Quercetin Alleviates Demyelination Through Regulating Microglial Phenotype Transformation to Mitigate Neuropsychiatric Symptoms in Mice with Vascular Dementia

Tan, Zihu; Yang, Guang; Qiu, Jing; Yan, Wei; Liu, Yu; Ma, Zhengling; Li, Jia; Liu, Jing; Shan, Nan

doi:10.1007/s12035-021-02712-3

Cited by 16 publications

(9 citation statements)

References 49 publications

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“…Quercetin, an important component of Epimedium, can improve cognitive impairment and enhance memory during VaD (Jakaria et al, 2019 ). It facilitated secretion of anti-inflammatory cytokines (IL-4 and IL-10) and in turn decreased production of pro-inflammatory factors (TNF-α and IL-1β) due to regulating microglial phenotype transformation (Tan et al, 2022 ). Its strong antioxidant and anti-inflammatory properties can effectively inhibit oxidative stress-mediated neuronal damage and down-regulate the expression of chemokines and pro-inflammatory cytokines to reduce the inflammatory response of neurons (Suganthy et al, 2016 ; Yang et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, the inflammation during VaD can initiate the apoptosis and pyroptosis of oligodendrocytes (Márquez-Martín et al, 2012 ), which may impair the synthesis and repair of myelin and exacerbate the demyelination process (Poh et al, 2021 ). Research showed that quercetin can alleviate the extent of demyelination and the thickness decrease of myelin sheath, thereafter, enhancing the microglial engulfment ability of myelin fragments in vitro and in vivo (Tan et al, 2022 ). In this study, the cellular component (CC) terms identified by GO enrichment analysis of the hub genes enriched in extracellular space, caveola, cell surface, plasma membrane, extracellular matrix, neuron projection, and axon.…”

Section: Discussionmentioning

confidence: 99%

“…An increasing number of recent studies have shown the efficacy of Epimedium-containing formulations in brain diseases, including Alzheimer’s dementia, ischaemic brain diseases, vascular dementia, depression, and aging (Zhang, 1999 ; Du and Yao, 2000 ; Yi and Gu, 2012 ; Lin et al, 2013 ). Modern pharmacological studies have also demonstrated that Quercetin, luteolin, kaempferol, Icariin, the active components of Epimedium, contribute to the alleviation of VaD (Zhou et al, 2011 ; Deng et al, 2017 ; Zhou and Li, 2020 ; Tan et al, 2022 ). However, systemic research on the direct role and mechanism of Epimedium in VaD is still lacking.…”

Section: Introductionmentioning

confidence: 99%

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Molecular mechanism of Epimedium in the treatment of vascular dementia based on network pharmacology and molecular docking

Xie

Tang

Liu

et al. 2022

Front. Aging Neurosci.

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Backgroud: Vascular dementia is the second most common cause of dementia after Alzheimer’s disease, accounting for an estimated 15% of cases. Recently, Epimedium has attracted great attention for its potential neuroprotective benefit. However, the direct role and mechanism of Epimedium on vascular dementia still lack systematic research. To systematically explore the possible pharmacological mechanism of Epimedium for the treatment of vascular dementia, network pharmacology, molecular docking, combined with experiment validation were conducted.Methods: The bioactive compounds and targets of Epimedium were obtained from the TCMSP database. The potential targets of vascular dementia were identified from the DrugBank, OMIM, Genecards, Therapeutic Target Database, and DisGeNET databases. GO and KEGG pathway analyses were performed. Molecular docking was applied to validate the interaction between active components and hub targets. The bilateral common carotid artery occlusion (BCCAO) method was used for construction of a vascular dementia model in mice. The effects of Epimedium on learning and memory ability were examined by behavioral tests. The mechanisms of the cerebral protective effects of Epimedium were evaluated by WB, RT-PCR, and immunofluorescence.Results: A total of 23 Epimedium active ingredients, and 71 intersecting targets of Epimedium against vascular dementia were obtained. The top five hub targets AKT1, TNF, IL1β, IL6, and MMP9 were identified, and molecular docking showed good binding. GO enrichment showed a total of 602 enrichment results, with 458 (80.56%) key targets mainly focused on biological processes (BP). The response to hypoxia, positive regulation of nitric oxide biosynthetic process, aging, inflammatory response, cellular response to lipopolysaccharide, negative regulation of apoptotic process were well ranked. KEGG pathway enrichment analysis identified the TNF signaling pathway as an important pathway, with the MAPK/extracellular signal-regulated kinase (ERK) and NF-κB signaling pathways as the key pathways involved. Consistently, in vivo experiments showed that Epimedium treatment improved learning and memory functions in mice with vascular dementia. In addition, Epimedium attenuated the activation of microglia and astrocytes in the hippocampal region after BCCAO. RT-qPCR and Western blot analysis showed that Epimedium not only affected the expression of AKT, TNF, IL1β, IL6, and MMP9, but also suppressed the TNF signaling pathway.Conclusion: Epimedium may exert a protective effect against vascular dementia through the alleviation of oxidative stress, neuroinflammation, BBB dysfunction, apoptosis through TNF signaling pathway. This study explored the mechanism of Epimedium on vascular dementia systematically through network pharmacological and in vivo experiment approach, which provides insight into the treatment of vascular dementia.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Molecular mechanism of Epimedium in the treatment of vascular dementia based on network pharmacology and molecular docking

Xie

Tang

Liu

et al. 2022

Front. Aging Neurosci.

