RSC Advances
·
2019
·Vol. 9
·期 32
·18308-18319
·
IF 3.049
Mengying Wei,Yuanyuan Liu,Zifeng Pi,Kexin Yue,Shizhe Li,Mingxin Hu,Zhiqiang Liu,Fengrui Song,Zhongying Liu
Alzheimer's disease (AD) has become one of the major diseases endangering the health of the elderly. Clarifying the features of each AD animal model is valuable for understanding the onset and progression of diseases and developing potential treatments in the pharmaceutical industry. In this study, we aimed to clarify plasma metabolomics and neurotransmitter dysfunction in the process of AD model rat induced by amyloid beta 25-35 (Aβ 25-35). Firstly, Morris Water Maze (MWM) test was used to investigate cognitive impairment in AD rat after 2, 4 and 8 weeks of modelling. Based on this, the effects on levels of AD-related enzymes and eight neurotransmitters were analyzed. And plasma metabolomics analysis based on ultra high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) was used to research the metabolic disturbances in the process of AD rat. The results shown the injury on the spatial learning ability of AD rats was gradually aggravated within 4 weeks, reached the maximum at 4 weeks and then was stable until 8 weeks. During 8 weeks of modeling, the levels of enzymes including β-secretase, γ-secretase, glycogen synthase kinase-3β (GSK-3β), acetyl cholinesterase (AchE) and nitric oxide synthase (NOS) were significant increased in the plasma of AD rats. The neurotransmitter dysfunction was mainly involved in γ-aminobutyric acid (GABA), acetyl choline (Ach), glutamic acid (Glu), 5-hydroxytryptamine (5-HT), dopamine (DA) and norepinephrine (NE). 17 endogenous metabolites correlated with AD were successfully detected in the metabolomics analysis. These metabolites were mainly involved in fatty acids, sphingolipids, and sterols metabolisms, vitamin metabolism, and amino acid metabolism. These metabolites might be the potential biomarkers that correctly mark different stages of AD. The study on peripheral plasma indices reflecting the process of AD laid the foundation for understand the pathophysiology of AD and find an effective and radical cure. And the rules of endogenous metabolic disorder in AD rats also have a certain guiding significance for the future study of food–drug interactions at different stages of AD.
研究领域:
神经科学
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代谢组学
·
药理学
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产品关联
DOI
PubMed
高影响因子
PSYCHOPHARMACOLOGY
·
2021
·Vol. 239
·期 1
·215-227
·
IF 4.53
Wang Chen,Zheng Dongpeng,Weng Fanglin,Jin Yongzeng,He Ling
Rationale Energy metabolism disorder is a widespread feature that exists in the early clinical stages of Alzheimer’s disease (AD). Astrocyte is the most numerous and the largest glial cell in the brain. By transporting energetic fuels such as lactate and ketones to neurons, astrocytes play a pivotal role in maintaining the cerebral energy homeostasis. Sodium butyrate (NaB), a type of short-chain fatty acid; its anti-inflammatory effect; and inhibition on histone deacetylases have been widely studied. Methods Spatial memory and cognitive ability of mice were assessed by using behavioral tests. Western blotting and ELISA kits were used to detect related protein levels and other biochemical markers, respectively. Objectives To prove the therapeutic effect of NaB on AD cognitive impairment and provide possible research ideas for mechanism exploration. Results Administration of NaB could improve the cognitive impairments induced by Aβ 25–35 in mice. Furthermore, NaB could promote the differentiation of astrocytes towards A2-neuron-protective subtype, astroglial mitochondrial function, and lactate shuttle between astrocytes and neurons. Conclusion These findings reveal the effect of sodium butyrate on astrocytes, which may improve the pathological status of AD and provide experimental basis for sodium butyrate treatment of AD.
