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CLC number: R285.5

On-line Access: 2015-07-03

Received: 2014-12-09

Revision Accepted: 2015-03-12

Crosschecked: 2015-06-16

Cited: 10

Clicked: 2334

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Li-li JI

http://orcid.org/0000-0001-6159-2626

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Journal of Zhejiang University SCIENCE B 2015 Vol.16 No.7 P.602-610

10.1631/jzus.B1400346


Chlorogenic acid prevents acetaminophen-induced liver injury: the involvement of CYP450 metabolic enzymes and some antioxidant signals


Author(s):  Chun Pang, Yu-chen Sheng, Ping Jiang, Hai Wei, Li-li Ji

Affiliation(s):  Shanghai Key Laboratory of Complex Prescription, the MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; more

Corresponding email(s):   lichenyue1307@126.com

Key Words:  Chlorogenic acid, Acetaminophen, CYP450, Oxidative stress injury


Chun Pang, Yu-chen Sheng, Ping Jiang, Hai Wei, Li-li Ji. Chlorogenic acid prevents acetaminophen-induced liver injury: the involvement of CYP450 metabolic enzymes and some antioxidant signals[J]. Journal of Zhejiang University Science B, 2015, 16(7): 602-610.

@article{title="Chlorogenic acid prevents acetaminophen-induced liver injury: the involvement of CYP450 metabolic enzymes and some antioxidant signals",
author="Chun Pang, Yu-chen Sheng, Ping Jiang, Hai Wei, Li-li Ji",
journal="Journal of Zhejiang University Science B",
volume="16",
number="7",
pages="602-610",
year="2015",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1400346"
}

%0 Journal Article
%T Chlorogenic acid prevents acetaminophen-induced liver injury: the involvement of CYP450 metabolic enzymes and some antioxidant signals
%A Chun Pang
%A Yu-chen Sheng
%A Ping Jiang
%A Hai Wei
%A Li-li Ji
%J Journal of Zhejiang University SCIENCE B
%V 16
%N 7
%P 602-610
%@ 1673-1581
%D 2015
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1400346

TY - JOUR
T1 - Chlorogenic acid prevents acetaminophen-induced liver injury: the involvement of CYP450 metabolic enzymes and some antioxidant signals
A1 - Chun Pang
A1 - Yu-chen Sheng
A1 - Ping Jiang
A1 - Hai Wei
A1 - Li-li Ji
J0 - Journal of Zhejiang University Science B
VL - 16
IS - 7
SP - 602
EP - 610
%@ 1673-1581
Y1 - 2015
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1400346


Abstract: 
chlorogenic acid (CGA), a polyphenolic compound, is abundant in fruits, dietary vegetables, and some medicinal herbs. This study investigated the prevention of CGA against acetaminophen (AP)-induced hepatotoxicity and its engaged mechanisms. CGA reversed the decreased cell viability induced by AP in L-02 cells in vitro. In addition, CGA reduced the AP-induced increased serum levels of alanine/aspartate aminotransferase (ALT/AST) in vivo. The effect of CGA on cytochrome P450 (CYP) enzymatic (CYP2E1, CYP1A2, and CYP3A4) activities showed that CGA caused very little inhibition on CYP2E1 and CYP1A2 enzymatic activities, but not CYP3A4. The measurement of liver malondialdehyde (MDA), reactive oxygen species (ROS), and glutathione (GSH) levels showed that CGA prevented AP-induced liver oxidative stress injury. Further, CGA increased the AP-induced decreased mRNA expression of peroxiredoxin (Prx) 1, 2, 3, 5, 6, epoxide hydrolase (Ephx) 2, and polymerase (RNA) II (DNA directed) polypeptide K (Polr2k), and nuclear factor erythroid-2-related factor 2 (Nrf2). In summary, CGA ameliorates the AP-induced liver injury probably by slightly inhibiting CYP2E1 and CYP1A2 enzymatic properties. In addition, cellular important antioxidant signals such as Prx1, 2, 3, 5, 6, Ephx2, Polr2k, and Nrf2 also contributed to the protection of CGA against AP-induced oxidative stress injury.

CYP450代谢酶和一些抗氧化信号参与调控了绿原酸抑制对乙酰氨基酚的肝毒性

目的:本研究旨在观察绿原酸对乙酰氨基酚诱导肝损伤的解毒作用及其机理。
创新点:发现CYP450代谢酶和一些重要的抗氧化信号分子(如Prx家族蛋白等)参与调控了绿原酸抑制对乙酰氨基酚的肝毒性。
方法:检测小鼠血清转氨酶含量,检测体外CYP2E1、CYP3A4和CYP1A2酶活性,检测肝组织中丙二醛(MDA)、谷胱甘肽(GSH)和活性氧(ROS)含量,用实时聚合酶链反应(real-time PCR)检测肝组织中Prx1-6、Ephx2、Polr2k、Fmo5、Nrf2等的mRNA表达情况。
结论:绿原酸可以明显抑制对乙酰氨基酚造成的急性肝损伤。给药组小鼠血清中的转氨酶与模型组相比均有显著下降,绿原酸在体外可以微弱抑制CYP2E1和CYP1A2代谢酶的活性,通过MDA、GSH和ROS分析发现绿原酸可以抑制对乙酰氨基酚造成的氧化应激损伤。通过real-time PCR分析发现对乙酰氨基酚降低了抗氧化酶Prx家族、Ephx2、Polr2k和Nrf2的基因表达,而绿原酸可以逆转对乙酰氨基酚降低的这些基因的表达。

关键词:绿原酸;对乙酰氨基酚;CYP450;氧应激损伤

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

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