Department of Psychology, The Third People's Hospital of Ganzhou City, Ganzhou, 341000, Jiangxi, China.
Department of Neurology, Xinfeng County People's Hospital, Ganzhou, 341000, Jiangxi, China.
Sci Rep. 2023 Apr 5;13(1):5595. doi: 10.1038/s41598-022-21298-x.
Imperatorin, an active ingredient extracted from Angelica and Qianghuo, has anti-inflammatory, anti-oxidative stress damage, blocking calcium channels, and other properties. Our preliminary findings revealed the protective role of imperatorin in the treatment of vascular dementia, we further explored the underlying mechanisms concerning the neuroprotection function of imperatorin in vascular dementia. The cobalt chloride (CCl2)-induced chemical hypoxia and hypoglycemia of hippocampal neuronal cells was applied as in vitro vascular dementia model. Primary neuronal cells was isolated from the hippocampal tissue of SD suckling rats within 24 h of birth. Hippocampal neurons were identified by immunofluorescence staining of microtubule-associated protein 2. Silencing or overexpression of Nrf2 was conducted by transfection of corresponding plasmids in hippocampal neuronal cells. Cell viability was detected by MTT assay to determine the optimal modeling concentration of CoCl2. Mitochondrial membrane potential, intracellular reactive oxygen species and apoptosis rate was measured by flow cytometry. The expression of anti-oxidative proteins was detected by quantitative real-time PCR and western blot, including Nrf2, NQO-1 and HO-1. Nrf2 nuclear translocation was detected using laser confocal microscopy. The modeling concentration of CoCl2 was 150umol/l, and the best interventional concentration of imperatorin was 7.5umol/l. Significantly, imperatorin facilitated the nuclear localization of Nrf2, promoted the expressions of Nrf2, NQO-1, and HO-1 relative to the model-control group. Moreover, imperatorin reduced the mitochondrial membrane potential and ameliorated CoCl2-induced hypoxic apoptosis in hippocampal neurons. On the contrary, silencing Nrf2 completely abrogated the protective effects of imperatorin. Imperatorin might be an effective drug for preventing and treating vascular dementia.
欧前胡素是从当归和羌活中提取的一种活性成分，具有抗炎、抗氧化应激损伤、阻断钙通道等特性。我们的初步研究结果表明，欧前胡素在治疗血管性痴呆方面具有保护作用，我们进一步探讨了其在血管性痴呆中神经保护作用的潜在机制。本研究采用氯化钴（CCl2）诱导的海马神经元细胞化学缺氧和低血糖模拟体外血管性痴呆模型。原代神经元细胞取自出生后 24 小时内 SD 乳鼠海马组织，通过微管相关蛋白 2 免疫荧光染色鉴定海马神经元。通过转染相应质粒沉默或过表达 Nrf2。用 MTT 法检测细胞活力，确定 CoCl2 的最佳建模浓度。用流式细胞术检测线粒体膜电位、细胞内活性氧和细胞凋亡率。用实时定量 PCR 和 Western blot 检测抗氧化蛋白的表达，包括 Nrf2、NQO-1 和 HO-1。用激光共聚焦显微镜检测 Nrf2 的核转位。CoCl2 的建模浓度为 150μmol/L，欧前胡素的最佳干预浓度为 7.5μmol/L。结果表明，欧前胡素促进 Nrf2 的核转位，与模型对照组相比，促进 Nrf2、NQO-1 和 HO-1 的表达。此外，欧前胡素降低了线粒体膜电位，改善了 CoCl2 诱导的海马神经元缺氧凋亡。相反，沉默 Nrf2 完全阻断了欧前胡素的保护作用。欧前胡素可能是一种预防和治疗血管性痴呆的有效药物。
