Inhibitory effect of panaxytriol on BV-2 microglial cell activation

Hiramatsu, Genki; Uta, Daisuke; Mihara, Kenichi; Andoh, Tsugunobu; Kume, Toshiaki

doi:10.1016/j.jphs.2021.01.001

Cited by 10 publications

(9 citation statements)

References 21 publications

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“…The PCR experiment was performed as previously described [ 84 ] with minor modifications. The brain tissue was crushed with the SK mill (Token) and mixed with TRIzol (Thermo Fisher Scientific) for RNA extraction.…”

Section: Methodsmentioning

confidence: 99%

APP Knock-In Mice Produce E22P-Aβ Exhibiting an Alzheimer’s Disease-like Phenotype with Dysregulation of Hypoxia-Inducible Factor Expression

Maki

Sawahata

Akutsu

et al. 2022

IJMS

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Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that requires further pathological elucidation to establish effective treatment strategies. We previously showed that amyloid β (Aβ) toxic conformer with a turn at positions 22–23 is essential for forming highly toxic oligomers. In the present study, we evaluated phenotypic changes with aging in AD model AppNL-P-F/NL-P-F (NL-P-F) mice with Swedish mutation (NL), Iberian mutation (F), and mutation (P) overproducing E22P-Aβ, a mimic of toxic conformer utilizing the knock-in technique. Furthermore, the role of the toxic conformer in AD pathology was investigated. NL-P-F mice produced soluble toxic conformers from an early age. They showed impaired synaptic plasticity, glial cell activation, and cognitive decline, followed by the accumulation of Aβ plaques and tau hyperphosphorylation. In addition, the protein expression of hypoxia-inducible factor (HIF)-1α was increased, and gene expression of HIF-3α was decreased in NL-P-F mice. HIF dysregulation due to the production of soluble toxic conformers may be involved in AD pathology in NL-P-F mice. This study could reveal the role of a highly toxic Aβ on AD pathogenesis, thereby contributing to the development of a novel therapeutic strategy targeting the toxic conformer.

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Section: Methodsmentioning

confidence: 99%

APP Knock-In Mice Produce E22P-Aβ Exhibiting an Alzheimer’s Disease-like Phenotype with Dysregulation of Hypoxia-Inducible Factor Expression

Maki

Sawahata

Akutsu

et al. 2022

IJMS

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“…The cell culture protocol was followed in a previous study. 17) To induce the chronic condition of BV-2 microglia, we administered the following treatment: BV-2 microglia (1 × 10 5 cell/well) were cultured in 12-well plates overnight and preincubated for 24 h with LPS from Escherichia coli O111 (FUJIFILM Wako Pure Chemical Corporation, Osaka, Japan) and E22P-Aβ42. After that, the BV-2 microglia were washed and cultured in the culture medium for three days.…”

Section: Cell Culture and Treatmentmentioning

confidence: 99%

“…11) Griess Assay The Griess assay was conducted based on a previous study. 17) The concentration of nitrite, as an indicator of nitric oxide (NO), in the medium released by BV-2 microglia was determined.…”

Section: Cell Culture and Treatmentmentioning

confidence: 99%

Chronic Treatment with Aβ42 with a Toxic Conformer and LPS Induces Inflammatory Responses in BV-2 Microglia with Dysregulation of Hypoxia-Inducible Factor Expression

