Aged Citrus Peel (Chenpi) Prevents Acetaminophen-Induced Hepatotoxicity by Epigenetically Regulating Nrf2 Pathway
Journal
American Journal of Chinese Medicine
Journal Volume
47
Journal Issue
8
Pages
1833-1851
Date Issued
2019
Author(s)
Abstract
Excessive consumption of analgesic drug acetaminophen (APAP) can cause severe oxidative stress-mediated liver injury. Here, we investigated the protective effect and mechanism of aged citrus peel (Chenpi, CP), a Chinese herb usually used in foods in Asia, against APAP-induced hepatotoxicity. CP water (CP-WE), ethanolic (CP-EE), and water extraction residue ethanolic (CP-WREE) extracts were prepared. We found that CP-WREE contained higher content of bioactive flavonoids, including narirutin, nobiletin, and tangeretin, and more effectively enhanced the Nrf2 pathway in ARE-luciferase reporter gene transfected human HepG2-C8 cells. In mouse AML-12 hepatocytes, CP-WREE minimized APAP-induced damage and lipid peroxidation and increased mRNA and protein expressions of Nrf2 and its downstream defense enzymes (HO-1, NQO1, and UGT1A). CP-WREE also downregulated HDACs and DNMTs, upregulated KDMs, and increased the unmethylated Nrf2 promoter level. Additionally, CP-WREE blocked in vitro DNA methyltransferase activity. Taken together, CP-WREE might attenuate oxidative stress-induced hepatotoxicity through epigenetically regulating Nrf2-mediated cellular defense system. ? 2019 World Scientific Publishing Company.
Subjects
Acetaminophen; Aged Citrus Peel; Epigenetics; Hepatotoxicity; Liver; Nrf2
SDGs
Other Subjects
DNA methyltransferase; glucuronosyltransferase; heme oxygenase 1; herbaceous agent; histone deacetylase; messenger RNA; nad(p)h quinone oxidoreductase 1; narirutin; nobiletin; oxidoreductase; paracetamol; tangeretin; transcription factor Nrf2; unclassified drug; flavonoid; herbaceous agent; paracetamol; reactive oxygen metabolite; transcription factor Nrf2; AML12 cell line; animal cell; Article; citrus processing waste; controlled study; down regulation; drug mechanism; epigenetics; Hep-G2 cell line; human; human cell; in vitro study; lipid peroxidation; liver protection; liver toxicity; mouse; mRNA expression level; nonhuman; phytochemistry; promoter region; protein expression level; upregulation; animal; chemistry; Citrus; drug effect; genetics; liver; liver cell; metabolism; oxidative stress; toxic hepatitis; Acetaminophen; Animals; Chemical and Drug Induced Liver Injury; Citrus; Drugs, Chinese Herbal; Flavonoids; Hep G2 Cells; Hepatocytes; Humans; Liver; Mice; NF-E2-Related Factor 2; Oxidative Stress; Reactive Oxygen Species
Type
journal article