Effect of PI3K-mediated Nrf2 Phosphorylated Activation in Quercetin in Inhibiting Clivorine-induced Hepatotoxicity / 中国实验方剂学杂志

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), NADPHquinone 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 (PPPPPPPConclusion: Quer alleviates Cliv-induced hepatotoxicity by inducing Nrf2 phosphorylated activation, and PI3K plays an important role in regulating Quer-induced Nrf2 phosphorylated activation.