Antioxidants
·
2025
·Vol. 14
·期 4
·490
·
IF 6.6
Chao Ma,Yu Nie,Donglei Zhang,Lulu Ran,Su Xu,Xun Ran,Junya Huang,Lingshuai Meng
Background: Blueberry anthocyanin such as Cyanidin-3-O-glucoside may help prevent Alzheimer’s disease. We aimed to investigate the preventive and therapeutic effects of Cyanidin-3-O-glucoside against Aβ1–42-induced apoptosis of SH-SY5Y cells as well as the underlying mechanisms. Methods: Cell viability and intracellular and mitochondrial reactive oxygen species were detected by MTT, a reactive oxygen species detection kit, and a MitoSOX red mitochondrial superoxide indicator. The mitochondrial membrane potential, intracellular calcium ion content, and adenotriphophate (ATP) were identified via a mitochondrial membrane potential detection kit, calcium ion detection kit, and ATP detection kit, and apoptosis was detected via flow cytometry. Transcription of apoptosis-related genes was detected using real-time fluorescence quantitative polymerase chain reaction, and expression of apoptosis-related proteins was identified using Western blot. Results: We found that Cyanidin-3-O-glucoside could downregulate the expression of cytochrome c, caspase 9, caspase 3, and other genes and proteins, which consequently reduced the rate of apoptosis. Additionally, it could upregulate Bcl-2 gene and protein expression, downregulate Bax gene and protein expression, regulate mitochondrial membrane permeability and calcium-release channels, reduce calcium influx into mitochondria, maintain intracellular calcium ion levels, reduce intracellular levels of reactive oxygen species and increase ATP levels, maintain the mitochondrial membrane potential at a normal level, maintain normal mitochondrial functioning, and prevent apoptosis. Discussion: Taken together, Cyanidin-3-O-glucoside showed dose-dependent preventive and therapeutic effects against Aβ1–42-induced apoptosis of SH-SY5Y cells. Conclusions: Cyanidin 3-O-glucoside showed a better preventive effect than therapeutic effect against Aβ1–42-induced apoptosis in SH-SY5Y cells.
研究领域:
神经生物学
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药理学
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DOI
PubMed
高影响因子
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
·
2020
·Vol. 393
·期 9
·1739-1752
·
IF 2.05
Song Lin,Yao Lifen,Zhang Limei,Piao Zhongyuan,Lu Yichan
Autophagy, a lysosomal degradative pathway, is crucial for the pathogenesis of Alzheimer’s disease (AD). Schizandrol A (SchA) shows multiple pharmacological effects. However, the potential effects and mechanisms of SchA on amyloid-β (Aβ)-induced autophagy remain unclear. In this study, differentiated SH-SY5Y cells or primary hippocampal neurons were pretreated with SchA (2 μg/ml) for 1 h before subjected to Aβ 1–42 (10 μM) for 24 h to test its effects on cell viability, apoptosis, oxidative stress, and autophagy. Then an mTOR inhibitor (rapamycin) and a PI3K inhibitor (LY294002) were employed to explore the role of PI3K/AKT/mTOR pathway. The results showed that SchA significantly inhibited Aβ 1–42 -triggered reduction of viable cells, increases of apoptotic cell number and pro-apoptotic protein expressions, as well as alterations of oxidative stress markers. In addition, the increases of LC3-II/LC3-I and Beclin-1 and decrease of p62 were suppressed by SchA. At the molecular level, we found that the inactivation of PI3K/AKT/mTOR pathway was ameliorated by SchA. Inhibition of PI3K/AKT/mTOR pathway deteriorated the protective effects of SchA against Aβ 1–42 -induced autophagy activation, cell death, and apoptosis. In conclusion, we demonstrate that SchA attenuates Aβ 1–42 -induced autophagy through activating PI3K/AKT/mTOR signaling pathway. SchA may be a novel drug for the prevention and treatment of AD.
