Therapeutic propensity of ginsenosides Rg1 and Rg3 in rhabdomyolysis-induced acute kidney injury and renohepatic crosstalk in rats

Background: Ginseng is a traditional herbal medicine used for thousands of years in Southeast Asian countries because of its medicinal properties. Ginsenosides Rg1 and Rg3 have demonstrated therapeutic properties against a broad spectrum of diseases. Purpose: Here in this study, we investigated the therapeutic efficacy of Rg1 and Rg3 in alleviating glycerol-induced acute kidney injury, also known as rhabdomyolysis-induced acute kidney injury (RAKI). Methods: AKI was induced in male Wistar rats through intramuscular injection of 10 mL/kg glycerol and simultaneous oral treatment of ginsenosides Rg1 and Rg3 for 3 days. We also evaluated the therapeutic potential of Rg1 and Rg3 on human embryonic kidney epithelial (HEK-293). Cell viability and LDH assay were performed on HEK-293 cells to evaluate the toxicity of Rg1 and Rg3. Evaluation of important kidney damage markers such as creatinine and blood urea nitrogen (BUN) was carried out at different time points from the rat serum. His-topathological analysis was performed on kidney tissues. We also performed experiments such as ELISA assay, immunohistochemistry, immunofluorescence staining, COMET assay, western blotting, TUNEL assay, and flow cytometry to obtain results. Results: Rg1 and Rg3 significantly downregulated the expression of kidney damage markers such as creatinine and BUN in a dose-dependent manner. Histopathological analysis revealed damage across the glomerulus, tu-bules, and collecting duct rendering the kidney dysfunctional in glycerol treatment groups. However, Rg1 and Rg3 treated groups showed a significant reduction in tubular necrosis at both 10 and 20 mg/kg. There was also a sharp downregulation of oxidative and ER stress markers. Additionally, we observed nuclear translocation of Nrf2 which were more prominent in kidney tissues. Rg1 and Rg3 were also able to mitigate apoptotic cell death in vitro and in vivo evaluated through immunofluorescence staining for p53, TUNEL assay, flow cytometry, and immunoblotting for intrinsic apoptosis markers.Conclusion: In summary, we conclude that Rg1 and Rg3 exhibited natural therapeutic remedy against AKI.

Automated summary

In this study, the therapeutic efficacy of ginsenosides Rg1 and Rg3 in glycerol-induced acute kidney injury (AKI) was investigated. The results showed that Rg1 and Rg3 significantly alleviated kidney damage by reducing the expression of kidney damage markers, decreasing tubular necrosis, and downregulating oxidative and ER stress markers. Additionally, Rg1 and Rg3 exhibited a protective effect against apoptotic cell death. Therefore, Rg1 and Rg3 could be considered as natural therapeutic remedies for AKI.