Administration of glycyrrhetinic acid reinforces therapeutic effects of mesenchymal stem cell-derived exosome against acute liver ischemia-reperfusion injury.

Abstract

Recent studies have shown that mesenchymal stem cell‐derived exosome could attenuate ischaemia‐reperfusion (I/R) injury by suppressing inflammatory response in the liver. Glycyrrhetinic acid was also shown to be capable of repressing the TLR4 signalling pathway. However, it remains to be explored as whether the combined administration of mesenchyma stem cell (MSC)‐derived exosome and glycyrrhetinic acid (GA) could increase their therapeutic effects on I/R injury. Western blot was performed to evaluate the expression of proteins associated with inflammatory response in THP‐1 cells and I/R rat models treated under different conditions. Flow cytometry was carried out to analyse the proportions of different subtypes of peripheral blood cells in I/R rats. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured to assess the liver injury in I/R rats. Combined treatment with MSC‐derived exosome and GA effectively maintained the expression of key proteins involved in inflammatory response in LPS stimulated THP‐1 cells and THP‐1 cells treated under hypoxia conditions. In the established of I/R rat models, GA administration reinforced the therapeutic efficiency of MSC‐derived exosomes by maintaining the proportion of different subgroups of peripheral blood cells, decreasing the concentration of ALT and AST, and restoring the expression of dysregulated proteins associated with inflammation. Our results demonstrated that treatment with exosomes derived from mesenchymal stem cells (MSCs) attenuated liver I/R injury, while the pre‐treatment with GA may further promote the therapeutic effect of mesenchymal stem cell‐derived exosome against acute liver ischaemia‐reperfusion injury.