Aged Citrus Peel (Chenpi) Prevents Acetaminophen-Induced Hepatotoxicity by Epigenetically Regulating Nrf2 Pathway.
Am J Chin Med
; 47(8): 1833-1851, 2019.
Article
in En
| MEDLINE
| ID: mdl-31795743
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Drugs, Chinese Herbal
/
Citrus
/
NF-E2-Related Factor 2
/
Chemical and Drug Induced Liver Injury
Type of study:
Etiology_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Am J Chin Med
Year:
2019
Document type:
Article
Affiliation country:
Taiwan