School of Medicine, Hangzhou City University, Hangzhou, China.
Department of Neurology, Zhejiang Provincial Hospital of Traditional Chinese Medicine, Hangzhou, China.
Chem Biol Drug Des. 2024 Jan;103(1):e14354. doi: 10.1111/cbdd.14354. Epub 2023 Sep 24.
Jasminoidin (JAS) can alleviate ischemic stroke (IS) injury, but its molecular mechanism remains undefined. The polarization of microglia affects IS process. This research is powered to probe whether the molecular mechanism of JAS for IS treatment is coupled with microglia polarization. IS modeling in mice was accomplished by middle cerebral artery occlusion (MCAO) and model mice were injected with 25 and 50 mg/mL JAS, followed by determination of infarct volume, brain water content, and histological changes in mouse brains. The microglia modeling was performed by 1-h oxygen-glucose deprivation and 24-h reoxygenation. Oxygen-glucose deprivation/reoxygenation (OGD/R)-induced microglia were treated with JAS and transfected with Per-Arnt-Sim kinase (PASK)-overexpressing plasmid, subsequent to which cell viability and lactate dehydrogenase (LDH) level were determined. The mRNA or protein expressions of examined genes in microglia and brain tissues were detected by quantitative real-time polymerase chain reaction or western blot. MCAO-induced massive infarction, edema, and injury in mouse brain tissues, upregulated interleukin-1 beta (IL-1β), FcγRIIB (CD32), tumor necrosis factor alpha (TNF-α), PASK, p-eukaryotic elongation factor 1A1 (EEF1A1), and p-EEF1A1/EEF1A1 levels, but downregulated mannose receptor 1 (CD206), arginase-1 (Arg-1) and interleukin-10 (IL-10), and EEF1A1 expressions, which was reversed by JAS. OGD/R treatment decreased microglial viability as well as expressions of CD206, Arg-1, IL-10, and EEF1A1, yet increased cytotoxicity and levels of IL-1β, CD32, TNF-α, PASK, p-EEF1A1, and p-EEF1A1/EEF1A1, which was reversed by JAS. PASK overexpression reversed the effects of JAS on microglia. JAS reduces IS injury by regulating microglia polarization via PASK-EEF1A1 axis.
栀子黄素(JAS)可减轻缺血性脑卒中(IS)损伤,但具体分子机制尚不清楚。小胶质细胞极化影响 IS 进程。本研究旨在探讨 JAS 治疗 IS 的分子机制是否与小胶质细胞极化有关。通过大脑中动脉阻塞(MCAO)建立 IS 小鼠模型,对 25 和 50mg/mL JAS 进行注射,检测小鼠脑梗死体积、脑含水量和组织学变化。通过 1 小时氧葡萄糖剥夺和 24 小时复氧建立小胶质细胞模型,用 JAS 处理氧葡萄糖剥夺/复氧(OGD/R)诱导的小胶质细胞,并转染过表达 Per-Arnt-Sim 激酶(PASK)的质粒,检测细胞活力和乳酸脱氢酶(LDH)水平。通过定量实时聚合酶链反应或蛋白质印迹检测小胶质细胞和脑组织中受检基因的 mRNA 或蛋白表达。MCAO 诱导的大量脑梗死、水肿和损伤,上调白细胞介素-1β(IL-1β)、FcγRIIB(CD32)、肿瘤坏死因子-α(TNF-α)、PASK、磷酸化真核延伸因子 1A1(p-eukaryotic elongation factor 1A1)和 p-eukaryotic elongation factor 1A1/elongation factor 1A1(p-EEF1A1/EEF1A1)水平,但下调甘露糖受体 1(CD206)、精氨酸酶-1(Arg-1)和白细胞介素-10(IL-10)和 EEF1A1 表达,JAS 可逆转这一趋势。OGD/R 处理降低小胶质细胞活力和 CD206、Arg-1、IL-10 和 EEF1A1 的表达,增加细胞毒性和 IL-1β、CD32、TNF-α、PASK、p-EEF1A1 和 p-EEF1A1/EEF1A1 水平,JAS 可逆转这一趋势。过表达 PASK 逆转了 JAS 对小胶质细胞的作用。JAS 通过 PASK-EEF1A1 轴调节小胶质细胞极化来减轻 IS 损伤。