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Am J Chin Med. 2019;47(8):1833-1851. doi: 10.1142/S0192415X19500939. Epub 2019 Dec 3.

Aged Citrus Peel (Chenpi) Prevents Acetaminophen-Induced Hepatotoxicity by Epigenetically Regulating Nrf2 Pathway.

Author information

1
Department of Bioscience Technology, Chung Yuan Christian University, Taoyuan City, Taiwan.
2
Institute of Food Science and Technology, National Taiwan University, Taipei, Taiwan.
3
Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan.
4
Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan.

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.

KEYWORDS:

Acetaminophen; Aged Citrus Peel; Epigenetics; Hepatotoxicity; Liver; Nrf2

PMID:
31795743
DOI:
10.1142/S0192415X19500939

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