Protective effect of

Background: Low-density lipoproteins are oxidized and modified by macrophages. This process leads to the formation of macrophage-derived cholesterol-rich foam cells, which are a hallmark of early atherosclerosis. The accumulation of these form cells plays a crucial role in atherosclerosis progression. Objective: This study aims to explore the effect of Design: THP-1 cells were differentiated by phorbol 12-myristate 13-acetate (PMA) (1 μM) for 48 h. Subsequently, they were treated with either AHWE or cycloalliin for 48 h. THP-1 macrophages were treated with combined ox-LDL (20 μg/mL) and LPS (500 ng/mL) for 24 h. Cell viability was assessed using MTT assays, while lipid accumulation was visualized through Oil Red O staining. The levels of corresponding proteins and mRNA were quantified using western blotting and quantitative polymerase chain reactions. Results: THP-1 cells were differentiated with PMA (1 μM) for 48 h and then treated with or without AHWE and cycloalliin for 48 h. Subsequently, THP-1 macrophages were treated with combined ox-LDL (20 μg/mL) and LPS (500 ng/mL) for 24 h before harvesting. Ox-LDL and LPS treatment for 24 h enhanced the lipid accumulation in foam cells compared to those in untreated cells using Oil red O staining. Conversely, AHWE and cycloalliin treatment inhibited lipid accumulation in foam cells. These treatments significantly upregulated cholesterol efflux-related genes, including ATP binding cassette subfamily A member 1 (ABCA1), liver-X-receptor ɑ (LXRɑ), and peroxisome proliferator-activated receptor gamma (PPARγ) expression. Additionally, AHWE and cycloalliin decreased lipid accumulation-related genes, including lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), cluster of differentiation 36 (CD36), and scavenger receptor A1 (SR-A1) expression. Furthermore, the combined treatment of ox-LDL and LPS increased the activation and expression of nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2), and pro-inflammatory cytokines (tumor necrosis factor-α [TNF-α] and IL-6) compared with those in untreated cells. However, AHWE and cycloalliin suppressed the expression of NF-κB, COX-2, TNF-α, and IL-6. Conclusions: AHWE and cycloalliin potentially play a crucial role in suppressing and protecting against early-stage foam cell formation by modulating lipid accumulation and cholesterol efflux. AHWE and cycloalliin have the potential to be effective agents for preventing atherosclerosis.