Flavonoid fisetin reverses impaired hippocampal synaptic plasticity and cognitive function by regulating the function of AMPARs in a male rat model of schizophrenia

Zhan, Jin-Qiong; Chen, Chunnuan; Wu, Sixian; Wu, Hong; Xiong, Jian; Wei, Bo; Yang, Yuan-Jian

doi:10.1111/jnc.15370

Cited by 11 publications

(9 citation statements)

References 64 publications

(105 reference statements)

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“…Fisetin is recommended to be active therapeutic in many disorders, including neurological diseases, while its role in SAE is still unclear. 16 , 17 , 18 , 19 In this study, we confirmed the neuroprotective effects of fisetin on cognitive deficits caused by SAE. Furthermore, we explored the potential mechanism of fisetin on SAE, which might be relevant to increased mitophagy, scavenged ROS, inactivated NLRP3 inflammasome in CMECs, along with decreased caspase‐1 levels, and reduced secretion of IL‐1β into CNS.…”

Section: Discussionsupporting

confidence: 81%

Fisetin ameliorates cognitive impairment by activating mitophagy and suppressing neuroinflammation in rats with sepsis‐associated encephalopathy

Ding

Chen

et al. 2021

CNS Neurosci Ther

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Background Fisetin, the effective ingredient of the traditional Chinese medicine named Cotinus coggygria, is recommended to be active therapeutic in many disorders. However, its role in sepsis‐associated encephalopathy (SAE) remains unclarified. Methods Cecal ligation and puncture (CLP) operation was performed to establish a rat model of SAE. Rats were grouped according to the surgery operation and fisetin administration. Cognitive impairment was assessed by Morris water maze test. Disruption of blood‐brain barrier (BBB) integrity was detected by Evan's blue staining. The mitophagy, reactive oxygen species (ROS) generation, NLRP3 inflammasome activation, and pro‐inflammatory cytokines levels were measured through western blot and double immunofluorescence labeling. A transmission electron microscope was applied for the observation of mitochondrial autophagosomes. Results Rats in the CLP group presented increased expression of IL‐1R1, pNF‐κB, TNF‐α, and iNOS in microglial cells, indicating severe inflammation in the central nervous system (CNS). Nevertheless, there was no increase in BBB permeability. Meanwhile, NLRP3 inflammasome was activated in cerebral microvascular endothelial cells (CMECs), presented with an elevation of caspase‐1 expression and IL‐1β secretion into CNS. In addition, we found fisetin significantly improved cognitive dysfunction in rats with SAE. Neuroprotective effects of fisetin might be associated with inhibition of neuroinflammation, represented with decreased expression of IL‐1R1, pNF‐κB, TNF‐α, and iNOS in microglia. Furthermore, fisetin induced mitophagy, scavenged ROS, blocked NLRP3 inflammasome activation of CMECs, as evidenced by decreased expression of caspase‐1 and reduced release of IL‐1β into CNS. Conclusion Collectively, fisetin‐blocked NLRP3 inflammasome activation via promoting mitophagy in CMECs may suppress the secretion of IL‐1β into CNS, reduce neuroinflammation, and contribute to the amelioration of cognitive impairment.

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Section: Discussionsupporting

confidence: 81%

Fisetin ameliorates cognitive impairment by activating mitophagy and suppressing neuroinflammation in rats with sepsis‐associated encephalopathy

Ding

Chen

et al. 2021

CNS Neurosci Ther

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“…This flavonoid increases the surface expression of the GluA1 subunit of AMPA receptor. It also continues the phosphorylation of the AMPA receptors, as well as CaMKII, CREB, ERK1/2 ( Zhan et al, 2021 ).…”

Section: Role Of Fisetin In Other Neurological Disordersmentioning

confidence: 99%

The neuroprotective effects of fisetin, a natural flavonoid in neurodegenerative diseases: Focus on the role of oxidative stress

