Sun Qian, Zhang Xiangjian, Fan Jingyi, Zhang Lan, Ji Hui, Xue Jing, Zhang Cong, Chen Rong, Zhao Jing, Chen Junmin, Liu Xiaoxia, Song Degang
Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, China.
Hebei Collaborative Innovation Center for Cardio-Cerebrovascular Disease and Hebei Key Laboratory of Vascular Homeostasis, Shijiazhuang, Hebei, China.
Transl Neurosci. 2023 Jun 9;14(1):20220273. doi: 10.1515/tnsci-2022-0273. eCollection 2023 Jan 1.
Accumulated evidence indicates that geniposide exhibits neuroprotective effects in ischemic stroke. However, the potential targets of geniposide remain unclear.
We explore the potential targets of geniposide in ischemic stroke.
Adult male C57BL/6 mice were subjected to the middle cerebral artery occlusion (MCAO) model. Mice were randomly divided into five groups: Sham, MCAO, and geniposide-treated (i.p. twice daily for 3 days before MCAO) at doses of 25, 75, or 150 mg/kg. We first examined the neuroprotective effects of geniposide. Then, we further explored via biological information analysis and verified the underlying mechanism and .
In the current study, geniposide had no toxicity at concentrations of up to 150 mg/kg. Compared with the MCAO group, the 150 mg/kg group of geniposide significantly ( < 0.05) improved neurological deficits, brain edema (79.00 ± 0.57% vs 82.28 ± 0.53%), and infarct volume (45.10 ± 0.24% vs 54.73 ± 2.87%) at 24 h after MCAO. Biological information analysis showed that the protective effect was closely related to the inflammatory response. Geniposide suppressed interleukin-6 (IL-6) and inducible nitric oxide synthase (iNOS) expression in the brain homogenate, as measured by enzyme-linked immunosorbent assay (ELISA). Geniposide upregulated A20 and downregulated TNF receptor-associated factor-6 and nuclear factor kappa-B phosphorylation in the MCAO model and lipopolysaccharide-treated BV2 cells at 100 μM.
Geniposide exhibited a neuroprotective effect via attenuating inflammatory response, as indicated by biological information analysis, and experiments, which may provide a potential direction for the application of geniposide in the treatment of ischemic stroke.
越来越多的证据表明，京尼平苷在缺血性中风中具有神经保护作用。然而，京尼平苷的潜在靶点仍不清楚。
我们探索京尼平苷在缺血性中风中的潜在靶点。
成年雄性C57BL/6小鼠接受大脑中动脉闭塞（MCAO）模型。小鼠被随机分为五组：假手术组、MCAO组以及在MCAO前每天腹腔注射两次、剂量分别为25、75或150mg/kg的京尼平苷治疗组，持续3天。我们首先检测了京尼平苷的神经保护作用。然后，我们通过生物信息分析进一步探索并验证了其潜在机制。
在本研究中，京尼平苷在浓度高达150mg/kg时没有毒性。与MCAO组相比，150mg/kg京尼平苷组在MCAO后24小时显著（P<0.05）改善了神经功能缺损、脑水肿（79.00±0.57%对82.28±0.53%）和梗死体积（45.10±0.24%对54.73±2.87%）。生物信息分析表明，其保护作用与炎症反应密切相关。通过酶联免疫吸附测定（ELISA）测量，京尼平苷抑制了脑匀浆中白细胞介素-6（IL-6）和诱导型一氧化氮合酶（iNOS）的表达。在100μM时，京尼平苷在MCAO模型和脂多糖处理的BV2细胞中上调了A20并下调了肿瘤坏死因子受体相关因子-6和核因子κB磷酸化。
生物信息分析和实验表明，京尼平苷通过减轻炎症反应发挥神经保护作用，这可能为京尼平苷在缺血性中风治疗中的应用提供一个潜在方向。
