Berberine Repairs Intestinal Mucosal Barrier by Targeting HSP90AA1 and MAPK14
- Pharmgenomics Pers Med. 2025 Nov 15:18:263-278. doi: 10.2147/PGPM.S547308.
- 1. Department of Gastroenterology, Hangzhou Red Cross Hospital/Hospital of Integrated Chinese and Western Medicine, Hangzhou, People's Republic of China.
- 2. Department of Chinese Medicine, Seventh People's Hospital of Nanning, Nanning, People's Republic of China.
- 3. The First School of Clinical Medicine of Zhejiang Chinese Medical University, Hangzhou, People's Republic of China.
- 4. Department of Gastroenterology, Pujiang County Hospital of Traditional Chinese Medicine, Jinhua, People's Republic of China.
- 5. Hangzhou TCM Hospital Affiliated with Zhejiang Chinese Medical University, Hangzhou, People's Republic of China.
- # Contributed equally.
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.