Neuroprotective effect of formononetin in ameliorating learning and memory impairment in mouse model of Alzheimer’s disease

Hong-xin, Fei; Zhang, Yingbo; Liu, Ting; Zhang, Xiaojie; Wu, Shuliang

doi:10.1080/09168451.2017.1399788

Cited by 45 publications

(27 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…BBB dysfunction can activate β and γ secretase and generate and increase Aβ level in AD (Cai et al, 2018). Aβ transport through BBB is regulated by low density lipoprotein-1 (LRP-1) and receptor for advanced glycation end products (RAGE) expressed on the surface of the endothelial cells (Fei et al, 2018). Loss of pericytes and astrocyte abnormalities increases Aβ level in AD brains.…”

Section: Stress and Alzheimer’s Diseasementioning

confidence: 99%

Mast Cells in Stress, Pain, Blood-Brain Barrier, Neuroinflammation and Alzheimer’s Disease

Kempuraj

Mentor

Thangavel

et al. 2019

Front. Cell. Neurosci.

103

View full text Add to dashboard Cite

Mast cell activation plays an important role in stress-mediated disease pathogenesis. Chronic stress cause or exacerbate aging and age-dependent neurodegenerative diseases. The severity of inflammatory diseases is worsened by the stress. Mast cell activation-dependent inflammatory mediators augment stress associated pain and neuroinflammation. Stress is the second most common trigger of headache due to mast cell activation. Alzheimer's disease (AD) is a progressive irreversible neurodegenerative disease that affects more women than men and woman's increased susceptibility to chronic stress could increase the risk for AD. Modern life-related stress, social stress, isolation stress, restraint stress, early life stress are associated with an increased level of neurotoxic beta amyloid (Aβ) peptide. Stress increases cognitive dysfunction, generates amyloid precursor protein (APP), hyperphosphorylated tau, neurofibrillary tangles (NFTs), and amyloid plaques (APs) in the brain. Stress-induced Aβ persists for years and generates APs even several years after the stress exposure. Stress activates hypothalamic-pituitary adrenal (HPA) axis and releases corticotropin-releasing hormone (CRH) from hypothalamus and in peripheral system, which increases the formation of Aβ, tau hyperphosphorylation, and blood-brain barrier (BBB) disruption in the brain. Mast cells are implicated in nociception and pain. Mast cells are the source and target of CRH and other neuropeptides that mediate neuroinflammation. Microglia express receptor for CRH that mediate neurodegeneration in AD. However, the exact mechanisms of how stress-mediated mast cell activation contribute to the pathogenesis of AD remains elusive. This mini-review highlights the possible role of stress and mast cell activation in neuroinflammation, BBB, and tight junction disruption and AD pathogenesis.

show abstract

Section: Stress and Alzheimer’s Diseasementioning

confidence: 99%

Mast Cells in Stress, Pain, Blood-Brain Barrier, Neuroinflammation and Alzheimer’s Disease

Kempuraj

Mentor

Thangavel

et al. 2019

Front. Cell. Neurosci.

103

View full text Add to dashboard Cite

show abstract

“…FMT has a bioavailability of 21.8% and shows different absorption in all gastrointestinal segments ( Luo et al., 2018 ). An increasing body of evidence suggests that FMT exerts notable anti-inflammatory, anti-allergic, antioxidant, anti-hepatic steatosis, antiproliferative, and anticancer effects in vitro and animal models of many disease ( Wang et al., 2012 ; Xu and An, 2017 ; Fei et al., 2018 ; Li et al., 2018 ; Ong et al., 2019 ; Wang X. S. et al., 2019 ). Some reports demonstrate that FMT has neuroprotective effect in LPS-stimulated BV2 microglia and high-fat diet-induced cognitive disorder mice ( El-Bakoush and Olajide, 2018 ; Fu et al., 2019 ; Wang Y. et al., 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Formononetin Attenuates Airway Inﬂammation and Oxidative Stress in Murine Allergic Asthma

