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

doi:10.1016/j.bcp.2018.01.026

	Baicalein and baicalin alleviate acetaminophen-induced liver injury by activating Nrf2 antioxidative pathway: The involvement of ERK1/2 and PKC
	Shi, Liang; Hao, Zhanxia; Zhang, Shaobo; Wei, Mengjuan; Lu, Bin; Wang, Zhengtao; Ji, Lili
刊名	Biochemical pharmacology
	2018-04
卷号	150 页码:9-23
ISSN号	1873-2968
DOI	10.1016/j.bcp.2018.01.026
文献子类	Article
英文摘要	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.
语种	英语
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/266576]
专题	中国科学院上海药物研究所
通讯作者	Ji, Lili
作者单位	The MOE Key Laboratory for Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
推荐引用方式 GB/T 7714	Shi, Liang,Hao, Zhanxia,Zhang, Shaobo,et al. Baicalein and baicalin alleviate acetaminophen-induced liver injury by activating Nrf2 antioxidative pathway: The involvement of ERK1/2 and PKC[J]. Biochemical pharmacology,2018,150:9-23.
APA	Shi, Liang.,Hao, Zhanxia.,Zhang, Shaobo.,Wei, Mengjuan.,Lu, Bin.,...&Ji, Lili.(2018).Baicalein and baicalin alleviate acetaminophen-induced liver injury by activating Nrf2 antioxidative pathway: The involvement of ERK1/2 and PKC.Biochemical pharmacology,150,9-23.
MLA	Shi, Liang,et al."Baicalein and baicalin alleviate acetaminophen-induced liver injury by activating Nrf2 antioxidative pathway: The involvement of ERK1/2 and PKC".Biochemical pharmacology 150(2018):9-23.