Ginsenoside Rg1 protects against acetaminophen-induced liver injury via activating Nrf2 signaling pathway in vivo and in vitro

被引：40

作者：

Ning, Chenqing ^{[1
]}

Gao, Xiaoguang ^{[1
]}

Wang, Changyuan ^{[1
,2
]}

Kong, Yulong ^{[1
]}

Liu, Zhihao ^{[1
,2
]}

Sun, Huijun ^{[1
,2
]}

Sun, Pengyuan ^{[1
,2
]}

Huo, Xiaokui ^{[1
,2
]}

Ma, Xiaodong ^{[1
,2
]}

Meng, Qiang ^{[1
,2
]}

Liu, Kexin ^{[1
,2
]}

机构：

[1] Dalian Med Univ, Coll Pharm, Dept Clin Pharmacol, 9 West Sect,Lvshun South Rd, Dalian 116044, Peoples R China

[2] Dalian Med Univ, Key Lab Pharmacokinet & Transport Liaoning Prov, Dalian 116044, Peoples R China

来源：

REGULATORY TOXICOLOGY AND PHARMACOLOGY | 2018年 / 98卷

基金：

中国国家自然科学基金;

关键词：

Nuclear factor erythroid-2-related factor 2 (Nrf2); Acetaminophen (APAP); Acute liver injury; Oxidative stress; Ginsenoside Rg1; INDUCED HEPATOTOXICITY; ISCHEMIA/REPERFUSION INJURY; OXIDATIVE STRESS; EXPRESSION; ACID; MICE; PHARMACOLOGY; PRETREATMENT; GLUTATHIONE; INDUCTION;

D O I：

10.1016/j.yrtph.2018.07.012

中图分类号：

DF [法律]; D9 [法律]; R [医药、卫生];

学科分类号：

0301 ; 10 ;

摘要：

Acetaminophen (APAP) is a worldwide used drug for treating fever and pain. However, APAP overdose is the leading cause of drug-induced liver injury. The purpose of the current study is to evaluate the hepatoprotective effect of ginsenoside Rgl (Rgl), the main pharmacologically active compounds of Panax ginseng, against APAP-induced acute liver injury, and further to elucidate the involvement of Nrf2 signaling pathway by in vivo and in vitro experiments. Male C57BL/6 mice were treated with Rgl for 3 days before injection of APAP. Serum and liver tissue samples were collected 6 h later. The results indicated that Rgl significantly attenuated APAP-induced hepatotoxicity and oxidative stress in a dose-dependent manner. Rgl effectively enhanced antioxidant and detoxification capacity, which is largely dependent on up-regulating Nrf2 nuclear translocation, reducing Keapi protein expression and up-regulating Nrf2 target genes including GCLC, GCLM, HO-1, NQO1, Ugtlal, Ugt1a6, Ugt2b1, Sult2a1, Mrp2, Mrp3 and Mrp4. Furthermore, Rgl repressed the activities of Cyp2e1, Cyp3a1 1, Cypla2, which are important enzymes in the formation of APAP toxic metabolite N-acetyl-p-benzoquinone imine. However, the changes in transporters and enzymes, as well as ameliorative liver histology induced by Rgl were abrogated by Nrf2 antagonist all-transretinoic acid in vivo and Nrf2 siRNA in vitro. In conclusion, Rgl produced hepatoprotective effects against APAP-induced acute liver injury via Nrf2 signaling pathway. Rgl might be an effective approach for the prevention against acute liver injury.

引用

页码：58 / 68

页数：11

共 47 条

[11] High sensitivity of Nrf2 knockout mice to acetaminophen hepatotoxicity associated with decreased expression of ARE-regulated drug metabolizing enzymes and antioxidant genes [J].