# Astragaloside IV Alleviates Ulcerative Colitis Progression by Inhibiting WDR5‐Mediated ENO1 H3K4me3 Modification

## TL;DR

Astragaloside IV helps reduce ulcerative colitis by inhibiting WDR5, which affects ENO1 gene activity and inflammation.

## Contribution

This study reveals a novel mechanism by which Astragaloside IV alleviates UC through WDR5-mediated ENO1 regulation.

## Key findings

- ASI reduced colon shortening, histological damage, and pro-inflammatory cytokines in UC mice.
- WDR5 overexpression counteracted ASI's effects, indicating its role in ENO1 regulation.
- Silencing ENO1 reduced cell apoptosis and UC-like symptoms in mice.

## Abstract

Ulcerative colitis (UC) has become a prevalent global health concern. This study scrutinized the influence of Astragaloside IV (ASI) on DSS‐induced UC, with particular emphasis on the role of WDR5 in mediating ENO1 expression. The therapeutic efficacy of ASI was assessed in a mouse model of UC by evaluating disease activity index, pathology, colon length, and inflammatory factor contents. Through bioinformatics analysis, the UC‐related differentially expressed genes were predicted using the GSE38713 database and intersected with the lists of ASI targets and transcription factors, and the protein–protein network was constructed to screen the key target transcription factors. ASI inhibited the shortening of colon length, reduced histological damage scores, ameliorated pathology, and the overproduction of pro‐inflammatory cytokines. After ASI treatment, DSS‐stimulated human NCM460 cells showed increased cell viability, decreased levels of pro‐inflammatory cytokines and cleaved‐Caspase‐3, and enhanced ZO‐1 and claudin‐3 expression. WDR5 was a target of ASI in UC, and overexpression of WDR5 compromised the effects of ASI. WDR5 promoted the H3K4me3 modification of the ENO1 promoter and thereby regulated ENO1 transcriptional activation. Silencing of ENO1, again, repressed NCM460 cell apoptosis and alleviated UC‐like symptoms in mice. In conclusion, ASI mitigated UC by inhibiting WDR5 and reducing H3K4me3‐mediated ENO1 activation.