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
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产品关联
DOI
PubMed
高影响因子
Applied Materials Today
·
2021
·
IF 10.041
Xinlian Zhao,Lulu Jin,Zhixin Zhu,Haohao Lu,Haifei Shi,Qi Zhong,Joaquim Miguel Oliveira,Rui L. Reis,Changyou Gao,Zhengwei Mao
Spinal cord injury (SCI) is a severe refractory disabling condition accompanied by complicated pathological processes, such as excessive glutamate release in the extracellular environment and massive influx of Ca 2+ into cells. Dextran can absorb extracellular glutamate and Ca 2+ to attenuate persistent excitatory processes that are detrimental to normal cells. Calcium channel inhibitors reduce the influx of Ca 2+ , thereby relieving subsequent cytotoxicity such as mitochondria damage. Here, a bifunctional microgel was designed for delivering GVIA, an N-type calcium ion channel blocker, to achieve a combinational therapy of simultaneously reducing the Ca 2+ and glutamate concentrations in extracellular environment and inhibiting excess Ca 2+ influx. The obtained dextran microgels could effectively encapsulate GVIA peptide, which displayed sustained release. Microgels loaded with GVIA (DexGVIA) played an excellent neuroprotective role by relieving the influx of Ca 2+ in vitro . DexGVIA also exhibited promising therapeutic effect in vivo via reducing the lesion cavity, saving neurons and gliacytes from the injury, and improving continuity and integrity of the spinal cord, thus distinctly accelerated motor functional recovery of SCI rats. Our work provided a combinational strategy against excitotoxicity, with potential applications not only in SCI, but also in other pathologically similar conditions of the central nervous system.
研究领域:
神经科学
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药学
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生物医学工程
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产品关联
DOI
高影响因子
Neural Regeneration Research
·
2021
·
IF 5.135
Rui Zhao,Xue Wu,Xue-Yuan Bi,Hao Yang,Qian Zhang
Baicalin is a natural active ingredient isolated from Scutellariae Radix that can cross the blood-brain barrier and exhibits neuroprotective effects on multiple central nervous system diseases. However, the mechanism behind the neuroprotective effects remains unclear. In this study, rat models of spinal cord injury were established using a modified Allen's impact method and then treated with intraperitoneal injection of Baicalin. The results revealed that Baicalin greatly increased the Basso, Beattie, Bresnahan Locomotor Rating Scale score, reduced blood-spinal cord barrier permeability, decreased the expression of Bax, Caspase-3, and nuclear factor κB, increased the expression of Bcl-2, and reduced neuronal apoptosis and pathological spinal cord injury. SH-SY5Y cell models of excitotoxicity were established by application of 10 mM glutamate for 12 hours and then treated with 40 μM Baicalin for 48 hours to investigate the mechanism of action of Baicalin. The results showed that Baicalin reversed tight junction protein expression tendencies (occludin and ZO-1) and apoptosis-related protein expression (Bax, Bcl-2, Caspase-3, and nuclear factor-κB), and also led to up-regulation of PI3K and Akt phosphorylation. These effects on Bax, Bcl-2, and Caspase-3 were blocked by pretreatment with the PI3K inhibitor LY294002. These findings suggest that Baicalin can inhibit blood-spinal cord barrier permeability after spinal cord injury and reduce neuronal apoptosis, possibly by activating the PI3K/Akt signaling pathway. This study was approved by Animal Ethics Committee of Xi’an Jiaotong University on March 6, 2014.
研究领域:
神经科学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
NEUROREPORT
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2018
·Vol. 29
·期 5
·432
·
IF 1.266
Zhang Jinghui,Qiao Nana,Ding Xiufang,Wang Jiwen
Excitotoxicity and neuronal death following epilepsy involve α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). It forms a protein complex with glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and co-internalizes upon activation of AMPA receptors after epilepsy. Disruption of the GluA2 /GAPDH complex with an interfering peptide , TAT- GluA2 NT1-3-2 , protects cells against AMPAR-mediated excitotoxicity, which have been identified in in-vitro and in-vivo models of brain ischemia. We postulated that disruption of the GluA2 /GAPDH interaction with the TAT- GluA2 NT1-3-2 peptide would also protect against AMPAR-induced neuronal injury in an in-vivo model of status epilepticus (SE). In the present study, we divided pilocarpine -induced SE Wistar rats into three main groups: the TAT- GluA2 NT1-3-2 peptide group, the TAT- GluA2 NT-scram peptide group, and the normal saline group, and injected different doses of peptides stereotaxically into the hippocampus of SE rats to investigate whether the GluA2 /GAPDH interaction could be disrupted by our TAT- GluA2 NT1-3-2 peptide and determine its most appropriate dose. Then, the dose was administered stereotaxically at different time points after SE to determine the best administration time of neuronal protection. We found that the TAT- GluA2 NT1-3-2 peptide can disrupt the GluA2 /GAPDH interaction and protects against epilepsy-induced neuronal damage. The GluA2 /GAPDH interaction may be a novel therapeutic target for epilepsy.
研究领域:
神经科学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Nano Today
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2024
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IF 13.2
Ziyao Chen,Dongju Zhao,Meng Cheng,Fan Yang,Yining Liu,Jin Chang,Yan Dou
Alzheimer's disease (AD) has much higher incidence and mortality in women, largely attributed to the dramatic decline in estrogen levels during menopause. Therefore, tailoring therapeutic strategies targeting estrogen deprivation is essential to achieve female-specific AD treatment. Herein, we developed a multifunctional phytoestrogen nanomodulator (LQ-LPs) and revealed its feasibility and key pharmacological mechanisms for female-sensitive AD management. Benefiting from the greatly improved bioavailability and pharmacokinetics by liposomes , LQ-LPs amplified multiple biological properties of loaded liquiritigenin against estrogen-deprived AD progression, including enhancing synaptoprotective and anti-apoptotic effects through activation of ERβ/BDNF/ERK signaling, as well as simultaneously inhibiting Ca 2+ influx spike, oxidative damage , and cholinergic dysfunction caused by glutamate excitotoxicity . Taking advantage of the favorable brain-targeting properties conferred by intranasal delivery, LQ-LP administration exhibited remarkable anti-AD efficacy in reversing ovariectomy-induced neuropathology and rescuing cognitive deficits in estrogen-deprived AD mice. This work reveals for the first time the attractive promise of phytoestrogen-derived versatile nanotherapeutics for female-specific AD management, providing advanced insights into precision drug development for female AD.
研究领域:
药理学
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纳米技术
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神经科学
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老年医学
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女性健康研究
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）