Paeoniflorin-6'-O-benzene sulfonate protected the intestinal epithelial barrier by restoring the inhibitory effect of GRK2 and β-arrestin 2 on ERK1/2-NF-κB.

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. © 2022 John Wiley & Sons Ltd.

Citation

Mengya Jiang, Caihong Tang, Mei Yang, Ying Li, Wu Wang, Chun Wang, Wei Wei, Jingyu Chen. Paeoniflorin-6'-O-benzene sulfonate protected the intestinal epithelial barrier by restoring the inhibitory effect of GRK2 and β-arrestin 2 on ERK1/2-NF-κB. Phytotherapy research : PTR. 2023 Feb;37(2):743-758

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PMID: 36223242

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