Poster Presenter

Lithospermic Acid B Protects Beta-Cells From Cytokine-Induced Apoptosis By Hemo Oxygenase-1 Induction
Eun Jig Lee, Hyun Chul Lee, Sung Wan Chun, Soo Hyun Kim, Byung-Wan Lee, ManKil Jung.
South Korea

Objective: Lithospermic acid B (LAB), a potent antioxidant for diabetic vasculopathy, was reported to have anti-apoptotic effects. In this study, we investigated whether LAB has a protective role under cytokine-induced apoptosis in INS-1 cells and ameliorates the development of diabetes in OLETF rats

Methods: INS-1 cells were incubated with 1000 U/ml IFN-Y and 100 U/ml IL-1B in the absence or presence of 50 uM LAB. Cell viability and apoptosis were evaluated by MTT and caspase-3 expression, respectively. Activation of apoptotic pathway was determined by PI3 kinase, MAP kinase (p42/44, p38, and c-JNK) and NFkb, downstream apoptotic signaling by activation of p53 and caspase-3. Activation of antiapoptotic pathway was also determined by Sirt1-Nrf2-HO-1 pathway. The inhibitor and siRNA of HO-1 were used to investigate the role of HO-1 antiapoptotic pathway.

LAB (20 mg/kg) was given orally once daily to 10-week-old male OLETF rats for 60 weeks. At 60 weeks of age, an oral glucose tolerance test, insulin sensitivity test, TUNEL assay and histologic examination were performed.

Results: Of the cytokine-induced apoptotic signals, LAB alleviated cytokine-induced p38 and c-JNK activation. LAB induced PI3-kinase-dependent Akt phosphorylation in INS-1 cells. The major protective effect of LAB on cytokine-induced INS-1 apoptosis was induction of Sirt1-Nrf2-HO-1 antiapoptotic pathway which were inhibited and knockdown by ZnPP and HO-1 siRNA
LAB treatment decreased beta-cell apoptosis, preserved beta-cell mass and improved glucose tolerance in OLETF rats.

Conclusion: LAB has potential cytoprotective effects on bata-cells under cytokine-induced apoptosis as in diabetes by its Sirt1-Nrf2-HO-1 antioxidant properties. Although these findings suggest that LAB has beneficial effects on the beta-cell protection and prevention of T2D through the activation of HO-1, further clinical studies are needed to evaluate the use of LAB for T2D treatment.