PHARMACEUTICAL CHEMISTRY JOURNAL
·
2023
·Vol. 57
·期 5
·712-724
·
IF 0.9
Li Danqi,Li Weihong,Shi Wenhao,Wu XiaoJing,Liu Xuegui,Gao Pinyi
Depression is a common mental health disease, with the characteristics of significant and persistent low mood. Traditionally, Ziziphus jujuba Mill . was used to treat depression. However, its chemical pharmacologic profiles remain to be elucidated. The present study was aimed to explore the potential targets and mechanisms of Z. jujuba in the treatment of depression using network pharmacology and in vitro neuroprotective experiment. In this study, 11 compounds of Z. jujuba were obtained by multiple column chromatography. Based on the network pharmacology, the C-T network was established by the results of molecular docking. The information on target proteins was enriched via DAVID database, followed by the analysis of GO and KEGG. The results indicated that 10 compounds, 5 target proteins and 3 signaling pathways played important roles in treating depression. Based on the predicted result of network pharmacology, compounds 1 , 9 and 10 were identified with significant neuroprotective effects by in vitro cell experiments with human neuroblastoma cell line SH-SY5Y. This study was the first to investigate the mechanisms of Z. jujuba action in the treatment of depression from the system level, and could provide the basis of the mechanism with action of compounds for the in-depth utilization of Z. jujuba.
研究领域:
中药学
·
神经科学
·
生物信息学
✓ 已验证
DOI
高影响因子
NEUROCHEMICAL RESEARCH
·
2020
·Vol. 46
·期 2
·367-378
·
IF 3.038
Xiang Biao,Li Daowen,Chen Yiqiang,Li Meng,Zhang Yuan,Sun Tun,Tang Shusheng
Impaired homeostasis of copper has been linked to different pathophysiological mechanisms in neurodegenerative diseases and oxidative injury has been proposed as the main mechanism. This study aims to use curcumin, a widely used antioxidative and anti-apoptotic agent, to exert the neuroprotective effect against copper in vitro and illuminate the underlying mechanism. The effect of curcumin was examined by using a cell counting kit-8 assay, flow cytometry, immunofluorescence, spectrophotometer, and western blot. Results revealed that after pretreatment with curcumin for 3 h, copper-induced toxicity and apoptosis show a significant decline. Further experiments showed that curcumin not only decreased the production of ROS and MDA but also increased the activities of the ROS scavenging enzymes SOD and CAT. Moreover, curcumin treatment alleviated the decrease in mitochondrial membrane potential and the nuclear translocation of cytochrome c induced by copper. The protein levels of pro-caspase 3, pro-caspase 9, and PARP1 were up-regulated and the Bax/Bcl-2 ratio was down-regulated in the presence of curcumin. Taken together, our study demonstrates that curcumin has neuroprotective properties against copper in SH-SY5Y cells and the potential mechanisms might be related to oxidative stress and mitochondrial apoptosis.
研究领域:
神经科学
·
药理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NATURAL PRODUCT RESEARCH
·
2021
·
IF 2.862
Yi Lin,Jingjing Liang,Xiaogang Peng,Hanli Ruan
Three new phenolic compounds, 2,3,4-trihydroxy-1-(4′-hydroxybenzyl)benzoic acid (1), 2,3,4-trihydroxy-1-(4′-hydroxy-3′-methoxybenzyl)benzoic acid (2), and 2-(4′-hydroxy-3′-methoxybenzyl)-3,5-dimethoxy-1,4-benzoquinone (3), were isolated from the fresh pericarps of Juglans sigillata Dode. Their structures were elucidated by integrated spectroscopic techniques. Bioactivity screening results showed that compounds 1–3 exhibited moderate neuroprotective effects against H2O2-induced or CoCl2-induced cellular damage in human neuroblastoma SH-SY5Y cell line.
研究领域:
植物化学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR AND CELLULAR BIOCHEMISTRY
·
2011
·Vol. 363
·期 1
·309-313
·
IF 2.168
Zhao Hui,Li Ling,Fan Hua-Jun,Wang Fei,Jiang Li-Ming,He Pin-Gang,Fang Yu-Zhi
Communication between cells by release of specific chemical messengers via exocytosis plays crucial roles in biological process. Catecholamines, like dopamine, epinephrine, and norepinephrine, which are types of neurotransmitters released from cells, can be oxidized and detected by the microelectrodes, and amperometric detection of exocytosis is an effective method for studying the communication between cells. The experimental results depend on many factors, among which the property of the microelectrode, cell states, and their positions to each other are particularly important. A type of indium tin oxide (ITO) micro-pore electrodes, which is characterized by its stability, has been developed with photolithography. SH-SY5Y cells can adhere and spread on ITO micro-pore electrodes. Therefore, it is possible to investigate the correlation between cell morphology and exocytosis. The results show that cells with clear process have higher release frequency of norepinephrine compared with cells in spherical shape. Combined with fluorescence observation, this technique provides a simple and convenient methodology for cell study.
