Ginsenoside Rb1 ameliorates autophagy via the AMPK/mTOR pathway in renal tubular epithelial cells in vitro and in vivo.

Abstract

Although ginsenoside Rb1 (G-Rb1) has exerted an inhibitory effect on renal fibrosis and progression of chronic kidney disease (CKD), its mechanism remains unknown. This study aims to explore the anti-fibrosis effect of G-Rb1 in unilateral ureter obstruction (UUO) mouse model and underlying mechanisms in HBSS-induced HK-2 cells. In vivo, renal function, kidney histological pathology, and autophagy-related protein molecules were assessed. Additionally, rapamycin, Deptor overexpression plasmid, Akt inhibitor, metformin, and a p38-MAPK inhibitor, as well as an ERK-MAPK inhibitor were used to evaluate the effect of AMPK/mTOR, Akt and MAPK signal pathways on the protective effect of G-Rb1 in HK-2 cells. Treatment with G-Rb1 significantly improved renal dysfunction. G-Rb1 reversed UUO-induced downregulation of p62, and upregulation of LC3 and the ratio of LC3 I/II, indicating that G-Rb1 restrained UUO-induced activation of autophagy. Furthermore, we found that treatment of HBSS-induced HK-2 cells with G-Rb1 resulted in AMPK/mTOR and ERK, p38 MAPKs signaling pathways regulated autophagy inhibition. These findings may explain, in part, the molecular mechanisms by which G-Rb1 could be applied in the treatment of patients with CKD, further suggesting that autophagy and its associated molecular signaling pathway may be new targets for the treatment of renal fibrosis and CKD.

• Authors: Xianghua Liu, Jinwei Chen, Ning Sun, Ningning Li, Zhenqiang Zhang, Tao Zheng, Zhenzhen Li
• Journal: International journal of biological macromolecules (Int J Biol Macromol) Vol. 163 Pg. 996-1009 (Nov 15 2020) ISSN: 1879-0003 [Electronic] Netherlands
• PMID: 32659400 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Chemical References

• Biomarkers
• Ginsenosides
• ginsenoside Rb1
• Proto-Oncogene Proteins c-akt
• TOR Serine-Threonine Kinases
• AMP-Activated Protein Kinases

Topics

• AMP-Activated Protein Kinases (metabolism)
• Autophagy (drug effects)
• Biomarkers
• Cell Line
• Epithelial Cells (metabolism)
• Ginsenosides (pharmacology)
• Humans
• Immunohistochemistry
• Kidney Tubules (metabolism)
• Male
• Models, Molecular
• Proto-Oncogene Proteins c-akt (metabolism)
• Signal Transduction (drug effects)
• TOR Serine-Threonine Kinases (metabolism)