<i>Bacillus</i> subtilis-fermented brown seaweed<i> Laminaria</i><i> japonica</i> inhibits foam cell formation via CD36-dependent signaling pathway

Abstract

Foam cell formation is a crucial process in the progression of atherosclerosis, a chronic inflammatory disease characterized by the accumulation of plaques in the arteries. This study aimed to examine the physiochemical changes in Laminaria japonica during fermentation with Bacillus subtilis and assess the inhibitory effects of the fermented sample on the oxidation of low-density lipoprotein (LDL) and the formation of foam cells. Polysaccharide decompositions and increase of total phenols and reducing power of L. japonica were observed during fermentation. The Fourier-transform infrared spectroscopy analysis revealed the peaks of seaweed polysaccharides of the fermented L. japonica (F sample). The presence of F sample reduced the oxidative stress induced by Cu2+ on LDL and inhibited foam cell formation. Additionally, the levels of proteins involved in foam cell activation, such as CD36, scavenger receptor-A, TLR4, and TLR6, were significantly decreased. Further proteomic analysis revealed that out of 1439 proteins up-regulated by oxidized LDL (oxLDL) in macrophages, 953 were downregulated in the presence of the F sample. The Ingenuity Pathway Analysis identified the activation of canonical pathways associated with atherosclerosis by oxLDL, which were subsequently suppressed by the F sample treatment. Protein-protein interaction network analysis uncovered the role of MAPK3 in regulating multiple pathways. This study suggests that B. subtilis-fermented brown seaweed L. japonica can inhibit LDL oxidation and foaming cell production. Additionally, it offers mechanistic insights for future research in this area.