The liver is a critical organ responsible for the major detoxification and metabolism in the human body. Acetaminophen (APAP) is a widely used analgesic and antipyretic drug, but it has been demonstrated to be a cancer-initiating agent to induce liver cancer. Aged Citrus peel (Chenpi, CP) is a Chinese herb with hepatoprotective potential to be usually used as foods in Taiwan. Three extracts of CP were prepared in this study, including water extract (CP-WE), ethanol extract (CP-EE), and water extraction residue ethanol extract (CP-WREE). Among these extracts, we found CP-WREE (100 μg/mL) can effectively enhance the Nrf2-ARE pathway in HepG2-C8 cell line which is stably transfected ARE-luciferase construct. CP-WREE (50 μg/mL) also exhibit a significant protective effect on the mouse AML12 hepatocytes from APAP-induced damage. We further find that CP-WREE enhances the activity of some glutathione-related enzymes and inhibits lipid peroxidation in AML12 cells. Furthermore, CP-WREE can also increase the expressions of Nrf2 and Nrf2 downstream enzymes while the expressions of some epigenetic modifying enzymes are regulated. Therefore, CP-WREE may have beneficial effects to protect liver carcinogenesis caused by APAP-induced damage through the regulation of Nrf2/antioxidant pathway as well as epigenetic modification.

Citation Format: Zi-Han Lin, Wan-Tzu Luo, Yen-Fan Chan, Zheng-Yuan Su. Chemopreventive effect of aged citrus peel (Chenpi) extracts against tumor initiator acetaminophen-induced hepatotoxicity through regulating Nrf2 pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-177. doi:10.1158/1538-7445.AM2017-LB-177