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PubMed
高影响因子
Heliyon
·
2023
·
IF 4
Lanxin Li,Yang Zhang,Zhengqian Chen,Ruyong Yao,Zhongqiu Xu,Can Xu,Fujie He,Haitao Pei,Cui Hao
Parkinson's disease (PD) is the second most common neurodegenerative disease in the world, which is distinguished by the loss of dopaminergic (DA) neurons in the substantia nigra and the formation of intraneuronal. Numerous studies showed that the damage and dysfunction of mitochondria may play key roles in DA neuronal loss. Thus, it is necessary to seek therapeutic measures for PD targeting mitochondrial function and biogenesis. In this study, through screening the purchased compound library, we found that marine derived vidarabine had significant neuroprotective effects against rotenone (ROT) induced SH-SY5Y cell injury. Further studies indicated that vidarabine pretreatment significantly protected ROT-treated SH-SY5Y cells from toxicity by preserving mitochondrial morphology, improving mitochondrial function, and reducing cell apoptosis. Vidarabine also reduced the oxidative stress and increased the expression levels of PGC-1α, NRF1, and TFAM proteins, which was accompanied by the increased mitochondrial biogenesis. However, the neuroprotective effects of vidarabine were counteracted in the presence of SIRT1-specific inhibitor Ex-527. Besides, vidarabine treatment attenuated the weight loss, alleviated the motor deficits and inhibited the neuronal injury in the MPTP induced mouse model. Thus, vidarabine may exert neuroprotective effects via a mechanism involving specific connections between the SIRT1-dependent mitochondrial biogenesis and its antioxidant capacity, suggesting that vidarabine has potential to be developed into a novel therapeutic agent for PD.
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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神经退行性疾病
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DOI
PubMed
高影响因子
FOLIA NEUROPATHOLOGICA
·
2020
·Vol. 58
·期 1
·10-21
·
IF 1.278
Chengyan Sun,Ning Jia,Rui Li,Ze Zhang,Yi Zhong,Kun Han
IntroductionAlzheimer’s disease (AD) is still the fifth leading cause of death and most common dementia worldwide. To date, there is no efficient strategy that can slow down the progression of AD owing to delayed diagnosis and limited therapies. MiR-143-3p is up-regulated in serum of AD patients, yet the exact role it plays in AD pathology is still poorly understood. The aim of this study was to investigate the effect of miR-143-3p on neuronal survival.Material and methodsWe induced neuronal differentiation in SH-SY5Y cells using all-trans-retinoic acid (RA), and Aβ1-42 was used to establish the in vitro AD cell model. The expression of tubulin β III and neuregulin-1 (NRG1) was evaluated by immunofluorescence. TUNEL assay was performed to assess cell apoptosis. Cell viability was evaluated using the Cell Counting Kit-8 assay. The binding interaction between miR-143-3p and NRG1 was verified using the luciferase reporter assay.ResultsTypical neuronal-like axons were observed in RA-induced SH-SY5Y cells, followed by increased tubulin β III. A dramatically increased apoptotic rate and reduced cell viability were observed in the AD cell model. Then we silenced the miR-143-3p expression, and Aβ1-42 induced cell apoptosis was alleviated after miR-143-3p inhibition, accompanied by decreased cleaved caspase-3 and cleaved caspase-9 levels. Additionally, NRG1 was confirmed to be a downstream target of miR-143-3p, increased cell viability and suppressed cell apoptosis after miR-143-3p inhibition was abolished by NRG1 knockdown.ConclusionsOur findings reveal that miR-143-3p inhibition promotes neuronal survival in an in vitro cell model via targeting NRG1, and the miR-143-3p/NRG1 axis is a potential therapeutic target and promising biomarker for AD treatment.
研究领域:
神经科学
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分子生物学
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细胞生物学
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神经退行性疾病
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DOI
PubMed
高影响因子
Antioxidants
·
2022
·Vol. 11
·期 5
·908
·
IF 7.675
Yuan Zhang,Tun Sun,Meng Li,Yanling Lin,Yue Liu,Shusheng Tang,Chongshan Dai
