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

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

doi:10.3389/fphar.2022.873938

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

Front Pharmacol. 2022 Apr 26:13:873938. doi: 10.3389/fphar.2022.873938. eCollection 2022.

Authors

Qianqian Xu¹, Yanfang Deng¹, Jiaxiong Ming¹, Zengwei Luo¹, Xia Chen², Tianqi Chen¹, Yafen Wang¹, Shan Yan¹, Jiajun Zhou¹, Lina Mao¹, Weiguang Sun¹, Qun Zhou¹, Hong Ren³, Yonghui Zhang¹

Affiliations

¹ Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
² Hubei Key Laboratory of Biotechnology of Chinese Traditional Medicine, National & Local Joint Engineering Research Center of High-throughput Drug Screening Technology, School of Life Sciences, Hubei University, Wuhan, China.
³ Biobank, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Abstract

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-d-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 (CCl₄)-induced acute liver injury. As a result, MCGP inhibited cell death and apoptosis induced by APAP or CCl₄, and suppressed the reactive oxygen species (ROS) generation stimulated by H₂O₂ in liver AML12 cells. In vivo, MCGP alleviated APAP/CCl₄-induced hepatic necrosis and resumed abnormal aminotransferase activities and liver antioxidase activities. In addition, MCGP depressed APAP- or CCl₄-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-/CCl₄-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.

Keywords: acute liver injury; hepatocyte apoptosis; liver regeneration; methyl 6-O-cinnamoyl-α-d-glucopyranoside; oxidative stress.