Rosmarinic acid liposomes suppress ferroptosis in ischemic brain via inhibition of TfR1 in BMECs.
Phytomedicine
; 132: 155835, 2024 Sep.
Article
em En
| MEDLINE
| ID: mdl-38968791
ABSTRACT
BACKGROUND:
Iron deposition and ferroptosis are involved in ischemic stroke injury, but the choice of drugs for treatment is limited.PURPOSE:
To investigate the potential neuroprotective effects of Rosmarinic acid (RosA) encapsulated within nanoliposomes (RosA-LIP) on ischemic stroke.METHODS:
Wild-type (WT) and TfR1EC cKO (specific knockout of the TfR1 gene in BMECs) mice used to establish a dMCAO model, with simultaneous administration of RosA-LIP (20 mg/kg/d, i.p.) or RosA (20 mg/kg/d, i.p.).RESULTS:
The successful synthesis of RosA-LIP resulted in enhanced stability and precise delivery in both the serum and brain. The administration of RosA-LIP effectively mitigated ischemia-induced behavioral abnormalities and pathological damage. RosA-LIP inhibited ferroptosis by ameliorating mitochondrial abnormalities, increasing GPX4 levels, and decreasing ACSL4/LPCAT3/Lox-dependent lipid peroxidation. RosA-LIP effectively improved bloodâbrain barrier (BBB) permeability, increased tight junctions (TJs) protein expression and reduced iron levels in ischemic tissue and brain microvascular endothelial cells (BMECs) by modulating FPN1 and TfR1 levels. Furthermore, RosA-LIP suppressed TfR1 to attenuate ACSL4/LPCAT3/Lox-mediated ferroptosis in TfR1EC cKO mice subjected to dMCAO.CONCLUSION:
RosA-LIP effectively increased the brain level of RosA and protected against ferroptosis through the regulation of TfR1 in BMECs.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Receptores da Transferrina
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Barreira Hematoencefálica
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Cinamatos
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Células Endoteliais
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Depsídeos
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Ferroptose
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Ácido Rosmarínico
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Lipossomos
Limite:
Animals
Idioma:
En
Revista:
Phytomedicine
Assunto da revista:
TERAPIAS COMPLEMENTARES
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China