Ivermectin (IVM) could cause potential neurotoxicity; however, the precise molecular mechanisms remain unclear. This study explores the cytotoxicity of IVM in human neuroblastoma (SH-SY5Y) cells and the underlying molecular mechanisms. The results show that IVM treatment (2.5–15 μM) for 24 h could induce dose-dependent cell death in SH-SY5Y cells. Compared to the control, IVM treatment significantly promoted the production of ROS, mitochondrial dysfunction, and cell apoptosis. IVM treatment also promoted mitophagy and autophagy, which were charactered by the decreased expression of phosphorylation (p)-Akt and p-mTOR proteins, increased expression of LC3II, Beclin1, ATG5, PINK, and Pakin1 proteins and autophagosome formation. N-acetylcysteine treatment significantly inhibited the IVM-induced production of ROS and cell death in SH-SY5Y cells. Autophagy inhibitor (e.g., 3-methyladenine) treatment significantly inhibited IVM-induced autophagy, oxidative stress, and cell apoptosis. Taken together, our results reveal that IVM could induce autophagy and apoptotic cell death in SH-SY5Y cells, which involved the production of ROS, activation of mitochondrial pathway, and inhibition of Akt/mTOR pathway. Autophagy inhibition improved IVM-induced oxidative stress and apoptotic cell death in SH-SY5Y cells. This current study provides new insights into understanding the molecular mechanism of IVM-induced neurotoxicity and facilitates the discovery of potential neuroprotective agents.Keywords:ivermectin;neurotoxicity;oxidative stress;apoptosis;autophagy;Akt/mTOR pathway
研究领域:
神经科学
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细胞生物学
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药理学
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DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2026
·
IF 5.2
Fanying Deng,Jinhong Xue,Yu Wang,Yue Sun,Peng Jiang,Yumeng Luo,Zhenqiang Liu,Zhichao Hao,Mengmeng Li,Wei Guan,Qingshan Chen,Lili Zhang,Xiaochi Ma,Haixue Kuang,Yan Liu
Extraction of Paeoniae Radix Rubra polysaccharide (PRRP). • Firstly, the PRRP was extracted by Natural Deep Eutectic Solvent (NADES). • Firstly, the PRRP was extracted by ChCl-CA (1.5, 3:2) with 40% ( w / w ) water. • AGREEprep and BAGI confirmed ChCl-CA’s greenness: polysaccharide yield >9%, solvent recovery >80%. • Firstly, the neuroprotective activity of PRRP in Parkinson's disease was evaluated. Firstly, natural deep eutectic solvents (NADES) were used to extract polysaccharides from Paeoniae Radix Rubra (PRR). Using polysaccharide yield and neuroprotective cell activity as evaluation criteria, a solvent composed of 40% ( w / w ) water, choline chloride (ChCl), and citric acid (CA) was selected as the optimal solvent. It exhibited low viscosity, high surface tension, moderate polarity, and strong acidity. Fourier-transform infrared (FT-IR) spectra of the ChCl-CA confirmed the formation of hydrogen bonding. Response surface methodology (RSM) optimized conditions: molar ratio: 1.5 (3:2), extraction temperature: 60 °C, extraction duration: 64 min, solvent-solid ratio: 36 mL·g −1 , the polysaccharide yield reached 16.74%, which was 1.89 times that of the hot water extraction, and the SH-SY5Y cell activity in the methyl-4-phenylpyridinium (MPP + )-induced PD model was 86.86%. The obtained PRR polysaccharides (PRRP) were further characterized, with protein content of 5.23% and uronic acid content of 19.09%. PRRP was mainly composed of arabinose, glucose, and galacturonic acid. Its molecular weights are 73.381, 11.475, and 3.539 kDa. PRRP was characterized via Ultraviolet-Visible (UV–Vis) and FT-IR spectroscopy, confirming typical polysaccharide structures. After 6 cycles, the polysaccharide yield of recycled NADES decreased from 16.26% to 9.22% in the final extraction, a 43.30% decrease. Two classical green evaluation models quantitatively confirmed the process's environmental friendliness. In addition, in vitro experiments showed that PRRP could increase dopamine (DA) and tyrosine hydroxylase (TH) levels, reduce lactate dehydrogenase (LDH) release, and decrease α -synuclein ( α -Syn) accumulation. This study highlights the efficiency of ChCl-CA as a green extractant and reveals the neuroprotective effect of PRRP. Download: Download high-res image (162KB) Download: Download full-size image Graphical abstract created in BioRender. com
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高影响因子
Metallomics
·
2019
·Vol. 11
·期 7
·1200-1206
·
IF 3.571
Huang Hui,Zhou Mengxue,Ruan Lifo,Wang Dongqing,Lu Huiru,Zhang Jiayu,Chen Jun,Hu Yi,Chai Zhifang
Environmental factors may play a critical role in the etiology and pathogenesis of Parkinson's disease (PD). However, the association of PD with specific chemical species remains largely unknown. Here we prepared three kinds of iron oxide nanoparticles and examined their cytotoxicity in a cellular model of PD. We found that lysosome-targeted nanoparticles showed significant cytotoxicity in SH-SY5Y cells. Inhibition of AMPK could aggravate the neurotoxicity of lysosome-targeted nanoparticles as well as mitochondrion-targeted nanoparticles. Alteration of mitochondrial membrane potentials was found to be in agreement with the neurotoxicity of iron nanoparticles. These results suggested an important role of AMPK in regulating iron nanoparticle-associated neurotoxicity.
