OxLDL-Induced Foam Cell Formation Inhibitory Activity of Pepsin Hydrolysate of Ark Shell (Scapharca subcrenata (Lischke, 1869)) in RAW264.7 Macrophages

Inhibitory effect of ark shell (Scapharca subcrenata (Lischke, 1869)) proteolytic hydrolysates (ASHs) on oxidized low-density lipoprotein (oxLDL)-induced macrophage foam cell formation was investigated. Two types of ASHs were prepared by Alcalase (R) and pepsin, ASAH (ark shell-Alcalase (R) hydrolysates), and ASPH (ark shell-pepsin hydrolysate). Oil Red O staining results showed that ASPH suppressed foam cell formation and lipid accumulation more than ASAH in oxLDL-induced foam cell formation of RAW264.7 macrophages. ASPH reduced the levels of total cholesterol, cholesterol ester, and free cholesterol in oxLDL-treated RAW264.7 macrophages. It was found that ASPH increased cholesterol efflux and decreased cholesterol influx rate. In this regard, protein expressions of CD36 and scavenger receptor class A1 (SR-A1) for cholesterol influx and ATP-binding cassette transporter A1 and G1 (ABCA1 and ABCG1) for cholesterol efflux were investigated. ASPH treatment resulted in an increase of ABCA1 and ABCG1 expression but downregulated CD36 and SR-A1 expression. Furthermore, ASPH suppressed production of proinflammatory cytokines, including tumor necrosis factor-alpha and interleukin-6 and -1 beta, through regulating nuclear factor-kappa B (NF-kappa B) in oxLDL-induced foam cell formation of RAW264.7 macrophages. Taken together, our data indicate that ASPH might be a useful ingredient in functional foods for ameliorating atherosclerosis by preventing foam cell formation.