Astragaloside IV (AS-IV), a natural product derived from Radix Astragali (Astragalus membranaceus), is beneficial for the treatment of Alzheimer’s disease (AD), but the mechanisms underlying this benefit are not completely understood. Peroxisome proliferator-activated receptor gamma (PPARγ) and brain-derived neurotrophic factor (BDNF) are potential therapeutic targets for AD. In this study, we found that amyloid β protein fragment 1–42 oligomers (AβO) suppressed BDNF and PPARγ expression, and inhibited tyrosine receptor kinase B (TrkB) phosphorylation in cultured hippocampal neurons; these changes were ameliorated by treatment with AS-IV. Inhibition of PPARγ by genetic and pharmacological methods also blocked the effect of AS-IV on BDNF expression in AβO-treated cells. Importantly, exogenous BDNF protected against neurotoxicity and apoptosis induced by AβO, whereas inhibition of PPARγ reversed protective effects of AS-IV against these outcomes. In vivo data further revealed that AS-IV improved AβO-induced memory impairment and reduced apoptosis of hippocampal neurons. Moreover, AS-IV suppressed the AβO-induced reduction in BDNF by promoting PPARγ activation in the hippocampus. Taken together, these results indicate that AS-IV prevents AβO-induced memory impairment and hippocampal neuronal apoptosis, probably by promoting the PPARγ/BDNF signaling pathway.

黄芪甲苷（AS-IV），一种来源于黄芪（Astragalus membranaceus）的天然产物)，有利于治疗阿尔茨海默病 (AD)，但尚未完全了解这种益处的潜在机制。过氧化物酶体增殖物激活受体 γ (PPARγ) 和脑源性神经营养因子 (BDNF) 是 AD 的潜在治疗靶点。在本研究中，我们发现淀粉样蛋白 β 蛋白片段 1-42 寡聚体 (AβO) 抑制了 BDNF 和 PPARγ 的表达，并抑制了培养的海马神经元中的酪氨酸受体激酶 B (TrkB) 磷酸化；这些变化通过 AS-IV 治疗得到改善。通过遗传和药理学方法抑制 PPARγ 也阻断了 AS-IV 对 AβO 处理细胞中 BDNF 表达的影响。重要的是，外源性 BDNF 可防止 AβO 诱导的神经毒性和细胞凋亡，体内数据进一步显示，AS-IV 改善了 AβO 诱导的记忆障碍并减少了海马神经元的凋亡。此外，AS-IV 通过促进海马中 PPARγ 的激活来抑制 AβO 诱导的 BDNF 减少。总之，这些结果表明 AS-IV 可能通过促进 PPARγ/BDNF 信号通路来预防 AβO 诱导的记忆障碍和海马神经元凋亡。