Berberine improves intestinal epithelial tight junctions by upregulating A20 expression in IBS-D mice

Qiuke Hou, Shuilian Zhu, Changrong Zhang, Yongquan Huang, Yajuan Guo, Peiwu Li, Xinlin Chen, Yi Wen, Simon Q B HAN, Fengbin Liu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

To investigate effects of berberine exerts on A20 expression and regulation of intestinal epithelial tight junctions via the TNF-α-NF-κB-MLCK pathway in Diarrhea-Predominant Irritable Bowel Syndrome (IBS-D). C57BL/6 wild type (WT) and A20 IEC-KO mice (48 each) were randomly divided into normal control (NC), model control (MC), rifaximin and berberine groups (12 mice per group). An experimental model of IBS-D was established using 4% acetic acid and evaluated by haematoxylin-eosin (HE) staining. rifaximin and berberine mice were treated with rifaximin and berberine, respectively. Intestinal epithelial space of WT berberine mice improved more than A20 IEC-KO berberine mice compared to MC mice. WT berberine mice exhibited greater expression of A20 compared with MC mice(P < 0.01). TNF-α, NF-kB p65, MLCK, MLC, TRAF6 and RIP1 levels in A20 IEC-KO and WT berberine mice were all decreased compared to MC mice(P all<0.05). NF-κB p65, MLCK and TRAF6 levels were increased in A20 IEC-KO berberine mice as compared to WT berberine mice (P all<0.05). Intestinal epithelial levels of occludin, claudin-1, ZO-1 and F-actin increased in all berberine mice (P all<0.01-0.05), while occludin, claudin-1, and ZO-1 levels were lower in A20 IEC-KO berberine mice(P < 0.05). Berberine downregulates abnormal activation of the TNF-α-NF-κB-MLCK pathway by upregulating expression of A20 in a mouse model of IBS-D, thereby protecting intestinal epithelial tight junctions and repairing the damage IBS-D causes to the intestinal epithelial barrier.

Original languageEnglish
Article number109206
JournalBiomedicine and Pharmacotherapy
Volume118
DOIs
Publication statusPublished - Oct 2019

Scopus Subject Areas

  • Pharmacology

User-Defined Keywords

  • A20
  • Berberine
  • IBS-D
  • Intestinal epithelial barrier
  • TNF-α-NF-κB-MLCK pathway

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