Artemisia Argyi essential oil ameliorates acetaminophen-induced hepatotoxicity via CYP2E1 and γ-glutamyl cycle reprogramming.

Phytomedicine

Henan Key Laboratory of Rehabilitation Medicine, Henan Joint International Research Laboratory of Chronic Liver Injury, Henan Workshop of Chronic Liver Injury for Outstanding Overseas Scientists, Zhengzhou Key Laboratory of Metabolic-dysfunction-associated Fatty Liver Disease, Department of Pharmacy, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China. Electronic address:

Published: December 2024

AI Article Synopsis

  • - The study investigates the protective effects of Artemisia argyi essential oil (AAEO) against liver damage caused by acetaminophen (APAP) in mice, as APAP is known to induce hepatotoxicity.
  • - Through various methods, including liver enzyme analysis and metabolic profiling, researchers found that AAEO mitigates liver damage by enhancing antioxidant activity and regulating liver metabolism.
  • - Results indicated that AAEO helps reduce harmful levels of APAP in the liver by promoting the synthesis of glutathione (GSH), which helps detoxify the liver and prevent further damage.

Article Abstract

Background: The hepatotoxicity induced by acetaminophen (APAP), a commonly used antipyretic, analgesic and anti-inflammatory drug in clinical practice, has received accumulated attention. Artemisia argyi essential oil (AAEO), a volatile oil component extracted from traditional Chinese medicine Artemisia argyi H.Lév. & Vaniot, has great hepatoprotective effects. However, the potential role of AAEO in APAP-induced hepatotoxicity has not been characterized. The present study aimed to investigate the effects of AAEO on hepatic metabolic changes in mice exposed to APAP.

Methods: In this study, 300.00 mg/kg acetaminophen was used to establish liver injury model in C57BL/6 J mice. Hepatoprotective effect of AAEO on APAP-induced hepatotoxicity in mice was investigated by detecting liver function enzymes and histopathological examination. Secondly, UPLC-MS/MS was used to analyze the to analyze the small molecule metabolites and metabolic pathways induced by AAEO treatment; In addition, the effect of AAEO on APAP-induced oxidative stress and inflammation were evaluated by detecting the levels of glutathione peroxidase 4, malondialdehyde, reactive oxygen species and inflammatory factors. Finally, the active components of AAEO were preliminarily screened by cellular assays. The hepatoprotective effect of AAEO against APAP-induced hepatotoxicity was examined through the Western blotting, after the CYP2E1 gene was knocked down in AML12 cells by siRNA transfection.

Results: Compared with the APAP group, AAEO could reduce the abnormal increase in the levels of liver function enzymes caused by APAP. AAEO could enhance the antioxidant capacity by down-regulating the biosynthesis pathway of unsaturated fatty acids and promoting the activity of antioxidant enzymes SOD and CAT in liver tissue induced by APAP. Our study revealed that AAEO promoted GSH synthesis and covalently combined to form APAP-GSH conjugates to reduce the accumulation of APAP in liver tissue. In addition, the chemical constituents in AAEO were analyzed by GC-MS/MS, and it was determined to identify that dihydro-beta-ionone and (-)-verbenone in AAEO might have a significant protective effect on hepatocyte survival after APAP exposure. Further studies on the hepatoprotective mechanism of AAEO indicated that it might reduce the production of toxic metabolites by regulating CYP2E1 levels.

Conclusion: AAEO exerted hepatoprotective effects on acetaminophen-induced hepatotoxicity in mice via regulating the activity of CYP2E1 and regulating the γ-glutamyl cycle pathway.

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Source
http://dx.doi.org/10.1016/j.phymed.2024.156106DOI Listing

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