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已发表论文
小檗碱通过靶向 HSP90AA1 和 MAPK14 修复肠黏膜屏障
Authors Zhao D , Zhai Y , Chen C, Chen J, Chen D, Yang Q, Yu Z, Shao S, Huang Y, Shu J
Received 16 June 2025
Accepted for publication 3 November 2025
Published 15 November 2025 Volume 2025:18 Pages 263—278
DOI https://doi.org/10.2147/PGPM.S547308
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Martin H Bluth
Danya Zhao,1,* Yang Zhai,2,* Chen Chen,3,* Junkang Chen,4 Dongya Chen,1 Qiang Yang,5 Zhexuan Yu,3 Shisi Shao,3 Yao Huang,3 Jianlong Shu2
1Department of Gastroenterology, Hangzhou Red Cross Hospital/Hospital of Integrated Chinese and Western Medicine, Hangzhou, People’s Republic of China; 2Department of Chinese Medicine, Seventh People’s Hospital of Nanning, Nanning, People’s Republic of China; 3The First School of Clinical Medicine of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 4Department of Gastroenterology, Pujiang County Hospital of Traditional Chinese Medicine, Jinhua, People’s Republic of China; 5Hangzhou TCM Hospital Affiliated with Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Jianlong Shu, Email jianlong0214@yeah.net
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.
Keywords: Crohn’s disease, berberine, Mendelian randomization, molecular dynamics, experimental validation
1Department of Gastroenterology, Hangzhou Red Cross Hospital/Hospital of Integrated Chinese and Western Medicine, Hangzhou, People’s Republic of China; 2Department of Chinese Medicine, Seventh People’s Hospital of Nanning, Nanning, People’s Republic of China; 3The First School of Clinical Medicine of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 4Department of Gastroenterology, Pujiang County Hospital of Traditional Chinese Medicine, Jinhua, People’s Republic of China; 5Hangzhou TCM Hospital Affiliated with Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Jianlong Shu, Email jianlong0214@yeah.net
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.
Keywords: Crohn’s disease, berberine, Mendelian randomization, molecular dynamics, experimental validation