title: Lithospermic acid B protects β-cells from cytokine-induced apoptosis by alleviating apoptotic pathways and activating anti-apoptotic pathways of Nrf2-HO-1 and Sirt1.
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-oxygenase)-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.
authors.affiliation: Department of Internal Medicine, Yonsei University College of Medicine, 134 Shinchon-Dong Seodaemun-Gu, Seoul 120-752, Republic of Korea.
authors.forename: Byung-Wan
authors.initials: BW
authors.lastname: Lee
authors.forename: Sung Wan
authors.initials: SW
authors.lastname: Chun
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Yongho
authors.initials: Y
authors.lastname: Lee
authors.forename: Eun Seok
authors.initials: ES
authors.lastname: Kang
authors.forename: Bong-Soo
authors.initials: BS
authors.lastname: Cha
authors.forename: Hyun Chul
authors.initials: HC
authors.lastname: Lee
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001572:Benzofurans / Q000494:pharmacology*; D002478:Cells, Cultured; D016207:Cytokines / Q000633:toxicity*; D053630:Depsides / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000517:prevention & control; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D020011:Protective Agents / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D020334:Rats, Inbred OLETF; D020318:Rats, Long-Evans; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D056564:Sirtuin 1 / Q000378:metabolism*
chemical_list: D001572:Benzofurans; D016207:Cytokines; D053630:Depsides; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D020011:Protective Agents; C076944:salvianolic acid B; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; C488368:Sirt1 protein, rat; D056564:Sirtuin 1