Maki

Sawahata

Uta

et al. 2023

Biological & Pharmaceutical Bulletin

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Amyloid β (Aβ) plays a key role in the pathology of Alzheimer's disease (AD) and is toxic owing to its ability to aggregate into oligomers and fibrils. Aβ has high aggregative ability and potent toxicity due to the "toxic turn" at positions 22 and 23. Furthermore, APP knock-in mice producing E22P-Aβ with the toxic turn exhibited AD-related phenotypes such as cognitive impairment, Aβ plaque accumulation, and tau hyperphosphorylation. In these mice, it is suggested that the activation of neuroinflammation and dysregulation of hypoxia-inducible factor (HIF) expression in the hippocampus contribute to the pathogenesis of AD-related phenotype. However, it remains unclear which cells are responsible for the dysregulation of HIF expression and the neuroinflammation which was induced by E22P-Aβ with the toxic turn. Here, we investigated the effects of chronic treatment with E22P-Aβ42 and lipopolysaccharides (LPS) on the inflammatory response in BV-2 microglia. Chronic treatment with E22P-Aβ42 and LPS increased nitric oxide production and the expression of interleukin-6 (IL-6), whereas it reduced the expression of HIF-1α and HIF-3α in BV-2 microglia. The reduction of HIF-1α caused by E22P-Aβ42 and LPS was milder than that caused by LPS. Furthermore, chronic treatment with E22P-Aβ42 and LPS increased the nuclear translocation of nuclear factor-kappaB (NF-κB). E22P-Aβ42 could enhance the inflammatory response of microglia with abnormal HIF signaling and contribute to the progression of AD pathology.

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“…Treatment. BV2 cells were treated with or without LPS (10 ng/mL), in the presence or absence of isoschaftoside (200 μM) [12]. For the cellular signaling pathway study, BV2 cultures were pretreated with CoCl 2 (100 μM) and Kc7f2 (10 μM), respectively, followed by lipopolysaccharide (10 ng/ mL) and/or isoschaftoside (200 μM) treatment accordingly.…”

Section: Cellmentioning

confidence: 99%

Isoschaftoside Inhibits Lipopolysaccharide-Induced Inflammation in Microglia through Regulation of HIF-1α-Mediated Metabolic Reprogramming

Guan

Sun

Wang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Isoschaftoside is a C-glycosyl flavonoid extracted from the root exudates of Desmodium uncinatum and Abrus cantoniensis. Previous studies suggested that C-glycosyl flavonoid has neuroprotective effects with the property of reducing oxidative stress and inflammatory markers. Microglia are key cellular mediators of neuroinflammation in the central nervous system. The aim of this study was to investigate the effect of isoschaftoside on lipopolysaccharide-induced activation of BV-2 microglial cells. The BV-2 cells were exposed to 10 ng/ml lipopolysaccharide and isoschaftoside (0–1000 μM). Isoschaftoside effectively inhibited lipopolysaccharide-induced nitric oxide production and proinflammatory cytokines including iNOS, TNF-α, IL-1β, and COX2 expression. Isoschaftoside also significantly reduced lipopolysaccharide-induced HIF-1α, HK2, and PFKFB3 protein expression. Induction of HIF-1α accumulation by CoCl2 was inhibited by isoschaftoside, while the HIF-1α specific inhibitor Kc7f2 mitigated the metabolic reprogramming and anti-inflammatory effect of isoschaftoside. Furthermore, isoschaftoside attenuated lipopolysaccharide-induced phosphorylation of ERK1/2 and mTOR. These results suggest that isoschaftoside can suppress inflammatory responses in lipopolysaccharide-activated microglia, and the mechanism was partly due to inhibition of the HIF-1α-mediated metabolic reprogramming pathway.

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Inhibitory effect of panaxytriol on BV-2 microglial cell activation

Cited by 10 publications

References 21 publications

APP Knock-In Mice Produce E22P-Aβ Exhibiting an Alzheimer’s Disease-like Phenotype with Dysregulation of Hypoxia-Inducible Factor Expression

APP Knock-In Mice Produce E22P-Aβ Exhibiting an Alzheimer’s Disease-like Phenotype with Dysregulation of Hypoxia-Inducible Factor Expression

Chronic Treatment with Aβ42 with a Toxic Conformer and LPS Induces Inflammatory Responses in BV-2 Microglia with Dysregulation of Hypoxia-Inducible Factor Expression

Isoschaftoside Inhibits Lipopolysaccharide-Induced Inflammation in Microglia through Regulation of HIF-1α-Mediated Metabolic Reprogramming

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