BIOLOGICAL & PHARMACEUTICAL BULLETIN
·
2018
·Vol. 41
·期 6
·885-890
·
IF 1.694
Zhen-zhen Yuan,You-rui Suo,Xue-yan Hao,Shu-lin Wang,Gang Li,Hong-lun Wang
Six triterpenic acids were separated and purified from the ethyl acetate extractive fraction of ethanol extracts of Potentilla parvifolia FISCH. using a variety of chromatographic methods. The neuroprotective effects of these triterpenoids were investigated in the present study, in which the okadaic acid induced neurotoxicity in human neuroblastoma SH-SY5Y cells were used as an Alzheimer’s disease cell model in vitro. The cell model was established with all trans-retinoic acid (5 µmol/L, 4 d) and okadaic acid (40 nmol/L, 6 h) treatments to induce tau phosphorylation and synaptic atrophy. Subsequently, the neuroprotective effects of these triterpenic acids were evaluated in vitro by this cell model. Results from the Western blot and morphology analysis suggested that compounds 3–6 had the better neuroprotective effects. Furthermore, we tested the level of mitochondrial reactive oxygen species and mitochondrial membrane potential of these compounds in SH-SY5Y cells by flow cytometry technology to investigate the potential neuroprotective mechanism of these compounds. All of the results indicated that maybe the mechanism of compounds 5 and 6 is to protect the cell from mitochondrial oxidative stress injuries.
研究领域:
药理学
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神经科学
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化学
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细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
Heliyon
·
2024
·
IF 3.4
Jiwen Zhu,Qi Liu,Yan Chen,JiaMing Zhang,Qinghua Xu,Zhengwei Wu
Neurodegenerative disorders are chronic conditions that progressively damage and destroy parts of the nervous system, and are currently considered permanent and incurable. Alternative strategies capable of effectively healing neuronal damage have been actively pursued. Here, we report the neuroprotective effects of baicalin (BA) combined with plasma-activated medium (PAM) against glutamate-induced excitotoxicity in SH-SY5Y cells. Through in vitro assays, the cell viability, inflammation, apoptosis, and oxidative stress were evaluated. The co-application of BA and PAM significantly enhanced cell viability, reduced pro-inflammatory markers (TNF-α and NF-κB), decreased apoptotic proteins (Bax and Caspase-3) and boosted antioxidative defenses (increased SOD activity and lowered ROS levels). This study confirms the potential of combining BA with PAM as an effective therapeutic strategy for mitigating the effects of excitotoxicity. PAM is a promising adjunct and potential drug delivery method in neuroprotective therapy, providing a new avenue for developing treatments for diseases characterized by neuronal damage.
研究领域:
神经科学
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药理学
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产品关联
DOI
PubMed
高影响因子
CHINESE JOURNAL OF CHEMISTRY
·
2022
·Vol. 40
·期 15
·1821-1830
·
IF 5.56
Xin Lu,Yijun Liu,Nan Qin,Chenxi Du,Yanyu Hu,Yao Chen,Haopeng Sun
Comprehensive Summary The cholinesterases are essential targets implicated in the pathogenesis of Alzheimer's disease (AD). We have identified tryptophan-tetrahydroisoquinoline derivatives as selective micro-nanomolar butyrylcholinesterase (BChE) inhibitors. Molecular docking was applied for the rational design and binding mode analysis. They were defined according to their target inhibitory activity, low cytotoxicity, predicted permeability through the blood-brain barrier (BBB), and in vivo cognitive improvement. Additionally, the preferred compound showed ability to decrease self-induced Aβ 1-42 aggregation and Aβ 1-42 induced SH-SY5Y cell injury. Altogether, these factors indicated their potential as unique lead compounds for AD treatment.
研究领域:
神经科学
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药物化学
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
Analytical Cellular Pathology
·
2021
·
IF 2.916
Teng Zhang,Xiaomin Chen,Yueqing Qu,Yanbing Ding
Oxidative stress-induced neuronal damage is a main cause of ischemia/reperfusion injury. Curcumin (Cur), the principal constituent extracted from dried rhizomes of Curcuma longa L. (turmeric), exhibits excellent antioxidant effects. Previous studies have indicated that miR-1287-5p was downregulated in patients with ischemic stroke. Additionally, we predicted that Lon Peptidase 2, Peroxisomal (LONP2), which is involved in oxidative stress regulation, is targeted by miR-1287-5p. The aim of the current study is to investigate the effect of Cur on ischemia/reperfusion damage and its underlying mechanism. To mimic ischemia/reperfusion damage environment, SH-SY5Y cells were subjected to oxygen-glucose-deprivation/reperfusion (OGD/R). OGD/R treatment downregulated miR-1287-5p and upregulated LONP2 in SH-SY5Y cells, but Cur alleviated OGD/R-induced oxidative damage and reversed the effect of OGD/R on the expression of miR-1287-5p and LONP2. Furthermore, we confirmed the interactive relationship between miR-1287-5p and LONP2 (negative regulation). We revealed that miR-1287-5p overexpression alleviated OGD/R-induced oxidative damage alleviation, similar to the effect of Cur. MiR-1287-5p inhibition accentuated OGD/R-induced oxidative damage in SH-SY5Y cells, which was reversed by Cur. The expression of LONP2 in OGD/R-treated SH-SY5Y cells was decreased by miR-1287-5p overexpression and increased by miR-1287-5p inhibition, and Cur counteracted the increase in LONP2 expression induced by miR-1287-5p inhibition. In conclusion, we suggest that Cur alleviates OGD/R-induced oxidative damage in SH-SY5Y cells by regulating the miR-1287-5p/LONP2 axis. The findings provide a theoretical basis for the clinical application of curcumin.
