Glabridin ameliorates hemorrhagic shock induced acute kidney injury by activating Nrf2/HO-1 pathway.

Glabridin, a bioactive compound extracted from licorice, exhibits anti-inflammatory and antioxidative stress effects. It has rarely been reported in hemorrhagic shock (HS)-induced acute kidney injury (AKI). Here, the effects and potential mechanisms of Glabridin on HS-induced kidney injury was investigated. The active ingredient target network of licorice for HS-induced acute kidney injury was analyzed using network pharmacology. The study also examined the target gene-related biological processes and signaling pathways. To explore the impact of Glabridin on the kidney, a HS-induced rat model was established by femoral artery bleeding following tail vein injection of Glabridin. Glabridin improved kidney function evidenced by reduced levels of creatinine, urea nitrogen, neutrophil gelatinase-associated lipocalin in the serum, and the urinary protein/creatinine ratio in HS rats. This was inseparable from the inhibitory effect on apoptosis and kidney tubule injury. In addition, the protection of Glabridin on mitochondrial function was evident in the improvement of mitochondrial morphology, reduction of reactive oxygen species, increase in adenosine triphosphate, and upregulation of peroxisome proliferator-activated receptor γ coactivator 1-alph. These effects help reduce inflammation in kidney tissue. Hypoxia/reoxygenation-induced HK-2 cells were studied in vitro, and the same results were obtained in the cell model. Mechanically, Glabridin activated the Nrf2/HO-1 signaling pathway in vivo and in vitro, which may be a potential mechanism through which Glabridin protects kidney tissue. This study revealed the preventive effect of Glabridin on the kidney of HS rats, and provided insights for the development of Glabridin as a small molecule drug.