Title:Exploring the Targets and Molecular Mechanisms of Thalidomide in the Treatment of Ulcerative Colitis: Network Pharmacology and Experimental
Validation
Volume: 29
Issue: 34
Author(s): Jun Li, Qin Tao, Yang Xie, Peng Wang, Ruiri Jin, Xia Huang, Youxiang Chen*Chunyan Zeng*
Affiliation:
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang
330006, Jiangxi, China
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang
330006, Jiangxi, China
Keywords:
Thalidomide, ulcerative colitis, treatments, network pharmacology, molecular docking, PI3K/AKT signaling pathway.
Abstract:
Background: Ulcerative colitis (UC) is a chronic, nonspecific, inflammatory disease of the intestine
with an unknown cause. Thalidomide (THA) has been shown to be an effective drug for the treatment of UC.
However, the molecular targets and mechanism of action of THA for the treatment of UC are not yet clear.
Objectives: Combining network pharmacology with in vitro experiments, this study aimed to investigate the
potential targets and molecular mechanisms of THA for the treatment of UC.
Methods: Firstly, relevant targets of THA against UC were obtained from public databases. Then, the top 10
hub targets and key molecular mechanisms of THA for UC were screened based on the network pharmacology
approach and bioinformatics method. Finally, an in vitro cellular inflammation model was constructed using
lipopolysaccharide (LPS) induced intestinal epithelial cells (NCM460) to validate the top 10 hub targets and
key signaling pathways.
Results: A total of 121 relevant targets of THA against UC were obtained, of which the top 10 hub targets
were SRC, LCK, MAPK1, HSP90AA1, EGFR, HRAS, JAK2, RAC1, STAT1, and MAP2K1. The PI3K-Akt
pathway was significantly associated with THA treatment of UC. In vitro experiments revealed that THA treatment
reversed the expression of HSP90AA1, EGFR, STAT1, and JAK2 differential genes. THA was able to
up- regulate the mRNA expression of pro-inflammatory factor IL-10 and decrease the mRNA levels of anti-inflammatory
factors IL-6, IL-1β, and TNF-α. Furthermore, THA also exerted anti-inflammatory effects by inhibiting
the activation of the PI3K/Akt pathway.
Conclusion: THA may play a therapeutic role in UC by inhibiting the PI3K-Akt pathway. HSP90AA1,
EGFR, STAT1, and JAK2 may be the most relevant potential therapeutic targets for THA in the treatment of
UC.