研究领域:
神经科学
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毒理学
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纳米技术
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细胞生物学
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DOI
PubMed
高影响因子
LIFE SCIENCES
·
2019
·
IF 3.448
Lingfeng Wang,Zhijun Pu,Mingxin Li,Kaixuan Wang,Lijuan Deng,Wei Chen
Aims Dauricine has been found that has significant neuroprotective effect on Alzheimer's disease (AD), but the mechanism is unclear, so we further investigated the possible mechanism of dauricine on AD. Main methods Cell counting kit-8 (CCK8) was applied to measure the cytotoxicity of dauricine on SH-SY5Y cells that overexpress the Swedish mutant form of human β-amyloid precursor protein (APPsw) and control cells (Neo). We used the Cu 2+ to induce oxidative damage on APPsw cells, then tested the effect of dauricine on the damage and relative factors including reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and superoxide dismutase (SOD) activity. The secretion level of amyloid beta 1–42(Aβ 1 – 42 ), protein expression of apoptosis-related factors and the components of nuclear factor erythroid 2-related factor 2 (Nrf2) pathway were determined by western blotting. Aβ 1 – 42 -transgenic Caenorhabditis elegans GMC101 , a model of AD, was applied to evaluate the neuroprotective effect of dauricine through the behavioral experiment and relative anti-oxidative tests. Key findings In vitro, dauricine decreased the secretion level of Aβ 1 – 42 , significantly reduced the level of Cu 2+ -induced ROS, and restored MMP and SOD activity in APPsw cells. Meanwhile, dauricine could suppress the activation of caspase-3 and to upregulate the expression of Bcl-2. Dauricine also regulated the proteins levels of Nrf2, and Kelch-like ECH-associated protein 1 (Keap1) that is necessary for the activation of Nrf2 in APPsw cell. As oxidative stress induced by Aβ or paraquat (PQ), dauricine showed protective effects in the survival experiment of GMC101 worms. Significance Those data revealed that dauricine has the pharmacological activity of anti-oxidative and anti-apoptosis, and shows the potential therapeutic value for 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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DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
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2020
·
IF 4.831
Shaochun Shi,Huibin Wang,Jian Wang,Yvxi Wang,Xiaobian Xue,Zilin Hou,Guo-Dong Yao,Xiao-Xiao Huang,Hongwei Zhao,Qingbo Liu,Shao-Jiang Song
7- O -galloyltricetiflavan (GTF), a natural flavonoid, is known to exert anti-oxidation and neuroprotective activity, which are related to the prevention of Alzheimer’s disease (AD). In this study, three series of GTF hybrids have been designed, synthesized and evaluated as multifunctional agents for treatment AD. The biological assays indicated that most of them showed strong inhibitory effect on self-induced β -amyloid (A β ) aggregation, and a significant ability to inhibit ChEs. Among them, compound A15 exhibited best inhibition of A β aggregation (78.81% at 20 μM), potent AChE inhibitory potencies (IC 50 , 0.56 μM), and compound C4 presented the highest ability to inhibit BuChE (IC 50 , 5.77 μM). Furthermore, kinetic, molecular modeling and molecular dynamics studies revealed that A15 and C4 could interact with the catalytic active site of AChE and BuChE, respectively. In addition, compounds A15 and C4 could cross the blood–brain barrier in vitro. More importantly, A15 and C4 also showed excellent neuroprotective activities against H 2 O 2 -induced human neuroblastoma SH-SY5Y cells damage and nearly no toxicity on SH-SY5Y cells. All of these outstanding in vitro results indicated A15 and C4 as the leading structure worthy of further investigation.
研究领域:
药理学
·
神经科学
·
药物化学
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DOI
PubMed
高影响因子
Sensors and Actuators Reports
·
2022
·
IF 0
Chuyue Tang,Zhuo Zou,Taotao Liang,Chengsong Yuan,Jiechang Gao,Kanglai Tang,Chang Ming Li
Dopamine plays a critical role in some fatal diseases including Parkinson's disease, schizophrenia, Tourette syndrome and HIV infection studies but its detection sensitivity demands further improvement. Aptamer-based biosensor has good selectivity to detect biologically active substances; however, it is very challenging to achieve high sensitivities for practical applications. Here an electrochemical biosensor is constructed by hollow carbon spheres, aptamer and methylene blue (MB) to monitor dopamine released from Parkinson's disease model (SH-SY5Y) cells with a low detection limit, wide detection range, high sensitivity and good selectivity for much better performance than reported aptamer sensors. Investigation discovers that MB intercalation in aptamers can offer two sites to absorb two dopamine through π-π interaction instead of one DA absorption on an aptamer alone, thereby doubling the detection sensitivity. The sensor was further used to monitor dopamine released from SH-SY5Y cells, clearly confirming the effect of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine on dopamine synthesis in SH-SY5Y cells and demonstrating the great potential of the sensor in real-time detect dopamine released from living cells. This work renders a new avenue to amplify the detection sensitivity by intercalating redox small molecule to increase the aptamer reaction sites while bridging the interfacial electron transfer.
