Costunolide and dehydrocostus lactone alleviate ulcerative colitis via regulating TLR4, NF-κB and PI3K expression

Area of Science:

• Pharmacology
• Immunology
• Gastroenterology

Background:

• Ulcerative colitis (UC) is a chronic inflammatory bowel disease with limited treatment options.
• Costunolide (COS) and dehydrocostus lactone (DEH) are natural compounds with potential therapeutic benefits.
• Understanding the molecular mechanisms of COS and DEH in UC is crucial for developing new treatments.

Purpose of the Study:

• To elucidate the therapeutic mechanism of COS and DEH in ulcerative colitis (UC).
• To identify key molecular targets and pathways involved in the action of COS and DEH against UC.
• To validate the predicted mechanisms through molecular docking and animal experiments.

Main Methods:

• Network pharmacology was employed to predict compound-disease target proteins.
• Protein-protein interaction (PPI) network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed.
• Molecular docking and dextran sulfate sodium (DSS)-induced mouse model of UC were used for experimental validation.

Main Results:

• 39 common target proteins were identified between COS, DEH, and UC.
• Key targets including TLR4, PIK3R1, and RELA were pinpointed through network analysis.
• COS and DEH demonstrated efficacy in reducing UC-induced pathological changes and downregulating the expression of TLR4, PIK3R1, and RELA in mice.

Conclusions:

• COS and DEH exhibit protective effects against ulcerative colitis (UC) in a mouse model.
• The therapeutic mechanism involves the downregulation of TLR4, PIK3R1, and RELA signaling pathways.
• These findings support the potential of COS and DEH as novel therapeutic agents for UC treatment.