The aim of this study was to investigate the neuroprotective effects of gastrodin (GAS), one of the major bioactive components of Gastrodia elata Blume (Tian Ma), against amyloid β (Aβ) (1-42)-induced neurotoxicity in primary neural progenitor cells (NPCs). We found that pretreatment with GAS not only prevents a loss in cell viability following treatment with Aβ (1-42) but also counteracts Aβ (1-42)-triggered release of pro-inflammatory cytokines and nitric oxide (NO) in a dose-dependent manner. Additionally, GAS was able to attenuate Aβ (1-42)-induced apoptosis in NPCs, evidenced by the decreased percentage of apoptotic cells and altered expression of apoptosis-related proteins in response to GAS pretreatment prior to Aβ (1-42) exposure. Furthermore, in Aβ (1-42)-injected C57BL/6 mice, we found that systemic administration of GAS could improve hippocampal neurogenesis, manifested by the increased number of SOX-2 and doublecortin (DCX)-positive cells in the DG area. Mechanistic studies revealed that in NPCs, GAS could reverse the Aβ (1-42)-induced increase in phosphorylation of MEK-1/2, extracellular signal-regulated kinases (ERK), and c-Jun N-terminal kinase (JNK). When combining GAS with the MEK inhibitor U0126 or the JNK inhibitor SP600125, we observed a synergistic effect against Aβ (1-42)-induced reduction in cell viability of NPCs. Taken together, these results show the efficacy and underlying mechanism of GAS against amyloid β (1-42)-induced neurotoxicity and provide substantial insight into the potential merits of GAS for its clinical application in the treatment of Alzheimer's disease.
Keywords: Amyloid β (1–42); Gastrodin; Hippocampal neurogenesis; Neural progenitor cells.