Hydroxysafflor yellow A inhibits endothelial cell ferroptosis in diabetic atherosclerosis mice by regulating miR-429/SLC7A11

Autor: Jianjie Rong, Chuanyong Li, Qiang Zhang, Guangfeng Zheng, Weijian Fan, Zhichang Pan, Shuming Shi
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Pharmaceutical Biology, Vol 61, Iss 1, Pp 404-415 (2023)
Druh dokumentu: article
ISSN: 13880209
1744-5116
1388-0209
DOI: 10.1080/13880209.2023.2225543
Popis: AbstractContext Ferroptosis may play an essential role in lipid peroxidation and endothelial dysfunction of aortic endothelial cells (ECs) in type 2 diabetes mellitus (T2DM) with atherosclerosis (AS). Hydroxysafflor yellow A (HSYA) has shown substantial antioxidant stress and anti-ferroptosis.Objective This study confirms whether HSYA improves symptoms in a mouse model of T2DM/AS and elucidates the underlying mechanisms.Materials and methods ApoE-/- mice were fed with high fat combined with 30 mg/kg streptozotocin to establish a T2DM/AS model. Then mice were treated with intraperitoneal injections of 2.25 mg/kg HSYA for 12 weeks. Human Umbilical Vein Endothelial cells (HUVEC) induced by 33.3 mM d-glucose +100 μg/mL ox-LDL were used to construct a high lipid and high glucose cell model treated with 25 μM HSYA. The changes in oxidative stress- and ferroptosis-related markers were detected, and the regulatory effect of HSYA on the miR-429/SLC7A11 was also verified. Normal ApoE-/- mice or HUVEC cells were used as the control group.Results HSYA effectively reduced atherosclerotic plaque formation in the T2DM/AS mouse model and inhibited HUVEC ferroptosis, such as upregulating GSH-Px, SLC7A11 and GPX4, but inhibited ACSL4. Furthermore, HSYA also downregulated the expression of miR-429, which further regulated SLC7A11 expression. After miR-429 mimic or SLC7A11 siRNA transfection in the HUVEC, the antioxidative stress and anti-ferroptosis effects of HSYA were significantly abolished.Conclusions HSYA is expected to become an important health drug to prevent the occurrence and development of T2DM/AS.
Databáze: Directory of Open Access Journals
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