A single fraction from<i>Uncaria sinensis</i>exerts neuroprotective effects against glutamate-induced neurotoxicity in primary cultured cortical neurons

Kim, Ha Neui; Jang, Ji Yeon; Choi, Byung Tae

doi:10.5115/acb.2015.48.2.95

Cited by 7 publications

(2 citation statements)

References 37 publications

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“…Cortical neurons were maintained in culture and excitotoxicity experiments were performed on the 9 th day of culture (DIV9). Previous studies demonstrated that neurons at DIV9 are appropriate to study glutamate toxicity as the cells are mature enough in terms of receptor expression and glutamate sensitivity [68][69][70][71]. An in vitro excitotoxicity model was established by treating cortical neurons with 100 µM glutamate for 1 hour followed by analysis at 24 hours post treatment.…”

Section: Establishment Of Glutamate Toxicity Model In Rat Primary Cormentioning

confidence: 99%

Neuroprotective derivatives of tacrine that target NMDA receptor and acetyl cholinesterase - Design, synthesis and biological evaluation

Remya

Vijayan

Reddy

et al. 2021

Preprint

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The complex and multifactorial nature of neuropsychiatric diseases demands multi-target drugs that can intervene with various sub-pathologies underlying disease progression. Targeting the impairments in cholinergic and glutamatergic neurotransmissions with small molecules has been suggested as one of the potential disease-modifying approaches for Alzheimer’s disease (AD). Tacrine, apotent inhibitor of acetylcholinesterase (AChE) is the first FDA approved drug for the treatment of AD. Tacrine is also a low affinity antagonist of N-methyl-D-aspartate receptor (NMDAR). However, tacrine was withdrawn from its clinical use later due to its hepato-toxicity. With an aim to develop novel high affinity multi-target directed ligands (MTDLs) against AChE and NMDAR, with reduced hepatotoxicity, we performed in silico structure-based modifications on tacrine, chemical synthesis of the derivatives and in vitro validation of their activities. Nineteen such derivatives showed inhibition with IC50 values in the range of 18.53±2.09 to 184.09±19.23 nM against AChE and 0.27±0.05 to 38.84±9.64 μM against NMDAR. Some of the selected compounds also protected rat primary cortical neurons from glutamate induced excitotoxicity. Two of the tacrine derived MTDLs, 201 and 208 exhibited in vivo efficacy in rats by protecting against behavioral impairment induced by administration of the excitotoxic agent, monosodium glutamate. Additionally, several of these synthesized compounds also exhibited promising inhibitory activities against butyrylcholinesterase and β-secretase. Given the therapeutic potential of MTDLs in disease-modifying therapy, our studies revealed several promising MTDLs of which 201 appears to be a potential candidate for immediate preclinical and clinical evaluations.

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Section: Establishment Of Glutamate Toxicity Model In Rat Primary Cormentioning

confidence: 99%

Neuroprotective derivatives of tacrine that target NMDA receptor and acetyl cholinesterase - Design, synthesis and biological evaluation

Remya

Vijayan

Reddy

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Cortical neurons were maintained in culture and excitotoxicity experiments were performed on the 9th day of culture (DIV9). Previous studies demonstrated that neurons at DIV9 are appropriate to study glutamate toxicity as the cells are mature enough in terms of NMDA receptor expression and glutamate sensitivity [86] , [87] , [88] , [89] , [90] . An in vitro excitotoxicity model was established by treating cortical neurons with 100 µM glutamate for 1 h followed by analysis at 24 h post treatment.…”

Section: Resultsmentioning

confidence: 99%

Neuroprotective derivatives of tacrine that target NMDA receptor and acetyl cholinesterase – Design, synthesis and biological evaluation

Remya

Dileep

Reddy

et al. 2021

Computational and Structural Biotechnology Journal

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Neuroprotection by chotosan , a Kampo formula, against glutamate excitotoxicity involves the inhibition of GluN2B-, but not GluN2A-containing NMDA receptor-mediated responses in primary cultured cortical neurons

Sasaki-Hamada

Suzuki

Sanai

et al. 2017

Journal of Pharmacological Sciences

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Chotosan (CTS), a traditional herbal formula called Kampo medicine, was shown to be effective in the treatment of vascular dementia in a clinical study, and exerted protective effects against transient cerebral ischemia-induced cognitive impairment in mice. In the present study, we investigated the neuroprotective effects of CTS using primary cultured rat cortical neurons. CTS (250-1000 μg/mL) inhibited neuronal death induced by 100 μM glutamate. This glutamate-induced neuronal death was blocked by a GluN2B-, but not GluN2A-containing NMDA receptor antagonist. Therefore, the neuroprotective effects of CTS were related to an inhibition of GluN2B-containing NMDA receptor-mediated responses.

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A single fraction fromUncaria sinensisexerts neuroprotective effects against glutamate-induced neurotoxicity in primary cultured cortical neurons

Cited by 7 publications

References 37 publications

Neuroprotective derivatives of tacrine that target NMDA receptor and acetyl cholinesterase - Design, synthesis and biological evaluation

Neuroprotective derivatives of tacrine that target NMDA receptor and acetyl cholinesterase - Design, synthesis and biological evaluation

Neuroprotective derivatives of tacrine that target NMDA receptor and acetyl cholinesterase – Design, synthesis and biological evaluation

Neuroprotection by chotosan , a Kampo formula, against glutamate excitotoxicity involves the inhibition of GluN2B-, but not GluN2A-containing NMDA receptor-mediated responses in primary cultured cortical neurons

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