Shan Guan-Yue, Shi Yun-Peng, Zhang Yu-Xin, Wan Hui, Gao Zhi-Cheng, Li Hai-Jun
Laboratory for Tumor Immunology, The First Hospital of Jilin University, Changchun 130061, PR China; Department of Bioengineering, Jilin University School of Pharmaceutical Sciences, Changchun 130021, PR China.
Department of Hepatobiliary and Pancreatic Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, PR China.
Phytomedicine. 2025 Aug;144:156941. doi: 10.1016/j.phymed.2025.156941. Epub 2025 Jun 2.
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.
The protective effect of Rg5 on acute liver injury (ALI) and the related mechanisms will be discussed.
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.
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.
The protective role of Rg5 against LPS-triggered ALI was mediated via autophagy/Nrf2-dependent suppression of ferroptosis.
人参是一种广为人知的中草药，其药理作用主要通过人参皂苷发挥。人参皂苷-Rg5是从人参中分离出来的，已被证明具有保护肝脏和激活Nrf2表达的作用。
探讨Rg5对急性肝损伤（ALI）的保护作用及其相关机制。
在体外实验中，使用HepG2细胞建立ALI模型。采用DCFH-DA、JC-1和亚铁离子荧光探针检测活性氧水平、线粒体膜电位变化和铁离子水平。通过生化分析检测氧化应激指标。采用蛋白质免疫印迹法检测自噬、Nrf2和铁死亡信号通路。在体内实验中，给C57BL/6 J小鼠注射脂多糖以建立ALI模型。
在体外，Rg5显著抑制活性氧的产生，同时恢复线粒体膜电位。生化分析表明，Rg5提高了超氧化物歧化酶和谷胱甘肽水平，同时显著降低了丙二醛和铁离子水平。在体内，Rg5降低了肝体比、血清谷丙转氨酶和谷草转氨酶水平。Rg5抑制自噬相关蛋白表达，促进Nrf2和铁死亡负调控蛋白的表达。本研究首次证实Rg5通过抑制铁死亡对肝脏发挥保护作用，丰富了Rg5的药理特性。
Rg5对脂多糖诱导的ALI的保护作用是通过自噬/Nrf2依赖性抑制铁死亡介导的。