研究领域:
神经生物学
·
细胞生物学
·
电化学分析
✓ 已验证
DOI
PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY
·
2023
·
IF 4.5
Zhihui Li,Yan Shi,Yougang Wang,Haomin Qi,Haiyu Chen,Jinquan Li,Li Li
Cadmium (Cd) is a hypertoxic heavy metal that may be exposed to environmental pollutants by humans and animals. It can lead to cognitive disfunction, and is linked to neurodegenerative diseases. Cadmium reportedly can induce endoplasmic reticulum (ER) stress, but few studies have concentrated on it in nerve cells, and the connection between ER stress and neuroinflammation. In this study, in vitro experiments on SH-SY5Y neuroblastoma cells were carried out. We aimed at exploring whether Cd attributed to the cell pyroptosis and the role of PERK in promoting this form of cell damage which can induce strong inflammatory responses. Our results demonstrated that CdCl 2 treatment induced excess reactive oxygen species (ROS) production, caused significant modifications in the expression of PERK and increased TXNIP, NLRP3, IL-1β, IL-18, and caspase1 in SH-SY5Y cells. In addition, scavenging ROS with N -acetylcysteine or inhibiting the expression of PERK by using GSK2606414, rescued the SH-SY5Y cells from cadmium-induced pyroptosis. In conclusion, the results suggest that Cd induces pyroptotic death of SH-SY5Y cells through ER stress, and this may be the potential mechanism of Cd incurring neurological diseases.
研究领域:
神经毒理学
·
细胞生物学
·
分子生物学
·
环境毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Brain Sciences
·
2023
·Vol. 13
·期 3
·382
·
IF 3.3
Jian-Chao Peng,Yue Deng,Han-Xiao Song,Yuan-Yuan Fang,Cui-Liu Gan,Jun-Jie Lin,Jing-Jing Luo,Xiao-Wei Zheng,Michael Aschner,Yue-Ming Jiang
Background: Combined exposure to lead and cadmium is common in occupational environments. However, the effects of co-exposure to Pb-Cd on neurotoxicity have not been fully clarified. Sodium para-aminosalicylic acid (PAS-Na) has previously been shown to protect neurons from Pb-induced toxicity. This study aimed to investigate the beneficial effect of PAS-Na against co-exposure to Pb-Cd-induced neurodegeneration in SH-SY5Y cells. Methods: The MTT assay was used to detect the effects of Pb and Cd alone, or in combination, on SH-SY5Y cell survival. The effects of Pb and Cd alone or in combination on oxidative stress were assessed by reactive oxygen species (ROS) level. Nrf2, the master switch for antioxidant responses, was detected by immunofluorescence. Protein expression levels of PI3K, Akt, p-Akt, Nrf2 and HO-1 were determined by Western blot analysis. Results: MTT assay results established that the survival rate of SH-SY5Y cells was not significantly affected by exposure to 1 μmol/L lead, 0.25 μmol/L cadmium, and 1-fold Pb-Cd mixture (1 μmol/L Pb + 0.25 μmol/L Cd), while 10-fold Pb-Cd combined exposure (10 μmol/L Pb + 2.5 μmol/L Cd) significantly reduced the survival rate of SH-SY5Y cells. Combined Pb-Cd exposure significantly increased intracellular ROS levels, and N-Acetyl-L-cysteine (NAC) treatment in the 10 μmol/L Pb + 2.5 μmol/L Cd group significantly decreased ROS expression levels, attenuating the levels of oxidative stress. Protein expression of PI3K and p-Akt significantly decreased in the 10 μmol/L Pb + 2.5 μmol/L Cd group, while the expression of PI3K and p-Akt protein increased after PAS-Na intervention. Immunofluorescence analysis showed that levels of Nrf2 in the nucleus increased in the 10 μmol/L Pb + 2.5 μmol/L Cd group, along with Nrf2 protein levels, suggesting that Nrf2 was translocated from the cytoplasm into the nucleus upon combined Pb-Cd exposure. In addition, HO-1 protein expression level, a downstream gene product of Nrf2, was increased. In response to NAC intervention, HO-1 protein expression levels significantly decreased. PAS-Na had the same intervention effect as NAC. Conclusion: Combined exposure to Pb-Cd induced oxidative stress and cytotoxicity in SH-SY5Y cells. PAS-Na displayed antagonistic effects on neurodegenerative changes induced by combined Pb-Cd exposure; hence, it may afford a novel treatment modality for exposure to these metals.Keywords:lead;cadmium;oxidative stress;co-exposure
研究领域:
神经科学
·
毒理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2019
·Vol. 20
·期 1
·529-538
·
IF 1.851
Shasha Chen,Feng Cai,Jirong Wang,Zhouxin Yang,Chi Gu,Guofu Wang,Genxiang Mao,Jing Yan