研究领域:
神经科学
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药理学
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神经退行性疾病
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DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2023
·
IF 3.4
Siyue Li,Yuanfang Sun,Yutong Gao,Xinying Yu,Chun Zhao,Xiuping Song,Fei Han,Jia Yu
Alzheimer’s disease (AD) threatens elderly human health and still lacks effective treatment. Our previous work showed that LGZGD possessed a neuroprotective effect on the Aβ 25-35 -induced neurotoxicity in differentiated PC12 cells, indicating that LGZGD may be a potential drug for treatment of AD. However, its pharmacodynamic substances which show anti-inflammatory and anti-oxidant stress activities are still unrevealed. This research aims to reveal the pharmacodynamic substances of LGZGD on Aβ 25-35 -induced PC12 cell model of AD based on a spectrum-effect relationship study by using HPLC-FT-ICR-MS method and multivariate statistical analysis. Firstly, the chemical composition spectra of different combinations of LGZGD were recorded by HPLC-FT-ICR MS. Subsequently, Aβ 25-35 -induced PC12 cell model of AD was established and pharmacodynamic experiments were conducted to evaluate their anti-inflammatory and anti-oxidant activities, respectively. Finally, the potential pharmacodynamic substances were screened out through spectrum-effect relationship study accompanied by multivariate statistical analysis including bivariate correlation analysis (BCA), grey relational analysis (GRA), principal component analysis (PCA), partial least squares regression analysis (PLSR). As a result, a total of 96 chemical consistents in different combinations of LGZGD were discovered. Among them, 7 components such as isoglabrolide, licorice saponin E2, licorice saponin N2 and licoisoflavanone were directly linked with the anti-inflammatory effects, and 14 constituents such as tumulosic acid, polyporenic acid C, dehydrotumulosic acid, dehydropachymic acid, and pachymic acid were directly correlated with the anti-oxidative stress activities. In conclusion, we combined the HPLC-FT-ICR-MS spectra with pharmacodynamic indicators to develop the spectrum-effect relationships of LGZGD for the first time, and successfully revealed its potential pharmacodynamic substances in the treatment of AD from the anti-inflammatory and antioxidant pathways in the cell model.
研究领域:
药理学
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神经科学
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分析化学
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中医药
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2024
·
IF 5.3
Jia Xi Ye,Jia Ying Wu,Liang Ai,Min Zhu,Yun Li,Dong Yin,Qihui Huang
Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the significant involvement of amyloid-beta (Aβ) peptide in its pathogenesis. Geniposide, derived from the versatile medicinal of Gardenia jasminoides , is one of the active compounds studied extensively. The objective was to explore the impact of geniposide on Aβ 25-35 -induced damage in HT22 cells, specifically focusing on its modulation of PINK1/Parkin-mediated mitophagy. In our investigation, geniposide exhibited remarkable restorative effects by enhancing cell viability and preserving the mitochondrial membrane potential. Moreover, it effectively reduced and mitigated the oxidative stress and apoptosis rates induced by Aβ 25-35 . Notably, geniposide exhibited the capacity to enhance autophagic flux, upregulate LC3II and Beclin-1 expression, and downregulate the expression of p62. Furthermore, geniposide positively influenced the expression of PINK1 and Parkin proteins, with molecular docking substantiating a strong interaction between geniposide and PINK1/Parkin proteins. Intriguingly, the beneficial outcomes of geniposide on alleviating the pronounced apoptosis rates, the overproduction of reactive oxygen species, and diminished the PINK1 and Parkin expression induced by Aβ 25-35 were compromised by the mitophagy inhibitor cyclosporine A (CsA). Collectively, these findings suggested that geniposide potentially shields HT22 cells against neurodegenerative damage triggered by Aβ 25-35 through the activation of mitophagy. The insights contribute valuable references to the defensive consequences against neurological damage of geniposide, thereby highlighting its potential as a therapeutic intervention in AD.
研究领域:
神经科学
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药理学
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细胞生物学
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分子生物学
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神经退行性疾病
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DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2022
·
IF 5.307
Yingda Zang,Jingwen Ning,Ke Liu,Meiyu Shang,Caixia Zang,Chuangjun Li,Jie Ma,Xinyi Chen,Jingwei Ma,Gen Li,Yang Yang,Xiuqi Bao,Dan Zhang,Dongming Zhang
A series of novel pyranocarbazole alkaloids were designed and synthesized as derivatives of Claulansine F and CZ-7. Some of the compounds showed strong neuroprotective effects and anti-lipid peroxidation capacity. Among these compounds, 10b , introduced leucine at the C-3 position of pyranocarbazole, was the most active in inhibiting the programmed death of SH-SY5Y cells. This compound exhibited stronger free radical scavenging activity than Edaravone. Furthermore, 10b could penetrate the blood–brain barrier (BBB). More importantly, 10b showed a tendency of improvement in learning and memory in the dose range of 10–40 mg/kg. The research on mechanisms indicated that 10b could reduce oxidative stress in the brain of Aβ 25-35 -intoxicated mice, and then improve the cognitive function of Aβ 25-35 -intoxicated mice. Our findings suggest that 10b may be promising for further evaluation as an intervention for Alzheimer’s Disease.
