https://scholars.lib.ntu.edu.tw/handle/123456789/566061
標題: | Aged Citrus Peel (Chenpi) Prevents Acetaminophen-Induced Hepatotoxicity by Epigenetically Regulating Nrf2 Pathway | 作者: | Lin, Z.-H. Chan, Y.-F. Pan, M.-H. Tung, Y.-C. Su, Z.-Y. MIN-HSIUNG PAN |
關鍵字: | Acetaminophen; Aged Citrus Peel; Epigenetics; Hepatotoxicity; Liver; Nrf2 | 公開日期: | 2019 | 卷: | 47 | 期: | 8 | 起(迄)頁: | 1833-1851 | 來源出版物: | American Journal of Chinese Medicine | 摘要: | 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. |
URI: | https://www.scopus.com/inward/record.url?eid=2-s2.0-85075929962&partnerID=40&md5=936b27e0d5d7a470781e351921257614 https://scholars.lib.ntu.edu.tw/handle/123456789/566061 |
DOI: | 10.1142/S0192415X19500939 | SDG/關鍵字: | 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 |
顯示於: | 食品科技研究所 |
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