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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2019.00782

The Essential Oils and Eucalyptol from Artemisia Vulgaris L. Prevent Acetaminophen-induced Liver Injury by Activating Nrf2-Keap1 and Enhancing APAP Clearance through Non-toxic Metabolic Pathway

 Zhihui Jiang1, Xiao Guo2, Kunpeng Zhang1, Ganesh Sekaran2, 3, Baorui Cao1, Qingqing Zhao1, Shouquan Zhang4,  Gordon M Kirby5 and  XY Zhang1, 5, 6*
  • 1Anyang Institute of Technology, China
  • 2Northwest A&F University, China
  • 3Nehru Arts and Science College, India
  • 4Tangyin Administrative Office of Pharmaceutical Industry, China
  • 5Ontario Veterinary College, University of Guelph, Canada
  • 6College of Veterinary Medicine, Northwest A&F University, China

Artemisia has long been used in traditional medicine and as a food source for different functions in eastern Asia. Artemisia vulgaris L. (AV) is a species of the genus Artemisia. Essential oils (EOs) were extracted from AV by subcritical butane extraction. EO contents were detected by electronic nose and headspace solid-phase microextraction coupled with gas chromatography (HS-SPME-GC-MS). To investigate the hepatoprotective effects, mice subjected to liver injury were treated intragastrically with EOs or eucalyptol for 3 days. Acetaminophen (APAP) alone caused severe liver injury characterized by significantly increased serum AST and ALT levels, ROS and hepatic malondialdehyde (MDA), as well as liver superoxide dismutase (SOD) and catalase (CAT) depletions. EOs significantly attenuated APAP-induced liver damages. Further study confirmed that eucalyptol is an inhibitor of Keap1, the affinity KD of eucalyptol and Keap1 was 1.42×10-5, which increased the Nrf2 translocation from the cytoplasm into the mitochondria. The activated Nrf2 increased the mRNA expression of uridine diphosphate glucuronosyltransferases (UGTs) and sulfotransferases (SULTs), also inhibiting CYP2E1 activities. Thus, the activated Nrf2 suppressed toxic intermediate formation, promoting APAP hepatic non-toxicity, whereby APAP was metabolized into APAP-gluc and APAP-sulf. Collectively, APAP non-toxic metabolism was accelerated by eucalyptol in protecting the liver against APAP-induced injury, indicating eucalyptol or EOs from AV potentials as a natural source of hepatoprotective agent.

Keywords: Artemisia vulgaris, Essential oil, eucalyptol, Acetaminophen, Nrf2-Keap1, Liver

Received: 28 Feb 2019; Accepted: 17 Jun 2019.

Edited by:

Yibin Feng, The University of Hong Kong, Hong Kong

Reviewed by:

Ren-You Gan, School of Agriculture and Biology, Shanghai Jiao Tong University, China
Hua-Bin Li, Sun Yat-sen University, China  

Copyright: © 2019 Jiang, Guo, Zhang, Sekaran, Cao, Zhao, Zhang, Kirby and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. XY Zhang, Anyang Institute of Technology, Anyang, China, zhang@bio.uminho.pt