Three polymethoxyflavones from the peel of Citrus reticulata “Chachi” inhibits oxidized low-density lipoprotein-induced macrophage-derived foam cell formation

Citations Over TimeTop 10% of 2022 papers

Abstract

Foam cell formation is the hallmark of the development and progression of atherosclerosis. The aim of this study was to investigate the regulatory effects of three polymethoxyflavones (PMFs), namely, tangeretin (TAN), 5,6,7,3',4',5'-hexamethoxyflavone (HxMF), and 3,5,6,7,8,3',4'-heptamethoxyflavone (HpMF) on macrophage-derived foam cell formation and to further explore the molecular mechanisms. The RAW264.7 macrophage-derived foam cell model was successfully induced by oxidized low-density lipoprotein (ox-LDL) (80 μg/ml). It showed that TAN, HxMF, and HpMF alleviated ox-LDL-induced NO release while also inhibiting the expression of IL-1β, IL-6, and TNF-α in RAW264.7 cells. Uptake of excess ox-LDL was inhibited by TAN, HxMF, and HpMF, resulting in the reduction of its foam cell formation. Moreover, TAN, HxMF, and HpMF promoted HDL-mediated cholesterol efflux. Western blot experiment showed that TAN, HxMF, and HpMF inhibited the expression of scavenger receptor class A type I (SRA1) and cluster of differentiation 36 (CD36), while upregulating peroxisome proliferator-activated receptor γ (PPARγ), liver X receptor α (LXRα), phospholipid ATP-binding cassette transporter G1 (ABCG1), and scavenger receptor class B type I (SRB1) expression. Together, our findings suggested that PMFs inhibited foam cell formation might inhibit lipid uptake via downregulating SRA1/CD36 expression and promote cholesterol efflux from foam cells via upregulating PPARγ/LXRα/ABCG1/SRB1 expression. This antiatherosclerotic activity is expected to provide new insights into the development of healthcare uses for PMFs.

Related Papers

• → LXR/RXR activation enhances basolateral efflux of cholesterol in CaCo-2 cells(2002)204 cited
• → Cholesterol efflux is LXRα isoform-dependent in human macrophages(2014)35 cited
• → E17110 promotes reverse cholesterol transport with liver X receptor β agonist activity in vitro(2016)12 cited
• → Setosphapyrone C and D accelerate macrophages cholesterol efflux by promoting LXRα/ABCA1 pathway(2020)7 cited
• → RIP140 as a novel therapeutic target in the treatment of atherosclerosis(2015)3 cited