Gelidium amansii Attenuates Hypoxia/Reoxygenation-Induced Oxidative Injury in Primary Hippocampal Neurons through Suppressing GluN2B Expression

Abstract

Oxidative stress is known to be critically implicated in the pathophysiology of several neurological disorders, including Alzheimer’s disease and ischemic stroke. The remarkable neurotrophic activity of Gelidium amansii, which has been reported consistently in a series of our previous studies, inspired us to investigate whether this popular agarophyte could protect against hypoxia/reoxygenation (H/R)-induced oxidative injury in hippocampal neurons. The primary culture of hippocampal neurons challenged with H/R suffered from a significant loss of cell survival, accompanied by apoptosis and necrosis, DNA damage, generation of reactive oxygen species (ROS), and dissipation of mitochondrial membrane potential (ΔΨm), which were successfully attenuated when the neuronal cultures were preconditioned with ethanolic extract of G. amansii (GAE). GAE also attenuated an H/R-mediated increase of BAX and caspase 3 expressions while promoting Bcl-2 expression. Moreover, the expression of N-methyl-d-acetate receptor subunit 2B (GluN2B), an extrasynaptic glutamate receptor, was significantly repressed, while synaptic GluN2A expression was preserved in GAE-treated neurons as compared to those without GAE intervention. Together, this study demonstrates that GAE attenuated H/R-induced oxidative injury in hippocampal neurons through, at least in part, a potential neuroprotective mechanism that involves inhibition of GluN2B-mediated excitotoxicity and suppression of ROS production, and suggests that this edible seaweed could be a potential source of bioactive metabolites with therapeutic significance against oxidative stress-related neurodegeneration, including ischemic stroke and neurodegenerative diseases.

Mn3O4 nanoparticles: Synthesis, characterization and their antimicrobial and anticancer activity against A549 and MCF-7 cell lines

“…To determine MIC, Standard McFarland inoculum was prepared using Muller Hilton broth using overnight grown culture of the tested strains. 100 µg/ml Mn 3 O 4 NPs was added to the broth solution containing the standard culture and incubated at optimum temperature and time as for the previous protocol ( Hannan et al, 2020 ). The Muller Hilton agar plates were swabbed with the broth inoculum containing the Mn 3 O 4 NPs.…”

Neuroprotective Potentials of Marine Algae and Their Bioactive Metabolites: Pharmacological Insights and Therapeutic Advances

“…Porphyra yezoensis and its compound taurine facilitated neuronal development and maturation of primary hippocampal neurons [ 152 ]. Gelidium amansii [ 153 , 154 , 155 , 156 ], Sargassum fulvellum [ 157 ], Undaria pinnatifida and Saccharina japonica [ 158 ], Gracilariopsis chorda [ 150 , 159 ], and carrageenophyte Kappaphycus alvarezii [ 160 , 161 , 162 , 163 ] promoted neuronal morphology and functions. Of these, G. amansii that exhibited neuromodulatory potentials in several studies [ 153 , 154 , 155 , 156 ] could be the most promising candidate for further isolation of neurotrophic agents and thus expects special attention of natural product chemists.…”

“…In addition, extracts from several marine algae have shown neuroprotective activity in various in vitro models. The neuroprotective algae include Ulva conglobata that protected against glutamate-induced neurotoxicity in murine hippocampal HT22 cell line [ 108 ], Botryococcus braunii , and Nannochloropsis oculata against H 2 O 2 -induced cytotoxicity in dopaminergic SH-SY5Y cells [ 126 ], Padina pavonica, Sargassum muticum, Saccorhiza polyschides, Codium tomentosum , and Ulva compressa [ 214 ], and Bifurcaria bifurcata [ 215 ] against 6-hydroxidopamine-induced cytotoxicity in neuroblastoma cells, Cystoseira tamariscifolia and Cystoseira nodicaulis against H 2 O 2 -induced cytotoxicity in SH-SY5Y cells [ 127 ], Gracilaria corticata against aluminium-induced neurotoxicity in the hippocampus, and cerebral cortexes of rat brains [ 216 ], Australian macroalgae against Aβ 1-42-induced neurotoxicity in PC-12 cells [ 217 ], Ishige foliacea against H 2 O 2 - or Aβ-induced cell death in human neuroblastoma SH-SY5Y cells [ 128 ], Undaria pinnatifida against endoplasmic reticulum stress in hypothalamic neurons [ 218 ] and Gracilariopsis corda [ 219 ] and Gelidium amansii [ 153 ] against H/R-induced oxidative damage in primary hippocampal neurons, indicating that these algae could offer some potential compounds with encouraging neuroprotective activity, and, therefore, demand further investigation.…”

Neuroprotection Against Oxidative Stress: Phytochemicals Targeting TrkB Signaling and the Nrf2-ARE Antioxidant System

“…OS, oxidative stress; ER, endoplasmic reticulum; NFT, neurofibrillary tangle; AD, Alzheimer's disease; PD, Parkinson's disease; GSH, glutathione; GPx, glutathione peroxidase; SOD; superoxide dismutase; CAT, catalase; MDA, malondialdehyde; 8-OHdG, 8-hydroxy-2 -deoxyguanosine, NDD, neurodegenerative disease. (Sivandzade et al, 2019;Hannan et al, 2020a). Inappropriate levels of antiapoptotic proteins [e.g., Bcl-2 (B-cell lymphoma 2)] and proapoptotic proteins [e.g., Bax (Bcl-2-associated X protein)] contribute to mitochondrial dysfunction and OSinduced apoptosis (Wu et al, 2019).…”

“…Stroke is the second leading cause of death ( Donkor, 2018 ) and an important cause of permanent disability in adults worldwide ( Feigin et al, 2017 ), and is caused by a sudden interruption in brain blood supply due to vascular occlusion. As a consequence, a portion of the brain experiences oxygen and nutrient insufficiencies, which cause depolarization of neuronal membranes and glutamate surge into synapses, resulting in a cascade of events, including calcium overload, dissipation of mitochondrial membrane potentials, OS, and inflammation ( Sivandzade et al, 2019 ; Hannan et al, 2020a ). Inappropriate levels of antiapoptotic proteins [e.g., Bcl-2 (B-cell lymphoma 2)] and proapoptotic proteins [e.g., Bax (Bcl-2-associated X protein)] contribute to mitochondrial dysfunction and OS-induced apoptosis ( Wu et al, 2019 ).…”