Ginsenoside Rg1 ameliorates glomerular fibrosis during kidney aging by inhibiting NOX4 and NLRP3 inflammasome activation in SAMP8 mice

Xiaoyan Shen; Xianan Dong; Yuli Han; Yan Li; Shixin Ding; Han Zhang; Zhenghao Sun; Yanyan Yin; Weiping Li; Weizu Li

doi:10.1016/j.intimp.2020.106339

Ginsenoside Rg1 ameliorates glomerular fibrosis during kidney aging by inhibiting NOX4 and NLRP3 inflammasome activation in SAMP8 mice

Int Immunopharmacol. 2020 Feb 27:82:106339. doi: 10.1016/j.intimp.2020.106339. Online ahead of print.

Authors

Xiaoyan Shen¹, Xianan Dong¹, Yuli Han¹, Yan Li¹, Shixin Ding¹, Han Zhang¹, Zhenghao Sun¹, Yanyan Yin¹, Weiping Li², Weizu Li³

Affiliations

¹ Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Department of Pharmacology, Basic Medicine College, Anhui Medical University, Hefei 230032, Anhui, China.
² Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Department of Pharmacology, Basic Medicine College, Anhui Medical University, Hefei 230032, Anhui, China; Anqing Medical and Pharmaceutical College, Anqing 246052, Anhui, China. Electronic address: lwp19@126.com.
³ Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Department of Pharmacology, Basic Medicine College, Anhui Medical University, Hefei 230032, Anhui, China. Electronic address: liweizu@126.com.

PMID: 32114413
DOI: 10.1016/j.intimp.2020.106339

Abstract

Aging is closely related to the progress of renal fibrosis, which eventually results in renal dysfunction. Ginsenoside Rg1 (Rg1) has been reported to have an extensive anti-aging effect. However, the role and mechanism of Rg1 in aging-related renal fibrosis remain unclear. The present study aimed to evaluate the protective effect and mechanism of Rg1 in renal fibrosis during kidney aging in a model of SAMP8 mice. Taking SAMR1 mice as the control group, SAMP8 mice were administered Apocynin (50 mg/kg), Tempol (50 mg/kg), or Rg1 (5, 10 mg/kg) intragastrically for 9 weeks as treatment groups. The results showed that the elevated levels of blood urea nitrogen, serum creatinine and senescence-associated β-galactosidase (β-Gal) were markedly decreased, the glomerular mesangial proliferation was significantly alleviated and the increased levels of collagen IV and TGF-β1 were significantly downregulated by Rg1 in SAMP8 mice. In addition, the generation of ROS and the expression of NADHP oxidase 4 (NOX4) in the renal cortex were significantly reduced by Rg1 treatment. The expression levels of NLRP3 inflammasome-related proteins and the inflammation-related cytokine IL-1β were also inhibited by Rg1 treatment in the SAMP8 mice. These results suggested that Rg1 could delay kidney aging and inhibit aging-related glomerular fibrosis by reducing NOX4-derived ROS generation and downregulating NLRP3 inflammasome expression.

Keywords: Ginsenoside Rg1; Kidney aging; NADPH oxidase 4 (NOX4); NLRP3 inflammasome; Renal fibrosis.