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

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.