Lithospermic acid B protects beta-cells from cytokine-induced apoptosis by alleviating apoptotic pathways and activating anti-apoptotic pathways of Nrf2-HO-1 and Sirt1

Byung Wan Lee, Sung Wan Chun, Soo Hyun Kim, Yongho Lee, Eun Seok Kang, Bong Soo Cha, Hyun Chul Lee

Research output: Contribution to journalArticle

31 Citations (Scopus)

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 languageEnglish
Pages (from-to)47-54
Number of pages8
JournalToxicology and Applied Pharmacology
Volume252
Issue number1
DOIs
Publication statusPublished - 2011 Apr 1

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Pharmacology

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