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Nobiletin alleviates atherosclerosis by inhibiting lipid uptake via the PPARG/CD36 pathway.
Wang, Heng; Tian, Qinqin; Zhang, Ruijing; Du, Qiujing; Hu, Jie; Gao, Tingting; Gao, Siqi; Fan, Keyi; Cheng, Xing; Yan, Sheng; Zheng, Guoping; Dong, Honglin.
Afiliación
  • Wang H; Department of Vascular Surgery, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
  • Tian Q; Department of Vascular Surgery, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
  • Zhang R; Department of Nephrology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
  • Du Q; Jiangyin People's Hospital, Wuxi, Jiangsu, China.
  • Hu J; Shanxi Bethune Hospital, Third Hospital of Shanxi Medical University, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, Shanxi, China.
  • Gao T; Department of Vascular Surgery, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
  • Gao S; Department of Vascular Surgery, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
  • Fan K; Department of Vascular Surgery, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
  • Cheng X; Department of Vascular Surgery, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
  • Yan S; Department of Vascular Surgery, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
  • Zheng G; Department of Vascular Surgery, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
  • Dong H; Department of Vascular Surgery, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China. guoping.zheng@sydney.edu.au.
Lipids Health Dis ; 23(1): 76, 2024 Mar 11.
Article en En | MEDLINE | ID: mdl-38468335
ABSTRACT

BACKGROUND:

Atherosclerosis (AS) is a persistent inflammatory condition triggered and exacerbated by several factors including lipid accumulation, endothelial dysfunction and macrophages infiltration. Nobiletin (NOB) has been reported to alleviate atherosclerosis; however, the underlying mechanism remains incompletely understood.

METHODS:

This study involved comprehensive bioinformatic analysis, including multidatabase target prediction; GO and KEGG enrichment analyses for function and pathway exploration; DeepSite and AutoDock for drug binding site prediction; and CIBERSORT for immune cell involvement. In addition, target intervention was verified via cell scratch assays, oil red O staining, ELISA, flow cytometry, qRT‒PCR and Western blotting. In addition, by establishing a mouse model of AS, it was demonstrated that NOB attenuated lipid accumulation and the extent of atherosclerotic lesions.

RESULTS:

(1) Altogether, 141 potentially targetable genes were identified through which NOB could intervene in atherosclerosis. (2) Lipid and atherosclerosis, fluid shear stress and atherosclerosis may be the dominant pathways and potential mechanisms. (3) ALB, AKT1, CASP3 and 7 other genes were identified as the top 10 target genes. (4) Six genes, including PPARG, MMP9, SRC and 3 other genes, were related to the M0 fraction. (5) CD36 and PPARG were upregulated in atherosclerosis samples compared to the normal control. (6) By inhibiting lipid uptake in RAW264.7 cells, NOB prevents the formation of foam cell. (7) In RAW264.7 cells, the inhibitory effect of oxidized low-density lipoprotein on foam cells formation and lipid accumulation was closely associated with the PPARG signaling pathway. (8) In vivo validation showed that NOB significantly attenuated intra-arterial lipid accumulation and macrophage infiltration and reduced CD36 expression.

CONCLUSIONS:

Nobiletin alleviates atherosclerosis by inhibiting lipid uptake via the PPARG/CD36 pathway.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Flavonas / PPAR gamma / Aterosclerosis Límite: Animals Idioma: En Revista: Lipids Health Dis Asunto de la revista: BIOQUIMICA / METABOLISMO Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Flavonas / PPAR gamma / Aterosclerosis Límite: Animals Idioma: En Revista: Lipids Health Dis Asunto de la revista: BIOQUIMICA / METABOLISMO Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido