Kaempferol Has Potent Protective and Antifibrillogenic Effects for α-Synuclein Neurotoxicity In Vitro

Inden, Masatoshi; Takagi, Atsutoshi; Kitai, Hazuki; Ito, Taisei; Kurita, Hisaka; Honda, Ryo; Kamatari, Yuji O.; Nozaki, Sora; Wen, Xiaopeng; Hijioka, Masanori; Kitamura, Yoshihisa; Hozumi, Isao

doi:10.3390/ijms222111484

Cited by 19 publications

(18 citation statements)

References 27 publications

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“…[ 20 ] Kaempferol can reduce the accumulation of α -Syn, which is implicated in the pathogenesis of MSA, provide significant protection against α -Syn-related neurotoxicity and prevent neuronal cell death. [ 21 ] Amyloid β -protein is highly neurotoxic after precipitating and accumulating in the cell matrix, leading to neurodegenerative diseases, and destroying the blood-brain barrier. However, isorhamnetin can destroy the stability of amyloid β -protein aggregates and protect cells from Amyloid β -protein-induced cytotoxicity.…”

Section: Discussionmentioning

confidence: 99%

Exploring the mechanism of astragalus membranaceus in the treatment of multiple system atrophy based on network pharmacology and molecular docking

Yang

et al. 2023

Medicine

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Multiple system atrophy (MSA) is a fatal neurodegenerative disease, it causes functional degradation of multiple organs and systems throughout the body. Astragalus membranaceus (AM), a well-known traditional Chinese medicine, has been used to improve muscle wasting-related disorders for a long history. In this study, we used network pharmacology and molecular docking to predict the mechanism underlying AM for the treatment of MSA. We screened the active compounds of AM and its related targets, as well as the target proteins of MSA. We made a Venn diagram to obtain the intersecting targets and then constructed a protein-protein interaction network to find the core targets and build an active ingredient-target network map. After subjecting the intersecting targets to gene ontology and Kyoto encyclopedia of genes and genomes analysis, the binding ability of core compounds and core target proteins were validated by molecular docking. A total of 20 eligible compounds and 274 intersecting targets were obtained. The core components of treatment are quercetin, kaempferol, and isorhamnetin, and the core targets are TP53, RELA, and TNF. The main biological processes are related to cellular responses and regulation. Molecular functions are mainly associated with apoptosis, inflammation, and tumorigenesis. Molecular docking results show good and standard binding abilities. This study illustrates that AM treats MSA through multiple targets and pathways, and provides a reference for subsequent research.

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Section: Discussionmentioning

confidence: 99%

Exploring the mechanism of astragalus membranaceus in the treatment of multiple system atrophy based on network pharmacology and molecular docking

Yang

et al. 2023

Medicine

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“…Besides, KA ameliorates neuropathic pain by inhibiting the TLR4/NF‐ĸB signaling pathway as a neuroprotectant 32 . Also, KA protects against α‐synuclein‐induced neurotoxicity 33 . In line with these findings, we demonstrated that KA pretreatment inhibited BU‐induced decrease in the DRG neuron viability and increase in the LDH leakage, decreased BU‐caused DRG neuron apoptosis, reduced the BU‐triggered production of pro‐inflammatory cytokines (IL‐6, IL‐1β, and TNF‐α), and abrogated the levels of oxidative stress indicators (CAT, SOD, GSH‐Px, and MDA) in BU‐stimulated DRG neurons.…”

Section: Discussionmentioning

confidence: 99%

Kaempferol counteracts bupivacaine‐induced neurotoxicity in mouse dorsal root ganglia neurons by regulating TRAF6‐dependent NF‐κB signaling

Chen¹,

Zhuang²

2023

The Kaohsiung J of Med Scie

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Kaempferol (KA), a widely recognized anti-oxidation and anti-inflammation agent, has been reported to have neuroprotective effects. This work aimed to investigate whether KA protects mouse dorsal root ganglia (DRG) neurons against bupivacaine (BU)-stimulated neurotoxicity and explore the underlying mechanisms. In this study, BU treatment suppressed DRG neuron viability and promoted LDH leakage, which was partially abated by KA. Besides, BU-triggered DRG neuron apoptosis, and changes in Bax and Bcl-2 levels were attenuated by KA treatment. In addition, pretreatment with KA substantially reduced interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α levels in BU-treated DRG neurons. In addition, KA administration abrogated BU-induced decline in CAT, SOD, and GSH-Px levels, as well as the increase in the malondialdehyde level. Interestingly, we found that KA significantly attenuated BU-induced TNF receptor-associated factor 6 (TRAF6) upregulation as well as NF-κB activation. Furthermore, oe-TRAF6-mediated TRAF6 overexpression promoted NF-κB activation and partly abolished KA-induced protection against BU-triggered neurotoxic effects on DRG neurons. Our results revealed that KA mitigated BU-induced neurotoxic effects on DRG neurons by deactivating the TRAF6/NF-κB signaling.

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“…These pathways together lead to cognitive impairment caused by pesticide poisoning. Kaempferol has a neuroprotective effect on brain damage caused by neurodegenerative diseases (87,88). Hussein et al (89) used kaempferol (21 mg/kg/d BW by injection) to interfere with the rat model of neurodegenerative disease induced by CPF (18 mg/kg/d BW by injection) for 14 days.…”

Section: Nf-κbmentioning

confidence: 99%

Pesticides as a risk factor for cognitive impairment: Natural substances are expected to become alternative measures to prevent and improve cognitive impairment

Lian-kui

Miao²,

Di³

et al. 2023

Front. Nutr.

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Pesticides are the most effective way to control diseases, insects, weeds, and fungi. The central nervous system (CNS) is damaged by pesticide residues in various ways. By consulting relevant databases, the systemic relationships between the possible mechanisms of pesticides damage to the CNS causing cognitive impairment and related learning and memory pathways networks, as well as the structure–activity relationships between some natural substances (such as polyphenols and vitamins) and the improvement were summarized in this article. The mechanisms of cognitive impairment caused by pesticides are closely related. For example, oxidative stress, mitochondrial dysfunction, and neuroinflammation can constitute three feedback loops that interact and restrict each other. The mechanisms of neurotransmitter abnormalities and intestinal dysfunction also play an important role. The connection between pathways is complex. NMDAR, PI3K/Akt, MAPK, Keap1/Nrf2/ARE, and NF-κB pathways can be connected into a pathway network by targets such as Ras, Akt, and IKK. The reasons for the improvement of natural substances are related to their specific structure, such as polyphenols with different hydroxyl groups. This review’s purpose is to lay a foundation for exploring and developing more natural substances that can effectively improve the cognitive impairment caused by pesticides.

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Kaempferol Has Potent Protective and Antifibrillogenic Effects for α-Synuclein Neurotoxicity In Vitro

Cited by 19 publications

References 27 publications

Exploring the mechanism of astragalus membranaceus in the treatment of multiple system atrophy based on network pharmacology and molecular docking

Exploring the mechanism of astragalus membranaceus in the treatment of multiple system atrophy based on network pharmacology and molecular docking

Kaempferol counteracts bupivacaine‐induced neurotoxicity in mouse dorsal root ganglia neurons by regulating TRAF6‐dependent NF‐κB signaling

Pesticides as a risk factor for cognitive impairment: Natural substances are expected to become alternative measures to prevent and improve cognitive impairment

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