Modified Yuejuwan Inhibited Cholesterol Accumulation and Inflammation in THP-1 Macrophage-Derived Foam Cells by Inhibiting the Activity of the TRIM37/TRAF2/NF-κB Pathway.

Abstract

Background:

This study aimed to explore the function of modified Yuejuwan (MYJ) on THP-1 macrophage-derived foam cells.

Methods:

First, human THP-cells were obtained, and then, grouping was made to the following: control group, foaming group, foaming group +0.2 mg/mL Jiawei Yueju pill, foaming group +0.5 mg/mL Jiawei Yueju pill, and foaming group +1 mg/mL Jiawei Yueju pill. An Oil Red O staining assay was used to examine the uptake of oxidatively modified low-density lipoprotein (oxLDL). The secretion of interleukin (IL)-1β and tumor necrosis factor (TNF)-α were determined using an enzyme-linked immunosorbent assay (ELISA). Real-time quantitative PCR (qRT-PCR) and Western blot were used to quantify genes and proteins expression levels.

Results:

Our results indicated that MYJ inhibited the accumulation of total cholesterol (TC), free cholesterol (FC), and cholesteryl ester (CE) in foam cells. Moreover, the secretion of IL-1β and TNF-α also downregulated in foam cells after treatment of MYJ. Furthermore, we found that tripartite motif-containing 37 (TRIM37) was significantly upregulated in foam cells. Knockdown of TRIM37 promoted cholesterol efflux and presented an anti-inflammation effect in foam cells. Furthermore, TRIM37 positively mediated the translocation of NF-κB to nuclear. It negatively regulated its ubiquitination in foam cells after interacting with TRAF2. Importantly, MYJ profoundly suppressed the function of TRIM37 in foam cells and functioned as a TRIM37 inhibitor.

Conclusions:

This study demonstrated that MYJ might alleviate oxLDL-induced foam cell formation by inhibiting the TRIM37/TRAF2/NF-κB pathway activity. MYJ was a potential agent in preventing atherosclerosis and indicated its potential signaling pathway in foam cells.

• Authors: Mingtai Gui, Lei Yao, Bo Lu, Jianhua Li, Jing Wang, Xunjie Zhou, Deyu Fu
• Journal: Evidence-based complementary and alternative medicine : eCAM (Evid Based Complement Alternat Med) Vol. 2022 Pg. 6400517 ( 2022) ISSN: 1741-427X [Print] United States
• PMID: 35310029 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Mingtai Gui et al.