PHARMACEUTICAL BIOLOGY
·
2015
·
IF 1.241
Nian-Gui Xu,Zhi-Jie Xiao,Ting Zou,Zhi-Ling Huang
Context: Polygonum cuspidatum Sieb. Et Zucc. (Polygonaceae) has been traditionally used in folk medicine to treat various diseases.Objective: This study investigates the ameliorative effects of physcion 8-O-β-glucopyranoside (PSG) isolated from P. cuspidatum on learning and memory in dementia rats induced by Aβ1–40.Materials and methods: Dementia rats were prepared by intracerebroventricular injection of Aβ1–40. PSG (5, 10, 20, and 40 mg/kg/d, for 5 d) was administered orally. Ameliorative activity of PSG in dementia rats was evaluated by the Morris water maze (MWM) test, and its mechanisms were explored by evaluating AchE activity, levels of DA, NE, and 5-HT in hippocampus, and drebrin protein expressions in hippocampus.Results: Our results indicated that PSG (5, 10, 20, and 40 mg/kg/d) significantly inhibited the prolonged latency in dementia rats (p < 0.05), and inhibitory rates were 16.5, 22.7, 33.0, and 44.8% after 5 d of learning, indicating that PSG improves learning and memory of dementia rats. Furthermore, PSG significantly decreased AchE activity (10, 20, and 40 mg/kg/d; p < 0.05), increased 5-HT (20 and 40 mg/kg/d, p < 0.05), NE (10, 20, and 40 mg/kg/d; p < 0.05), and DA levels (5, 10, 20, and 40 mg/kg; p < 0.05) in the hippocampus. Additionally, PSG obviously decreased the Aβ contents in hippocampus (10, 20, and 40 mg/kg/d; p < 0.05), and up-regulated drebrin protein expressions (5, 10, 20, and 40 mg/kg/d; p < 0.05).Conclusions: PSG can significantly enhance learning and memory in Aβ1–40-induced dementia rats, and the mechanisms may be related to increase levels of Ach, 5-HT, NE, and DA, decrease Aβ contents, and up-regulation of drebrin proteins in hippocampus.
研究领域:
药理学
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神经科学
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传统医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2019
·Vol. 20
·期 3
·2135-2142
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IF 1.851
Ming Yu,Demei Zang,Yuhao Xu,Jie Meng,Shengnan Qian
Advanced glycation end products (AGEs) are important pathogenic substances involved in diabetes mellitus (DM) and its complications. AGEs also serve important roles in promoting the development of Alzheimer's disease (AD). Macrophage migration inhibitory factor (MIF), an inflammatory stimulant and a pathogenic factor involved in DM, was previously reported to be present at increased levels in the cerebrospinal fluid of patients with AD and mild cognitive impairment compared with age‑matched healthy controls. By investigating the association between AGEs and MIF, and the effects of neuroinflammation on AD, the present study aimed to increase understanding of the specific molecular mechanisms involved in the pathogenesis of DM and AD, and the connection between these diseases. PC12 cells were cultured in vitro; the levels of MIF mRNA and protein were determined using reverse transcription‑quantitative (RT‑q)PCR and western blot analyses. The optimal concentrations of AGEs and amyloid β 1‑40 (Aβ1‑40) were also determined in the cell model of AD using Cell Counting Kit‑8 and MTT assays. Cell numbers and morphological changes were observed following the treatment of Aβ1‑40‑stimulated PC12 cells with AGEs and the MIF inhibitor (S,R)‑3‑(4‑hydroxyphenyl)‑4,5‑dihydro‑5‑isoxazole acetic acid methyl ester (ISO‑1). The mRNA expression levels of interleukin (IL)‑1β, IL‑6, tumor necrosis factor‑α (TNF‑α) and MIF were determined via RT‑qPCR analysis. The results showed that the levels of MIF mRNA and protein were significantly increased in cells treated with AGEs compared with the control group. In the AD model group, the inhibition of PC12 cell growth was significantly increased, and the mRNA expression levels of IL‑1β, IL‑6, TNF‑α and MIF were also increased. Compared with treatment with AGEs alone, the combination of AGEs treatment with ISO‑1 significantly improved the survival rate and resulted in the reduced expression of inflammatory mediators in the AD cell model. Thus, ISO‑1 reduced AGEs‑mediated damage in the AD cell model. This may be a consequence of AGEs‑mediated MIF expression promoting neuritis in the AD cell model, whereas ISO‑1 decreased the expression of neuroinflammatory mediators.
研究领域:
医学
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神经科学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Science Advances
·
2024
·Vol. 10
·期 13
·
IF 11.7
Shun Hu,Liding Zhang,Ying Su,Xiaohan Liang,Jie Yang,Qingming Luo,Haiming Luo
Blood exosomes are emerging as potential biomarkers for diagnosing brain diseases such as Alzheimer’s disease (AD). There is currently a lack of an ultrasensitive technology for identifying core AD biomarkers in blood exosomes to optimize the utility of biomarkers in clinical practice. Here, an immunomagnetic exosomal polymerase chain reaction (iMEP) platform was developed using DNA-conjugated antibodies for the rapid detection of amyloid-β (Aβ1–40 and Aβ1–42) and phosphorylated tau (p-tau396,404 and p-tau181) in clinical blood exosomes. The toehold shift–mediated DNA affinity pulldown eliminates the high detection background, which allows the detection of biomarkers at concentrations down to 10 femtograms per milliliter. With the iMEP assay, exosomal Aβ1–42 was more accurate in differentiating patients with AD from healthy individuals compared with exosomal p-tau181 and p-tau396,404, with a sensitivity of 95.0% and a specificity of 95.0%. The iMEP technique is also adept at quantifying the levels of different exosomal biomarkers associated with disease pathogenesis.
研究领域:
神经科学
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分子生物学
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临床诊断
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生物标志物研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）