Ginsenoside Rg1 attenuates LPS-induced chronic renal injury by inhibiting NOX4-NLRP3 signaling in mice.

Abstract

Chronic renal injury (CRI) is a common pathological damage in chronic renal disease, and the therapeutic options for preventing its progression are limited at present. Ginsenoside Rg1 (Rg1) is reported to have a protective effect on renal injury by improving oxidative stress and inflammation. Lipopolysaccharide (LPS) plays important roles in inducing inflammatory and high-dose LPS is often used to perform acute renal injury. However, little is known about the effect of low-dose LPS on CRI, and the protective effect of Rg1 against chronic LPS-induced CRI. Here, we reported the protective effect and mechanism of Rg1 against LPS-induced CRI in mice. In this study, the results demonstrated that low-dose LPS (0.25 mg/kg) exposure for 14 days significantly induced renal function impairment and renal injury and fibrosis. Meanwhile, LPS exposure significantly increased reactive oxygen species (ROS) generation, NADPH oxidase 4 (NOX4) and NLRP3 inflammasome expression in renal cortex. However, treatment with Rg1, tempol (a superoxide dismutase mimetic), and apocynin (a NOX inhibitor) significantly improved renal function impairment and renal fibrosis, and significantly decreased the levels of TGF-β, IL-1β, KIM-1, β-Gal, and collagen IV in the kidneys. And Rg1 treatment also significantly reduced ROS generation and inhibited the activation of NOX4 and NLRP3 inflammasome. Overall, these results suggest that Rg1 treatment can ameliorate LPS-induced chronic kidney injury and renal fibrosis, the mechanisms may be involved in reducing NOX2-mediated oxidative stress and inhibiting NLRP1 inflammasome.

• Authors: Duoduo Zhang, Pengmin Ji, Ran Sun, Huimin Zhou, Lei Huang, Liangliang Kong, Weiping Li, Weizu Li
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 150 Pg. 112936 (Jun 2022) ISSN: 1950-6007 [Electronic] France
• PMID: 35421784 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Chemical References

• Ginsenosides
• Inflammasomes
• Lipopolysaccharides
• NLR Family, Pyrin Domain-Containing 3 Protein
• Nlrp3 protein, mouse
• Reactive Oxygen Species
• NADPH Oxidase 4
• Nox4 protein, mouse
• ginsenoside Rg1

Topics

• Animals
• Ginsenosides (pharmacology)
• Inflammasomes (metabolism)
• Kidney (metabolism)
• Lipopolysaccharides (pharmacology)
• Mice
• NADPH Oxidase 4 (metabolism)
• NLR Family, Pyrin Domain-Containing 3 Protein (metabolism)
• Reactive Oxygen Species (metabolism)
• Signal Transduction (drug effects)