Ginsenoside Rg5 ameliorates lipopolysaccharide (LPS)-induced acute liver injury via interfering Autophagy/Nrf2/Ferroptosis signal axis

Background: Ginseng is a widely known Chinese herb, exerts its pharmacological effects primarily through ginsenosides. Ginsenoside-Rg5 is isolated from ginseng, has been shown to protect the liver and activate Nrf2 expression.

Purpose: The protective effect of Rg5 on acute liver injury (ALI) and the related mechanisms will be discussed.

Methods: In vitro experiments, an ALI model was established using HepG2 cells. The DCFH-DA, the JC-1 and the ferrous ion fluorescent probe detected the ROS level, the mitochondrial membrane potential change, and the iron ions level. The oxidative stress indexes were detected by biochemical analysis. Western Blot was used to detected the Autophagy, Nrf2, and Ferroptosis signaling pathways. In vivo experiments, C57BL/6 J mice were injected with LPS to create ALI model.

Results: In vitro, Rg5 significantly inhibited the production of ROS, while restoring mitochondrial membrane potential. Biochemical analysis showed that Rg5 increased the SOD and GSH levels while decreased the MDA and ferric ion significantly. In vivo, Rg5 reduced the liver/body ratio, serum ALT and AST levels. Rg5 suppressed autophagy-related protein expression, promote Nrf2 and the Ferroptosis negative regulatory proteins. This study first confirms that Rg5 exerts a protective effect on the liver by inhibiting Ferroptosis, enriching the pharmacological properties of Rg5.

Conclusion: The protective role of Rg5 against LPS-triggered ALI was mediated via Autophagy/Nrf2-dependent suppression of Ferroptosis.

Acute liver injury; Ginsenoside Rg5; Nrf2, Autophagy, Ferroptosis.