Natural Polyphenol-Mediated Inhibition of Ferroptosis Alleviates Oxidative Damage and Inflammation in Acute Liver Injury.
Yangjing Su, Yunong Zeng, Minjie Zhou, Meihui Liao, Ping Qin, Rong Wu, Jiaochan Han, Xiaoqi Liang, Ze Wang, Jingjing Jiang, Zhichao Yu, Xintao Huang, Kaixin Ding, Peiheng Guo, Yi He, Ying Du, Tingting Duan, Haitao Yuan, Yuewei Ge, Ali Chen, Wei Xiao
Author Information
Yangjing Su: Center for Drug Research and Development, Guangdong Provincial Key Laboratory for Research and Evaluation of Pharmaceutical Preparations, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Yunong Zeng: School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Minjie Zhou: Department of Organ Transplantation, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Meihui Liao: Center for Drug Research and Development, Guangdong Provincial Key Laboratory for Research and Evaluation of Pharmaceutical Preparations, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Ping Qin: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China.
Rong Wu: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China.
Jiaochan Han: Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, China.
Xiaoqi Liang: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China.
Ze Wang: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China.
Jingjing Jiang: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China.
Zhichao Yu: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China.
Xintao Huang: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China.
Kaixin Ding: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China.
Peiheng Guo: School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China.
Yi He: Department of Rheumatology and Immunology, The Third Affiliated Hospital, Southern Medical University, Guangzhou 510665, China.
Ying Du: Consun Pharmaceutical Group, Guangzhou 510765, China.
Haitao Yuan: Center for Drug Research and Development, Guangdong Provincial Key Laboratory for Research and Evaluation of Pharmaceutical Preparations, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Yuewei Ge: School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Ali Chen: Center for Drug Research and Development, Guangdong Provincial Key Laboratory for Research and Evaluation of Pharmaceutical Preparations, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Wei Xiao: Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Acetaminophen (APAP) overdose has long been recognized as the main cause of drug-induced liver injury (DILI), characterized by glutathione (GSH) depletion and reactive oxygen species (ROS) accumulation, leading to ferroptosis and inflammatory responses. There is an urgent need for liver-protective agents to combat ferroptosis, modulate oxidative stress, and ameliorate inflammation. Catechin, a well-known polyphenol compound, has been shown to have antioxidant potential. However, its protective role on APAP-induced liver injury (AILI) has not been elucidated. In this study, we evaluated the modulating effects of catechin on AILI and observed that catechin attenuated liver injury by reducing inflammation. Mechanistically, catechin alleviated hepatic oxidative stress by inhibiting ROS accumulation, malondialdehyde (MDA) production, and GSH depletion. Furthermore, catechin, as a hepatic injury reparative agent, could counteract APAP-induced hepatocyte ferroptosis by activating the xCT/GPX4 pathway, and is expected to be a novel natural inhibitor of ferroptosis. Additionally, the transcriptomic results indicated that the inhibition of by catechin is important for the management of AILI. Inhibition of signal transducer and activator of transcription 1 (STAT1) expression, achieved through the use of the STAT1 inhibitor fludarabine in vivo and small interfering RNA (siRNA) in vitro, was confirmed to attenuate APAP-induced ferroptosis. In conclusion, the present study identified a novel natural drug inhibitor of ferroptosis and revealed its mechanism of action to inhibit ferroptosis, regulate oxidative stress, and ameliorate inflammation in AILI. This further provides new insights into the novel natural ferroptosis inhibitors for the treatment of ROS-related inflammatory diseases.
References
World J Gastroenterol. 2014 Oct 28;20(40):14787-804
[PMID: 25356040]
