Scope: The purpose of this research is to investigate the specific role of HSP90 paralogs in ulcerative colitis (UC), and to explore the mechanisms behind the inhibitory effects of galangin (Gal) on UC by inhibiting HSP90𝜷 in vivo. Methods and results: In order to achieve this, publicly available gene expression data and molecular biology techniques are used. The results show that the expression of HSP90𝜷 is significantly increased in the mucosal biopsies of UC patients and in the colons of colitis mice, and that there is a significant correlation between HSP90𝜷 levels and disease severity. Then, Gal is found to bind directly to HSP90𝜷 and downregulates the level of p-AKT, as well as the stability and oligomerization of HSP90𝜷, indicating Gal as an HSP90𝜷 inhibitor. Moreover, the findings reveal that HSP90𝜷 plays a critical role in controlling UC, and that Gal can alleviate colitis by inhibiting HSP90𝜷 and perturbing fatty acid synthesis-mediated NLRP3 inflammasome activation. Conclusion: These results not only provide insight into the potential therapeutic use of Gal in the treatment of UC, but also offer new perspectives on the role of HSP90𝜷 in this disease.

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