6-Gingerol attenuates arsenic trioxide-induced liver injury by inhibiting pyroptosis and ROS-NLRP3 inflammatory signaling pathway: Based on network pharmacology analysis and experiment verification

Abstract

6-Gingerol (6G) is the main phenolic active component of ginger, which has a certain protective effect against liver injury induced by drugs, and chemical pollutants. However, the mechanism of protection of 6G against arsenic trioxide (ATO)-induced liver injury remains unclear. The network pharmacology and animal experiment results respectively indicated that oxidative stress and inflammatory responses were closely related to ATO-induced liver injury. 6G can alleviate ATO-induced liver injury and oxidative stress. Furthermore, 6G can attenuate the release of pro-inflammatory factors induced by ATO and reduce the expressions of NLRP3, ASC, Caspase-1 and gasdermin-D. The results showed that the activation of NLRP3 inflammatory and its induced pyroptosis play critical roles in liver injury caused by ATO. Furthermore, 6G can suppress the ROS-NLRP3 inflammasome signaling pathway, which may be an effective strategy for the treatment of ATO-induced liver injury.

Keywords

• 6-gingerol
• Arsenic trioxide
• Liver injury
• Network pharmacology
• Pyroptosis
• Inflammation