研究领域:
神经科学
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分子生物学
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药理学
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细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2024
·
IF 3.9
Yiren Xiong,Jiayi He,Shanshan He,Zuqing Hu,Di Ouyang,Renyi Liu,Zhenjie Gao,Weiguang Zhang,Zhujun Kang,Shuyi Lan,Yang Wang,Fatoumata Diallo,Dalin Hu
Lead is a ubiquitous environmental chemical with various toxic damage to human body. This investigation aimed to explore the intervention effect of human umbilical cord mesenchymal stem cells derived exosomes (HUC-MSC-exo) on the neurotoxicity of lead and the relevant mechanism. Differential gradient ultracentrifugation was adopted to isolate HUC-MSC-exo. Nanoparticle tracking assay (NTA), Transmission electron microscope (TEM) technology and exosomal specific biomarkers CD9, CD63 and CD81 were adopted for exosomal characterization. Human neuroblastoma cell (SH-SY5Y) was used as the recipient cell. Confocal laser scanning microscope analysis was conducted to confirm the intake of HUC-MSC-exo by SH-SY5Y cells. Cell migration ability, apoptosis, IL-6, IL-1β and TNF-α were analyzed. The role of miR-26a-5p/PTEN axis was assessed. The result showed that the exposure of SH-SY5Y cells to lead activated the miR-26a-5p/PTEN pathway by down-regulating miR-26a-5p and up-regulating PTEN expression, which was related to the significantly decreased cell migration and increased apoptosis, as well as significantly enhanced levels of inflammatory cytokine as compared with the control. While HUC-MSC-exo could significantly alleviate the cytotoxicity, apoptosis and inflammatory effects induced by lead on SH-SY5Y cells via partially restoring miR-26a-5p/PTEN pathway. Herein, we conclude that HUC-MSC-exo can alleviate lead-induced toxic effects on SH-SY5Y cells partially through miR-26a-5p/PTEN pathway.
研究领域:
毒理学
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干细胞研究
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神经科学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2017
·
IF 2.759
Jun Hua,Nuo Yin,Beibei Yang,Ji Zhang,Jianhua Ding,Yi Fan,Gang Hu
The accumulation of aggregated forms of the α-Synuclein (α-Syn) is associated with the pathogenesis of Parkinson's disease (PD), a chronic progressive neurodegenerative disorder. Extensive evidences have shown the promising effects of Ginkgo biloba consumption on motor activity after PD. However, the mechanisms underline the α-Syn-induced cell damage and whether ginkgolides exert neuroprotection against this injury are unclear. Here we showed that aggregated recombinant human α-Syn, but not α-Syn monomers, triggered cell injury in cultured human neuroblastoma cell line SH-SY5Y in an apoptosis way by using flow cytometry and western blot assay. Moreover, pre-treatment with the Ginkgolide B (GB) or Bilobalide (BB) protected SH-SY5Y cells against α-Syn-induced cell viability decreases, and reduced cell apoptosis after aggregated α-Syn stimulation. Together, we firstly find that aggregated α-Syn induced cell apoptosis and GB and BB may attenuate aggregated α-Syn-induced cell apoptosis, which gives us an insight into the novel therapy for PD in future.
