LAUSR

Peoniflorin‐6′‐O‐benzene sulfonate (CP‐25) inhibited the activity of GRK2 to exert anti‐inflammatory and immunomodulatory effects. This study aimed to investigate the effect of CP‐25 the intestinal epithelial barrier and the mechanism. CaCO‐2 cell monolayer and dextran sulfate salt (DSS)‐induced colitis mouse model was used to evaluate intestinal epithelial barrier function in vitro and in vivo, respectively. Results showed that CP‐25 prevented dysfunction of the intestinal epithelial barrier and inhibited NF‐κB p65 activation in TNF‐α‐induced CaCO‐2 cells. The colon structure destroyed in DSS‐induced colitis mice was improved by CP‐25. CP‐25 has a role in inhibition membrane translocation of GRK2‐β‐arrestin 2 complex, stabilization of the binding of GRK2 and β‐arrestin 2 to ERK1/2 in cytoplasm. Subsequently down‐regulated the nuclear transcription and transactivation of NF‐κB p65 via inhibiting its phosphorylation of Ser536, and Ser276, respectively and restored the epithelial barrier function. In conclusion, CP‐25 inhibited ERK1/2‐NF‐κB activation and thereby protected the intestinal epithelial barrier, which was associated with restoring the inhibition of GRK2 and β‐arrestin 2 on ERK1/2.