Repeated systemic administration of the nutraceutical alpha-linolenic acid exerts neuroprotective efficacy, an antidepressant effect and improves cognitive performance when given after soman exposure

Pan, Hongna; Piermartiri, Tetsadê C. B.; Chen, Jun; McDonough, John H.; Oppel, Craig; Driwech, Wafae; Winter, K; McFarland, Emylee; Black, Katelyn L.; Figueiredo, Taíza H.; Grunberg, Neil E.; Marini, Ann M.

doi:10.1016/j.neuro.2015.09.006

Cited by 27 publications

(28 citation statements)

References 106 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, derivative compounds bearing an oxazolopyridine core were identified as sirtuin activators and proposed to be used for treating a wide variety of diseases associated with aging [ 62 ]. Neuroprotective properties of α-linolenic acid, a plant-derived essential omega-3 polyunsaturated fatty acid, were also highlighted in several recent studies [ 63 – 65 ]. However, due to the complexity of crude extracts and limitation of LC-MS analysis, the compounds proposed here need to be confirmed in the near future with other identification techniques such as liquid chromatography-tandem mass spectrometry (LC-MS/MS) or quantitative HPLC.…”

Section: Discussionmentioning

confidence: 91%

Ethanolic extract of Streblus asper leaves protects against glutamate-induced toxicity in HT22 hippocampal neuronal cells and extends lifespan of Caenorhabditis elegans

Prasansuklab

Meemon

Sobhon

et al. 2017

BMC Complement Altern Med

View full text Add to dashboard Cite

BackgroundAlthough such local herb as Streblus asper (family Moraceae) has long been recognized for traditional folk medicines and important ingredient of traditional longevity formula, its anti-neurodegeneration or anti-aging activity is little known. This study aimed to investigate the neuroprotective effect of S. asper leaf extracts (SA-EE) against toxicity of glutamate-mediated oxidative stress, a crucial factor contributing to the neuronal loss in age-associated neurodegenerative diseases and the underlying mechanism as well as to evaluate its longevity effect.MethodsUsing mouse hippocampal HT22 as a model for glutamate oxidative toxicity, we carried out MTT and LDH assays including Annexin V-FITC/propidium iodide staining to determine the SA-EE effect against glutamate-induced cell death. Antioxidant activities of SA-EE were evaluated using the radical scavenging and DCFH-DA assays. To elucidate the underlying mechanisms, SA-EE treated cells were analyzed for the expressions of mRNA and proteins interested by immunofluorescent staining, western blot analysis and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) techniques. The longevity effect of SA-EE was examined on C. elegans by lifespan assay.ResultsWe demonstrate that a concentration-dependent reduction of glutamate-induced cytotoxicity was significant after SA-EE treatment as measured by MTT and LDH assays. Annexin V-FITC/propidium iodide and immunofluorescent staining showed that co-treatment of glutamate with SA-EE significantly reduced apoptotic-inducing factor (AIF)-dependent apoptotic cell death. DCFH-DA assay revealed that this extract was capable of dose dependently attenuating the ROS caused by glutamate. Western blot analysis and qRT-PCR showed that nuclear factor erythroid 2-related factor 2 (Nrf2) protein levels in the nucleus, as well as mRNA levels of antioxidant-related genes under Nrf2 regulation were significantly increased by SA-EE. Furthermore, this extract was capable of extending the lifespan of C. elegans.ConclusionsSA-EE possesses both longevity effects and neuroprotective activity against glutamate-induced cell death, supporting its therapeutic potential for the treatment of age-associated neurodegenerative diseases.

show abstract

Section: Discussionmentioning

confidence: 91%

Ethanolic extract of Streblus asper leaves protects against glutamate-induced toxicity in HT22 hippocampal neuronal cells and extends lifespan of Caenorhabditis elegans

Prasansuklab

Meemon

Sobhon

et al. 2017

BMC Complement Altern Med

View full text Add to dashboard Cite

show abstract

“…It is noteworthy that this compound also exerts a beneficial effect on cognition and memory enhancement [ 32 , 62 , 63 ]. Furthermore, we proposed 6 additional compounds, namely, betaine, verbacoside, skimmin, loliolide, andrographolide, and α-linolenic acid, which were identified according to m/z values against the database and selected due to either earlier reports of their antioxidant defense function or their potential neuroprotection roles [ 64 – 72 ]. Nevertheless, due to the complexity of crude extracts and limitations of the single mass analysis, all compounds proposed here need to be confirmed using other identification techniques, such as quantitative HPLC or liquid chromatography-tandem mass spectrometry (LC-MS/MS).…”

Section: Discussionmentioning

confidence: 99%

Acanthus ebracteatus leaf extract provides neuronal cell protection against oxidative stress injury induced by glutamate