研究领域:
神经科学
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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
Journal of Integrative Neuroscience
·
2021
·Vol. 20
·期 1
·67-75
·
IF 2.117
Dong-Xing Liu,Di Zhang,Wei-Min Hu,Yan-Fang Chang,Xiao-Hui Wang,Lin Li
Overactivation of the PI3-K/Akt/mTOR signaling pathway and inhibition of autophagy in the brain are involved in Alzheimer’s disease. The present paper’s goal was to explore the potential mechanisms of geniposide to protect against Alzheimer’s disease. We treated the human neuroblastoma SH-SY5Y cell line with Aβ1-42 as an Alzheimer’s disease in vitro model to explore the potential mechanisms of geniposide to protect against Alzheimer’s disease. Further, SH-SY5Y cells damaged by Aβ1-42 were treated with geniposide. Akt/mTOR-related proteins and autophagy-associated proteins were measured to reveal the molecular mechanisms by which geniposide protects against Aβ1-42-induced toxicity. Results showed that Akt and mTOR’s geniposide inhibited phosphorylation induced by Aβ1-42, enhanced expression of the LC3II/LC3I ratio, and Atg7 and Beclin1 expression and inhibited expression of p62 induced by Aβ1-42. Our results lead us to hypothesize that inhibition of the Akt/mTOR signaling pathway and autophagy enhancement are fundamental molecular mechanisms for geniposide to protect against Aβ toxicity.
研究领域:
神经科学
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药理学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR PHYSIOLOGY
·
2019
·Vol. 234
·期 10
·18480-18491
·
IF 4.522
Shi Xu,Beibei Yang,Tingting Tao,Ji Zhang,Yun Liu,Jun Hu,Yi Fan,Guangdong Zhang
Epidemiologic studies have shown a reduced risk of developing Parkinson's disease (PD) among cigarette smokers. Nicotine, as a key component in tobacco products, is thought as a possible candidate for action of smoking in neuroprotection. α7 nicotinic acetylcholine receptors (α7-nAChRs) is one of the most abundant nAChRs in the mammalian brain. Although nicotine is thought to exert this protective action by acting on nicotinic receptors, including the α7-nAChRs; the mechanisms underlying how α7-nAChRs protect against dopaminergic neuron loss are highly complex. Using nicotine and a selective α7-nAChR agonist PNU-282987, we first confirmed that their addition to SH-SY5Y cells challenged with 1-methyl-4-phenylpyridinium (MPP + ) could afford neuroprotection and result in a reduction in apoptotic cell death. Then, we found that the pretreatment with nicotine and PNU-282987 showed the neuroprotective antiapoptotic effects via activating the α7-nAChRs/MAPK/p53 axis. Furthermore, we used RNA interference to silence the expression of α7-nAChRs in SH-SY5Y cells and found that suppressing α7-nAChR expression diminished the antiapoptotic effects of nicotine and PNU-282987, not the toxic effects of MPP + . Moreover, α7-nAChR knockdown could only decrease the inhibitory effects of nicotine and PNU-282987 on the phosphorylated extracellular signal-regulated kinase (ERK), not c-Jun amino-terminal kinase and p38. Therefore, our findings indicate the important roles of ERK/MAPK signaling in the neuroprotective effects of α7-nAChRs and suggest that α7-nAChR agonists may be validated as novel treatments for PD.
研究领域:
神经科学
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药理学
·
细胞生物学
·
神经退行性疾病
✓ 已验证
DOI
PubMed
高影响因子
HUMAN GENE THERAPY
·
2020
·
IF 4.51
Kaihua Zhai,Boyu Liu,Lin Gao
Long-noncoding RNA taurine upregulated gene 1 (TUG1) participates in nervous system diseases, but its function in Parkinson's disease (PD) remains unclear. This study explored the function and mechanism of TUG1 in PD. A PD model was constructed using SH-SY5Y cells induced by 1-methyl-4-phenylpyridinium (MPP+) in vitro and mice treated by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in vivo. The expressions of TUG1, miR-152-3p, phosphatase and tensin homologue (PTEN), tyrosine hydroxylase (TH), and Bcl-2, and cleaved caspase-3 expressions were determined by quantitative reverse transcription-PCR and Western blotting. The viability, apoptosis, reactive oxygen species, and release of inflammatory factors from SH-SY5Y cells and substantia nigra tissues were detected by commercial kits. The interaction between TUG1 and miR-152-3p was analyzed by dual-luciferase reporter assay. Hematoxylin/eosin and immunohistochemical staining was performed for assessing the pathological damage and proportion of TH-positive cells. In PD cell model and mice model, TUG1 expression was upregulated and that of miR-152-3p was downregulated. Further research showed that TUG1 sponged and regulated miR-152-3p expression. Silencing of TUG1 not only protected SH-SY5Y cells against cell apoptosis, oxidative stress, and neuroinflammation in vitro, pathological damage and neuroinflammation in vivo, but also suppressed the expressions of PTEN and cleaved caspase-3, and increased the expressions of TH and Bcl-2 in MPP+-treated SH-SY5Y cells. However, the protective role of siTUG1 in SH-SY5Y cells was significantly inhibited by the miR-152-3p inhibitor. Thus, knocking down TUG1 might have a protective effect on PD through the miR-152-3p/PTEN pathway.
