The flavonoid baicalein rescues synaptic plasticity and memory deficits in a mouse model of Alzheimer’s disease

Gu, Xun-Hu; Xu, Lijun; Liu, Zhiqiang; Wei, Bo; Yang, Yuan-Jian; Xu, Guogang; Yin, Xiaoping; Wang, Wei

doi:10.1016/j.bbr.2016.05.052

Cited by 91 publications

(68 citation statements)

References 62 publications

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“…As many bioflavonoids, baicalein inhibits phosphorylation of many fundamental signaling protein kinases, leading to its typical anti-inflammatory activity, e.g., it inhibits the ERK/MAPK signaling cascade, acting on the phosphorylation of MEK-1 by Raf-1 and inducing dampening of NF-κB (8). This anti-phoshorylation property was reported also by Gu et al as baicalein should exert its action by preventing the phosphorylation of tau protein in APP/PS1 mice (1). Still, a metabolic, anti-oxidant activity from baicalein, besides its targeting glutamatergic neurotransmission, may explain some evidence reported (1).…”

supporting

confidence: 64%

“…This anti-phoshorylation property was reported also by Gu et al as baicalein should exert its action by preventing the phosphorylation of tau protein in APP/PS1 mice (1). Still, a metabolic, anti-oxidant activity from baicalein, besides its targeting glutamatergic neurotransmission, may explain some evidence reported (1). …”

supporting

confidence: 64%

“…A recent article by Gu et al reported that the long-term oral administration of baicalein in mouse, inhibited the activity of lipooxygenase 12/15 LXO and glycogen synthase kinase 3β (GSK-3β) in hippocampal slices, also reducing the activity of β-secretase enzyme (BACE1) and the concentration of total beta-amyloid proteins (Aβ), leading to the in vivo restoration of spine number, synaptic plasticity, and memory deficits (1). …”

mentioning

confidence: 99%

“…According to the authors, baicalein is able to prevent the impairment in the hippocampal long-term potentiation (LTP) induced by β-amyloids (Aβ) and improve cognitive deficit associated with AD (1). Recently, also metformin exhibited positive effects on AD quite comparable to baicalein, i.e., the inhibition of the activity of Aβ on LTP in a high fat diet (HFD) rat model (5).…”

mentioning

confidence: 99%

“…The authors showed that Aβ binding to synapse-related sites mediates the reduction of synaptic loss and also modulates the damage of the glutamatergic synaptic transmission, while baicalein can prevent this damage (1). Furthermore, the paper by Gu et al would suggest whether the mechanism by which baicalein acts on AD may resemble some other neuro-protective compound, in order to focus onto commonly shared targets.…”

mentioning

confidence: 99%

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Commentary: The Flavonoid Baicalein Rescues Synaptic Plasticity and Memory Deficits in a Mouse Model of Alzheimer’s Disease

Chirumbolo

Bjørklund

2016

Front. Neurol.

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supporting

confidence: 64%

supporting

confidence: 64%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Commentary: The Flavonoid Baicalein Rescues Synaptic Plasticity and Memory Deficits in a Mouse Model of Alzheimer’s Disease

Chirumbolo

Bjørklund

2016

Front. Neurol.

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Progress in the development of naturally derived active metabolites‐based drugs: Potential therapeutics for Alzheimer's disease

Mani

Sulthana

Muthusamy

et al. 2022

Biotech and App Biochem

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Alzheimer's disease (AD) is an extensive age-associated neurodegenerative disorder. In spite of wide-ranging progress in understanding the AD pathology for the past 50 years, clinical trials based on the hypothesis of amyloid-beta (Aβ) have reserved worsening particularly at late-stage human trials. Consequently, very few old drugs are presently used for AD with inadequate clinical consequences and various side effects. We focus on widespread pharmacological and beneficial principles for existing as well as future drugs. Multitargeting approaches by means of general antioxidant and anti-inflammatory mechanisms allied with particular receptor and/or enzyme-mediated actions in neuroprotection and neurodegeneration. The plant kingdom comprises a vast range of species with an incredible diversity of bioactive metabolites with diverse chemical scaffolds. In recent times, an increasing body of facts recommended the use of phytochemicals to decelerate AD's onset and progression. The definitive goal of AD investigation is to avert the onset of neurodegeneration, thereby allowing successful aging devoid of cognitive decline. At this point, we discussed the neurological protective role of natural products and naturally derived therapeutic agents for AD from various natural polyphenolic compounds and medicinal plants. In conclusion, medicinal plants act as a chief source of different bioactive constituents.

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Computational Study of the Aza‐Michael Addition of the Flavonoid (+)‐Taxifolin in the Inhibition of β‐Amyloid Fibril Aggregation

Ginex

Trius

Luque

2018

Chemistry A European J

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Inhibition of abnormal protein self-aggregation is an attractive strategy against amyloidogenic diseases, but has found limited success due to the complexity of protein self-assembly, the absence of fully reproducible aggregation assays, and the scarce knowledge of the inhibition mechanisms by small molecules. In this context, catechol-containing compounds may lead to covalent adducts with amyloid fibrils that interfere with the aggregation process. In particular, the covalent adduct formed between the oxidized form of (+)-taxifolin and an β-amyloid (Aβ42) suggests the involvement of a specific recognition motif that enables the chemical reaction with Aβ42. In this study, we have examined the mechanisms implicated in the aza-Michael addition of the o-quinone species of (+)-taxifolin with Aβ42 fibrils. The results support the binding of (+)-taxifolin to the hydrophobic groove delimited by the edges defined by Lys16 and Glu22 residues in the fibril. The chemical reaction proceeds through the nucleophilic attack of the deprotonated amino group of a Lys16 residue in a process activated by the interaction between the o-quinone ring with a vicinal Lys16 residue, as well as by a water-assisted proton transfer, which is the rate-limiting step of the reaction. This specific inhibition mechanism, which may explain the enhanced anti-aggregating activity of oxidized flavonoids compared to fresh compounds, holds promise for developing disease-modifying therapies.

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The flavonoid baicalein rescues synaptic plasticity and memory deficits in a mouse model of Alzheimer’s disease

Cited by 91 publications

References 62 publications

Commentary: The Flavonoid Baicalein Rescues Synaptic Plasticity and Memory Deficits in a Mouse Model of Alzheimer’s Disease

Commentary: The Flavonoid Baicalein Rescues Synaptic Plasticity and Memory Deficits in a Mouse Model of Alzheimer’s Disease

Progress in the development of naturally derived active metabolites‐based drugs: Potential therapeutics for Alzheimer's disease

Computational Study of the Aza‐Michael Addition of the Flavonoid (+)‐Taxifolin in the Inhibition of β‐Amyloid Fibril Aggregation

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