This study aimed to screen the bioactive components of TWH and elucidate the targets that contribute to its therapeutic effect, thereby further explaining its mechanism of action in CD treatment by network pharmacology. Compared with experimental pharmacology methods, network pharmacology emphasizes multi-channel regulation of signaling pathways, therefore especially suitable for the explanation of the mechanism of traditional Chinese medicine (TCM) with multiple chemical components and molecular targets. Network pharmacology is an approach to drug design that encompasses systems biology, network analysis, connectivity, redundancy and pleiotropy. In recent years, clinical studies have found that TWH can effectively induce CD remission and maintain remission, however, the specific mechanism of TWH in CD treatment is poorly understood. As early as in Li Shizhen’s book “Compendium of Materia Medical” of the sixteenth century, there are records that TWH can anti-rheumatism, promote blood circulation, reduce swelling, and relieve pain. It contains a variety of chemical components such as alkaloids, diterpenoids, triterpenoids and sesquiterpenes. Tripterygium wilfordii Hook (TWH) is a woody vine of the genus Tripterygium. And as an important part of complementary and alternative medicines, traditional Chinses medicine have been widely reported to treat inflammatory bowel disease. Recent studies have revealed that patients in North America and Europe using complementary and alternative medicines as a strategy has risen from 21 to 60%. It is urgent to develop more effective therapeutic strategies for affected patients.
Yet the cause of CD is still unknown, and the use of drugs currently cannot completely control or relieve the symptoms. However, the number of people with CD has been steadily increasing, particularly in Eastern countries where some districts are undergoing fast urbanization. For instance, CD’s prevalence is greater in developed regions than in developing areas. The incidence of CD varies based on geographic region, ethnic groups and environment. Meanwhile, abdominal pain, diarrhea, anemia, fever, and weight loss also consist of the common symptoms of active CD. The entire layer of the intestinal wall can be affected, which can easily lead to complications such as intestinal obstruction, intestinal perforation, and an intestinal fistula. It is typically characterized by transmural inflammation of the intestine and could affect any part of the gastrointestinal tract from mouth to anus. TWH can play a multi-target and multi-channel synergistic treatment of CD by anti-angiogenesis, anti-apoptosis, anti-inflammation and immune regulation.Ĭrohn’s disease (CD) is a chronic inflammatory bowel disease with multi-factors that genetics and environment interact to manifest the disease. Network analysis indicated that main targets of main active components of TWH were target genes such as VEGFA, MAPK8 and CASP3, which are involved in the regulation of cancer pathway, TNF signal pathway, hepatitis B pathway, apoptosis pathway, NF-kappa B signal pathway and so forth. The database results showed that there were 30 active ingredients (14 key active ingredients) in TWH and 36 targets were screened out for CD treatment. The DAVID 6.8 online tool was used to perform gene ontology (GO) and kyoto encyclopedia of genes and genome (KEGG) pathway enrichment analysis of overlapping targets.
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The Cytoscape 3.7.1 software was used to construct a Chinese medicine compound-target network and STRING database to construct a protein-protein interaction network (PPI).
“Crohn’s disease” was used as a search term to search for related targets of CD from GeneCards database and OMIM database, thereby obtaining the targets of TWH against CD. Traditional Chinese Medicine Systems Pharmacology database and analysis platform (TCMSP) was used to obtain the active constituents and targets of TWH. To explore the mechanism of action of Tripterygium wilfordii Hook (TWH) in the treatment of Crohn’s disease (CD) by network pharmacology.
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