Lithospermic acid B (LAB) protects pancreatic beta cells from cytokine-induced apoptosis by both alleviating apoptotic pathways and activating anti-apoptotic pathways of Nrf2\2013HO-1 and Sirt1

Abstract

Lithospermic acid B (LAB) has been reported to protect Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an established type 2 diabetic animal model, from the development of diabetes-related vascular complications.We investigated whether magnesium LAB has a protective role under cytokine-induced apoptosis in INS-1 cells in vitro and whether it slows the development of diabetes in OLETF rats in vivo.Pretreatment with 50 μM LAB significantly reduced the 1000 U/mL INF-γ plus 100 U/mL IL-1β-induced INS-1 cell death. LAB significantly alleviated cytokine-induced phosphorylations of p38 and c-Jun N-terminal kinase (JNK) in accordance with a decrease in cleaved caspase-3 activity in beta cells. LAB also protected against the cytokine-induced caspase-3 apoptotic pathway via significant activation of nuclear factor E2-related factor 2 (Nrf2) - heme-oxigenase-1 (HO-1) and silent information regulator T1 (Sirt1) expression. OLETF rats treated with 40 mg/kg/day LAB showed a significant improvement in glucose tolerance compared to untreated OLETF control rats in vivo.This study suggested that the protective effects of LAB on pancreatic beta cells were related with both alleviating apoptotic pathways and activating anti-apoptotic pathways of Nrf2–HO-1 and Sirt1