2. Academic Validation
  3. Ginsenoside Rh2 attenuates CDAHFD-induced liver fibrosis in mice by improving intestinal microbial composition and regulating LPS-mediated autophagy

Ginsenoside Rh2 attenuates CDAHFD-induced liver fibrosis in mice by improving intestinal microbial composition and regulating LPS-mediated autophagy

  • Phytomedicine. 2022 Jul;101:154121. doi: 10.1016/j.phymed.2022.154121.
Siyu Chen 1,  Ziwei He 1,  Wei Xie 2,  Xuan Chen 1,  Zhuofeng Lin 2,  Jisheng Ma 2,  Zhi Liu 1,  Shihai Yang 3,  Yanfang Wang 4
Affiliations

Affiliations

  • 1 College of Chinese Medicinal Materials, JiLin Agricultural University, Changchun,130118, China.
  • 2 School of Pharmaceutical Sciences, WenZhou Medical University, Wenzhou 325035, China.
  • 3 College of Chinese Medicinal Materials, JiLin Agricultural University, Changchun,130118, China; Laboratory for cultivation and breeding of medicinal plants of National Administrition of Traditional Chinese Medicine, JiLin Agricultural University, Changchun,130118, China. Electronic address: [email protected].
  • 4 College of Chinese Medicinal Materials, JiLin Agricultural University, Changchun,130118, China; Laboratory for cultivation and breeding of medicinal plants of National Administrition of Traditional Chinese Medicine, JiLin Agricultural University, Changchun,130118, China. Electronic address: [email protected].
PMID: 35489327 DOI: 10.1016/j.phymed.2022.154121
Abstract

Background: Nowadays, liver diseases are threatening more and more people all over the world and one of the main causes is liver fibrosis. However, there is no effective way to reverse liver fibrosis.

Purpose: To investigate whether ginsenoside Rh2 (G-Rh2) can alleviate liver fibrosis and elucidate its underlying mechanism.

Methods: In vivo and in vitro methods were adopted in this research. Choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) was used to feed mice to induce liver fibrosis, and HSC-T6 cells were used to establish an LPS-induced model of liver fibrosis. Through histopathological staining, hematoxylin-eosin (H&E) staining, western blot analysis, intestinal bacteria 16SrRNA sequencing, and other technical means, the research explored whether G-Rh2 possesses anti-fibrotic activity.

Results: G-Rh2 could notably alleviate CDAHFD-induced liver fibrosis in mice. In particular, it could alleviate liver injury and reduce plasma lipopolysaccharide (LPS) levels. Additionally, G-Rh2 could repair intestinal injury as well as regulate intestinal microbial diversity and composition. HSC-T6 cells could be activated and Autophagy could be induced further by LPS in vitro. After being treated with G-Rh2, Autophagy was restrained and activation of hepatic stellate cells (HSCs) was controlled. Deeper research showed that G-Rh2 restrained the activation of HSCs via stimulating the AKT-mTOR signaling pathway, restraining Autophagy.

Conclusion: The results of our studies clearly suggest that G-Rh2 repairs intestinal injury, improves intestinal microbial composition, reduces plasma LPS levels, and activates the AKT-mTOR signaling pathway to restrain LPS-mediated Autophagy, thus playing an important role in anti-hepatic fibrosis. G-Rh2 was found to have the potential to effectively alleviate liver fibrosis.

Keywords

Autophagy; Ginsenoside Rh2; Hepatic stellate cells; Intestinal microflora; Lipopolysaccharide; Liver fibrosis.

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