2. Academic Validation
  3. Ginsenoside Rb1 targets to HO-1 to improve sepsis by inhibiting ferroptosis

Ginsenoside Rb1 targets to HO-1 to improve sepsis by inhibiting ferroptosis

  • Free Radic Biol Med. 2025 Jan:226:13-28. doi: 10.1016/j.freeradbiomed.2024.11.007.
Shasha He 1,  Haoran Ye 1,  Qian Wang 2,  Yidong He 3,  Xin Liu 4,  Jin Song 4,  Chunxia Zhao 1,  Yahui Hu 1,  Lianxiang Luo 5,  Yuhong Guo 6,  Qingquan Liu 7
Affiliations

Affiliations

  • 1 Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, China; Beijing Institute of Traditional Chinese Medicine, Beijing, 100010, China; Beijing Key Laboratory of Basic Research with Traditional Chinese Medicine on Infectious Diseases, Beijing, 100010, China.
  • 2 State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China.
  • 3 The Marine Biomedical Research Institute of Guangdong Zhanjiang, School of Ocean and Tropical Medicine, Guangdong Medical University, Zhanjiang, 524023, China.
  • 4 Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, China; Beijing Institute of Traditional Chinese Medicine, Beijing, 100010, China.
  • 5 The Marine Biomedical Research Institute of Guangdong Zhanjiang, School of Ocean and Tropical Medicine, Guangdong Medical University, Zhanjiang, 524023, China. Electronic address: luolianxiang321@gdmu.edu.cn.
  • 6 Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, China; Beijing Institute of Traditional Chinese Medicine, Beijing, 100010, China; Beijing Key Laboratory of Basic Research with Traditional Chinese Medicine on Infectious Diseases, Beijing, 100010, China. Electronic address: docgyh2022@163.com.
  • 7 Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, China; Beijing Institute of Traditional Chinese Medicine, Beijing, 100010, China; Beijing Key Laboratory of Basic Research with Traditional Chinese Medicine on Infectious Diseases, Beijing, 100010, China. Electronic address: liuqingquan_2003@126.com.
PMID: 39510452 DOI: 10.1016/j.freeradbiomed.2024.11.007
Abstract

Sepsis remains the leading cause of mortality among Intensive Care Unit (ICU) patients, with its pathogenesis and treatment not yet fully elucidated. Ferroptosis plays a critical role in sepsis, suggesting that ferroptosis-related genes may serve as potential therapeutic targets. This study aims to identify key ferroptosis-related genes in sepsis and explore targeted therapeutics. Through differential expression analysis of the GSE13940 and GSE26440 datasets, heme oxygenase-1 (HO-1) was identified as a hub gene associated with Ferroptosis. Additionally, single-cell analysis of the GSE175453 dataset revealed a significant upregulation of HO-1 expression in monocyte lineages during sepsis. The cecal ligation and puncture (CLP) method was employed to induce sepsis in a mouse model, lung and intestinal tissues exhibited typical Ferroptosis characteristics, with a significant increase in HO-1 expression. However, treatment with the HO-1 inhibitor zinc protoporphyrin (ZNPP) significantly ameliorated Ferroptosis in CLP-induced lung and intestinal tissues, as well as in lipopolysaccharide (LPS)-induced THP-1 cells. Subsequently, molecular docking, surface plasmon resonance (SPR), and microscale thermophoresis (MST) experiments demonstrated that ginsenoside Rb1 specifically targets HO-1, identifying K18A as the key binding residue. Finally, experiments conducted both in vitro and in vivo verified that ginsenoside Rb1 significantly reduces HO-1 expression, inhibits Ferroptosis in sepsis-induced lung, and intestinal tissues and THP-1 cells, and improves sepsis-induced pulmonary and intestinal damage. In conclusion, this study identifies HO-1 as a key Ferroptosis target in sepsis and suggests ginsenoside Rb1 as a potential novel HO-1 inhibitor for the therapeutic approach of sepsis-induced organ dysfunction.

Keywords

Ferroptosis; Ginsenoside Rb1; HO-1; Intestinal; Lung; Sepsis.

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