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

BACKGROUND: 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. MATERIALS AND METHODS: 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 (n = 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. RESULTS: Network pharmacology revealed that caspase-1 was one of the crucial targets. In vivo 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. CONCLUSION: 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.