Study on the mechanism of Tianshui Dichang Decoction in the treatment of ulcerative colitis based on network pharmacology and experimental verification
10.3760/cma.j.cn115398-20220802-00023
- VernacularTitle:基于网络药理学探讨天水涤肠汤治疗溃疡性结肠炎作用机制及实验验证
- Author:
Peitong LI
1
;
Xiaomeng LIU
;
Yujing MA
;
Ziwei DONG
;
Sen YANG
;
Qian YANG
;
Jianping LIU
;
Xiaomeng LANG
Author Information
1. 河北中医学院研究生院,石家庄 050000
- Keywords:
Colitis, ulcerative;
Tianshui Dichang Decoction;
Network pharmacology;
STAT3 transcription factor;
Mechanism of action
- From:
International Journal of Traditional Chinese Medicine
2023;45(11):1399-1407
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the potential mechanism of Tianshui Dichang Decoction in the treatment of ulcerative colitis through network pharmacology and experimental verification.Methods:The active components and targets of Tianshui Dichang Decoction were screened by TCMSP. The related targets of ulcerative colitis were screened by OMIM, GeneCard and TTD databases, and the effective component targets of Tianshui Dichang Decoction were intersected with the potential targets of ulcerative colitis. The PPI network was constructed by STRING database to screen the core targets, and the "Chinese materia medica-disease-active components-target" network was constructed by Cytoscape 3.8.0 software. GO function and KEGG pathway enrichment analysis were carried out using Metascape database. 48 mice were divided into control group, model group, mesalazine group (0.3 g/kg) and Tianshui Dichang Decoction low-, medium-, and high-dosage groups (7.5,15 and 30 g/kg) according to random number table method, with 8 mice in each group. Except the control group, the ulcerative colitis model was established in other groups. After 7 days of intervention with corresponding drugs, the disease activity index (DAI) was scored, the pathological changes of colon were observed by HE staining, and the expressions of IL-6, STAT3mRNA and protein in colon tissue were detected by PCR and Western blot methods.Results:Totally 127 active components in Tianshui Dichang Decoction and 560 targets of ulcerative colitis were obtained. 89 intersecting targets of Tianshui Dichang Decoction and ulcerative colitis were obtained, and the core targets included IL6, TNF, IL1B, AKT1, TP53, VEGFA, JUN, PTGS2, CXCL8, CCL2, STAT3, MMP9 and so on. Oxidative stress response, lipopolysaccharide metabolism, bacterial response, signal transduction and other biological processes were mainly involved, mainly through the cancer pathway, IL17, TNF, MAPK and other signal pathways to play a role in the treatment of ulcerative colitis. The results of experimental verification showed that the DAI score, the expressions of IL-6 and STAT3 protein in colon tissue of Tianshui Dichang Decoction medium- and high-dosage groups.decreased ( P<0.05). The levels of IL-6 and STAT3 mRNA in colon tissue decreased in the Tianshui Dichang Decoction low-, medium- and high-dosage groups.groups ( P<0.05). Conclusion:Tianshui Dichang Decoction has a certain therapeutic effect on UC through component-multitarget-signal pathway, and its mechanism is related to regulating IL-6/STAT3 signal pathway and inhibiting intestinal mucosal inflammation.