AUTHOR=Xu Qianqian , Deng Yanfang , Ming Jiaxiong , Luo Zengwei , Chen Xia , Chen Tianqi , Wang Yafen , Yan Shan , Zhou Jiajun , Mao Lina , Sun Weiguang , Zhou Qun , Ren Hong , Zhang Yonghui 

TITLE=Methyl 6-O-cinnamoyl-α-d-glucopyranoside Ameliorates Acute Liver Injury by Inhibiting Oxidative Stress Through the Activation of Nrf2 Signaling Pathway

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.873938

DOI=10.3389/fphar.2022.873938

ISSN=1663-9812

ABSTRACT=<p>Excessive stimulation of hepatotoxins and drugs often lead to acute liver injury, while treatment strategies for acute liver injury have been limited. Methyl 6-O-cinnamoyl-α-<sc>d</sc>-glucopyranoside (MCGP) is a structure modified compound from cinnamic acid, a key chemical found in plants with significant antioxidant, anti-inflammatory, and antidiabetic effects. In this study, we investigated the effects and underlying mechanisms of MCGP on acetaminophen (APAP)- or carbon tetrachloride (CCl<sub>4</sub>)-induced acute liver injury. As a result, MCGP inhibited cell death and apoptosis induced by APAP or CCl<sub>4</sub>, and suppressed the reactive oxygen species (ROS) generation stimulated by H<sub>2</sub>O<sub>2</sub> in liver AML12 cells<italic>. In vivo</italic>, MCGP alleviated APAP/CCl<sub>4</sub>-induced hepatic necrosis and resumed abnormal aminotransferase activities and liver antioxidase activities. In addition, MCGP depressed APAP- or CCl<sub>4</sub>-induced oxidative stress through the suppression of CYP2E1 and activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. MCGP also enhanced the number of PCNA-positive hepatocytes, increased hepatic PCNA and Bcl-XL, and decreased BAX expression in APAP-/CCl<sub>4</sub>-intoxicated mice. Furthermore, MCGP activated the GSDMD-N/cleaved caspase 1 pathway. In summary, MCGP might act as a potential therapeutic drug against drug-induced and chemical-induced acute liver injuries, and its underlying mechanisms might engage on the pressing of oxidative stress, refraining of hepatocyte apoptosis, and facilitating of liver regeneration.</p>