Isoforsythiaside confers neuroprotection against Alzheimer’s disease by attenuating ferroptosis and neuroinflammation in vivo and in vitro
Ferroptosis and neuroinflammation contribute to the development of Alzheimer's disease (AD). Isoforsythiaside (IFY) is a phenylethanoid glycoside isolated from the dried fruit of Forsythia suspensa (Thunb.) Vahl that has been confirmed to improve the memory and cognitive abilities of APP/PS1 mi...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Tsinghua University Press
2023-09-01
|
| Series: | Food Science and Human Wellness |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213453023000356 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832568804493754368 |
|---|---|
| author | Chunyue Wang Hongbo Jiang Honghan Liu Shanshan Chen Hangyu Guo Shuoshuo Ma Weiwei Han Yu Li Di Wang |
| author_facet | Chunyue Wang Hongbo Jiang Honghan Liu Shanshan Chen Hangyu Guo Shuoshuo Ma Weiwei Han Yu Li Di Wang |
| author_sort | Chunyue Wang |
| collection | DOAJ |
| description | Ferroptosis and neuroinflammation contribute to the development of Alzheimer's disease (AD). Isoforsythiaside (IFY) is a phenylethanoid glycoside isolated from the dried fruit of Forsythia suspensa (Thunb.) Vahl that has been confirmed to improve the memory and cognitive abilities of APP/PS1 mice in our previous study. The purpose of this study was to explore the anti-ferroptosis and anti-neuroinflammatory properties of IFY-mediated neuroprotection. In APP/PS1 mice, erastin-damaged HT22 cells, and LPS-exposed BV2 cells, the neuroprotective effects against ferroptosis and neuroinflammation were investigated using immunohistochemistry, label-free proteomics, western blot, ELISA, MTT, fluorescence, and TEM. IFY alleviated the expression levels of NO, IL-6, and IL-1β in LPS-exposed BV2 cells and improved the morphology of mitochondria in erastin-damaged HT22 cells. Additionally, IFY upregulated the expression levels of GPX4, FTH, FTL, p-GSK-3β, Nrf2, and NQO1, and downregulated the expression of TFR1, DMT1, p-Fyn, GFAP, p-IKKα+β, p-IκBα, p-NF-κB, and pro-inflammatory factors in the brains of APP/PS1 mice and erastin-damaged HT22 cells. In conclusion, IFY inhibits ferroptosis and neuroinflammation in erastin-damaged HT22 cells and APP/PS1 mice, at least partially by regulating the activation of Nrf2 and NF-κB signaling. IFY may prevent ferroptosis and neuroinflammation in AD and provide a new treatment strategy for AD. |
| format | Article |
| id | doaj-art-c5c5851294de44de99569b0cdaea5b62 |
| institution | Kabale University |
| issn | 2213-4530 |
| language | English |
| publishDate | 2023-09-01 |
| publisher | Tsinghua University Press |
| record_format | Article |
| series | Food Science and Human Wellness |
| spelling | doaj-art-c5c5851294de44de99569b0cdaea5b622025-02-03T00:27:37ZengTsinghua University PressFood Science and Human Wellness2213-45302023-09-0112517301742Isoforsythiaside confers neuroprotection against Alzheimer’s disease by attenuating ferroptosis and neuroinflammation in vivo and in vitroChunyue Wang0Hongbo Jiang1Honghan Liu2Shanshan Chen3Hangyu Guo4Shuoshuo Ma5Weiwei Han6Yu Li7Di Wang8School of Life Sciences, Jilin University, Changchun 130012, China; Engineering Research Center of Chinese Ministry of Education for Edible and Medicinal Fungi, Jilin Agricultural University, Changchun 130118, ChinaSchool of Life Sciences, Jilin University, Changchun 130012, ChinaSchool of Life Sciences, Jilin University, Changchun 130012, ChinaSchool of Life Sciences, Jilin University, Changchun 130012, ChinaSchool of Life Sciences, Jilin University, Changchun 130012, ChinaSchool of Life Sciences, Jilin University, Changchun 130012, ChinaSchool of Life Sciences, Jilin University, Changchun 130012, ChinaEngineering Research Center of Chinese Ministry of Education for Edible and Medicinal Fungi, Jilin Agricultural University, Changchun 130118, ChinaSchool of Life Sciences, Jilin University, Changchun 130012, China; Engineering Research Center of Chinese Ministry of Education for Edible and Medicinal Fungi, Jilin Agricultural University, Changchun 130118, China; Corresponding author at: School of Life Sciences, Jilin University, Changchun 130012, China.Ferroptosis and