Rutin Supplementation in the Diet has Protective Effects Against Toxicant-Induced Hippocampal Injury by Suppression of Microglial Activation and Pro-Inflammatory Cytokines

Koda, Tomoko; Kuroda, Yoshiki; Imai, Hideki

doi:10.1007/s10571-008-9344-4

Cited by 57 publications

(28 citation statements)

References 31 publications

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“…Another polyphenol, rutin, abundant in buckwheat, inhibits the activation of microglia, which might be responsible for the neuronal cell death induced by trimethyltin (Koda et al 2009). Polyphenols seem to somehow affect glial functions but the molecular mechanisms underlying these events remain totally unknown.…”

Section: Discussionmentioning

confidence: 99%

Grape Seed Extract Acting on Astrocytes Reveals Neuronal Protection Against Oxidative Stress via Interleukin-6-mediated Mechanisms

et al. 2009

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Grape polyphenols are known to protect neurons against oxidative stress. We used grape seed extract (GSE) from "Koshu" grapes (Vitis vinifera) containing a variety of polyphenols, and performed transcriptome analysis to determine the effects of GSE on primary cultures of astrocytes in the hippocampus. GSE upregulated various mRNAs for cytokines, among which interleukin-6 (IL-6) showed the biggest increase after treatment with GSE. The GSE-evoked increase in IL-6 mRNAs was confirmed by quantitative RT-PCR. We also detected IL-6 proteins by ELISA in the supernatant of GSE-treated astrocytes. We made an oxidative stress-induced neuronal cell death model in vitro using a neuron rich culture of the hippocampus. Treatment of the neurons with H(2)O(2) caused neuronal cell death in a time- and concentration-dependent manner. Exogenously applied IL-6 protected against the H(2)O(2)-induced neuronal cell death, which was mimicked by endogenous IL-6 produced by GSE-treated astrocytes. Taken together, GSE acting on astrocytes increased IL-6 production, which functions as a neuroprotective paracrine, could protect neuronal cells from death by oxidative stress.

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Section: Discussionmentioning

confidence: 99%

Grape Seed Extract Acting on Astrocytes Reveals Neuronal Protection Against Oxidative Stress via Interleukin-6-mediated Mechanisms

et al. 2009

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“…These effects were postulated to occur through the interaction of quercetin with AMP-activated protein kinase (AMPK). Further support for the actions of flavonols comes in the form of reports that rutin (0.75% (w/w), the rutiniside of quercetin (Koda et al, 2009) and fisetin, a flavonol mainly found in strawberries (Zheng et al, 2008) also inhibit neuroinflammatory processes. With regards to fisetin, its previously reported actions on cAMP response element-binding protein (CREB) phosphorylation in rat hippocampus and its ability to enhance memory (Maher et al, 2006), make it another candidate for neuroprotective potential in humans.…”

Section: Flavonolsmentioning

confidence: 99%

“…AMPK activation and iNOS, COX-2, TNF-a and IL-1b reduction. NF-jB inhibition In vivo (mice) Lu et al(2010)Rutin Hippocampal injury inhibition, microglial activation and IL-6/IL-1b reductionIn vivo (rats)Koda et al (2009) (continued on next page)…”

mentioning

confidence: 99%

Neuroinflammation: Modulation by flavonoids and mechanisms of action

Spencer

Vafeiadou

Williams

et al. 2012

Molecular Aspects of Medicine

276

213

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“…RUT is a robust antioxidant that possesses anti-inflammatory, antiarthritic, immunomodulatory, antidepressant, antiallergic, and anticancer properties along with potential cardioprotective, neuroprotective, and nephroprotective effects 22–24. RUT was found to inhibit proinflammatory cytokines and suppress microglial activation, which would otherwise lead to neuroinflammation 25. RUT was effective against trimethyltin-induced spatial memory deficits through amelioration of neuronal damage in hippocampal CA3 subregion, crucial for acquisition learning in rodents 26.…”

Section: Introductionmentioning

confidence: 99%

Rutin protects against neuronal damage in vitro and ameliorates doxorubicin-induced memory deficits in vivo in Wistar rats

Ramalingayya

Cheruku

Nayak

et al. 2017

DDDT

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Doxorubicin (DOX) is the most widely used broad-spectrum anticancer agent, either alone or in combination, for most cancers including breast cancer. Long-term use of chemotherapeutic agents to treat breast cancer patients results in cognitive complications with a negative impact on survivors’ quality of life. The study objective was to evaluate rutin (RUT) for its neuroprotective effect against DOX in human neuroblastoma (IMR32) cells in vitro and study its potential to ameliorate DOX-induced cognitive dysfunction in Wistar rats. Cell viability assay (3-[4,5 dimethyl thiazol-2-yl]-2,5-diphenyl tetrazolium bromide), neurite growth assay, detection of apoptosis by (acridine orange/ethidium bromide) staining, intracellular reactive oxygen species (ROS) assay, and flowcytometric analysis were carried out to assess neuroprotective potential against DOX. An in vivo study was conducted for assessing protective effect of RUT against memory deficit associated with DOX-induced chemobrain using object recognition task (ORT). Locomotion was assessed using open field test. Serum biochemistry, acetylcholinesterase, oxidative stress markers in hippocampus, and frontal cortex were assessed. Histopathological analysis of major organ systems was also carried out. Prior exposure to RUT at 100 µM protected IMR32 cells from DOX (1 µM) neurotoxicity. DOX exposure resulted in increased cellular death, apoptosis, and intracellular ROS generation with inhibition of neurite growth in differentiated IMR32 cells, which was significantly ameliorated by RUT. Cognitive dysfunction was induced in Wistar rats by administering ten cycles of DOX (2.5 mg/kg, intra-peritoneal, once in 5 days), as we observed significant impairment of episodic memory in ORT. Coadministration with RUT (50 mg/kg, per os) significantly prevented memory deficits in vivo without any confounding influence on locomotor activity. RUT also offered protection against DOX-induced myelosuppression, cardiotoxicity, and nephrotoxicity. In conclusion, RUT may be a possible adjuvant therapeutic intervention to alleviate cognitive and other complications associated with DOX chemotherapy.

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Rutin Supplementation in the Diet has Protective Effects Against Toxicant-Induced Hippocampal Injury by Suppression of Microglial Activation and Pro-Inflammatory Cytokines

Abstract: These results suggested that the neuroprotective effect of rutin on TMT-induced spatial memory impairment could be attributable to its inhibitory effect against microglial activation and its role in synapse formation via neurotrophic factors in the hippocampus.

Cited by 57 publications

References 31 publications

Grape Seed Extract Acting on Astrocytes Reveals Neuronal Protection Against Oxidative Stress via Interleukin-6-mediated Mechanisms

Grape Seed Extract Acting on Astrocytes Reveals Neuronal Protection Against Oxidative Stress via Interleukin-6-mediated Mechanisms

Neuroinflammation: Modulation by flavonoids and mechanisms of action

Rutin protects against neuronal damage in vitro and ameliorates doxorubicin-induced memory deficits in vivo in Wistar rats

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