et al. 2022

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Oxidative stress (OS) disrupts the chemical integrity of macromolecules and increases the risk of neurodegenerative diseases. Fisetin is a flavonoid that exhibits potent antioxidant properties and protects the cells against OS. We have viewed the NCBI database, PubMed, Science Direct (Elsevier), Springer-Nature, ResearchGate, and Google Scholar databases to search and collect relevant articles during the preparation of this review. The search keywords are OS, neurodegenerative diseases, fisetin, etc. High level of ROS in the brain tissue decreases ATP levels, and mitochondrial membrane potential and induces lipid peroxidation, chronic inflammation, DNA damage, and apoptosis. The subsequent results are various neuronal diseases. Fisetin is a polyphenolic compound, commonly present in dietary ingredients. The antioxidant properties of this flavonoid diminish oxidative stress, ROS production, neurotoxicity, neuro-inflammation, and neurological disorders. Moreover, it maintains the redox profiles, and mitochondrial functions and inhibits NO production. At the molecular level, fisetin regulates the activity of PI3K/Akt, Nrf2, NF-κB, protein kinase C, and MAPK pathways to prevent OS, inflammatory response, and cytotoxicity. The antioxidant properties of fisetin protect the neural cells from inflammation and apoptotic degeneration. Thus, it can be used in the prevention of neurodegenerative disorders.

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“…Fisetin, a substance with wide therapeutic potential, which includes effects on MAPK, NF-κB and PI3K, is a naturally occurring flavonoid compound found in various fruits and vegetables such as strawberries, apples, and onions [219]. Fisetin administration has been shown to have beneficial effects in preclinical animal models of diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, dementia, schizophrenia, stroke, traumatic brain injury, and the aging process [220][221][222][223][224][225][226]. This substance evokes a variety of pharmacological effects, such as anti-allergic, cancer-preventive and neuroprotective actions [227][228][229].…”

Section: Fisetin-a Mapk Nf-κb and Pi3k Modulator In Neuropathic Painmentioning

confidence: 99%

Advances in Neuropathic Pain Research: Selected Intracellular Factors as Potential Targets for Multidirectional Analgesics

Ciapała,

Mika

2023

Pharmaceuticals

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Neuropathic pain is a complex and debilitating condition that affects millions of people worldwide. Unlike acute pain, which is short-term and starts suddenly in response to an injury, neuropathic pain arises from somatosensory nervous system damage or disease, is usually chronic, and makes every day functioning difficult, substantially reducing quality of life. The main reason for the lack of effective pharmacotherapies for neuropathic pain is its diverse etiology and the complex, still poorly understood, pathophysiological mechanism of its progression. Numerous experimental studies, including ours, conducted over the last several decades have shown that the development of neuropathic pain is based on disturbances in cell activity, imbalances in the production of pronociceptive factors, and changes in signaling pathways such as p38MAPK, ERK, JNK, NF-κB, PI3K, and NRF2, which could become important targets for pharmacotherapy in the future. Despite the availability of many different analgesics, relieving neuropathic pain is still extremely difficult and requires a multidirectional, individual approach. We would like to point out that an increasing amount of data indicates that nonselective compounds directed at more than one molecular target exert promising analgesic effects. In our review, we characterize four substances (minocycline, astaxanthin, fisetin, and peimine) with analgesic properties that result from a wide spectrum of actions, including the modulation of MAPKs and other factors. We would like to draw attention to these selected substances since, in preclinical studies, they show suitable analgesic properties in models of neuropathy of various etiologies, and, importantly, some are already used as dietary supplements; for example, astaxanthin and fisetin protect against oxidative stress and have anti-inflammatory properties. It is worth emphasizing that the results of behavioral tests also indicate their usefulness when combined with opioids, the effectiveness of which decreases when neuropathy develops. Moreover, these substances appear to have additional, beneficial properties for the treatment of diseases that frequently co-occur with neuropathic pain. Therefore, these substances provide hope for the development of modern pharmacological tools to not only treat symptoms but also restore the proper functioning of the human body.

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Flavonoid fisetin reverses impaired hippocampal synaptic plasticity and cognitive function by regulating the function of AMPARs in a male rat model of schizophrenia

Cited by 11 publications

References 64 publications

Fisetin ameliorates cognitive impairment by activating mitophagy and suppressing neuroinflammation in rats with sepsis‐associated encephalopathy

Fisetin ameliorates cognitive impairment by activating mitophagy and suppressing neuroinflammation in rats with sepsis‐associated encephalopathy

The neuroprotective effects of fisetin, a natural flavonoid in neurodegenerative diseases: Focus on the role of oxidative stress

Advances in Neuropathic Pain Research: Selected Intracellular Factors as Potential Targets for Multidirectional Analgesics

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