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Food Science and Human Wellness 2023, 12(5): 1730-1742 https://doi.org/10.1016/j.fshw.2023.02.035
Research Article | Open Access | Issue | Published: 21 March 2023

Isoforsythiaside confers neuroprotection against Alzheimer’s disease by attenuating ferroptosis and neuroinflammation in vivo and in vitro

Show Author's Information Chunyue Wanga,b,1,  Hongbo Jianga,1,  Honghan Liua,  Shanshan Chena,  Hangyu Guoa,  Shuoshuo Maa,  Weiwei Hana,  Yu Lib,  Di Wanga,b( )
School 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

1 These authors contributed equally to this work.

Peer review under responsibility of KeAi Communications Co., Ltd.

Keywords:
Alzheimer's disease, Ferroptosis, Neuroinflammation, Isoforsythiaside
Cite this article:
Wang C, Jiang H, Liu H, et al. Isoforsythiaside confers neuroprotection against Alzheimer’s disease by attenuating ferroptosis and neuroinflammation in vivo and in vitro. Food Science and Human Wellness, 2023, 12(5): 1730-1742. https://doi.org/10.1016/j.fshw.2023.02.035
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Abstract Full text About this article

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.


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Isoforsythiaside confers neuroprotection against Alzheimer’s disease by attenuating ferroptosis and neuroinflammation in vivo and in vitro

Show Author's information Chunyue Wanga,b,1, Hongbo Jianga,1, Honghan Liua, Shanshan Chena, Hangyu Guoa, Shuoshuo Maa, Weiwei Hana, Yu Lib, Di Wanga,b( )
School 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

1 These authors contributed equally to this work.

Peer review under responsibility of KeAi Communications Co., Ltd.

Abstract

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.

Keywords: Alzheimer's disease, Ferroptosis, Neuroinflammation, Isoforsythiaside

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Received: 27 July 2021
Revised: 17 August 2021
Accepted: 29 October 2021
Published: 21 March 2023
Issue date: September 2023

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© 2023 Beijing Academy of Food Sciences.

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Acknowledgements

This work was supported by the Jilin Scientific and Technological Development Program (20191102027YY, 20200708037YY and 20200708068YY), the Special Project for Health of Jilin Province (2020SCZT077), Science and Technology Research Project, Education Department of Jilin Province of China (JJKH20200322KJ) and Innovation Capacity Building Project of Jilin Provincial Development and Reform Commission (2021C035-6).

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