Quercetin inhibits neuronal Ferroptosis and promotes immune response by targeting lipid metabolism-related gene PTGS2 to alleviate breast cancer-related depression.
Phytomedicine
; 130: 155560, 2024 Jul 25.
Article
em En
| MEDLINE
| ID: mdl-38815404
ABSTRACT
BACKGROUND:
Quercetin, the key ingredient in Xiaoyao Kangai Jieyu Formula, has been previously found to relieve breast cancer-related depression (BCRD).PURPOSE:
We want to explore the potential mechanisms and therapeutic targets of quercetin alleviating BCRD.METHODS:
BALB/c mice were injected subcutaneously with 4T1 cells and corticosterone (CORT) to create a BCRD mice model. The primary hippocampal neurons were co-induced with 10 µg/ml lipopolysaccharide (LPS) and 200 µM CORT for 6 h to establish an in vitro model of BCRD. Quercetin was applied to explore its effect on disease symptoms, gut microbiota, and lipid metabolism of BCRD mice. Lipid metabolism-related genes were screened based on network pharmacology. Molecular docking was employed to prove whether quercetin bound to prostaglandin-endoperoxide synthase 2 (PTGS2). PTGS2 overexpression was carried out to explore the underlying mechanism of quercetin treatment on BCRD.RESULTS:
Quercetin treatment not only altered the composition and abundance of gut microbiota but also alleviated abnormal lipid metabolism in BCRD mice. In particular, quercetin down-regulated BCRD and lipid metabolism-related genes screened by network pharmacology, especially PTGS2. Further, molecular docking verified the stable binding between quercetin and PTGS2. In hippocampal neurons, quercetin promoted proliferation but reduced ferroptosis-related markers (total Fe, Fe2+, MDA, and ROS) levels by targeting PTGS2. In BCRD mice, quercetin reduced the high immobility time and increased the sucrose preference rate and serotonin (5-HT), dopamine (DA), and noradrenaline (NE) levels. Meanwhile, quercetin increased CD4+/CD8+ T cells ratio and IL-2 and IFN-γ levels but reduced CA153 and IL-10 levels to alleviate BCRD development. However, PTGS2 overexpression reversed these effects of quercetin on BCRD.CONCLUSION:
Quercetin inhibited neuronal ferroptosis and promoted immune responses in BCRD mice by targeting the lipid metabolism-related gene PTGS2. This provided a reference for quercetin in the treatment of BCRD.Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Quercetina
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Depressão
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Ciclo-Oxigenase 2
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Metabolismo dos Lipídeos
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Simulação de Acoplamento Molecular
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Microbioma Gastrointestinal
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Ferroptose
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Camundongos Endogâmicos BALB C
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Neurônios
Limite:
Animals
Idioma:
En
Revista:
Phytomedicine
Assunto da revista:
TERAPIAS COMPLEMENTARES
Ano de publicação:
2024
Tipo de documento:
Article