研究领域:
药理学
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神经科学
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药物化学
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药物发现
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DOI
PubMed
高影响因子
INFLAMMOPHARMACOLOGY
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2024
·
IF 4.6
Li Ming-Jie,Xu Jing-Yi,Zhang Hua-Yue,Guo Min,Lan Meng-Ning,Kong Jie,Liu Shi-Wei,Zheng Hua-Jun
Alzheimer’s disease (AD) is a neurodegenerative disorder frequently accompanied by neuroinflammation and oxidative stress. The medicine and food homology (MFH) has shown potential for treating neuroinflammation and oxidative stress. This study aimed to provide a safe and efficient therapy for AD based on MFH. In this study, we develop a MFH formula consisting of egg yolk oil, perilla seed oil, raphani seed oil, cinnamon oil, and noni puree (EPRCN). To evaluate the ameliorative effects of EPRCN on AD-related symptoms, a mouse model of AD was constructed using intraperitoneal injection of scopolamine in ICR mice. Experimental results demonstrated that EPRCN supplement restored behavioral deficits and suppressed neuroinflammation and oxidative stress in the hippocampus of scopolamine-induced mice. An in vitro study was then performed using induction of Aβ (25–35) in glial (BV–2 and SW–1783) and neuron (SH–SY5Y) cell lines to examine the improvement mechanism of EPRCN on cognitive deficits. Multi-omics and in vitro studies demonstrated that these changes were driven by the anandamide (AEA)-Trpv1-Nrf2 pathway, which was inhibited by AM404 (an AEA inhibitor), AMG9810 (a Trpv1 inhibitor), and BT (an Nrf2 inhibitor). Consequently, EPRCN is an effective therapy on preventing cognitive deficits in mouse models of AD. In contrast to donepezil, EPRCN exhibits a novel modes action for ameliorating neuroinflammation. The mechanism of EPRCN on preventing cognitive deficits is mediated by improving neuroinflammation and oxidative stress via activating the AEA–Trpv1–Nrf2 pathway.
研究领域:
神经科学
·
药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Binbin Dong,Zong Hou,Zhong Zheng,Junpeng Xing,Ningning Zhao,Zhiqiang Liu,Shu Liu
The abundant ginseng neutral polysaccharide (GPN) has been neglected due to its lower activity compared to acidic polysaccharide in ginseng. Herein, the composite enzymes were used to modify the GPN and obtained the enzymatic-degradation-GPN (EGPN). The structural changes were further characterized by GPC, FT-IR, Congo red, XRD, zeta potential, TG, cryo-SEM and AFM. The antioxidant activity of GPNs in vitro was investigated by in vitro chemical experiments and oxidative stress-related indicators on PC12 cells damaged by Aβ 25 – 35 , and EGPN showed favorable antioxidant activity. In addition, EGPN metabolized by intestinal microbiota also significantly increased the viability of injured PC12 cells. Furthermore, in vitro fermentation model was used to investigate the differences of physicochemical properties of GPNs and their regulatory effects on the microbiota. EGPN enhanced the diversity of the microbiota and increased the concentration of short-chain fatty acids (SCFAs). Importantly, EGPN demonstrated a significant reduction in the presence of detrimental bacteria such as Enterococcus and Allobaculum , while simultaneously promoting the growth of beneficial microorganisms including Lactobacillus , Prevotella , and Ruminococcu . This study highlights the potential use of EGPN prepared by composite enzymatic degradation in antioxidant, neuroprotection and restoration of intestinal homeostasis.
研究领域:
药理学
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生物化学
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微生物学
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神经科学
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生物技术
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产品关联
DOI
PubMed
高影响因子
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