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

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.

The Effect of Ten Essential Oils on Several Cutaneous Drug-Resistant Microorganisms and Their Cyto/Genotoxic and Antioxidant Properties

“…Our results showed that the 24 h treatment of HaCaT cells with EOs affected TAS levels in a dose-dependent manner. These results are in accordance with previous studies [59][60][61], where essential oils increased the antioxidant effects in in vitro and in vivo systems (HepG2, IEC-6, hepatocytes of rat and mice). The results of Placha et al [62] demonstrated that lower concentrations of EOs improve the health status of animals.…”

Therapeutic Potential of Volatile Terpenes and Terpenoids from Forests for Inflammatory Diseases

“…In addition, nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor that is involved in cellular responses to oxidative damage and inflammation, is also regulated by several terpenes. Previous studies have shown that α-pinene, β-caryophyllene, borneol, 1,8-cineole, and linalool up-regulated Nrf2 activity to protect cells from oxidative damage [72,[128][129][130][131]. However, in the case of terpenes other than linalool, it is unclear whether the increased Nrf2 activity by these terpenes is associated with their anti-inflammatory action.…”

Polygonum minus essential oil modulates cisplatin-induced hepatotoxicity through inflammatory and apoptotic pathways

“…Previous studies have shown that essential oil has hepatoprotective effects in various animal models (Bouzenna et al, 2016[ 14 ]; Jiang et al, 2019[ 43 ]; Morales-López et al, 2017[ 58 ]; Özbek et al, 2016[ 62 ]; Selmi et al, 2015[ 73 ]). P. minus contains various medicinal values and yields high levels of essential oil (72.54 %) mainly of aliphatic aldehydes, terpenoids and organic acids (Baharum et al, 2010[ 10 ]).…”