et al. 2020

View full text Add to dashboard Cite

Allergic asthma has been considered as a respiratory disorder with pathological features of airway inflammation and remodeling, which involves oxidative stress. Formononetin (FMT) is a bioactive isoflavone obtained from Chinese herb Radix Astragali, and has been reported to have notable anti-inflammatory and antioxidant effects in several diseases. The purpose of our study was to elaborate the effects of FMT on asthma and the underlying mechanisms. To establish allergic asthma model, BALB/c mice were given ovalbumin (OVA) sensitization and challenge, treated with FMT (10, 20, 40 mg/kg) or dexamethasone (2 mg/kg). The effects of FMT on lung inflammation and oxidative stress were assessed. In OVA-induced asthmatic mice, FMT treatments significantly ameliorated lung function, alleviated lung inflammation including infiltration of inflammatory cells, the elevated levels of interleukin (IL)-4, IL-5, and IL-13, immunoglobulin (Ig) E, CC motif chemokine ligand 5 (CCL5, also known as RANTES), CCL11 (also called Eotaxin-1), and IL-17A. In addition, FMT treatments eminently blunted goblet cell hyperplasia and collagen deposition, and remarkably reduced oxidative stress as displayed by decreased reactive oxygen species (ROS), and increased superoxide diamutase (SOD) activity. Furthermore, to clarify the potential mechanisms responsible for the effects, we determined the inflammation and oxidation-related signaling pathway including nuclear factor kappa b (NF-kB), c-Jun N-terminal kinase (JNK), and the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2). FMT treatments appeared to dramatically inhibit the activation of NF-kB and JNK, significantly elevated the expression of heme oxygenase 1 (HO-1) but failed to activate expression of Nrf2. In conclusion, our study suggested that FMT had the therapeutic effects in attenuating airway inflammation and oxidative stress in asthma.

show abstract

“…Several studies have shown that formononetin has beneficial therapeutic effects in several diseases, including cancer, diabetes, neurological disease, and cardiovascular disease [5,6]. Recently, the neuroprotective effect of formononetin in patients with AD has been demonstrated in both in vivo and in vitro studies [7,8]. However, the detailed molecular mechanisms for the pharmacological and biological actions of formononetin remain unknown.…”

Section: Introductionmentioning

confidence: 99%

Pharmacological Targets and the Biological Mechanisms of Formononetin for Alzheimer’s Disease: A Network Analysis

et al. 2019

View full text Add to dashboard Cite

Background This study aimed to identify the pharmacological targets and mechanisms of action of the traditional Chinese medicine, formononetin, in the treatment of Alzheimer’s disease (AD) using network pharmacological analysis. Material/Methods Targets of AD were obtained by using DisGeNET gene discovery platform, the herbal ingredients target (HIT) database, the SuperPred, and the SwissTargetPrediction compound target prediction platforms. Pathogenic and therapeutic targets were imported to the STRING biological database, and Cytoscape network integration software was used to construct component-target and disease-target interaction networks. Core targets were identified by topological analysis and were further tested to identify the biological processes and signaling pathways. Results Seven key target genes for formononetin in the treatment of patients with AD were identified, including estrogen receptor alpha (ESR1), peroxisome proliferator-activated receptor gamma (PPARG), tumor protein p53 (TP53), sirtuin 1 (SIRT1), tumor necrosis factor (TNF), cytochrome P450 19A1 (CYP19A1), and nuclear factor (erythroid-derived 2)-like 2 (NFE2L2). The biological processes included hormone metabolism, regulation of nucleoside, nucleotide and nucleic acid metabolism, apoptosis, energy pathways, metabolism, cell communication, and signal transduction. The signaling pathways included histone acetylation and deacetylation (HDAC) class I, regulation of p38-alpha/beta, p38 mitogen-activated protein kinase (MAPK) signaling pathway, bone morphogenetic protein (BMP) receptor signaling, interleukin-1 (IL1) mediated signaling events, the tumor necrosis factor (TNF) receptor signaling pathway, and cytoplasmic and nuclear Smad2/3 signaling. Conclusions Pharmacological network analysis was used to identify the gene targets and mechanisms of formononetin treatment in patients with AD.

show abstract

Neuroprotective effect of formononetin in ameliorating learning and memory impairment in mouse model of Alzheimer’s disease

Cited by 45 publications

References 32 publications

Mast Cells in Stress, Pain, Blood-Brain Barrier, Neuroinflammation and Alzheimer’s Disease

Mast Cells in Stress, Pain, Blood-Brain Barrier, Neuroinflammation and Alzheimer’s Disease

Formononetin Attenuates Airway Inﬂammation and Oxidative Stress in Murine Allergic Asthma

Pharmacological Targets and the Biological Mechanisms of Formononetin for Alzheimer’s Disease: A Network Analysis

Contact Info

Product

Resources

About