neuroinflammation contribute to the development of Alzheimer's disease (AD). Isoforsythiaside (IFY) is a phenylethanoid glycoside isolated from the dried fruit of Forsythia suspensa (Thunb.) Vahl that has been confirmed to improve the memory and cognitive abilities of APP/PS1 mice in our previous study. The purpose of this study was to explore the anti-ferroptosis and anti-neuroinflammatory properties of IFY-mediated neuroprotection. In APP/PS1 mice, erastin-damaged HT22 cells, and LPS-exposed BV2 cells, the neuroprotective effects against ferroptosis and neuroinflammation were investigated using immunohistochemistry, label-free proteomics, western blot, ELISA, MTT, fluorescence, and TEM. IFY alleviated the expression levels of NO, IL-6, and IL-1β in LPS-exposed BV2 cells and improved the morphology of mitochondria in erastin-damaged HT22 cells. Additionally, IFY upregulated the expression levels of GPX4, FTH, FTL, p-GSK-3β, Nrf2, and NQO1, and downregulated the expression of TFR1, DMT1, p-Fyn, GFAP, p-IKKα+β, p-IκBα, p-NF-κB, and pro-inflammatory factors in the brains of APP/PS1 mice and erastin-damaged HT22 cells. In conclusion, IFY inhibits ferroptosis and neuroinflammation in erastin-damaged HT22 cells and APP/PS1 mice, at least partially by regulating the activation of Nrf2 and NF-κB signaling. IFY may prevent ferroptosis and neuroinflammation in AD and provide a new treatment strategy for AD.http://www.sciencedirect.com/science/article/pii/S2213453023000356FerroptosisNeuroinflammationIsoforsythiasideAlzheimer's disease |
| spellingShingle | Chunyue Wang Hongbo Jiang Honghan Liu Shanshan Chen Hangyu Guo Shuoshuo Ma Weiwei Han Yu Li Di Wang Isoforsythiaside confers neuroprotection against Alzheimer’s disease by attenuating ferroptosis and neuroinflammation in vivo and in vitro Food Science and Human Wellness Ferroptosis Neuroinflammation Isoforsythiaside Alzheimer's disease |
| title | Isoforsythiaside confers neuroprotection against Alzheimer’s disease by attenuating ferroptosis and neuroinflammation in vivo and in vitro |
| title_full | Isoforsythiaside confers neuroprotection against Alzheimer’s disease by attenuating ferroptosis and neuroinflammation in vivo and in vitro |
| title_fullStr | Isoforsythiaside confers neuroprotection against Alzheimer’s disease by attenuating ferroptosis and neuroinflammation in vivo and in vitro |
| title_full_unstemmed | Isoforsythiaside confers neuroprotection against Alzheimer’s disease by attenuating ferroptosis and neuroinflammation in vivo and in vitro |
| title_short | Isoforsythiaside confers neuroprotection against Alzheimer’s disease by attenuating ferroptosis and neuroinflammation in vivo and in vitro |
| title_sort | isoforsythiaside confers neuroprotection against alzheimer s disease by attenuating ferroptosis and neuroinflammation in vivo and in vitro |
| topic | Ferroptosis Neuroinflammation Isoforsythiaside Alzheimer's disease |
| url | http://www.sciencedirect.com/science/article/pii/S2213453023000356 |
| work_keys_str_mv | AT chunyuewang isoforsythiasideconfersneuroprotectionagainstalzheimersdiseasebyattenuatingferroptosisandneuroinflammationinvivoandinvitro AT hongbojiang isoforsythiasideconfersneuroprotectionagainstalzheimersdiseasebyattenuatingferroptosisandneuroinflammationinvivoandinvitro AT honghanliu isoforsythiasideconfersneuroprotectionagainstalzheimersdiseasebyattenuatingferroptosisandneuroinflammationinvivoandinvitro AT shanshanchen isoforsythiasideconfersneuroprotectionagainstalzheimersdiseasebyattenuatingferroptosisandneuroinflammationinvivoandinvitro AT hangyuguo isoforsythiasideconfersneuroprotectionagainstalzheimersdiseasebyattenuatingferroptosisandneuroinflammationinvivoandinvitro AT shuoshuoma isoforsythiasideconfersneuroprotectionagainstalzheimersdiseasebyattenuatingferroptosisandneuroinflammationinvivoandinvitro AT weiweihan isoforsythiasideconfersneuroprotectionagainstalzheimersdiseasebyattenuatingferroptosisandneuroinflammationinvivoandinvitro AT yuli isoforsythiasideconfersneuroprotectionagainstalzheimersdiseasebyattenuatingferroptosisandneuroinflammationinvivoandinvitro AT diwang isoforsythiasideconfersneuroprotectionagainstalzheimersdiseasebyattenuatingferroptosisandneuroinflammationinvivoandinvitro |