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Updated: Jul 1, 2025

LDL Cholesterol Uptake Assay Using Live Cell Imaging Analysis with Cell Health Monitoring
Published on: November 17, 2018
Nobiletin alleviates atherosclerosis by inhibiting lipid uptake via the PPARG/CD36 pathway
Heng Wang1, Qinqin Tian1, Ruijing Zhang2
1Department of Vascular Surgery, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
Insights
Nobiletin (NOB) alleviates atherosclerosis by inhibiting lipid uptake. This study identified key genes and pathways, demonstrating NOB
Area of Science:
- Biochemistry and Molecular Biology
- Pharmacology
- Cardiovascular Research
Background:
- Atherosclerosis (AS) is a chronic inflammatory disease driven by lipid accumulation and macrophage infiltration.
- Nobiletin (NOB) shows potential in alleviating AS, but its precise mechanism requires elucidation.
Purpose of the Study:
- To elucidate the molecular mechanisms by which Nobiletin (NOB) exerts its anti-atherosclerotic effects.
- To identify key genes, pathways, and cellular processes involved in NOB's action against atherosclerosis.
Main Methods:
- Comprehensive bioinformatic analyses including target prediction and pathway enrichment (GO, KEGG).
- In vitro assays (cell scratch, oil red O, ELISA, flow cytometry, qRT-PCR, Western blotting) and in vivo AS mouse models.
- Drug binding site prediction (DeepSite, AutoDock) and immune cell infiltration analysis (CIBERSORT).
Main Results:
- Identified 141 potential target genes for NOB intervention in atherosclerosis.
- Highlighted lipid metabolism and atherosclerosis, and fluid shear stress pathways as dominant.
- Confirmed NOB inhibits lipid uptake and foam cell formation in vitro, and attenuates AS lesions, lipid accumulation, and macrophage infiltration in vivo, linked to PPARG/CD36 signaling.
Conclusions:
- Nobiletin (NOB) effectively alleviates atherosclerosis.
- The mechanism involves the inhibition of lipid uptake through the Peroxisome proliferator-activated receptor gamma (PPARG)/CD36 pathway.
- NOB demonstrates therapeutic potential for atherosclerosis treatment.
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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