Exploring Mechanism of Action of Tuoli Xiaodu San in Treating Ulcerative Colitis Based on Integrated Pharmacology and Transcriptomics
10.13422/j.cnki.syfjx.20251316
- VernacularTitle:基于药理学与转录组学整合探究托里消毒散治疗溃疡性结肠炎的作用机制
- Author:
Longke MA
1
;
Linzhen LI
1
;
Haimei YANG
1
;
Juan WANG
2
;
Xudong WEN
3
;
Yihan MA
3
;
Xiaoxiang WANG
3
;
Fating LU
1
;
Qiaobo YE
1
Author Information
1. School of Basic Medical Sciences， Chengdu University of Traditional Chinese Medicine（TCM），Chengdu 611137， China
2. School of Public Health， Chengdu University of TCM， Chengdu 611137，China
3. Chengdu Integrated TCM and Western Medicine Hospital， Chengdu 610084， China
- Publication Type:Journal Article
- Keywords:
ulcreative colitis;
Tuoli Xiaodu San;
network pharmacology;
transcriptomics;
phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(14):205-215
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the material basis and mechanism of action of Tuoli Xiaodu San in treating ulcerative colitis （UC） by integrating transcriptomics， network pharmacology， and experimental validation. MethodsNetwork pharmacology was initially employed to screen the active components and potential mechanisms of Tuoli Xiaodu San for treating UC. A UC mouse model was established by dextran sulfate sodium （DSS） induction. The mice were divided into the following groups： normal， model， high-dose （11.3 g·kg-1） Tuoli Xiaodu San， low-dose （5.7 g·kg-1） Tuoli Xiaodu San， and positive control （mesalazine， 0.4 g·kg-1）. Intragastric administration commenced on day 1 of modeling and continued for 7 consecutive days. The disease activity index （DAI） was assessed daily. Hematoxylin-eosin （HE） staining was used to observe colonic pathological changes. Serum levels of tumor necrosis factor-alpha （TNF-α）， interleukin-1 beta （IL-1β） and interleukin-6 （IL-6） were measured by enzyme-linked immunosorbent assay （ELISA）. Transcriptome sequencing was performed on mouse colonic tissues， and the results were integrated with network pharmacology findings for in-depth analysis of Tuoli Xiaodu San's potential mechanisms in treating UC. Finally， the expression of key genes and proteins in the identified signaling pathways were detected using Western blot and Real-time polymerase chain reaction （Real-time PCR）. ResultsThe combined analysis of network pharmacology and transcriptomics results showed that the multi-pathway network with phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway as its core was the key mechanism of Tuoli Xiaodu San in the treatment of UC. Tuoli Xiaodu San administration significantly ameliorated weight loss， diarrhea， and bloody stools in UC mice， reduced the DAI scores （P<0.05， P<0.01）， lowered the colonic histopathological scores （P<0.01）， alleviated colon shortening （P<0.01）， and downregulated serum levels of TNF-α， IL-1β， and IL-6 （P<0.05， P<0.01）. Molecular biology experiments confirmed that Tuoli Xiaodu San significantly inhibited the mRNA and protein expression， as well as the phosphorylation levels， of PI3K， Akt， and p65 in colonic tissues （P<0.05， P<0.01）. ConclusionTuoli Xiaodu San can regulate the multi-pathway network with PI3K/Akt as its core through multi-component synergy， thereby reducing colonic inflammatory damage and exerting a therapeutic effect on UC.
