Department of Physiology, Medical School of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China.
Department of Physiology, Medical School of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China; Department of Clinical Research, Singapore General Hospital, Singapore.
Int Immunopharmacol. 2015 Oct;28(2):1044-9. doi: 10.1016/j.intimp.2015.08.020. Epub 2015 Sep 4.
Evodiamine has been reported to exhibit anti-inflammatory and anti-nociceptive effects, but the underlying mechanisms remain to be defined. P2X4 receptor (P2X4R) is a subtype of ATP receptors and plays important roles in pain, inflammatory and immune responses. We aimed to investigate whether evodiamine has beneficial effects on endothelial inflammatory injury mediated by chronic high glucose condition. We found that culturing human umbilical vein endothelial cells (HUVECs) with high glucose significantly increased the expression of P2X4 receptor in HUVECs, cytosolic Ca(2+) concentrations and intracellular reactive oxygen species (ROS) while decreasing nitric oxide (NO); these effects could be reversed by evodiamine. High glucose also significantly increased the expression of the pro-inflammatory activators (NF-κB) and TNFR-ɑ, which was accompanied by the elevation of P2X4R levels. Evodiamine was able to down-regulate the elevated NF-κB, TNFR-ɑ, P2X4R and ROS, and up-regulate the decreased NO. Thus the evodiamine may exert the anti-inflammation activity on high-glucose challenge HUVEC via suppressing the P2X4R signaling pathway, exhibiting beneficial ability to protect HUVECs from glucotoxicity.
吴茱萸碱已被报道具有抗炎和镇痛作用，但作用机制尚待阐明。P2X4 受体（P2X4R）是 ATP 受体的一种亚型，在疼痛、炎症和免疫反应中发挥重要作用。我们旨在研究吴茱萸碱是否对慢性高葡萄糖条件介导的内皮炎症损伤有有益作用。我们发现，用高葡萄糖培养人脐静脉内皮细胞（HUVEC）会显著增加 HUVEC 中 P2X4 受体的表达、细胞浆钙离子浓度和细胞内活性氧（ROS），同时降低一氧化氮（NO）；这些作用可以被吴茱萸碱逆转。高葡萄糖还显著增加了促炎激活物（NF-κB）和 TNFR-ɑ的表达，同时 P2X4R 水平升高。吴茱萸碱能够下调升高的 NF-κB、TNFR-ɑ、P2X4R 和 ROS，并上调降低的 NO。因此，吴茱萸碱可能通过抑制 P2X4R 信号通路对高葡萄糖刺激的 HUVEC 发挥抗炎作用，表现出保护 HUVEC 免受糖毒性的有益能力。
