Astaxanthin inhibits H₂O₂-mediated apoptotic cell death in mouse neural progenitor cells via modulation of p38 and MEK signaling pathways

In the present study, the neuroprotective effects of astaxanthin on H ₂O₂-mediated apoptotic cell death, using cultured mouse neural progenitor cells (mNPCs), were investigated. To cause apoptotic cell death, mNPCs were pretreated with astaxanthin for 8 h and followed by treatment of 0.3 mM H₂O₂. Pretreatment of mNPCs with astaxanthin significantly inhibited H₂O₂-mediated apoptosis and induced cell growth in a dose-dependent manner. In Western blot analysis, astaxanthin-pretreated cells showed the activation of p-Akt, p-MEK, p-ERK, and Bcl-2, and the reduction of p-P38, p-SAPK/JNK, Bax, p-GSK3b, cytochrome c, caspase-3, and PARP. Because H₂O₂ triggers caspases activation, this study examined whether astaxanthin can inhibit caspases activation in H₂O₂-treated mNPCs. After H ₂O₂ treatment, caspases activities were prominently increased, but astaxanthin pretreatment significantly inhibited H ₂O₂-mediated caspases activation. Astaxanthin pretreatment also significantly recovered the ATP production ability of H₂O ₂-treated cells. These findings indicate that astaxanthin inhibits H₂O₂-mediated apoptotic features in mNPCs. Inhibition assays with SB203580 (10 μM, a specific inhibitor of p38) and PD98059 (10 μM, a specific inhibitor of MEK) clearly showed that astaxanthin can inhibit H₂O₂-mediated apoptotic death via modulation of p38 and MEK signaling pathways.