研究领域:
神经科学
·
分子生物学
·
病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
·
2023
·Vol. 180
·期 13
·1690-1709
·
IF 7.3
Weimin Kong,Xueying Sun,Siyu Yu,Peihua Liu,Xiaoke Zheng,Jiaxin Zhang,Liang Zhu,Tianxin Jiang,Mengmeng Jin,Jinghui Gao,Xiaomin Fan,Xiaodong Liu,Li Liu
Background and Purpose Liver failure is associated with psychiatric alterations, partly resulting from the increased brain dopamine levels. We investigated the relationship between increased dopamine levels and mental abnormalities using bile duct ligation (BDL) rats and the mechanism by which liver failure increased dopamine levels in SH-SY5Y cells. Behavioural tests were carried out on day 13 and 27 following BDL, along with measurements of dopamine and metabolites, expressions of enzymes and transporters related to dopamine metabolism, and its transport into the cortex and the hippocampus. SH-SY5Y cells were used to investigate whether NH 4 Cl, bile acids and bilirubin affected expression of tyrosine hydroxylase or not. Tyrosine hydroxylase (TH) expression in SH-SY5Y cells co-incubated with bilirubin and signal pathway inhibitors was measured. Key Results Open-field test results demonstrated BDL rats showed anxiety-like behaviour, accompanied by increased dopamine levels and expression of TH protein in the cortex. Membrane bound long form (MB)-COMT, slightly but significantly decreased. SH-SY5Y cells indicated that increased bilirubin levels was a factor in inducing TH expression. Both inhibitor of NF-κB pathway BAY 11-7082 and silencing NF-κB p65 reversed bilirubin-induced upregulation of TH protein. NF-κB activator TNF-α increased expression of TH protein. Roles of bilirubin in increases of TH protein expressions and dopamine levels were measured using hyperbilirubinemia rats. Anxiety-like behaviour, was associated with increased dopamine levels and TH protein expressions in hyperbilirubinemia rats. Conclusion and Implications BDL significantly increased dopamine levels in rat cortex partly due to bilirubin-mediated TH induction. Increased bilirubin induced TH expression via activating NF-κB signalling pathway.
研究领域:
神经科学
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药理学
·
肝病学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEUROCHEMICAL RESEARCH
·
2022
·Vol. 48
·期 2
·591-603
·
IF 4.414
Chen Rui,Xu Wan,Sun Yifu,Zhi Rongrong,Xie Peng,Zhi Zhongwen,Tang Xiaohong,Zhang Caiyi
2-(2-benzofu-ranyl)-2-imidazoline (2-BFI) is a drug that has attracted much attention in recent years. It has a therapeutic effect on brain diseases in animal models such as Alzheimer’s disease and cerebral infarction. However, whether 2-BFI affords neuroprotection against the toxicity of fluoride, which can cross the blood–brain barrier and cause neurological dysfunction is not known. We investigated the cell viability and apoptosis of SH-SY5Y cells and primary cultures of cortical neurons exposed to fluoride, and 2-BFI was used to protect both two kinds of cells against the effects of fluoride. We found that 2-BFI can provide neuroprotection on SH-SY5Y cells and primary cultures of cortical neurons upon fluorosis by maintaining the stability of endoplasmic reticulum–mitochondria contact sites and inhibiting activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome. This study may provide a new method for protecting against the neurotoxicity induced by fluoride exposure.
研究领域:
神经科学
·
药理学
·
毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FITOTERAPIA
·
2016
·
IF 2.408
Ye Liu,Yan-Mei Wang,Wen-Ming Wu,Jian Song,Han-Li Ruan
Three new ( 1–3 ) and seven known ( 4–10 ) triterpenoids , together with one new ( 11 ) and fifteen known ( 12–26 ) dibenzocyclooctadiene lignans , were isolated from the fruit of Schisandra sphenanthera Rehd. et Wils. Their structures were elucidated by extensive analysis of spectroscopic methods, including HRESIMS, 1D and 2D NMR spectra and CD experiments. All of the isolated triterpenoids ( 1 − 10) were evaluated for their in vitro cytotoxicities against HepG2 human hepatocellular carcinoma cell line, and compounds 1 , 3–7 and 10 exhibited moderate antiproliferative effects against HepG2 cell line with IC 50 ranging from 18.12 to 49.52 μM. The lignans ( 11–26 ) were tested for their neuroprotective activities against CoCl 2 , H 2 O 2 and A β 25–35 -induced SH-SY5Y cell injuries and showed considerable neuroprotective effects of different degrees. And at the low concentration of 3.2 nM, compounds 14 , 17–19 , 23 in CoCl 2 -induced, compounds 11 , 13–15 , 17 , 19–20 , 22–24 in H 2 O 2 -induced, and compounds 12–14 , 19 , 25–26 in A β 25–35 -induced SH-SY5Y cell injury models, showed statistically significant neuroprotective activities compared with the negative control group, respectively.
研究领域:
药理学
·
植物化学
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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