Abstract
Lithospermic acid B (LAB) has been reported to protect OLETF rats, an established type 2 diabetic animal model, from the development of diabetes-related vascular complications. We investigated whether magnesium lithospermate B (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 and 100. U/mL IL-1β-induced INS-1 cell death. LAB significantly alleviated cytokine-induced phosphorylations of p38 and 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 Nrf2-HO (heme-oxigenase)-1 and 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. Our results suggest that the cytoprotective effects of LAB on pancreatic β-cells are related with both alleviating apoptotic pathways and activating anti-apoptotic pathways of Nrf2-HO-1 and Sirt1.
Original language | English |
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Pages (from-to) | 47-54 |
Number of pages | 8 |
Journal | Toxicology and Applied Pharmacology |
Volume | 252 |
Issue number | 1 |
DOIs | |
Publication status | Published - 2011 Apr 1 |
Bibliographical note
Funding Information:This study was supported by grants from the Korea Research Foundation Grant ( 7-2008-0398 ) from Korean Government and the Korean Diabetes Association (2010).
All Science Journal Classification (ASJC) codes
- Toxicology
- Pharmacology