KHG21834 attenuates glutamate-induced mitochondrial damage, apoptosis, and NLRP3 inflammasome activation in SH-SY5Y human neuroblastoma cells

Yang, Seung-Ju; Han, Arum; Kim, Eun-A.; Yang, Ji Woong; Ahn, Jee-Yin; Na, Jung-Min; Cho, Sung‐Woo

doi:10.1016/j.ejphar.2019.172412

Cited by 16 publications

(39 citation statements)

References 68 publications

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“…Therefore, to further confirm the antiapoptotic effect of OST-NE, Bax and caspase-3 were determined. L-Glu increased the expression of Bax and caspase-3, which was consistent with other studies [ 57 , 58 ]. OST-NE reversed the increased expression of Bax and caspase-3 induced by L-Glu.…”

Section: Discussionsupporting

confidence: 93%

Osthole‐Loaded Nanoemulsion Enhances Brain Target in the Treatment of Alzheimer’s Disease via Intranasal Administration

Song

Wang

et al. 2021

Oxidative Medicine and Cellular Longevity

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Osthole (OST) is a natural coumarin compound that exerts multiple pharmacologic effects. However, the poor water solubility and the low oral absorption of OST limit its clinical application for the treatment of neurologic diseases. A suitable preparation needs to be tailored to evade these unfavourable properties of OST. In this study, an OST nanoemulsion (OST-NE) was fabricated according to the pseudoternary phase diagram method, which was generally used to optimize the prescription in light of the solubility of OST in surfactants and cosurfactants. The final composition of OST-NE was 3.6% of ethyl oleate as oil phase, 11.4% of the surfactant (polyethylene glycol ester of 15-hydroxystearic acid: polyoxyethylene 35 castor oil = 1 : 1 ), 3% of polyethylene glycol 400 as cosurfactant, and 82% of the aqueous phase. The pharmacokinetic study of OST-NE showed that the brain-targeting coefficient of OST was larger by the nasal route than that by the intravenous route. Moreover, OST-NE inhibited cell death, decreased the apoptosis-related proteins (Bax and caspase-3), and enhanced the activity of antioxidant enzymes (superoxide dismutase and glutathione) in L-glutamate-induced SH-SY5Y cells. OST-NE improved the spatial memory ability, increased the acetylcholine content in the cerebral cortex, and decreased the activity of acetylcholinesterase in the hippocampus of Alzheimer’s disease model mice. In conclusion, this study indicates that the bioavailability of OST was improved by using the OST-NE via the nasal route. A low dose of OST-NE maintained the neuroprotective effects of OST, such as inhibiting apoptosis and oxidative stress and regulating the cholinergic system. Therefore, OST-NE can be used as a possible alternative to improve its bioavailability in the prevention and treatment of Alzheimer’s disease.

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Section: Discussionsupporting

confidence: 93%

Osthole‐Loaded Nanoemulsion Enhances Brain Target in the Treatment of Alzheimer’s Disease via Intranasal Administration

Song

Wang

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…The amino acid glutamate has previously been demonstrated to increase during ischemic conditions of glucose deprivation and hypoxia, which induced ER stress and TXNIP expression concurrent with IL-1β release [111]. Consistent with this finding, another study reported that glutamate activates the NLRP3 inflammasome via induction of ER oxidative stress [112]. Additionally, glutamate induces the influx of calcium and disrupts mitochondrial potential, which could be reversed using a synthetic antioxidative agent [112].…”

Section: Amino Acid Metabolismmentioning

confidence: 70%

“…Consistent with this finding, another study reported that glutamate activates the NLRP3 inflammasome via induction of ER oxidative stress [112]. Additionally, glutamate induces the influx of calcium and disrupts mitochondrial potential, which could be reversed using a synthetic antioxidative agent [112].…”

Section: Amino Acid Metabolismmentioning

confidence: 74%

The NLRP3 Inflammasome: Metabolic Regulation and Contribution to Inflammaging

Meyers

Zhu

2020

Cells

133

100

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In response to inflammatory stimuli, immune cells reconfigure their metabolism and bioenergetics to generate energy and substrates for cell survival and to launch immune effector functions. As a critical component of the innate immune system, the nucleotide-binding and oligomerization domain, leucine-rich repeat, and pyrin domain-containing 3 (NLRP3) inflammasome can be activated by various endogenous and exogenous danger signals. Activation of this cytosolic multiprotein complex triggers the release of the pro-inflammatory cytokines interleukin (IL)-1β and IL-18 and initiates pyroptosis, an inflammatory form of programmed cell death. The NLRP3 inflammasome fuels both chronic and acute inflammatory conditions and is critical in the emergence of inflammaging. Recent advances have highlighted that various metabolic pathways converge as potent regulators of the NLRP3 inflammasome. This review focuses on our current understanding of the metabolic regulation of the NLRP3 inflammasome activation, and the contribution of the NLRP3 inflammasome to inflammaging.

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“…Under physiological conditions, inflammasome‐induced IL‐1β expression is essential as trophic support to promote long‐term potentiation and memory formation (Yirmiya, Winocur, & Goshen, 2002). However, at high levels, IL‐1β becomes excitotoxic, alters synaptic activity (Huang, Smith, Ibáñez‐Sandoval, Sims, & Friedman, 2011) and modulates monoaminergic and glutamatergic synaptic transmission (Hu, Sheng, Ehrlich, Peterson, & Chao, 2000; Ramamoorthy et al, 1995; Yang et al, 2019). Interestingly, it has been suggested that the antidepressant effect of ketamine that reverses LPS‐induced depressive‐like behaviours in mice correlates with hippocampal over‐expression of NLRP3 and IL‐1β (Li et al, 2019).…”

Section: Immunity Central Nervous System and Neuroinflammationmentioning

confidence: 99%

“…and modulates monoaminergic and glutamatergic synaptic transmission (Hu, Sheng, Ehrlich, Peterson, & Chao, 2000;Ramamoorthy et al, 1995;Yang et al, 2019). Interestingly, it has been suggested that the antidepressant effect of ketamine that reverses LPS-induced depressive-like behaviours in mice correlates with hippocampal over-expression of NLRP3 and IL-1β (Li et al, 2019).…”

mentioning

confidence: 99%