AUTHOR=Zhao Pengyu , Hou Yusen , Yan Tingting , Kang Jie , Tian Ye , Li Jiaxin , Zeng Chenjuan , Geng Funeng , Liao Qi 

TITLE=Synthesis and biological evaluation of chrysin derivatives containing α-lipoic acid for the treatment of inflammatory bowel disease

JOURNAL=Frontiers in Chemistry

VOLUME=12

YEAR=2024

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2024.1406051

DOI=10.3389/fchem.2024.1406051

ISSN=2296-2646

ABSTRACT=<p>This study introduces newly discovered chrysin derivatives that show potential as candidate molecules for treating inflammatory bowel disease (IBD). Compound <bold>4b</bold>, among the synthesized compounds, displayed significant inhibitory effects on monocyte adhesion to colon epithelium induced by TNF-α, with an IC<sub>50</sub> value of 4.71 μM. Further mechanistic studies demonstrated that <bold>4b</bold> inhibits the production of reactive oxygen species (ROS) and downregulates the expression of ICAM-1 and MCP-1, key molecules involved in monocyte-epithelial adhesion, as well as the transcriptional activity of NF-κB. <italic>In vivo</italic> experiments have shown that compound <bold>4b</bold> exhibits a dose-dependent inhibition of 2, 4, 6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats, thereby validating its effectiveness as a colitis inhibitor in animal models. These results indicate that <bold>4b</bold> shows considerable promise as a therapeutic agent for managing IBD.</p>