Artemisinin alleviates ischemic stroke injury and promotes neurogenesis through PPARγ-mediated M2 polarization of microglia

作者：Lin Li, Huiqin Hu, Weifeng Jiang, Shihui Mao, Zheng Yang, Ting Lan, Xiaowei Hu, Yan Fang, Liang Xu, Jiadong Xu, Yan Yang, Weiru Jiang, Lisheng Chu · 发表于：Phytomedicine · 年份：2025 · DOI：10.1016/j.phymed.2025.156769 · 被引用次数：12 · 研究领域：Neuroinflammation and Neurodegeneration Mechanisms、Neurogenesis and neuroplasticity mechanisms、Neurological Disease Mechanisms and Treatments

BACKGROUND: Ischemic stroke (IS) remains a challenge in clinical treatment due to limited therapeutic options. While artemisinin (ART), an antimalarial drug, shields against acute IS via anti-inflammatory, antioxidant, and anti-apoptotic properties, the long-term benefits and specific underlying mechanisms have not been fully elucidated. Here, we investigate whether ART ameliorates IS injury and promotes neurogenesis by activating the peroxisome proliferator-activated receptor γ (PPARγ)-dependent M2 microglial polarization. METHODS: The experimental models included transient middle cerebral artery occlusion/reperfusion (MCAO/R) in rats and oxygen-glucose deprivation/reoxygenation (OGD/R) in primary microglial cultures to simulate IS. The therapeutic effects of ART were evaluated by neurological functions and infarct volume. PPARγ inhibitor T0070907 (T007) was intraperitoneally injected 24 h following MCAO/R at a dose of 2 mg/kg in vivo and a concentration of 10 μM for 30 min before OGD in vitro. We utilized real-time quantitative polymerase chain reaction (RT-qPCR) along with Western blot analyses to detect the microglia markers and PPARγ. The proliferation and differentiation of neural stem cells (NSCs) both in vivo and in vitro were assessed via immunofluorescence labeling. The neurogenic potential of ART-treated microglia was investigated by conditioned medium. The levels of brain-derived growth factor (BDNF) and insulin-like growth factor-1 (IGF-1) in microglia were measu...