Papain exerts an anti-atherosclerosis effect with suppressed MPA-mediated foam cell formation by regulating the MAPK and PI3K/Akt-NF-κB pathways

Papain possesses a potential anti-atherosclerosis (AS) effect. This study aimed to explore the inhibitory effects of papain on the monocyte-platelet aggregates (MPAs)-mediated production of foam cells in vitro and AS in vivo.THP-1 cells were treated by platelet, papain, nuclear factor-κB (NF-κB) inhibitor or activator. An AS rat model was treated with papain. The THP-1 cells, macrophages, and foam cells were detected, and CD36, CD11b and CCR2 (macrophages) and CD14 and CD41 (MPAs) were measured. The levels of inflammatory factors, lipoprotein, and MAPK and PI3K/Akt -NF-κB pathways proteins were determined. Finally, injury of the thoracic aorta of AS rats was observed.Papain reduced macrophage production, lipid accumulation, and foam cell formation in vitro and downregulated the expression of monocyte chemoattractant protein 1 (MCP-1), prostaglandin E2 (PGE2), and cyclooxygenase 2 (COX2), and that of p38, JNK, Akt, and p65. Moreover, NF-κB activator could reversed the inhibitory effects of papain. Similarly, papain alleviated aortic smooth muscle hyperplasia, lipid droplet accumulation, and collagen diffusion and inhibited the expression of inflammatory factors and p38, JNK, Akt, and p65 in vivo.Papain inhibited MPA-induced foam cell formation by inactivating the MAPK and PI3K/Akt-NF-κB pathways, thereby exerting an anti-AS effect.