[Effect of ophiopogonin D in resisting vascular endothelial cell apoptosis induced by Angâ
¡through up-regulating CYP2J2/EETs].
Zhongguo Zhong Yao Za Zhi
; 43(2): 377-384, 2018 Jan.
Article
em Zh
| MEDLINE
| ID: mdl-29552858
ABSTRACT
This study aimed to investigate the effect and mechanism of ophiopogonin D (OP-D) on Ang â
¡-induced HUVECs apoptosis, in order to provide a reliable basis for the safety and efficacy of traditional Chinese medicines. The effect of Ang â
¡ on survival and total proteins content of HUVECs were measured by MTT and Western blotting. The effect of OP-D on Ang â
¡-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 â
¡ 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 â
¡ had no significant effect on cell survival; treatment with Ang â
¡ at 1×10â»6 mol·L⻹ could increase the release of LDH (P<0.001), improve the JNK and c-Jun phosphorylation levels(P<0.01, P<0.001), increase the expression of caspase-3(P<0.01), and promote the apoptosis of HUVECs(P<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 â
¡ 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 â
¡ may be associated with JNK/c-Jun signaling pathway. OP-D-mediated CYP2J2 expression increased 11,12-EET levels, and could remarkably resist Ang â
¡-induced injury and apoptosis of cells, which is associated with the maintenance of endothelium homeostasis.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Saponinas
/
Espirostanos
/
Ácidos Araquidônicos
/
Apoptose
/
Sistema Enzimático do Citocromo P-450
/
Células Endoteliais da Veia Umbilical Humana
Limite:
Humans
Idioma:
Zh
Revista:
Zhongguo Zhong Yao Za Zhi
Assunto da revista:
FARMACOLOGIA
/
TERAPIAS COMPLEMENTARES
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
China