The antidepressant-like effect of formononetin on chronic corticosterone-treated mice

Zhang, Changjing; Zhu, Leilei; Lu, Shuaifei; Li, Mengyuan; Bai, Ming; Li, Yucheng; Xu, Erqi

doi:10.1016/j.brainres.2022.147844

Cited by 16 publications

(11 citation statements)

References 61 publications

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“…However, sevoflurane has a risk of causing perioperative neurocognitive disorders (PND). Xu et al (2022) showed that a 3% sevoflurane exposure induced cognitive impairment and the inhibition of adult hippocampal neurogenesis in the DG of aged (18-month-old) mice, but not adult (8-month-old) mice [48]. Consistently, downregulation of BDNF/TrkB and NT-3/TrkC were observed due to treatment with 3% sevoflurane.…”

Section: Neurotrophin Synaptic Function and Neurogenesismentioning

confidence: 79%

“…Therefore, to achieve an upregulation of BDNF to improve behavior of both psychiatric and neurodegenerative disorders, targeting the BDNF/TrkB system with natural products has been prioritized [ 49 ]. A mice model of depression established by chronic treatment with corticosterone, a stress hormone, showed decreased hippocampal neurogenesis [ 50 ]. Interestingly, the application of formononetin (FMN), a type of isoflavone, improved the reduced neurogenesis caused by chronic corticosterone treatment [ 50 ].…”

Section: Neurotrophin Synaptic Function and Neurogenesismentioning

confidence: 99%

“…A mice model of depression established by chronic treatment with corticosterone, a stress hormone, showed decreased hippocampal neurogenesis [ 50 ]. Interestingly, the application of formononetin (FMN), a type of isoflavone, improved the reduced neurogenesis caused by chronic corticosterone treatment [ 50 ]. Moreover, upregulation of the glucocorticoid receptor (GR) and BDNF was observed after the FMN treatment, in addition to an improvement in sucrose preference and a decrease in the immobility time in the forced swimming test in the animal model, suggesting that BDNF action stimulated by FMN is effective against depressive behaviors.…”

Section: Neurotrophin Synaptic Function and Neurogenesismentioning

confidence: 99%

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The Role of Neurotrophin Signaling in Age-Related Cognitive Decline and Cognitive Diseases

Numakawa

Odaka

2022

IJMS

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Neurotrophins are a family of secreted proteins expressed in the peripheral nervous system and the central nervous system that support neuronal survival, synaptic plasticity, and neurogenesis. Brain-derived neurotrophic factor (BDNF) and its high affinity receptor TrkB are highly expressed in the cortical and hippocampal areas and play an essential role in learning and memory. The decline of cognitive function with aging is a major risk factor for cognitive diseases such as Alzheimer’s disease. Therefore, an alteration of BDNF/TrkB signaling with aging and/or pathological conditions has been indicated as a potential mechanism of cognitive decline. In this review, we summarize the cellular function of neurotrophin signaling and review the current evidence indicating a pathological role of neurotrophin signaling, especially of BDNF/TrkB signaling, in the cognitive decline in aging and age-related cognitive diseases. We also review the therapeutic approach for cognitive decline by the upregulation of the endogenous BDNF/TrkB-system.

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Section: Neurotrophin Synaptic Function and Neurogenesismentioning

confidence: 79%

Section: Neurotrophin Synaptic Function and Neurogenesismentioning

confidence: 99%

Section: Neurotrophin Synaptic Function and Neurogenesismentioning

confidence: 99%

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The Role of Neurotrophin Signaling in Age-Related Cognitive Decline and Cognitive Diseases

Numakawa

Odaka

2022

IJMS

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“…The core active compounds mainly included flavonoids such as isosinensetin, formononetin, nobiletin and sterols such as stigmasterol, beta-sitosterol, and sitosterol. Formononetin is a type of isoflavone that upregulates the expression of the glucocorticoid receptor and brain-derived neurotrophic factor, protects neurons, and promotes neurogenesis in the hippocampus, thereby effectively reducing chronic corticosterone-induced depression-like behavior in mice ( 32 ). Nobiletin not only upregulates synaptic neurotransmission, improves memory impairment and monoamine function, but also produces antidepressant-like effects through the interaction of the serotonergic, noradrenergic and dopaminergic systems ( 33 ).…”

Section: Discussionmentioning

confidence: 99%

Potential mechanisms underlying the therapeutic roles of sinisan formula in depression: Based on network pharmacology and molecular docking study