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“…The third aspect is to search for marketed drugs with therapeutic effects on myelin sheath injury, such as clobetasol ( Su et al, 2020 ), trifluoperazine ( Khaledi et al, 2021 ), sildenafil ( Nunes et al, 2016 ), adrenomedullin ( Maki et al, 2015 ), omega-3 polyunsaturated fatty acids ( Pu et al, 2013 ), ascorbic acid ( Nam et al, 2019 ), fluoxetine ( Li et al, 2020a ), melatonin ( Abo Taleb and Alghamdi, 2020 ) and a mixture containing docosahexaenoic acid, arachidonic acid, vitamin B12, vitamin B9, iron and sphingomyelin ( Hauser et al, 2020 ). The fourth facet is to investigate Chinese herbal medicine and its extract that can treat myelin sheath injury, such as Honokiol ( Tan et al, 2022a ), Astaxanthin ( Lotfi et al, 2021 ), Shenling oral liquid ( Liu et al, 2020b ; Zheng et al, 2021 ), Rosmarinic acid ( Li et al, 2020b ), Naringenin ( Rong et al, 2017 ), Salvianolic acid B (78), Tanshinone IIA (79), Bushen Yisui capsule ( Rabinovich and Kacen, 2012 ; Zhao et al, 2018 ), the herbal medicine Ninjin ‘yoeito ( Seiwa et al, 2007 ) and Quercetin ( Naeimi et al, 2018 ; Tan et al, 2022b ), among other medicines.…”

Section: Deficiencies In the Study Of Myelin Sheath Injury And Treatm...mentioning

confidence: 99%

Myelin sheath injury and repairment after subarachnoid hemorrhage

Chen

Guo

et al. 2023

Front. Pharmacol.

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Subarachnoid hemorrhage (SAH) can lead to damage to the myelin sheath in white matter. Through classification and analysis of relevant research results, the discussion in this paper provides a deeper understanding of the spatiotemporal change characteristics, pathophysiological mechanisms and treatment strategies of myelin sheath injury after SAH. The research progress for this condition was also systematically reviewed and compared related to myelin sheath in other fields. Serious deficiencies were identified in the research on myelin sheath injury and treatment after SAH. It is necessary to focus on the overall situation and actively explore different treatment methods based on the spatiotemporal changes in the characteristics of the myelin sheath, as well as the initiation, intersection and common action point of the pathophysiological mechanism, to finally achieve accurate treatment. We hope that this article can help researchers in this field to further clarify the challenges and opportunities in the current research on myelin sheath injury and treatment after SAH.

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“…However, quercetin can upregulate the expression of H2AX and mitochondrial transcription factor A to minimize the damages in the mitochondrial structure and activity, while also reducing axonal and neuronal detriments ( 135 ). Also, quercetin can reduce the damage of myelin loss to white matter after cerebral hypoperfusion by promoting the secretion of IL-10 by M2-like microglia ( 136 ). Quercetin decreases the apoptosis of cortical neurons, improves degenerative lesions of the central nervous system, and plays a neuroprotective role in Alzheimer's disease ( 137 ).…”

Section: Quercetin Regulates the Mtor Signaling Pathway To Improve Scimentioning

confidence: 99%

Quercetin Can Improve Spinal Cord Injury by Regulating the mTOR Signaling Pathway

Wang

Botchway

et al. 2022

Front. Neurol.

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The pathogenesis of spinal cord injury (SCI) is complex. At present, there is no effective treatment for SCI, with most current interventions focused on improving the symptoms. Inflammation, apoptosis, autophagy, and oxidative stress caused by secondary SCI may instigate serious consequences in the event of SCI. The mammalian target of rapamycin (mTOR), as a key signaling molecule, participates in the regulation of inflammation, apoptosis, and autophagy in several processes associated with SCI. Quercetin can reduce the loss of myelin sheath, enhance the ability of antioxidant stress, and promote axonal regeneration. Moreover, quercetin is also a significant player in regulating the mTOR signaling pathway that improves pathological alterations following neuronal injury. Herein, we review the therapeutic effects of quercetin in SCI through its modulation of the mTOR signaling pathway and elaborate on how it can be a potential interventional agent for SCI.

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Quercetin Alleviates Demyelination Through Regulating Microglial Phenotype Transformation to Mitigate Neuropsychiatric Symptoms in Mice with Vascular Dementia

Cited by 16 publications

References 49 publications

Molecular mechanism of Epimedium in the treatment of vascular dementia based on network pharmacology and molecular docking

Molecular mechanism of Epimedium in the treatment of vascular dementia based on network pharmacology and molecular docking

Myelin sheath injury and repairment after subarachnoid hemorrhage

Quercetin Can Improve Spinal Cord Injury by Regulating the mTOR Signaling Pathway

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