Puerarin alleviates renal ischemia/reperfusion injury by inhibiting apoptosis and endoplasmic reticulum stress via Nrf2/HO-1 pathway

Iran J Basic Med Sci. 2025;28(2):187-193. doi: 10.22038/ijbms.2024.80438.17412.

Abstract

Objectives: To explore the effects of puerarin on renal ischemia/reperfusion injury and the possible mechanism.

Materials and methods: The experimental mice were injected with puerarin (50 or 100 mg/kg) per day or equal sterile saline by intraperitoneal injection for one week, and a renal I/R injury model was constructed. HK-2 cells were incubated with puerarin (1 uM and 10 uM) before the H/R model. Immunohistochemistry, immunocytochemistry, and Western blot analysis were used to detect the protein associated with apoptosis and endoplasmic reticulum stress.

Results: Puerarin could improve renal function and attenuate tissue structural damage after renal I/R. Meanwhile, puerarin alleviated apoptosis and endoplasmic reticulum stress by decreasing expression levels of specific biomarkers such as caspase-3, GRP78, CHOP, and p-elF2α/ elF2α in animals and HK-2 cells. The up-regulated expression of Nrf2 and HO-1 protein after puerarin treatment indicated that the Nrf2/HO-1 signaling pathway might mediate the protective mechanism of puerarin against renal I/R.

Conclusion: Our results suggest that puerarin alleviated renal ischemia/reperfusion injury by inhibiting apoptosis and endoplasmic reticulum stress via the Nrf2/HO-1 pathway and offered new insights for preventing and treating renal I/R.

Keywords: Apoptosis; Endoplasmic reticulum- stress; Nrf2/HO-1 pathway; Puerarin; Renal ischemia/reperfusion- injury.