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 Jiang,Kunpeng Zhang,Xiaoying Zhang,Baorui Cao,Ganesh Sekaran,Qingqing Zhao,Gordon M Kirby,Shouquan Zhang,Xiao Guo

doi:10.3389/fphar.2019.00782

Abstract

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 K D 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.

Highlights

Artemisia is a class of fragrant annual herb species of the composite family, distributed widely in Asia, Europe, and North America
Inter-species variations were calculated and the results showed that Sample 1 and Artemisia argyi showed the highest similarity (0.005), while Sample 2 and Artemisia vulgaris showed the highest similarity (0.003) as presented in S
The secondary structure of ITS2 of Sample 1 is similar to Artemisia argyi, while Sample 2 is similar to Artemisia vulgaris (Figure 1B)

Summary

Introduction

Artemisia is a class of fragrant annual herb species of the composite family, distributed widely in Asia, Europe, and North America. It has a long history of traditional and popular use as both medicine and food with medicinal literature documentation since the Eastern Han Dynasty in 1st-century China (Song et al, 2016). (AV) is a major and common Artemisia plant that was first recorded by Ben-Cao-Gang-Mu (Ming Dynasty, 16th century by Shizhen Li), who stated that the leaves should be collected and dried in summer for medical uses, including improving Yang-qi and decreasing skeleton raw Artemisia vulgaris L. (AV) is a major and common Artemisia plant that was first recorded by Ben-Cao-Gang-Mu (Ming Dynasty, 16th century by Shizhen Li), who stated that the leaves should be collected and dried in summer for medical uses, including improving Yang-qi and decreasing skeleton raw

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Conclusion