Effect of ophiopogonin D in resisting vascular endothelial cell apoptosis induced by AngⅡthrough up-regulating CYP2J2/EETs.
10.19540/j.cnki.cjcmm.20171027.019
- Author:
Xiao-Yan HUANG
1
;
Yu-Guang WANG
2
;
Yi WANG
1
;
Yue GAO
2
Author Information
1. Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.
2. Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing 100850, China.
- Publication Type:Journal Article
- Keywords:
CYP2J2/EETs;
JNK/c-Jun;
angiotensin Ⅱ;
cell apoptosis;
ophiopogonin D
- MeSH:
Angiotensin II;
Apoptosis;
Arachidonic Acids;
metabolism;
Cells, Cultured;
Cytochrome P-450 Enzyme System;
metabolism;
Human Umbilical Vein Endothelial Cells;
cytology;
drug effects;
Humans;
Phosphorylation;
Saponins;
pharmacology;
Signal Transduction;
Spirostans;
pharmacology
- From:
China Journal of Chinese Materia Medica
2018;43(2):377-384
- CountryChina
- Language:Chinese
-
Abstract:
This study aimed to investigate the effect and mechanism of ophiopogonin D (OP-D) on Ang Ⅱ-induced HUVECs apoptosis, in order to provide a reliable basis for the safety and efficacy of traditional Chinese medicines. The effect of Ang Ⅱ on survival and total proteins content of HUVECs were measured by MTT and Western blotting. The effect of OP-D on Ang Ⅱ-induced lactate dehydrogenase (LDH) release rate in HUVECs was measured by enzyme standard instrument. The effects of OP-D and 11,12-EET on phosphorylation of JNK/c-Jun induced by Ang Ⅱ were measured by Western blot and RT-PCR with the help of JNK specific inhibitor SP600125 and CYP450 isozymes selective inhibitor 6-(2-propargyloxyphenyl) hexanoic acid (PPOH). The cell apoptosis was assayed by flow cytometry. According to the results, different doses of Ang Ⅱ had no significant effect on cell survival; treatment with Ang Ⅱ at 1×10⁻⁶ mol·L⁻¹ could increase the release of LDH (<0.001), improve the JNK and c-Jun phosphorylation levels(<0.01, <0.001), increase the expression of caspase-3(<0.01), and promote the apoptosis of HUVECs(<0.001). The phosphorylation of JNK and c-Jun could be inhibited by the pre-treatment with SP600125, 11,12-EET and OP-D. Pre-treatment with OP-D could significantly reduce the release of LDH induced by Ang Ⅱ stimulation, decrease the expression of caspase-3, and diminish the apoptosis of cells. The protective effect of OP-D was suppressed, when being pretreated with PPOH. The experimental results showed that the apoptosis of HUVECs induced by Ang Ⅱ may be associated with JNK/c-Jun signaling pathway. OP-D-mediated CYP2J2 expression increased 11,12-EET levels, and could remarkably resist Ang Ⅱ-induced injury and apoptosis of cells, which is associated with the maintenance of endothelium homeostasis.
