Auraptene/Naringin-Rich Fruit Juice of &lt;i&gt;Citrus kawachiensis&lt;/i&gt; (Kawachi Bankan) Prevents Ischemia-Induced Neuronal Cell Death in Mouse Brain through Anti-Inflammatory Responses

Okuyama, Satoshi; Katoh, Mako; Kanzaki, Tomoko; Kotani, Yoshimi; Amakura, Yoshiaki; Yoshimura, Manabu; Fukuda, Naohiro; Tamai, Takahisa; Sawamoto, Atsushi; Nakajima, Miki; Furukawa, Yoshiko

doi:10.3177/jnsv.65.66

Cited by 16 publications

(6 citation statements)

References 28 publications

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“…In addition, we recently reported that the peel of C. kawachiensis, a rich source of AUR, is neuroprotective in LPS-induced systemic inflammatory model mice [4], senescence-accelerated mice [29], global cerebral ischemia model mice [30], type-2 diabetic db/db mice [31], and an LPS-induced mouse model of PD [32]. We also showed that the AUR-rich fruit juice of C. kawachiensis, made by the addition of peel paste to the raw juice, significantly suppressed the ischemia-induced neuronal cell death in the hippocampus of ischemic mice [33] and that this juice contributed to the preservation of cognitive function of healthy volunteers [34]. In these reports, we confirmed that the basis of this neuroprotective ability might have been anti-inflammatory effect of AUR.…”

Section: Discussionmentioning

confidence: 76%

Citrus Auraptene Induces Glial Cell Line-Derived Neurotrophic Factor in C6 Cells

Furukawa

Hara

Nakaya

et al. 2019

IJMS

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We previously demonstrated that auraptene (AUR), a natural coumarin derived from citrus plants, exerts anti-inflammatory effects in the brain, resulting in neuroprotection in some mouse models of brain disorders. The present study showed that treatment with AUR significantly increased the release of glial cell line-derived neurotrophic factor (GDNF), in a dose- and time-dependent manner, by rat C6 glioma cells, which release was associated with increased expression of GDNF mRNA. These results suggest that AUR acted as a neuroprotective agent in the brain via not only its anti-inflammatory action but also its induction of neurotrophic factor. We also showed that (1) the AUR-induced GDNF production was inhibited by U0126, a specific inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) 1/2, and by H89, a specific inhibitor of protein kinase A (PKA); and (2) AUR induced the phosphorylation of cAMP response element-binding protein (CREB), a transcription factor located within the nucleus. These results suggest that AUR-stimulated gdnf gene expression was up-regulated through the PKA/ERK/CREB pathway in C6 cells.

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Section: Discussionmentioning

confidence: 76%

Citrus Auraptene Induces Glial Cell Line-Derived Neurotrophic Factor in C6 Cells

Furukawa

Hara

Nakaya

et al. 2019

IJMS

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“…In the future, we would like to investigate the effect of AUR on microglial cells, for example, using N9 cells. The peel of Citrus grandis (Kawachi bankan), a rich source of AUR [21], might become a natural medicine in the future, as suggested previously [22][23][24][25][26][27].…”

Section: Discussionmentioning

confidence: 95%

Citrus Auraptene Induces Expression of Brain-Derived Neurotrophic Factor in Neuro2a Cells

et al. 2020

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(1) Background: Our published data have indicated that (1) auraptene (AUR), a citrus ingredient, has neuroprotective effects on the mouse brain, owing to its ability to suppress inflammation, such as causing a reduction in hyperactivation of microglia and astrocytes; (2) AUR has the ability to trigger phosphorylation (activation) of extracellular signal-related kinase (ERK) and cAMP response element-binding protein (CREB) in neuronal cells; (3) AUR has the ability to induce glial cell line-derived neurotrophic factor (GDNF) synthesis/secretion in rat C6 glioma cells. The well-established fact that the ERK-CREB pathway plays an important role in the production of neurotrophic factors, including GDNF and brain-derived neurotrophic factor (BDNF), prompted us to investigate whether AUR would also have the ability to induce BDNF expression in neuronal cells. (2) Methods: Mouse neuroblastoma neuro2a cells were cultured and the effects of AUR on BDNF mRNA expression and protein content were evaluated by RT-PCR and ELISA, respectively. (3) Results: The levels of BDNF mRNA and secreted BDNF were significantly increased by AUR in a dose- and time-dependent manner in neuro2a cells. (4) Conclusion: The induction of BDNF in neuronal cells might be, in part, one of the mechanisms accounting for the neuroprotective effects of AUR.

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“…Naringin has a strong ONOO − scavenging ability and can inhibit ONOO − -mediated mitosis, NADPH oxidase, iNOS, NO production, and protect against ischemia-reperfusion injury [63]. In addition, naringin can reduce neuronal death and inhibit the over activation of astrocytes and microglia after ischemic injury in tMCAO mice [64,65]. In the OGD model of neuronal cells, naringin pretreatment can activate the PI3K/AKT pathway, improve cell viability, and inhibit the secretion of inflammatory factors such as TNF-α and IL-6 [66].…”

Section: Flavonoidsmentioning

confidence: 99%

Research progress of natural products for the treatment of ischemic stroke

Li¹,

Zhao²,

Qiao³

et al. 2022

J. Integr. Neurosci.

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Stroke is a leading cause of death and disability world-widely. The incidence rate of stroke has been increasing due to the aging population and lifestyle changes. At present, the only drug approved by the US Food and Drug Administration (FDA) for the treatment of ischemic stroke is tissue plasminogen activator (t-PA), but its clinical application is greatly limited because of its narrow time window and bleeding risk. Natural products have a long history of being used in traditional medicine with good safety, making them an important resource for the development of new drugs. Indeed, some natural products can target a variety of pathophysiological processes related to stroke, including oxidative stress, in lammation and neuronal apoptosis. Therefore, the development of high-e ficiency, lowtoxicity, safe and cheap active substances from natural products is of great significance for improving the treatment alternatives of patients with stroke. This article reviews the neuroprotective e fects of 33 natural compounds by searching recent related literature. Among them, puerarin, pinocembrin, quercetin, epigallocatechin-3-gallate (EGCG), and resveratrol have great potential in the clinical treatment of ischemic stroke. This review will provide a powerful reference for screening natural compounds with potential clinical application value in ischemic stroke or synthesizing new neuroprotective agents with natural compounds as lead compounds.

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Auraptene/Naringin-Rich Fruit Juice of <i>Citrus kawachiensis</i> (Kawachi Bankan) Prevents Ischemia-Induced Neuronal Cell Death in Mouse Brain through Anti-Inflammatory Responses

Cited by 16 publications

References 28 publications

Citrus Auraptene Induces Glial Cell Line-Derived Neurotrophic Factor in C6 Cells

Citrus Auraptene Induces Glial Cell Line-Derived Neurotrophic Factor in C6 Cells

Citrus Auraptene Induces Expression of Brain-Derived Neurotrophic Factor in Neuro2a Cells

Research progress of natural products for the treatment of ischemic stroke

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