Prasansuklab

Tencomnao

2018

BMC Complement Altern Med

View full text Add to dashboard Cite

BackgroundAcanthus ebracteatus (AE), an herb native to Asia, has been recognized in traditional folk medicine not only for its antioxidant properties and various pharmacological activities but also as an ingredient of longevity formulas. However, its anti-neurodegenerative potential is not yet clearly known. This work aimed to evaluate the protective effect of AE leaf extract against glutamate-induced oxidative damage in mouse hippocampal HT22 cells, a neurodegenerative model system due to a reduction in glutathione levels and an increase in reactive oxygen species (ROS).MethodsCell viability, apoptosis, and ROS assays were performed to assess the protective effect of AE leaf extract against glutamate-induced oxidative toxicity in HT22 cells. The antioxidant capacity of AE was evaluated using in vitro radical scavenging assays. The subcellular localization of apoptosis-inducing factor (AIF) and the mRNA and protein levels of genes associated with the nuclear factor erythroid 2–related factor 2 (Nrf2) antioxidant system were determined to elucidate the mechanisms underlying the neuroprotective effect of AE leaf extract.ResultsWe demonstrated that AE leaf extract is capable of attenuating the intracellular ROS generation and HT22 cell death induced by glutamate in a concentration-dependent manner. Co-treatment of glutamate with the extract significantly reduced apoptotic cell death via inhibition of AIF nuclear translocation. The increases in Nrf2 levels in the nucleus and gene expression levels of antioxidant-related downstream genes under Nrf2 control were found to be significant in cells treated with the extract.ConclusionsThe results suggested that AE leaf extract possesses neuroprotective activity against glutamate-induced oxidative injury and may have therapeutic potential for the treatment of neurodegenerative diseases associated with oxidative stress.

show abstract

“…Cognitive and behavioral deficits have also been observed in animal models of OP nerve agents. Learning and memory impairments were demonstrated in rodents exposed to OP nerve agents [69,70,71,72,73] including deficits in the Morris water maze and passive avoidance test which are hippocampal-dependent memory tasks [74,75,76]. Deficits in fear-based learning were also shown to be present after exposure to OP nerve agents [77,78].…”

Section: Organophosphate (Op) Nerve Agent-induced Excitotoxicity Amentioning

confidence: 99%

α-Linolenic Acid, A Nutraceutical with Pleiotropic Properties That Targets Endogenous Neuroprotective Pathways to Protect against Organophosphate Nerve Agent-Induced Neuropathology

et al. 2015

Self Cite

View full text Add to dashboard Cite

α-Linolenic acid (ALA) is a nutraceutical found in vegetable products such as flax and walnuts. The pleiotropic properties of ALA target endogenous neuroprotective and neurorestorative pathways in brain and involve the transcription factor nuclear factor kappa B (NF-κB), brain-derived neurotrophic factor (BDNF), a major neuroprotective protein in brain, and downstream signaling pathways likely mediated via activation of TrkB, the cognate receptor of BDNF. In this review, we discuss possible mechanisms of ALA efficacy against the highly toxic OP nerve agent soman. Organophosphate (OP) nerve agents are highly toxic chemical warfare agents and a threat to military and civilian populations. Once considered only for battlefield use, these agents are now used by terrorists to inflict mass casualties. OP nerve agents inhibit the critical enzyme acetylcholinesterase (AChE) that rapidly leads to a cholinergic crisis involving multiple organs. Status epilepticus results from the excessive accumulation of synaptic acetylcholine which in turn leads to the overactivation of muscarinic receptors; prolonged seizures cause the neuropathology and long-term consequences in survivors. Current countermeasures mitigate symptoms and signs as well as reduce brain damage, but must be given within minutes after exposure to OP nerve agents supporting interest in newer and more effective therapies. The pleiotropic properties of ALA result in a coordinated molecular and cellular program to restore neuronal networks and improve cognitive function in soman-exposed animals. Collectively, ALA should be brought to the clinic to treat the long-term consequences of nerve agents in survivors. ALA may be an effective therapy for other acute and chronic neurodegenerative disorders.

show abstract

Repeated systemic administration of the nutraceutical alpha-linolenic acid exerts neuroprotective efficacy, an antidepressant effect and improves cognitive performance when given after soman exposure

Cited by 27 publications

References 106 publications

Ethanolic extract of Streblus asper leaves protects against glutamate-induced toxicity in HT22 hippocampal neuronal cells and extends lifespan of Caenorhabditis elegans

Ethanolic extract of Streblus asper leaves protects against glutamate-induced toxicity in HT22 hippocampal neuronal cells and extends lifespan of Caenorhabditis elegans

Acanthus ebracteatus leaf extract provides neuronal cell protection against oxidative stress injury induced by glutamate

α-Linolenic Acid, A Nutraceutical with Pleiotropic Properties That Targets Endogenous Neuroprotective Pathways to Protect against Organophosphate Nerve Agent-Induced Neuropathology

Contact Info

Product

Resources

About