Exosomes derived from Baicalin‐pretreated bone mesenchymal stem cells improve Th17/Treg imbalance after hepatic ischemia–reperfusion via FGF21 and the JAK2/STAT3 pathway.

Baicalin is an active compound extracted from Scutellaria baicalensis with antioxidant and anti‐inflammatory properties. Bone mesenchymal stem cells (BMSCs)‐derived exosomes have shown promise for the treatment of hepatic ischemia–reperfusion (I/R) injury. This study aims to investigate the role of Baicalin‐pretreated BMSCs‐derived exosomes in hepatic I/R injury and its mechanisms. BMSCs were pretreated with or without Baicalin, and their exosomes (Ba‐Exo and Exo) were collected and characterized. These exosomes were administered to mice via tail vein injection. Treatment with Exo and Ba‐Exo significantly suppressed the elevation of ALT and AST induced by hepatic injury. Additionally, both Exo and Ba‐Exo treatments resulted in a reduction in the liver weight‐to‐body weight ratio. RT‐PCR results revealed a significant downregulation of pro‐inflammatory cytokines with Exo and Ba‐Exo treatment. Both Exo and Ba‐Exo treatment improved the Th17/Treg cell imbalance induced by I/R and reduced hepatic injury. Additionally, exosomes were cocultured with normal liver cells, and the expression of fibroblast growth factor 21 (FGF21) in liver cells was elevated through Ba‐Exo treatment. After treatment, the JAK2/STAT3 pathway was inhibited, and FOXO1 expression was upregulated. Finally, recombinant FGF21 was injected into mouse tail veins to assess its effects. Recombinant FGF21 injection further inhibited the JAK2/STAT3 pathway, increased FOXO1 expression, and improved the Th17/Treg cell imbalance. In conclusion, this study confirms the protective effects of Exo and Ba‐Exo against hepatic I/R injury. Ba‐Exo mitigates hepatic I/R injury, achieved through inducing FGF21 expression in liver cells, inhibiting the JAK2/STAT3 pathway, and activating FOXO1 expression. Therefore, baicalin pretreatment emerges as a promising strategy to enhance the therapeutic capability of BMSCs‐derived exosomes for hepatic I/R. [ABSTRACT FROM AUTHOR]