Unveiling the multifaceted benefits of Simiao Pill in ulcerative colitis: Integrative analysis of signaling pathways, gut microbiota, and lipid metabolism.

Background: Ulcerative colitis (UC), a chronic idiopathic inflammatory bowel disease, is characterized by a prolonged and recurrent course. The classical Traditional Chinese Medicine (TCM) formula Simiao Pill (SMP) has demonstrated unique and widespread therapeutic effects on diarrhea and other intestinal inflammation. However, its material basis and potential mechanisms of action remain unclear.

Objective: This study aims to explore the mechanisms by which SMP alleviates UC, emphasizing its anti-inflammatory properties and its role in regulating gut microbiota.

Methods: The chemical composition of SMP was identified using UPLC-Q-TOF-MS/MS. Network pharmacology and molecular docking were applied to predict potential anti-UC targets and pathways. In vitro models in RAW264.7 cells and an in vivo mouse model induced by dextran sulfate sodium (DSS) were established to evaluate the potential mechanisms using molecular biology techniques. Additionally, gut microbiota changes were analyzed via 16S rRNA sequencing, and metabolic profiling was conducted using UPLC-Q-TOF-MS/MS.

Results: SMP significantly improved UC symptoms by targeting 148 protein-related pathways, including TLR4/PI3K/Akt/NF-κB, a key inflammatory regulator. Molecular docking confirmed strong interactions between SMP compounds and targets. SMP reduced inflammation, restored gut barrier integrity, and modulated gut microbiota and lipid metabolism in UC mice.

Conclusions: SMP alleviates UC by regulating the TLR4/PI3K/Akt/NF-κB pathway, balancing gut microbiota, and improving lipid metabolism. These findings support SMP's potential as a UC treatment and warrant further clinical exploration.