Oryzanol alleviates acetaminophen-induced liver injury: roles of modulating AMPK/GSK3/Nrf2 and NF-B signaling pathways

• Published in: Food & function 2019-10, Vol.1 (1), p.6858-6872
• Main Authors: Shu, Guangwen, Qiu, Yunhan, Hao, Ji, Fu, Qian, Deng, Xukun
• Format: Article
• ISSN: 2042-6496; 2042-650X
• DOI: 10.1039/c9fo01808e

Acetaminophen (APAP) overdose is a major cause of drug-induced liver injury worldwide. Our current study was performed to assess the potential protective effects of -oryzanol (ORY) on APAP-induced liver injury in mice and explore the underlying molecular mechanisms. We unveiled that ORY alleviated the APAP-induced death of HL-7702 hepatocytes in vitro and liver injury in mice. Moreover, ORY promoted the nuclear translocation of Nrf2, increased the expressions of Nrf2-downstream antioxidative enzymes, including HO-1, NQO1, GCLC, and GCLM, and thereby restrained APAP-induced oxidative stress in hepatocytes. Moreover, ORY modulated the AMPK/GSK3 axis that acts upstream of Nrf2 in hepatocytes. Compound C, an inhibitor of AMPK, prevented the ORY-mediated activation of Nrf2 and protection against APAP toxicity in HL-7702 hepatocytes. Additionally, in the liver of mice receiving APAP, ORY suppressed the nuclear translocation of the NF-B p65 subunit, downregulated the expressions of iNOS and COX-2, and reduced the levels of pro-inflammatory factors including TNF-, IL-1, IL-6, and NO. Taken together, our findings revealed that ORY is capable of ameliorating APAP-induced liver injury. The modulation of AMPK/GSK3/Nrf2 and NF-B signaling pathways is implicated in the hepatoprotective activity of ORY. -Oryzanol alleviates acetaminophen-induced liver injury in mice.