研究领域:
分析化学
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神经科学
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生物医学工程
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DOI
Biomed Research International
·
2021
·
IF 3.411
Wanchen Ning,Simin Li,Jokyab Tsering,Yihong Ma,Honghong Li,Yuezhu Ma,Anthony Chukwunonso Ogbuehi,Hongying Pan,Hanluo Li,Shaonan Hu,Xiangqiong Liu,Yupei Deng,Jianlin Zhang,Xianda Hu
Background. Oxidative stress is implicated in the progression of many neurological diseases, which could be induced by various chemicals, such as hydrogen peroxide (H2O2) and acrylamide. Triphala is a well-recognized Ayurvedic medicine that possesses different therapeutic properties (e.g., antihistamine, antioxidant, anticancer, anti-inflammatory, antibacterial, and anticariogenic effects). However, little information is available regarding the neuroprotective effect of Triphala on oxidative stress. Materials and Methods. An in vitro H2O2-induced SH-SY5Y cell model and an in vivo acrylamide-induced zebrafish model were established. Cell viability, apoptosis, and proliferation were examined by MTT assay, ELISA, and flow cytometric analysis, respectively. The molecular mechanism underlying the antioxidant activity of Triphala against H2O2 was investigated dose dependently by Western blotting. The in vivo neuroprotective effect of Triphala on acrylamide-induced oxidative injury in Danio rerio was determined using immunofluorescence staining. Results. The results indicated that Triphala plays a neuroprotective role against H2O2 toxicity in inhibiting cell apoptosis and promoting cell proliferation. Furthermore, Triphala pretreatment suppressed the phosphorylation of the mitogen-activated protein kinase (MARK) signal pathway (p-Erk1/2, p-JNK1/2, and p-p38), whereas it restored the activities of antioxidant enzymes (superoxide dismutase 1 (SOD1) and catalase) in the H2O2-treated SH-SY5Y cells. Consistently, similar protective effects of Triphala were observed in declining neuroapoptosis and scavenging free radicals in the zebrafish central neural system, possessing a critical neuroprotective property against acrylamide-induced oxidative stress. Conclusion. In summary, Triphala is a promising neuroprotective agent against oxidative stress in SH-SY5Y cells and zebrafishes with significant antiapoptosis and antioxidant activities.
研究领域:
神经科学
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药理学
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毒理学
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阿育吠陀医学
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PubMed
高影响因子
Green Processing and Synthesis
·
2023
·Vol. 12
·期 1
·
IF 4.3
Xin Zhang,Xutong Zhu,Lifa Huang,Zupeng Chen,Yuchen Wang,Yajun Liu,Ruihan Pan,Ling Lv
Tanshinone IIA has a potential therapeutic effect on cerebral ischemia/reperfusion injury (CIRI). In this study, tanshinone IIA was encapsulated in poly(lactic- co -glycolic acid)-block-poly (ethylene glycol)-carboxylic acid (PLGA-PEG-COOH) nanoparticles, and its therapeutic efficacy on CIRI was investigated. Morphology and dynamic light scattering analyses were performed to identify and optimize nano-formulations. A drug release test was conducted using the dialysis method. The cytotoxic effect of tanshinone IIA on human neuroblastoma cells (SH-SY5Y) and brain endothelial capillary cells (hCMEC/D3) was measured using the MTT assay. The protective effect of PLGA-PEG-COOH-encapsulated tanshinone IIA against CIRI was evaluated in oxygen and glucose deprivation/reoxygenation-induced SH-SY5Y/IR cells and middle cerebral artery occlusion (MCAO) rats. Results showed that PLGA-PEG-COOH-encapsulated tanshinone IIA promoted viability and inhibited apoptosis of SH-SY5Y/IR cells ( P < 0.01). Moreover, PLGA-PEG-COOH-encapsulated tanshinone IIA facilitated the invasion of SH-SY5Y/IR cells and repressed inflammation in MCAO rats ( P < 0.01). Noteworthy, PLGA-PEG-COOH-encapsulated tanshinone IIA combined with angiopep-2 peptide presented a better inhibitory effect on CIRI than tanshinone IIA alone ( P < 0.01). Angiopep-2 peptide contributes to traversing blood–brain barrier by recognizing lipoprotein-related protein expressed in the brain capillary endothelial cells. In conclusion, PLGA-PEG-COOH-encapsulated tanshinone IIA plus angiopep-2 peptide holds promising therapeutic potential toward CIRI.
研究领域:
药学
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神经科学
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纳米技术
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药理学
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DOI
高影响因子
危险品化学品经营许可证（带存储）