Mechanism of scutellarein inhibiting foaming of macrophages by promoting cholesterol efflux pathway
- Author:
Ruo-Lin WU
1
;
Yu-Hong HUANG
1
;
Jing-Da LI
1
;
Tian-Qi WANG
2
;
Wen-Long SUN
3
Author Information
- Publication Type:Journal Article
- Keywords: atherosclerosis; cholesterol efflux; macrophage foam cell formation; oxidized low density lipoprotein; PPARγ; scutellarein
- From: Chinese Pharmacological Bulletin 2023;39(12):2266-2273
- CountryChina
- Language:Chinese
- Abstract: Aim To investigate the effects of scutellarein on the macrophage foam cell formation and cholesterol efflux, and the underlying mechanism. Methods THP-1 cells were differentiated with PMA, and the cell viability was detected by MTT assays. The effects of scutellarein on the cholesterol efflux and macrophage foam cell formation were evaluated by using NBD-la-beled cholesterol and the cholesterol detection kit. The effects of scutellarein on the activation of PPARγ-LXRα-ABCA1 signaling pathway were determined by molecular docking, ELISA, dual-luciferase reporter and Western blot. The effects of PPARγ knowdown on scutellarein-induced cholesterol efflux and inhibiting macrophage foaming were analyzed by siRNA interference. Results Scutellarein dose-dependently inhibited oxLDL-induced cholesterol accumulation, accelerated cholesterol efflux and significantly increased the protein expression of LXRα and ABCA1. At the same time, scutellarein could bind PPARγ and initiate its downstream LXRa-ABCAl signaling pathway. In addition, gene silencing of PPARγ not only significantly inhibited scutellarein-induced LXRα-ABCA1 signaling pathway and cholesterol efflux, but also reversed the inhibitory effect of scutellarein on macrophage foaming. Conclusions Scutellarein could promote the cholesterol efflux by activating PPARγ and initiating the downstream LXR-ABCA1 signaling pathway, thereby prevent the macrophage foam cell formation.
