Asiaticoside ameliorates renal ischemia/reperfusion injury by promoting CD4⁺CD25⁺FOXP3⁺ treg cell differentiation

Ischemia/reperfusion injury (I/R) is the major cause of acute kidney injury, which becomes a global health problem. The effects of asiaticoside, as an anti-inflammatory drug, on renal ischemia-reperfusion injury have not been well defined. After the CD4⁺ cells were treated with asiaticoside, the CD4⁺CD25+FOXP3+ Treg cell differentiation was detected by flow cytometry. The viability and release of inflammatory factors of CD4⁺CD25+FOXP3+ Treg cell were detected by CCK-8 and ELISA. Renal I/R injury mice model was established, and the mice were pre-treated with asiaticoside or CD25 antibody or infused with Treg cells. The histological changes of renal tissue were evaluated by Hematoxylin-eosin, PAS, and Masson staining. The renal function markers were evaluated by colorimetry, the release of inflammatory factors was determined by ELISA. The Th17 and Treg cells in the blood and spleen were quantified by flow cytometry. The expressions of FOXP3 and RoR-γt in renal tissues were determined by western blotting. Asiaticoside promoted CD4⁺CD25+FOXP3+ Treg cell differentiation, increased the cell viability and down-regulated TNF-α, IL-1β, and IL-6, while up-regulated IL-10 of CD4⁺CD25+FOXP3+ Treg cells. Moreover, asiaticoside ameliorated the histological damage, decreased the Th17 cells and increased Treg cells, and down-regulated the TNF-α, IL-1β, IL-6, blood urea nitrogen, serum creatinine, and RoR-γt, while up-regulated IL-10 and FOXP3 of renal I/R injury mice. Effect of asiaticoside on renal I/R injury mice was reversed by CD25 antibody whose role was further reversed by Treg cell infusing. In conclusion, asiaticoside ameliorated renal I/R injury due to promoting CD4⁺CD25+FOXP3+ Treg cell differentiation.