Papain Exerts an Anti-atherosclerosis Effect with Suppressed MPA-mediated Foam Cell Formation by Regulating the MAPK and PI3K/Akt-NF-κB Pathways

by Selleckchem | Apr 13 2023

Background: 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.

Research design and methods: THP-1 cells were induced or treated by platelet, papain, nuclear factor-κB (NF-κB, p65) inhibitor, or NF-κB activator. An AS rat model was established and 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 mitogen-activated protein kinase (MAPK, p38) and phosphoInositide-3 Kinase (PI3K)/Akt(protein kinase B, PKB)-NF-κB pathways proteins were determined. Finally, injury of the thoracic aorta of AS rats was observed.

Results: 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, c-Jun N-terminal protein kinase (JNK), Akt, and p65. Moreover, the inhibitory effects of papain were reversed by the NF-κB activator. Similarly, papain alleviated aortic smooth muscle hyperplasia, lipid droplet accumulation, and collagen diffusion and inhibited the secretion of inflammatory factors and the expression of p38, JNK, Akt, and p65 in vivo.

Conclusions: Papain inhibited MPA-induced foam cell formation by inactivating the MAPK and PI3K/Akt-NF-κB pathways, thereby exerting an anti-AS effect.

Comments：

In this study, the researchers investigated the potential anti-atherosclerosis effect of papain by examining its inhibitory effects on monocyte-platelet aggregates (MPAs)-mediated production of foam cells in vitro and atherosclerosis in vivo. The study involved the use of THP-1 cells induced or treated with platelet, papain, NF-κB (p65) inhibitor, or NF-κB activator. An AS rat model was also established and treated with papain.

The researchers found that papain reduced macrophage production, lipid accumulation, and foam cell formation in vitro, and downregulated the expression of MCP-1, PGE2, and COX2, and that of p38, JNK, Akt, and p65. The inhibitory effects of papain were also reversed by the NF-κB activator. Moreover, papain alleviated aortic smooth muscle hyperplasia, lipid droplet accumulation, and collagen diffusion and inhibited the secretion of inflammatory factors and the expression of p38, JNK, Akt, and p65 in vivo.

From these results, the researchers concluded that papain inhibited MPA-induced foam cell formation by inactivating the MAPK and PI3K/Akt-NF-κB pathways, thereby exerting an anti-AS effect. This study suggests that papain may have therapeutic potential for preventing or treating atherosclerosis. However, further research is needed to confirm these findings and to determine the optimal dose and route of administration for papain.