Fei Xianming, Pan Lianlian, Yuan Wufen, Zhao Yan, Jiang Lei, Huang Qinghua, Wu Yan, Ru Guoqing
Laboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China.
Department of Laboratory Medicine, Sanmen People's Hospital of Taizhou, Taizhou, China.
Expert Opin Ther Targets. 2023 Mar;27(3):239-250. doi: 10.1080/14728222.2023.2194531. Epub 2023 Mar 24.
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 and AS .
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 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 .
Papain inhibited MPA-induced foam cell formation by inactivating the MAPK and PI3K/Akt-NF-κB pathways, thereby exerting an anti-AS effect.
木瓜蛋白酶具有潜在的抗动脉粥样硬化（AS）作用。本研究旨在探讨木瓜蛋白酶对单核细胞 - 血小板聚集体（MPAs）介导的泡沫细胞生成及AS的抑制作用。
用血小板、木瓜蛋白酶、核因子 - κB（NF - κB）抑制剂或激活剂处理THP - 1细胞。用木瓜蛋白酶处理AS大鼠模型。检测THP - 1细胞、巨噬细胞和泡沫细胞，并测定CD36、CD11b和CCR2（巨噬细胞）以及CD14和CD41（MPAs）。测定炎症因子、脂蛋白以及MAPK和PI3K/Akt - NF - κB信号通路蛋白的水平。最后，观察AS大鼠胸主动脉的损伤情况。
木瓜蛋白酶减少了巨噬细胞生成、脂质蓄积和泡沫细胞形成，并下调了单核细胞趋化蛋白1（MCP - 1）、前列腺素E2（PGE2）和环氧化酶2（COX2）以及p38、JNK、Akt和p65的表达。此外，NF - κB激活剂可逆转木瓜蛋白酶的抑制作用。同样，木瓜蛋白酶减轻了主动脉平滑肌增生、脂滴蓄积和胶原扩散，并抑制了炎症因子以及p38、JNK、Akt和p65的表达。
木瓜蛋白酶通过使MAPK和PI3K/Akt - NF - κB信号通路失活，抑制MPA诱导的泡沫细胞形成，从而发挥抗AS作用。
