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Exploring Key Target Genes of Tong Bian Bai Tou Weng Decoction for Ulcerative Colitis: A Combined Approach of
Can Cui1, Jia-Qi Jiang1, Zhi-Cheng Li1
1Department of Proctology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China.
Introduction:
Ulcerative colitis (UC) manifests as persistent inflammation and ulceration within the mucosal and submucosal layers of the colon. The present study sought to elucidate the principal targets of Tongbian Baitouweng Decoction (TBD) in UC.
Methods:
A total of 221 TBD-related and 1,270 UC-related genes were retrieved from public databases, with their intersection as candidate targets. Differential expression, machine learning, expression profiling, MR analysis, network construction, molecular docking, enrichment, and immune infiltration analyses were used to refine key targets and explore their functional associations with UC.
Results:
PPARG, STAT1, and IL1B emerged as the principal targets of TBD against UC. Among UC samples, IL1B and STAT1 were upregulated, whereas PPARG was downregulated. MR analysis revealed significant causal associations: STAT1 (OR = 1.17), IL1B (OR = 0.50), and PPARG (OR = 0.97). A network comprising three targets and 53 corresponding active compounds was established, with molecular docking demonstrating strong binding affinities, particularly with quercetin. Enrichment analysis indicated that the three targets were jointly involved in pathways such as "Toll-like receptor signaling". Immune infiltration analysis revealed that IL1B and STAT1 correlated positively with activated CD4 T cells, macrophages, and natural killer cells, whereas PPARG displayed an inverse pattern.
Discussion:
These findings align with existing evidence linking STAT1, PPARG, and IL1B to UC pathogenesis, highlighting TBD's therapeutic potential by targeting key inflammatory and barrier-regulatory pathways; future studies should validate these targets in preclinical models and explore the formula's clinical efficacy in large-scale trials.
Conclusion:
STAT1, PPARG, and IL1B were TBD's key UC therapeutic targets, with regulatory roles providing a UC research mechanistic framework.
Insights
Tongbian Baitouweng Decoction (TBD) targets key genes STAT1, PPARG, and IL1B for ulcerative colitis (UC). These targets are involved in inflammation and immune responses, offering a new therapeutic framework for UC.
Area of Science:
- Gastroenterology
- Immunology
- Pharmacology
Background:
- Ulcerative colitis (UC) is characterized by chronic inflammation and ulceration of the colon.
- Identifying therapeutic targets for UC is crucial for developing effective treatments.
Purpose of the Study:
- To identify the primary molecular targets of Tongbian Baitouweng Decoction (TBD) in the treatment of ulcerative colitis (UC).
Main Methods:
- Gene data retrieval and intersection analysis for TBD and UC.
- Machine learning, differential expression, Mendelian Randomization (MR) analysis, and network construction.
- Molecular docking, pathway enrichment, and immune cell infiltration analyses.
Main Results:
- PPARG, STAT1, and IL1B were identified as key targets of TBD in UC.
- STAT1 and IL1B were upregulated, while PPARG was downregulated in UC samples.
- Significant causal associations were found via MR analysis, and molecular docking showed strong compound binding, particularly quercetin.
Conclusions:
- STAT1, PPARG, and IL1B are validated as key therapeutic targets for TBD in UC.
- These targets play roles in inflammatory and barrier-regulatory pathways relevant to UC pathogenesis.
- The findings provide a mechanistic framework for TBD's efficacy in UC treatment.
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