Protective effect of ginsenoside Rg5 against kidney injury via inhibition of NLRP3 inflammasome activation and the MAPK signaling pathway in high-fat diet/streptozotocin-induced diabetic mice

Yanyan Zhu; Chenhui Zhu; Haixia Yang; Jianjun Deng; Daidi Fan

doi:10.1016/j.phrs.2020.104746

Protective effect of ginsenoside Rg5 against kidney injury via inhibition of NLRP3 inflammasome activation and the MAPK signaling pathway in high-fat diet/streptozotocin-induced diabetic mice

Pharmacol Res. 2020 May:155:104746. doi: 10.1016/j.phrs.2020.104746. Epub 2020 Mar 7.

Authors

Yanyan Zhu¹, Chenhui Zhu¹, Haixia Yang², Jianjun Deng³, Daidi Fan⁴

Affiliations

¹ Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, China; Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, Xi'an, 710069, China; Biotech. & Biomed. Research Institute, Northwest University, 229 North Taibai Road, Xi'an, 710069, China.
² Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
³ Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, China; Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, Xi'an, 710069, China; Biotech. & Biomed. Research Institute, Northwest University, 229 North Taibai Road, Xi'an, 710069, China. Electronic address: dengjianjun@nwu.edu.cn.
⁴ Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, China; Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, Xi'an, 710069, China; Biotech. & Biomed. Research Institute, Northwest University, 229 North Taibai Road, Xi'an, 710069, China. Electronic address: fandaidi@nwu.edu.cn.

PMID: 32156650
DOI: 10.1016/j.phrs.2020.104746

Abstract

Diabetic nephropathy (DN) is a common and serious complication of diabetes and causes kidney failure. Ginsenoside Rg5 (Rg5) is an important monomer in the main protopanaxadiol component of black ginseng. Rg5 has exhibited some beneficial biological effects, such as anti-cancer, neuroprotection, and anti-depression, but the effect of Rg5 on DN and its potential mechanism remains unclear. The aim of this study is to investigate the effect of Rg5 on kidney injury of C57BL/6 diabetic mice induced by high-fat diet and streptozotocin. After treatment with different concentration of Rg5 (30 and 60 mg kg^-1·d^-1) for 6 consecutive weeks, the fasting blood glucose, insulin levels, serum creatinine, serum urea, and serum UA in Rg5-treated DN mice were significantly reduced, while the renal histopathology was remarkably improved, compared with untreated DN mice. Moreover, ROS production, oxidative stress markers (MDA, SOD, and GSH-PX), Nox4 and TXNIP expressions of kidney in DN mice were significantly reduced after Rg5 treatment. Additionally, the expression levels of the NLRP3 inflammasome (NLRP3, ASC, and Caspase-1) and the inflammatory cytokines IL-1β and IL-18 were significantly inhibited, and the expression of NF-kB and the phosphorylation of p38 MAPK were also decreased with Rg5 treatment compared with no treatment in DN mice. Together, our results indicate that Rg5 attenuated renal injury in diabetic mice by inhibiting oxidative stress and NLRP3 inflammasome activation to reduce inflammatory responses, indicating that Rg5 is a potential compound to prevent or control diabetic renal injury.

Keywords: Diabetic mice; Ginsenoside Rg5; Kidney; MAPK; NLRP3 Inflammasome; ROS.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cytokines / immunology
Diabetes Mellitus, Experimental / drug therapy*
Diabetes Mellitus, Experimental / immunology
Diabetes Mellitus, Experimental / pathology
Diabetic Nephropathies / drug therapy*
Diabetic Nephropathies / immunology
Diabetic Nephropathies / pathology
Diet, High-Fat
Ginsenosides / pharmacology
Ginsenosides / therapeutic use*
Inflammasomes / immunology
Kidney / drug effects
Kidney / immunology
Kidney / pathology
MAP Kinase Signaling System / drug effects
Male
Mice, Inbred C57BL
NF-kappa B / immunology
NLR Family, Pyrin Domain-Containing 3 Protein / immunology
Oxidative Stress / drug effects
Protective Agents / pharmacology
Protective Agents / therapeutic use*

Substances

Cytokines
Ginsenosides
Inflammasomes
NF-kappa B
NLR Family, Pyrin Domain-Containing 3 Protein
Protective Agents
ginsenoside Rg5