MEDICAL SCIENCE MONITOR
·
2019
·
IF 1.98
Zhongfei Shen,Yun Xu,Xiaohong Jiang,Zhijian Wang,Yanjun Guo,Weiwei Pan,Jie Hou
Background Avicularin (AL, quercetin-3-α-l-arabinofuranoside), a glycoside of quercetin, has been reported to display diverse pharmacological properties. The present study aimed to investigate whether AL has an anti-depressant-like effect on a mouse model of depression induced by chronic unpredictable mild stress (CUMS). Material/Methods A mouse model of depression was established and treated with different concentrations of AL (1.25, 2.5 or 5.0 mg/kg/d) and fluoxetine (20 mg/kg/d). Then, behavioral tests – sucrose preference test (SPT), forced swimming test (FST), and the tail suspension test (TST) – were performed. The levels proinflammatory cytokines – interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) – in the hippocampi of mice were detected by enzyme-linked immunosorbent assay (ELISA). Apoptosis of hippocampal neuronal cells was determined using flow cytometry. Expression levels of phosphorylated (p)-MEK1/2, p-ERK1/2, p-NF-κB (p-p65), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), Caspase3, and B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax) were measured by Western blot assay or/and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. Results The results showed that AL significantly relieved CUMSinduced depressive-like behaviors. Compared with the model mice, AL treatment significantly increased the sucrose preference of the mice, and the immobility time in the FST and the TST were shortened. We also found that AL decreased CUMS-induced increases in the levels of IL-1β, IL-6, and TNF-α in the hippocampi of mice. AL significantly decreased the apoptosis rate of hippocampal neuronal cells in mice, which was increased by CUMS. Furthermore, activation of the MEK/ERK/NF-κB pathway induced by CUMS was inhibited by AL treatment. Conclusions Our results show the anti-depressant-like effects of AL on CUMS-induced depression in a mouse model.
研究领域:
药理学
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神经科学
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行为科学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEUROCHEMICAL RESEARCH
·
2024
·Vol. 50
·期 1
·1-15
·
IF 3.7
Luo Yuanfei,Yuan Linying,Liu Zhihui,Dong Weichen,Huang Li,Liao Anyu,Xie Yi,Liu Rui,Lan Wenya,Cai Yulong,Zhu Wusheng
Proprotein convertase substilin/kexin type 9 (PCSK9), a pivotal protein regulating lipid metabolism, has been implicated in promoting microthrombotic formation and inflammatory cascades, thereby contributing to cardiovascular ischemia/reperfusion (I/R) injury. However, its involvement in cerebral I/R injury and its potential role in microcirculation protection remain unexplored. In this investigation, we utilized a middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model to simulate ischemic stroke. Different concentrations of evolocumab (1, 5, 10 mg/kg, i.v.), a PCSK9 inhibitor, were administered to assess its impact. Immunofluorescence staining was employed to analyze changes in the expression of occludin, claudin-5, thrombocyte, ICAM-1, VCAM-1, and CD45, providing insights into blood-brain barrier integrity, platelet adhesion, and immune cell infiltration. Moreover, the Morris water maze and elevated plus maze were utilized to evaluate neurological and behavioral functions in MCAO/R mice, shedding light on the effects of PCSK9 inhibition. Our findings revealed a surge in plasma PCSK9 levels post-MCAO/R, peaking at 24 h post-reperfusion. Evolocumab (10 mg/kg) treatment significantly mitigated brain infarction and neurological deficits, evidenced by enhanced locomotor function and reduced post-stroke anxiety. However, it did not ameliorate cognitive impairment following MCAO/R. Additionally, evolocumab administration led to diminished leakage of evans blue solution and upregulated expression of occludin and claudin-5. Thrombocyte, ICAM-1, VCAM-1, and CD45 levels were notably reduced in the penumbral area post-evolocumab treatment. These protective effects are speculated to be mediated through the inhibition of the ERK/NF-κB pathway. The PCSK9 inhibitor evolocumab holds promise as a therapeutic agent during the acute phase of stroke, exerting its beneficial effects by modulating the ERK/NF-κB signaling pathway.
研究领域:
神经科学
·
药理学
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心血管研究
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免疫学
✓ 已验证
DOI
高影响因子
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