Icariin, astragaloside a and puerarin mixture attenuates cognitive impairment in APP/PS1 mice via inhibition of ferroptosis-lipid peroxidation.

Zhang, TC ; Lin, YC ; et al.

In: Neurochemistry international, Jg. 175 (2024-05-01), S. 105705

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Alzheimer's disease (AD) is a neurodegenerative disease that seriously threatens the quality of life of the elderly. Its pathogenesis has not yet been fully elucidated. Ferroptosis, a cell death caused by excessive accumulation of iron-dependent lipid peroxides, has been implicated in the pathogenesis of AD. Uncontrolled lipid peroxidation is the core process of ferroptosis, and inhibiting lipid peroxidation of ferroptosis may be an important therapeutic target for AD. Based on previous studies, we mixed standards of icariin, astragaloside IV, and puerarin, named the standard mixture YHG, and investigated the effect of YHG on ferroptosis -lipid peroxidation in APP/PS1 mice. DFX, a ferroptosis inhibitor, was used as a control drug. In this study, APP/PS1 mice were used as an AD animal model, and behavioral experiments, iron level detection, Transmission electron microscopy (TEM) observation, lipid peroxidation level detection, antioxidant capacity detection, immunofluorescence, Western blot and real-time qPCR were performed. It was found that YHG could reduce body weight, significantly improve abnormal behaviors and the ultrastructure of hippocampal neurons in APP/PS1 mice. The results of biochemical tests showed that YHG reduced the contents of iron, malondialdehyde (MDA) and lipid peroxide (LPO) in brain tissue and serum, and increased the levels of superoxide dismutase (SOD) and reduced glutathione (GSH). Immunofluorescence, WesternBlot and real-time qPCR results showed that YHG could promote the expression of solute carrier family 7 member 11 (SLC7A11), solute carrier family 3 member 2 (SLC3A2) and glutathione peroxidase 4(GPX4). Inhibited the expression of long-chain acyllipid coenzyme a synthetase 4(ACSL4) and lysophosphatidyltransferase 3 (LPCAT3). This study suggests that the mechanism by which YHG improves cognitive dysfunction in APP/PS1 mice may be related to the inhibition of ferroptosis-lipid peroxidation.

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Titel:	Icariin, astragaloside a and puerarin mixture attenuates cognitive impairment in APP/PS1 mice via inhibition of ferroptosis-lipid peroxidation.
Autor/in / Beteiligte Person:	Zhang, TC ; Lin, YC ; Sun, NN ; Liu, S ; Hu, WZ ; Zhao, Y ; Dong, XH ; He, XP
Link:	Zum Volltext
Zeitschrift:	Neurochemistry international, Jg. 175 (2024-05-01), S. 105705
Veröffentlichung:	Oxford [Elmsford, N. Y.] Pergamon Press., 2024
Medientyp:	academicJournal
ISSN:	1872-9754 (electronic)
DOI:	10.1016/j.neuint.2024.105705
Schlagwort:	Humans Aged Animals Mice Lipid Peroxidation Quality of Life Lipid Peroxides Iron 1-Acylglycerophosphocholine O-Acyltransferase Ferroptosis Neurodegenerative Diseases Cognitive Dysfunction Alzheimer Disease drug therapy Flavonoids Isoflavones Saponins Triterpenes
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Neurochem Int] 2024 May; Vol. 175, pp. 105705. <i>Date of Electronic Publication: </i>2024 Feb 25. MeSH Terms: Ferroptosis* ; Neurodegenerative Diseases* ; Cognitive Dysfunction* ; Alzheimer Disease* / drug therapy ; Flavonoids* ; Isoflavones* ; Saponins* ; Triterpenes* ; Humans ; Aged ; Animals ; Mice ; Lipid Peroxidation ; Quality of Life ; Lipid Peroxides ; Iron ; 1-Acylglycerophosphocholine O-Acyltransferase Contributed Indexing: Keywords: Alzheimer's disease; Astragaloside A; Astragaloside IV (Pubchem CID: 13943297); Ferroptosis-lipid peroxidation; Iacriin (Pubchem CID: 5318997); Icariin; Puerarin; Puerarin (Pubchem CID: 5281807) Substance Nomenclature: VNM47R2QSQ (icariin) ; Z9W8997416 (puerarin) ; 3A592W8XKE (astragaloside A) ; 0 (Lipid Peroxides) ; E1UOL152H7 (Iron) ; EC 2.3.1.23 (LPCAT3 protein, mouse) ; EC 2.3.1.23 (1-Acylglycerophosphocholine O-Acyltransferase) ; 0 (Flavonoids) ; 0 (Isoflavones) ; 0 (Saponins) ; 0 (Triterpenes) Entry Date(s): Date Created: 20240227 Date Completed: 20240408 Latest Revision: 20240408 Update Code: 20240408

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