Beneficial effects of evodiamine on P2X(4)-mediated inflammatory injury of human umbilical vein endothelial cells due to high glucose.
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.
Department of Physiology, Medical School of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China.
Qiulan
Q
Lv
Department of Physiology, Medical School of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China.
Yun
Y
Xue
Department of Physiology, Medical School of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China; Department of Clinical Research, Singapore General Hospital, Singapore.
Guodong
G
Li
Department of Physiology, Medical School of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China.
Lifang
L
Zou
Department of Physiology, Medical School of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China.
Xi
X
Zhang
Department of Physiology, Medical School of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China.
Mofeng
M
Ying
Department of Physiology, Medical School of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China.
Shouyu
S
Wang
Department of Physiology, Medical School of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China.
Lili
L
Guo
Department of Physiology, Medical School of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China.
Yun
Y
Gao
Department of Physiology, Medical School of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China.
Guilin
G
Li
Department of Physiology, Medical School of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China.
Hong
H
Xu
Department of Physiology, Medical School of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China.
Shuangmei
S
Liu
Department of Physiology, Medical School of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China; Key Laboratory of Molecular Medicine of JiangXi, The Second Affiliated Hospital of Nanchang University, People's Republic of China.
Jinyan
J
Xie
Department of Physiology, Medical School of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China; Institute of Life Science of Nanchang University, Nanchang, Jiangxi 330006, People's Republic of China. Electronic address: liangsd@hotmail.com.
Shangdong
S
Liang
D004365:Drugs, Chinese Herbal; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D032086:Evodia; D005947:Glucose / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D058848:Receptors, Purinergic P2X4 / Q000235:genetics / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D014471:Umbilical Veins / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects
D004365:Drugs, Chinese Herbal; D016328:NF-kappa B; D011799:Quinazolines; D017382:Reactive Oxygen Species; D058848:Receptors, Purinergic P2X4; D018124:Receptors, Tumor Necrosis Factor; D009569:Nitric Oxide; C049639:evodiamine; D005947:Glucose
Evodiamine; HUVECs; High glucose; Inflammation; P2X(4) receptor