Protects Insulin-Producing beta Cells against Glucotoxicity and Oxidative Stress-Induced Cell Death. PG - e1901009 LID - 10.1002/mnfr.201901009 [doi] AB - SCOPE: Aspalathin, the main polyphenolic phytochemical of rooibos (Aspalathus linearis), has been attributed with health promoting properties, including a glucose lowering effect that can prove interesting for application as nutraceutical or therapeutic in (pre-)diabetics. Preservation of beta cell mass in the pancreas is considered a key issue for diabetes prevention or treatment, therefore the aim is to investigate whether aspalathin also has beta cell cytoprotective potential. METHODS AND RESULTS: Rat pancreatic islets and the beta cell line Insulinoma 1E (INS1E) are studied in vitro after exposure to various cytotoxic agents, namely streptozotocin (STZ), hydrogen peroxide, or chronic high glucose. The effect of aspalathin on cell survival and apoptosis is studied. Expression of relevant cytoprotective genes is analyzed by qRT-PCR and proteins by Western blot. Aspalathin is found to protect beta cells against cytotoxicity and apoptosis. This is associated with increased translocation of nuclear factor erythroid 2-related factor 2 (NRF2) and expression of its antioxidant target genes heme oxygenase 1 (Hmox1), NAD(P)H quinone dehydrogenase 1 (Nqo-1), and superoxide dismutase 1 (Sod1). CONCLUSION: It is proposed that aspalathin protects beta cells against glucotoxicity and oxidative stress by increasing the expression of NRF2-regulated antioxidant enzymes. This indicates that aspalathin is an interesting beta cell cytoprotectant. CI - (c) 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. FAU - Moens, Celine AU - Moens C AUID- ORCID: 0000-0002-4125-4950 AD - Cell Differentiation Lab, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Jette, Brussels, Belgium. FAU - Bensellam, Mohammed AU - Bensellam M AD - Universite Catholique de Louvain, Institut de Recherche Experimentale et Clinique, Pole d'Endocrinologie, Diabete et Nutrition, Avenue Hippocrate 55, 1200 Brussels, Brussels, Belgium. FAU - Himpe, Eddy AU - Himpe E AD - Cell Differentiation Lab, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Jette, Brussels, Belgium. FAU - Muller, Christo J F AU - Muller CJF AD - Biomedical Research and Innovation Platform, South African Medical Research Council, Francie van Zijl Drive, 7505, Western Cape, Tygerberg, South Africa. FAU - Jonas, Jean-Christophe AU - Jonas JC AD - Universite Catholique de Louvain, Institut de Recherche Experimentale et Clinique, Pole d'Endocrinologie, Diabete et Nutrition, Avenue Hippocrate 55, 1200 Brussels, Brussels, Belgium. FAU - Bouwens, Luc AU - Bouwens L AD - Cell Differentiation Lab, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Jette, Brussels, Belgium. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200212 PL - Germany TA - Mol Nutr Food Res JT - Molecular nutrition & food research JID - 101231818 RN - 0 (Chalcones) RN - 0 (Protective Agents) RN - 0 (aspalathin) RN - 5W494URQ81 (Streptozocin) RN - BBX060AN9V (Hydrogen Peroxide) RN - EC 1.14.14.18 (Heme Oxygenase (Decyclizing)) RN - EC 1.14.14.18 (Hmox1 protein, rat) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Animals MH - Cell Death/drug effects MH - Cells, Cultured MH - Chalcones/administration & dosage/*pharmacology MH - Dose-Response Relationship, Drug MH - Gene Expression Regulation/drug effects MH - Glucose/toxicity MH - Heme Oxygenase (Decyclizing)/genetics MH - Hydrogen Peroxide/toxicity MH - Insulin-Secreting Cells/*drug effects MH - Male MH - Oxidative Stress/*drug effects/genetics MH - Protective Agents/*pharmacology MH - Rats, Wistar MH - Streptozocin/toxicity OTO - NOTNLM OT - apoptosis OT - aspalathin OT - diabetes OT - glucotoxicity OT - oxidative stress EDAT- 2020/02/06 06:00 MHDA- 2021/06/22 06:00 CRDT- 2020/02/04 06:00 PHST- 2019/09/23 00:00 [received] PHST- 2019/12/23 00:00 [revised] PHST- 2020/02/06 06:00 [pubmed] PHST- 2021/06/22 06:00 [medline] PHST- 2020/02/04 06:00 [entrez] AID - 10.1002/mnfr.201901009 [doi] PST - ppublish SO - Mol Nutr Food Res. 2020 Apr;64(8):e1901009. doi: 10.1002/mnfr.201901009. Epub 2020 Feb 12.