Pseudoginsenoside-F11 (PF11), an ocotillol-type saponin, has neuroprotective effects on permanent and transient cerebral ischemia in rats by alleviating autophagic/lysosomal defects and repressing calcium overload, respectively. Ischemic stroke triggers peripheral innate immune cells, mainly neutrophils and macrophages, to infiltrate the damaged brain. The polarization of neutrophils and macrophages after cerebral ischemia is essential for post-stroke damage/recovery. However, it remains elusive whether PF11 ameliorates ischemic neuron injury by regulating the polarization of neutrophils and macrophages. The present study demonstrated for the first time that conditioned media from ischemic neurons induced neutrophils and macrophages to polarize into N1 and M1 phenotypes, respectively. Furthermore, PF11 (30, 100 μM) inhibited the induction of N1 neutrophils by conditioned media from oxygen glucose deprivation/re-oxygenation (OGD/R)-induced ischemic neurons and promoted the polarization of neutrophils to N2 phenotypes. In addition, PF11 (100 μM) attenuated the exacerbation of N1 neutrophils and facilitated the protection of N2 neutrophils on OGD/R-induced neuronal damage. Similarly, PF11 (100 μM) inhibited the induction of M1 macrophages by conditioned media from ischemic neurons and facilitated the polarization of macrophages to M2 phenotypes. What's more, PF11 (100 μM) attenuated the aggravation of M1 macrophages and promoted the protection of M2 macrophages on OGD/R-induced primary neuron injury. In summary, the present study indicates that PF11 ameliorates ischemic neuron damage by regulating neutrophils and macrophages polarization, suggesting that neutrophils and macrophages may be promising targets for the treatment of cerebral ischemia.

蛇毒皂苷Pseudoginsenoside-F11（PF11）通过减轻自噬/溶酶体缺陷和抑制钙超载，对大鼠永久性和短暂性脑缺血具有神经保护作用。缺血性中风触发外周先天免疫细胞（主要是中性粒细胞和巨噬细胞）浸润受损的大脑。脑缺血后中性粒细胞和巨噬细胞的极化对于中风后损伤/恢复至关重要。但是，PF11是否通过调节嗜中性粒细胞和巨噬细胞的极化来改善缺血性神经元损伤尚不清楚。本研究首次证明来自缺血神经元的条件培养基诱导嗜中性粒细胞和巨噬细胞分别极化为N1和M1表型。此外，PF11（30，100μM）可抑制条件培养基对氧葡萄糖剥夺/再充氧（OGD / R）诱导的缺血性神经元的诱导，并促进中性粒细胞极化至N2表型。此外，PF11（100μM）减轻了N1中性粒细胞的恶化，并促进了N2中性粒细胞对OGD / R诱导的神经元损伤的保护作用。同样，PF11（100μM）抑制缺血神经元条件培养基对M1巨噬细胞的诱导，并促进巨噬细胞向M2表型的极化。此外，PF11（100μM）减弱了M1巨噬细胞的恶化，并增强了M2巨噬细胞对OGD / R诱导的原发性神经元损伤的保护作用。总之，本研究表明PF11通过调节嗜中性粒细胞和巨噬细胞极化来改善缺血性神经元损伤，