Effect of PI3K-mediated Nrf2 Phosphorylated Activation in Quercetin in Inhibiting Clivorine-induced Hepatotoxicity
10.13422/j.cnki.syfjx.20190423
- VernacularTitle: PI3K介导的Nrf2磷酸化激活在槲皮素抑制山岗橐吾碱肝细胞毒性中的作用
- Author:
Zhan-xia HAO
1
;
Liang SHI
1
;
Bin LU
1
;
Li-li JI
1
Author Information
1. Key Laboratory for Standardization of Chinese Medicines under Ministry of Education, Shanghai Key Laboratory for Compound Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
- Publication Type:Research Article
- Keywords:
quercetin;
phosphoinositide-3-kinase;
nuclear factor E2-related factor 2;
hepatotoxicity;
clivorine
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2019;25(5):112-118
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To observe the effect of phosphoinositide-3-kinase (PI3K)-mediated nuclear factor E2-related factor 2 (Nrf2) phosphorylated activation in quercetin (Quer) in prohibiting clivorine (Cliv)-induced cytotoxicity in L-02 cells. Method: Human normal liver L-02 cells were pre-incubated with Quer (1, 10, 25, 50 μmol·L-1) for 15 min, and then incubated with Cliv (50 μmol·L-1) for 48 h. The cell viability was evaluated by thiazolam blue(MTT) assay. Cellular reactive oxygen species (ROS) and reduced glutathione (GSH) were detected. The transcriptional activation of Nrf2 was measured by dual-luciferase reporter assay. The phosphorylation of Nrf2 and PI3K was measured by Western blot, and downstream genes, including heme oxygenase 1 (Hmox1), NADPH:quinone oxidoreductase 1 (Nqo1), catalytic subunit of glutamate-cysteine ligase (Gclc), modifier subunit of glutamate-cysteine ligase (Gclm), were measured by Real-time PCR. Result: Quer (10, 25, 50 μmol·L-1) reversed Cliv-induced decreased cell viability (P<0.05), GSH (P<0.05) and ROS levels (P<0.01). Quer induced phosphorylation of PI3K (P<0.05). Quer induced phosphorylation and subsequent transcriptional activation of Nrf2 (P<0.05), and enhanced mRNA expressions of Nrf2 downstream genes (P<0.05). The increased Hmox1 mRNA expression was reduced by PI3K inhibitor LY294002 (LY) (P<0.01). Conclusion: Quer alleviates Cliv-induced hepatotoxicity by inducing Nrf2 phosphorylated activation, and PI3K plays an important role in regulating Quer-induced Nrf2 phosphorylated activation.
