Effect of PI3K-mediated Nrf2 Phosphorylated Activation in Quercetin in Inhibiting Clivorine-induced Hepatotoxicity

Zhan-xia HAO; Liang SHI; Bin LU; Li-li JI

doi:10.13422/j.cnki.syfjx.20190423

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Effect of PI3K-mediated Nrf2 Phosphorylated Activation in Quercetin in Inhibiting Clivorine-induced Hepatotoxicity

Pharmacology | 更新时间：2021-02-09

- Effect of PI3K-mediated Nrf2 Phosphorylated Activation in Quercetin in Inhibiting Clivorine-induced Hepatotoxicity
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 5, Pages: 112-118(2019)
- 作者机构：
  
  上海中医药大学　中药研究所　中药标准化教育部重点实验室，上海市复方中药重点实验室，上海　 201203
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20190423
  CLC： R22;R242;R2-031;R285.5;R273
- Received：13 July 2018，
  
  Published Online：05 November 2018，
  
  Published：05 March 2019
- 稿件说明：
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Zhan-xia HAO, Liang SHI, Bin LU, et al. Effect of PI3K-mediated Nrf2 Phosphorylated Activation in Quercetin in Inhibiting Clivorine-induced Hepatotoxicity[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(5): 112-118.
DOI：

Zhan-xia HAO, Liang SHI, Bin LU, et al. Effect of PI3K-mediated Nrf2 Phosphorylated Activation in Quercetin in Inhibiting Clivorine-induced Hepatotoxicity[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(5): 112-118. DOI： 10.13422/j.cnki.syfjx.20190423.

摘要

目的：

观察磷脂酰肌醇-3-激酶(phosphoinositide-3-kinase

PI3K)介导的核转录因子E

Abstract

Objective:

To observe the effect of phosphoinositide-3-kinase (PI3K)-mediated nuclear factor E

-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

50 μmol·L

-1

) for 15min

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

50 μmol·L

-1

) reversed Cliv-induced decreased cell viability (

0.05)

GSH (

0.05) and ROS levels (

0.01). Quer induced phosphorylation of PI3K (

0.05). Quer induced phosphorylation and subsequent transcriptional activation of Nrf2 (

0.05)

and enhanced mRNA expressions of Nrf2 downstream genes (

0.05). The increased Hmox1 mRNA expression was reduced by PI3K inhibitor LY294002 (LY) (

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.

关键词

Keywords

references

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