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  2. Multi-omics approaches to explore the therapeutic mechanism for ginsenoside Rg1 against MASLD

Multi-omics approaches to explore the therapeutic mechanism for ginsenoside Rg1 against MASLD

  • Biochem Biophys Res Commun. 2025 Aug 30:776:152161. doi: 10.1016/j.bbrc.2025.152161.
Zhijian Wang 1 Yinuo Wang 2 Jia Zhang 3 Kunli Yin 4 Huating Luo 5 Wenxiang Huang 6
Affiliations

Affiliations

  • 1 Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China; Institute of Life Sciences, School of Basic Medicine, Chongqing Medical University, Chongqing, China. Electronic address: wangzhijian0327@163.com.
  • 2 Chongqing Medical University, Chongqing, 400016, China. Electronic address: wangyinuo3165@163.com.
  • 3 Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China. Electronic address: zhangjia2502@163.com.
  • 4 Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China. Electronic address: klyin2502@163.com.
  • 5 Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China. Electronic address: luo15123824843@163.com.
  • 6 Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China. Electronic address: wenxianghuang2018@163.com.
Abstract

Ginsenoside Rg1 (G-Rg1), a traditional Chinese medicine, alleviates metabolic dysfunction-associated steatotic liver disease (MASLD). However, the mechanism by which G-Rg1 improves metabolic disorders in MASLD by regulating the gut microbiota remains ambiguous‌. We constructed a diet-induced murine MASLD model and employed 16S rRNA Sequencing and non-targeted metabolomic analysis to ‌investigate the mechanism of G-Rg1 in treating MASLD, focusing on its regulatory effect on the gut microbiota. Our results revealed that G-Rg1 significantly increased the 5-hydroxyindoleacetic acid levels and activated the Aryl Hydrocarbon Receptor (AHR) by enhancing intestinal permeability, modulating the gut microbiota composition, and influencing tryptophan metabolism. Therefore, G-Rg1 improved immune function and reduced liver inflammation and lipid deposition in the MASLD mouse model. In contrast, the effect of G-Rg1 was impaired upon removal of the gut microbiota. Furthermore, fecal microbiota transplantation in G-Rg1-treated mice improved MASLD. These finding s suggest that regulating the gut microbiota may play an important role in G-Rg1's ability to protect against MASLD. G-Rg1 may exert its anti-MASLD effects through the gut microbiota, tryptophan metabolism, AHR activation, and interleukin-22 signaling, offering a novel approach for G-Rg1-mediated MASLD treatment.

Keywords

Ginsenoside Rg1; Gut microbiota; IL-17; Metabolic dysfunction-associated steatotic liver disease; Multi-omics approaches; Trp metabolism.

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