Aspalathin Protects Insulin-Producing β Cells against Glucotoxicity and Oxidative Stress-Induced Cell Death

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.