The abnormal aggregation of α‑synuclein (α‑syn), which is an important pathological feature of Parkinson's disease (PD), is cytotoxic to dopaminergic neurons and causes cellular damage and apoptosis. Salidroside (SAL) is the main active component of the traditional Chinese medicine Rhodiola rosea. Previous research has demonstrated that SAL exerts cellular protection against cell senescence and neurodegeneration. However, the role and mechanism of action of SAL in PD remain unclear. The present study used overexpression of the wild‑type and the A53T mutation of α‑syn to induce a neuronal model of PD in SH‑SY5Y cells, which led to neuronal toxicity and a reduced cell proliferation index. SAL increased the cell proliferation index of both PD model groups in a dose‑dependent manner. Additionally, SAL alleviated pathogenic phosphorylated (Ser129) α‑syn expression as well as the ratio of microtubule‑associated proteins 1A/1B light chain 3 (LC3)‑I to LC3‑II expression, which is related to autophagic function. Furthermore, the results suggested that the underlying mechanism for the SAL‑induced protection of PD model neurons may involve the preservation of autophagy, which attenuates the phosphorylation of α‑syn in neurons predominantly via mTOR/p70S6K, and is independent of the PI3K/Akt signaling pathway.
研究领域:
神经科学
·
药理学
·
细胞生物学
✓ 已验证
产品关联
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
·
药理学
✓ 已验证
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
·
药物化学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
Experimental and Therapeutic Medicine
·
2019
·Vol. 18
·期 5
·3643-3649
·
IF 1.448
Cui Huang,Jing Ma,Bai‑Xiang Li,Yan Sun
Wingless (Wnt) signaling regulates the proliferation and differentiation of midbrain dopamine (DA) neurons. Paraquat (PQ) and maneb (MB) are environmental pollutants that can be used to model Parkinson's disease (PD) in rodents. A previous study demonstrated that developmental exposure to PQ and MB affects the expression of Wnt1, Wnt5a, nuclear receptor‑related factor 1 (NURR1) and tyrosine hydroxylase (TH). However, how Wnt signaling regulates these developmental factors in vitro is yet to be determined. To explore this, SH‑SY5Y cells were exposed to PQ and MB. The results of the current study indicated that exposure to PQ and MB decreased Wnt1, β‑catenin, NURR1 and TH levels and increased Wnt5a levels. Furthermore, Wnt1 silencing has the same effect as exposure to PQ and MB. Additionally, the neurotoxicity induced by PQ and MB is more severe in siWnt1‑SH‑SY5Y cells compared with normal SH‑SY5Y cells. Therefore, Wnt1 may serve an important role in regulating developmental DA factors, and may be a candidate gene for PD diagnosis or gene therapy.
研究领域:
神经科学
·
毒理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY LETTERS
·
2018
·
IF 3.166
Lin Li,Jiahui Cui,Zi Liu,Xuejiao Zhou,Zengqiang Li,Yang Yu,Yuanyuan Jia,Daiying Zuo,Yingliang Wu
Silver nanoparticles (AgNPs) have many medical and commercial applications, but their effects on human health are poorly understood. The aim of this study was to assess the effect of AgNPs on the human neuroblastoma cell line SH-SY5Y and to explore their potential mechanisms of action. We found that AgNPs decreased SH-SY5Y cell viability in a dose- and time-dependent manner. Exposure to AgNPs activated endoplasmic reticulum (ER) stress, as reflected by upregulated expression of glucose-regulated protein 78 (GRP78), phosphorylated PKR-like endoplasmic reticulum kinase (p-PERK), phosphorylated eukaryotic translation initiation factor 2α (p-eIF2α), C/EBP homology protein (CHOP), spliced X-box binding protein-1 (XBP1), and phosphorylated inositol-requiring enzyme (p-IRE), all of which are involved in the cellular unfolded protein response. Prolonged exposure of cells to AgNPs damaged calcium (Ca 2+ ) homeostasis, increased the length of contact sites between the ER and mitochondria, altered IP 3 R function by the increased levels of phosphatase and tensin homolog deleted on chromosome ten (PTEN) in the ER and enhanced mitochondrial Ca 2+ uptake. Finally, Ca 2+ overload and disrupted homeostasis in the mitochondria triggered apoptotic cell death. Our results suggest that caution should be exercised in the use of AgNPs in humans.
研究领域:
纳米技术
·
细胞生物学
·
毒理学
·
神经科学
✓ 已验证
产品关联
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
·
干细胞研究
·
神经科学
·
分子生物学
✓ 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）