Exploring the mechanism of Tripterygium wilfordii against cancer using network pharmacology and molecular docking

Abstract

Background: The root of Tripterygium wilfordii (Tripterygii radix), a natural powerful traditional Chinese medicine (TCM) for various diseases treatment, has been used for centuries in the Asian countries as anti-rheumatoid arthritis (RA) agent, antioxidant agent, and anti-inflammatory agent. Its combination with other herbs in treating RA has been explored. The anti-RA effect of T. wilfordii for cancer treatment has been supported by some evidence. Aims and Objectives: To investigate the anticancer mechanism of T. wilfordii, bioinformatics databases were used to identify its active ingredients. Materials and Methods: Target proteins associated with cancer were determined using a network pharmacology analysis platform, and 25 key active compounds and 55 key targets of T. wilfordii were identified in our study. A common potential mechanism of T. wilfordii involvement in cancer was disclosed by in-depth network analysis of diseases, functions, and pathways. Finally, the analysis results of the TCM-disease target protein interaction network revealed 5 potential targets; subsequently, a total of 30 targets (these 5 targets, as well as 25 previously identified compounds) were subjected to molecular docking. Results: Our results showed that the therapeutic effect of T. wilfordii in cancer is characterized by multiple components, targets, and pathways. The regulation of signaling pathways such as Kaposi sarcoma-associated herpes virus infection, colorectal cancer, small-cell lung cancer, and prostate cancer may be the important pharmacodynamic basis of anticancer therapy. Conclusion: Triptonoditerpenic acid inhibited proliferation and induced apoptosis in SW480 cells. The mechanism may be related to the downregulation of Bcl-2 expression, upregulation of Bax mRNA expression, and expression inhibition of PTGS2.