Work

Berberine Repairs Intestinal Mucosal Barrier by Targeting HSP90AA1 and MAPK14

Year: 2025

Type: article

Abstract: Background: Berberine (BBR), a key compound in Coptis chinensis, has broad pharmacological properties, though its specific Crohn's disease (CD) targets and mechanisms are undefined. Materials and Methods: We employed network pharmacology, mendelian randomization (MR), molecular docking, and molecular dynamics simulations to identify potential target genes. Next, we assessed the efficacy of BBR in vitro and in vivo. Results: HSP90AA1 and MAPK14 were identified as potential target genes of BBR in the treatment of CD. In vitro experiments revealed that BBR downregulated LPS-induced HSP90AA1, MAPK14, and TNF-α while restoring tight junction proteins (ZO-1, Occludin, Claudin-1, JAM-A). Both HSP90AA1 inhibitor (17-AAG) and MAPK14 inhibitor (SB203580) significantly mitigated the reduction in ZO-1, Occludin, Claudin-1, and JAM-A expression caused by LPS. Furthermore, in vivo experiments revealed that BBR treatment effectively alleviated weight loss, the disease activity index (DAI), and colon shortening in a model of DSS-treated mice. BBR also ameliorated pathological changes in the colon, repaired goblet cells, reduced the expression of HSP90AA1, MAPK14, and TNF-α, and increased the expression of ZO-1, Occludin, Claudin-1, and JAM-A. Conclusion: BBR inhibits the expression of HSP90AA1 and MAPK14 both in vitro and in vivo, thereby facilitating the repair of the intestinal mucosal barrier.

Source: Pharmacogenomics and Personalized Medicine

DOI: 10.2147/pgpm.s547308