当前位置： SCI文献检索 > BIOCHEMICAL PHARMACOLOGY期刊下所有文献 > Baicalein and baicalin alleviate acetaminophen-induced liver injury by activating Nrf2 antioxidative pathway: The involvement of ERK1/2 and PKC.

Baicalein and baicalin alleviate acetaminophen-induced liver injury by activating Nrf2 antioxidative pathway: The involvement of ERK1/2 and PKC.

Abstract：

:Acetaminophen (APAP)-induced hepatotoxicity is the main cause of drug-induced liver injury. This study investigated the protection of baicalin and its aglycone baicalein against APAP-induced hepatotoxicity and its mechanism. Baicalein and baicalin alleviated APAP-induced hepatotoxicity both in vitro and in vivo. Moreover, this baicalin-provided protection was not diminished in hepatocytes or mice treated with β-glucuronidase inhibitor. Results of liver glutathione (GSH) and reactive oxygen species (ROS) formation demonstrated the alleviation of baicalein and baicalin on APAP-induced liver oxidative stress injury. Baicalein and baicalin induced the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) and increased the expression of its downstream antioxidant genes. Baicalein and baicalin-provided protection was diminished after the application of Nrf2 siRNA in hepatocytes and Nrf2 knock-out mice. Molecular docking results indicate the potential interaction of baicalein and baicalin with kelch-like ECH-associated protein-1 (Keap1). Baicalein and baicalin induced the sustained phosphorylation of extracellular regulated protein kinases (ERK)1/2 and protein kinase C (PKC). Moreover, ERK1/2 and PKC inhibitors both abrogated Nrf2 phosphorylation and its subsequent activation, and the protection against APAP-induced hepatotoxicity induced by baicalein and baicalin. In summary, baicalein and baicalin alleviate APAP-induced hepatotoxicity by activating Nrf2 via blocking the binding of Nrf2 with Keap1 and inducing Nrf2 phosphorylation. ERK1/2 and PKC are both critical for regulating the phosphorylation of Nrf2 induced by baicalein or baicalin.

journal_name

Biochem Pharmacol

journal_title

Biochemical pharmacology

authors

Shi L,Hao Z,Zhang S,Wei M,Lu B,Wang Z,Ji L

doi

10.1016/j.bcp.2018.01.026

subject

Has Abstract

pub_date

2018-04-01 00:00:00

pages

9-23

eissn

0006-2952

issn

1873-2968

pii

S0006-2952(18)30026-1

journal_volume

150

pub_type

杂志文章

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