Quercetin inhibits neuronal Ferroptosis and promotes immune response by targeting lipid metabolism-related gene PTGS2 to alleviate breast cancer-related depression

Quercetin, the key ingredient in Xiaoyao Kangai Jieyu Formula, has been previously found to relieve breast cancer-related depression (BCRD). We want to explore the potential mechanisms and therapeutic targets of quercetin alleviating BCRD. BALB/c mice were injected subcutaneously with 4T1 cells and...

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Veröffentlicht in:Phytomedicine (Stuttgart) 2024-07, Vol.130, p.155560, Article 155560
Hauptverfasser: Zhu, Qing, Han, Yuanshan, He, Ying, Meng, Pan, Fu, Yilan, Yang, Hui, He, Gefei, Long, Minghui, Shi, Yingrui
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container_start_page 155560
container_title Phytomedicine (Stuttgart)
container_volume 130
creator Zhu, Qing
Han, Yuanshan
He, Ying
Meng, Pan
Fu, Yilan
Yang, Hui
He, Gefei
Long, Minghui
Shi, Yingrui
description Quercetin, the key ingredient in Xiaoyao Kangai Jieyu Formula, has been previously found to relieve breast cancer-related depression (BCRD). We want to explore the potential mechanisms and therapeutic targets of quercetin alleviating BCRD. 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. 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. 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. [Display omitted]
doi_str_mv 10.1016/j.phymed.2024.155560
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We want to explore the potential mechanisms and therapeutic targets of quercetin alleviating BCRD. 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. 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. 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. [Display omitted]</description><identifier>ISSN: 0944-7113</identifier><identifier>ISSN: 1618-095X</identifier><identifier>EISSN: 1618-095X</identifier><identifier>DOI: 10.1016/j.phymed.2024.155560</identifier><identifier>PMID: 38815404</identifier><language>eng</language><publisher>Germany: Elsevier GmbH</publisher><subject>Breast cancer-related depression ; breasts ; corticosterone ; dopamine ; Ferroptosis ; genes ; Gut microbiota ; immune response ; ingredients ; interleukin-10 ; interleukin-2 ; intestinal microorganisms ; iron ; Lipid metabolism ; lipopolysaccharides ; Molecular docking ; Network pharmacology ; neurons ; norepinephrine ; pharmacology ; prostaglandin synthase ; Quercetin ; serotonin ; sucrose ; therapeutics</subject><ispartof>Phytomedicine (Stuttgart), 2024-07, Vol.130, p.155560, Article 155560</ispartof><rights>2024</rights><rights>Copyright © 2024. 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We want to explore the potential mechanisms and therapeutic targets of quercetin alleviating BCRD. 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. 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. 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. [Display omitted]</description><subject>Breast cancer-related depression</subject><subject>breasts</subject><subject>corticosterone</subject><subject>dopamine</subject><subject>Ferroptosis</subject><subject>genes</subject><subject>Gut microbiota</subject><subject>immune response</subject><subject>ingredients</subject><subject>interleukin-10</subject><subject>interleukin-2</subject><subject>intestinal microorganisms</subject><subject>iron</subject><subject>Lipid metabolism</subject><subject>lipopolysaccharides</subject><subject>Molecular docking</subject><subject>Network pharmacology</subject><subject>neurons</subject><subject>norepinephrine</subject><subject>pharmacology</subject><subject>prostaglandin synthase</subject><subject>Quercetin</subject><subject>serotonin</subject><subject>sucrose</subject><subject>therapeutics</subject><issn>0944-7113</issn><issn>1618-095X</issn><issn>1618-095X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNqFkdFqHCEUhqW0NNu0b1CKl72ZrY4649wUSmjSQCANSaF34oxnNi6OTtUJ7PPkResySS5bEBTPd_7D-X-EPlKypYQ2X_bb-f4wgdnWpOZbKoRoyCu0oQ2VFenE79doQzrOq5ZSdoLepbQnhPKuJW_RCZOSCk74Bj3eLBAHyNZj6-9tb3PCHpYYvHb4HGIMcw7JJqy9wXMMU8iQsJ2mxQOOkObgE-D-gLOOu6PMDjs7W4MnyLoPzqapiuB0BoN3UHp-3l3c1jgHrJ2DB1sKuI-gU8aD9gPEF9rAXPSTDf49ejNql-DD032Kfp1_vzv7UV1dX1yefbuqBsZ5rloie9rKxrCmo52ojYDyw8rOute87qQsDy5lX5MRytFjZ9p-JJITwUYQ7BR9XnXLnn8WSFlNNg3gnPYQlqQYFaypi3ft_1HSMC5kW9OC8hUdYkgpwqjmaCcdD4oSdUxS7dWapDomqdYkS9unpwlLf6w9Nz1HV4CvKwDFkgcLUaXBQrHQ2AhDVibYf0_4C8E5tL4</recordid><startdate>20240725</startdate><enddate>20240725</enddate><creator>Zhu, Qing</creator><creator>Han, Yuanshan</creator><creator>He, Ying</creator><creator>Meng, Pan</creator><creator>Fu, Yilan</creator><creator>Yang, Hui</creator><creator>He, Gefei</creator><creator>Long, Minghui</creator><creator>Shi, Yingrui</creator><general>Elsevier GmbH</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope><orcidid>https://orcid.org/0000-0002-2057-9422</orcidid></search><sort><creationdate>20240725</creationdate><title>Quercetin inhibits neuronal Ferroptosis and promotes immune response by targeting lipid metabolism-related gene PTGS2 to alleviate breast cancer-related depression</title><author>Zhu, Qing ; 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We want to explore the potential mechanisms and therapeutic targets of quercetin alleviating BCRD. 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. 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. 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. [Display omitted]</abstract><cop>Germany</cop><pub>Elsevier GmbH</pub><pmid>38815404</pmid><doi>10.1016/j.phymed.2024.155560</doi><orcidid>https://orcid.org/0000-0002-2057-9422</orcidid></addata></record>
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subjects Breast cancer-related depression
breasts
corticosterone
dopamine
Ferroptosis
genes
Gut microbiota
immune response
ingredients
interleukin-10
interleukin-2
intestinal microorganisms
iron
Lipid metabolism
lipopolysaccharides
Molecular docking
Network pharmacology
neurons
norepinephrine
pharmacology
prostaglandin synthase
Quercetin
serotonin
sucrose
therapeutics
title Quercetin inhibits neuronal Ferroptosis and promotes immune response by targeting lipid metabolism-related gene PTGS2 to alleviate breast cancer-related depression
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