Rice bran active peptide (RBAP) inhibited macrophage differentiation to foam cell and atherosclerosis in mice via regulating cholesterol efflux

Background: Atherosclerosis is a long-lasting inflammatory condition affecting the walls of arteries, marked by the buildup of fats, plaque formation, and vascular remodeling. Recent findings highlight the significance of Cholesterol removal pathways in influencing atherosclerosis, yet the connection between Cholesterol removal and regulation of macrophage inflammation remains poorly understood. RBAP could serve as an anti-inflammatory agent; however, its role in atherosclerosis and the mechanism behind it are still not well understood.

Purpose: The objective of this research is to explore how RBAP impacts Cholesterol efflux, which is a considerable element in the advancement of atherosclerosis.

Methods: An atherosclerosis mouse model was established by using an apoE KO strain mouse on a high-fat diet (HFD) to assess the effects of RBAP, conducted either orally or through injection. Additionally, in vitro experiments were conducted where the induction of THP-1 cells was conducted for the differentiation towards macrophages, and along with mouse RAW264.7 cells, were challenged with ox-LDL to evaluate the impact of RBAP.

Results: In this study, RBAP was found to reduce the production and downregulate TNF-α, IL-1β, and IL-6 levels and inhibited the activation of the TLR4/MyD88/NF-κB signaling in atherosclerosis model mice, as well as in ox-LDL-challenged THP-1 cells and mouse RAW264.7 macrophages. RBAP's effectiveness also improved the enhancement of reverse Cholesterol transport (RCT) and Cholesterol removal to HDL and apoA1 by increasing the activity of genes related to Cholesterol removal PPARγ/LXRα/ABCA1/ABCG1, both in apoE^-/- mice and in THP-1 cells and mouse RAW264.7 macrophages. Notably, RBAP exerted similar effects on atherosclerosis model mice and macrophages to those of TAK-242, an inhibitor of the TLR4 signaling. When RBAP and TAK-242 were applied simultaneously, the improvement was not enhanced compared with either RBAP or TAK-242 treatment alone.

Conclusion: These findings suggest that RBAP, as a TLR4 Inhibitor, has anti-atherosclerotic effects by improving inflammation and promoting Cholesterol effection, indicating its therapeutic potential in intervening atherosclerosis.

Atherosclerosis; Cholesterol efflux; Foam cells; Macrophages; Rice bioactive peptide.