Gao Yuxiao, Wang Jingjing, Zhang Cong, Wang Huan, Wang Bin, Zhang Xiangjian
Department of Neurology, Second Hospital of Hebei Medical University, No. 215, Hepingxi Road, Shijiazhuang, 050000, Hebei, PR China
Hebei Key Laboratory of Vascular Homeostasis and Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, No. 215, Hepingxi Road, Shijiazhuang, 050000, Hebei, PR China
Phytomedicine. 2025 Jul 25;143:156881. doi: 10.1016/j.phymed.2025.156881. Epub 2025 May 23.
Ischemic stroke remains a life-threatening condition with limited therapeutic options. Microglia-mediated neuroinflammation critically exacerbates acute ischemic injury. The active compound poliumoside (Pol) in Callicarpa kwangtungensis Chun exhibits significant anti-inflammatory effects. The therapeutic potential of Pol for ischemic stroke remains unknown and promising.
The current study aimed to investigate the effect of Pol on acute ischemic stroke in mice, and to elucidate the underlying mechanisms.
Ischemic stroke mice model was induced by transient middle cerebral artery occlusion model (tMCAO). Pol was administered by intraperitoneal injection after stroke. Neurological deficits were monitored up to 3 days after stroke. Microglial polarization, and microglia-associated inflammatory cytokines and blood-brain barrier (BBB) integrity were detected in the peri‑infarct cortex at day 1 after stroke. RNA-seq analysis was performed to identify potential pathways recruited by Pol. Primary cortical neuron, BV2 microglia cell lines and mouse brain microvascular endothelial cell lines(bEnd.3) were employed to explore the underlying mechanism in vitro.
Compared with the tMCAO group, Pol significantly alleviated neurological deficits and reduced infarct size in mice. In vitro and in vivo experiments demonstrated that Pol regulates microglial polarization, down-regulates inflammatory factor levels (IL-6 and TNF-α), and attenuates inflammation-mediated BBB damage while maintaining tight junction proteins expression (ZO-1, claudin-5, occludin). Through investigation of the underlying mechanism combined with RNA-seq analysis and experimental results, we established that Pol down-regulated the JAK/STAT3 pathway both in vitro and in vivo, which was corroborated by the use of the JAK inhibitor tofacitinib.
Pol regulates microglial polarization in ischemic stroke by down-regulating JAK/STAT3 signaling pathway, alleviating the microglia-mediated inflammatory response and the destruction of blood-brain barrier.
缺血性中风仍然是一种危及生命的疾病，治疗选择有限。小胶质细胞介导的神经炎症严重加剧急性缺血性损伤。广东紫珠中的活性化合物紫珠苷（Pol）具有显著的抗炎作用。Pol对缺血性中风的治疗潜力尚不清楚，但很有前景。
本研究旨在探讨Pol对小鼠急性缺血性中风的影响，并阐明其潜在机制。
采用短暂性大脑中动脉闭塞模型（tMCAO）诱导缺血性中风小鼠模型。中风后通过腹腔注射给予Pol。在中风后3天内监测神经功能缺损。在中风后第1天，检测梗死灶周围皮质中的小胶质细胞极化、小胶质细胞相关炎性细胞因子和血脑屏障（BBB）完整性。进行RNA测序分析以确定Pol激活的潜在途径。采用原代皮质神经元、BV2小胶质细胞系和小鼠脑微血管内皮细胞系（bEnd.3）在体外探索潜在机制。
与tMCAO组相比，Pol显著减轻小鼠神经功能缺损并减小梗死体积。体外和体内实验表明，Pol调节小胶质细胞极化，下调炎性因子水平（IL-6和TNF-α），减轻炎症介导的血脑屏障损伤，同时维持紧密连接蛋白表达（ZO-1、claudin-5、occludin）。通过结合RNA测序分析和实验结果研究潜在机制，我们发现Pol在体外和体内均下调JAK/STAT3途径，使用JAK抑制剂托法替布证实了这一点。
Pol通过下调JAK/STAT3信号通路调节缺血性中风中的小胶质细胞极化，减轻小胶质细胞介导的炎症反应和血脑屏障破坏。