Wang

Liu

et al. 2022

Front. Psychiatry

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BackgroundThe incidence of depression has been increasing globally, which has brought a serious burden to society. Sinisan Formula (SNSF), a well-known formula of traditional Chinese medicine (TCM), has been found to demonstrate an antidepressant effect. However, the therapeutic mechanism of this formula remains unclear. Thus, the present study aimed to explore the mechanism of SNSF in depression through network pharmacology combined with molecular docking methods.Materials and methodsBioactive compounds, potential targets of SNSF, and related genes of depression were obtained from public databases. Essential ingredients, potential targets, and signaling pathways were identified using bioinformatics analysis, including protein-protein interaction (PPI), the Gene Ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, Autodock software was further performed for conducting molecular docking to verify the binding ability of active ingredients to targets.ResultsA total of 91 active compounds were successfully identified in SNSF with the use of the comprehensive network pharmacology approach, and they were found to be closely connected to 112 depression-related targets, among which CREB1, NOS3, CASP3, TP53, ESR1, and SLC6A4 might be the main potential targets for the treatment of depression. GO analysis revealed 801 biological processes, 123 molecular functions, and 67 cellular components. KEGG pathway enrichment analysis indicated that neuroactive ligand-receptor interaction, serotonergic synapse pathways, dopaminergic synapse pathways, and GABAergic synapse pathways might have played a role in treating depression. Molecular docking suggested that beta-sitosterol, nobiletin, and 7-methoxy-2-methyl isoflavone bound well to the main potential targets.ConclusionThis study comprehensively illuminated the active ingredients, potential targets, primary pharmacological effects, and relevant mechanism of the SNSF in the treatment of depression. SNSF might exert its antidepressant effects by regulating the signaling pathway of 5-hydroxytryptamine, dopamine, GABA, and neuroactive ligand receptor interactions. Still, more pharmacological experiments are needed for verification.

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“…The results demonstrated that formononetin alleviated depression-like behaviors of model mice reflected by increasing the sucrose preference index and reducing immobility time in the forced swimming test. Mechanism study revealed that formononetin enhanced the expression level of the glucocorticoid receptor and BDNF, attenuated neuronal impairment and promoted neurogenesis in the hippocampus ( Zhang et al, 2022 ). The above researches laid a foundation for further studying the effects of formononetin on mental illness.…”

Section: Neuroprotective Effects Of Formononetinmentioning

confidence: 99%

Focusing on Formononetin: Recent Perspectives for its Neuroprotective Potentials

2022

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Nervous system is the most complex system of the human body, hence, the neurological diseases often lack effective treatment strategies. Natural products have the potential to yield unique molecules and produce integrative and synergic effects compared to standard therapy. Mounting evidence has shown that isoflavonoids contained in traditional medicinal plant or dietary supplementation may play a crucial role in the prevention and treatment of neurological diseases due to their pronounced biological activities correlating to nervous system. Formononetin, a non-steroidal isoflavonoid, is a bioactive constituent of numerous medicinal plants such as red clover (Trifolium pratense) and Astragalus membranaceus. Emerging evidence has shown that formononetin possesses considerable anti-inflammatory, antioxidant and anti-cancer effects. This review intends to analyze the neuropharmacological potential of formononetin on the therapy of nervous system disorders. The neuroprotective properties of formononetin are observed in multiple neurological disorders including Alzheimer’s disease, dementia, cerebral ischemia, traumatic brain injury, anxiety, and depression. The beneficial effects of formononetin are achieved partially through attenuating neuroinflammation and oxidative stress via the related signaling pathway. Despite its evident effects in numerous preclinical studies, the definite role of formononetin on humans is still less known. More well-designed clinical trials are required to further confirm the neuroprotective efficacy and safety profile of formononetin before its application in clinic.

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The antidepressant-like effect of formononetin on chronic corticosterone-treated mice

Cited by 16 publications

References 61 publications

The Role of Neurotrophin Signaling in Age-Related Cognitive Decline and Cognitive Diseases

The Role of Neurotrophin Signaling in Age-Related Cognitive Decline and Cognitive Diseases

Potential mechanisms underlying the therapeutic roles of sinisan formula in depression: Based on network pharmacology and molecular docking study

Focusing on Formononetin: Recent Perspectives for its Neuroprotective Potentials

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