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.

PubMed

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.
Abstract

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