Geniposide protected against cerebral ischemic injury through the anti-inflammatory effect via the NF-κB signaling pathway.

IF 1.8 4区 医学 Q4 NEUROSCIENCES
Qian Sun, Xiangjian Zhang, Jingyi Fan, Lan Zhang, Hui Ji, Jing Xue, Cong Zhang, Rong Chen, Jing Zhao, Junmin Chen, Xiaoxia Liu, Degang Song
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引用次数: 0

Abstract

Context: Accumulated evidence indicates that geniposide exhibits neuroprotective effects in ischemic stroke. However, the potential targets of geniposide remain unclear.

Objective: We explore the potential targets of geniposide in ischemic stroke.

Materials and methods: 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 in vivo and in vitro.

Results: 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 (P < 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.

Conclusions: Geniposide exhibited a neuroprotective effect via attenuating inflammatory response, as indicated by biological information analysis, in vivo and in vitro experiments, which may provide a potential direction for the application of geniposide in the treatment of ischemic stroke.

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京尼平苷通过NF-κB信号通路抗炎保护脑缺血损伤。
背景:积累的证据表明,京尼平苷在缺血性卒中中具有神经保护作用。然而,京尼平苷的潜在靶点仍不清楚。目的:探讨京尼平苷治疗缺血性脑卒中的潜在靶点。材料与方法:建立成年雄性C57BL/6小鼠大脑中动脉闭塞(MCAO)模型。小鼠随机分为5组:假药组、MCAO组和京尼泊苷组(MCAO前3天,每日两次),剂量分别为25mg /kg、75 mg/kg和150mg /kg。我们首先研究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,并在体内和体外验证其潜在机制。结果:在目前的研究中,京尼平苷在高达150mg /kg的浓度下没有毒性。与MCAO组比较,150 mg/kg京尼平苷组在MCAO后24 h的神经功能缺损、脑水肿(79.00±0.57% vs 82.28±0.53%)和梗死面积(45.10±0.24% vs 54.73±2.87%)显著改善(P < 0.05)。生物信息分析表明,其保护作用与炎症反应密切相关。通过酶联免疫吸附试验(ELISA)检测,京尼平苷抑制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100 μM的MCAO模型和脂多糖处理的BV2细胞中,京尼平苷上调A20,下调TNF受体相关因子-6和核因子κ b磷酸化。结论:生物信息分析和体内、体外实验表明,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脑卒中治疗中的应用提供了潜在的方向。
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来源期刊
CiteScore
3.00
自引率
4.80%
发文量
45
审稿时长
>12 weeks
期刊介绍: Translational Neuroscience provides a closer interaction between basic and clinical neuroscientists to expand understanding of brain structure, function and disease, and translate this knowledge into clinical applications and novel therapies of nervous system disorders.
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