Inhibition of caspase-1 by ginsenoside Rg1 ameliorates d-gal-induced renal aging and injury through suppression of oxidative stress and inflammation

The disruption of renal cell homeostasis caused by aging has attracted considerable attention. A traditional Chinese medicine, ginseng, is a potential drug for treating aging-related diseases. The study investigates the effect and mechanism of ginsenoside Rg1, an active component of ginseng, on renal aging and injury. The potential targets of ginsenoside Rg1 in relieving renal aging and injury were predicted using network pharmacology. d-Galactose (d-gal) was used to induce aging and mice were randomly divided into six groups: a wild-type control group, a wild-type d-gal group, and a wild-type d-gal with Rg1 group (20 mg/kg/d), a caspase-1^-/- control group, a caspase-1^-/- d-gal group, and a caspase-1^-/- d-gal with Rg1 group (<i>n</i> = 5). The duration of the study was 42 days. The effect of Rg1 was assessed by hematoxylin and eosin and Masson staining, quantitative reverse transcription PCR, enzyme-linked immunosorbent assay, and Western blotting. Network pharmacology revealed that caspase-1 was one of the crucial targets. <i>In vivo</i> experiments, ginsenoside Rg1 treatment resulted in lowered levels of β-Gal, p53, p21, blood urea nitrogen, serum creatinine, malondialdehyde, reactive oxygen species, tumor necrosis factor-α and renal fibrosis, along with a reduction of caspase-1, interleukin-1 and interleukin-18 in mice induced by d-gal. Additionally, knockout of caspase-1 can improve the above indicators and caspase-1^-/- mice treated with Rg1 showed better protective effects in alleviating renal senescence, ameliorating kidney injury, and mitigating inflammation and oxidative stress. The findings in this study provide experimental support for the clinical application of ginsenoside Rg1 in kidney aging. The underlying mechanisms require further experimental validation.