Berberine Mitigates Diclofenac-induced Intestinal Mucosal Mechanical Barrier Dysfunction Through the Restoration of Autophagy by Inhibiting Exosome-mediated LncRNA H19

Overview

Journal Inflammopharmacology

Specialty Pharmacology

Date 2024 May 17

PMID 38758516

Authors

Ruonan He

Ying Li

Yi He

Qianqian Wang

Shuo Zhang

Shanshan Chen

Affiliations

Soon will be listed here.

Abstract

Small intestine damage caused by diclofenac is called diclofenac enteropathy. Berberine (BBR), a class of isoquinoline alkaloids derived from Berberis vulgaris and Phellodendron amurense, is widely used in intestinal diseases. The present study evaluated the protective effect of BBR on the intestinal mucosal mechanical barrier in diclofenac enteropathy and its possible action mechanism. The in vitro animal experiment revealed that BBR downregulated the expression of long non-coding RNA H19 (lncRNA H19) in the small intestine and exosomes. In the co-culture experiment involving exosomes and intestinal epithelial cell-6 (IEC-6) cells, the results of qRT-PCR, western blotting, and immunofluorescence assays demonstrated that the elevated expression of lncRNA H19 in the small intestine, conveyed via exosomes derived from the diclofenac group, suppressed the expression levels of autophagy-associated protein 5 (Atg 5) and light chain 3 (LC 3), as well as and the tight junction (TJ) proteins zonula occludens-1 (ZO-1), claudin-1, and occluding, relative to the control group. BBR treatment attenuated exosomal lncRNA H19 levels, upregulated the expression of Atg5 and LC3 expression, enhanced TJ protein expression, and increased the light chain 3 (LC3)-II/LC3-I ratio. These findings significantly elucidated that BBR promoted the restoration of autophagy in IECs by inhibiting exosomal lncRNA H19, thereby mitigating the impairment of the intestinal mucosal mechanical barrier function in diclofenac enteropathy. The process involving exosomal lncRNA H19 regulating autophagy, thereby affecting the intestinal mucosal mechanical barrier, offers a novel perspective for the application of BBR in the treatment of diclofenac enteropathy.

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