Utilizing Network Pharmacology and Molecular Docking Integrated Surface Plasmon Resonance Technology to Investigate the Potential Targets and Mechanisms of Tripterygium wilfordii against Pulmonary Artery Hypertension

Abstract

Background. Pulmonary artery hypertension (PAH) is a rare, life-limiting cardiopulmonary disorder characterized by the progressive and remodeling of pulmonary vasculature. Although the development of the technology brings us many approaches for the treatment of PAH, the effect of treatment is unsatisfactory. Tripterygium wilfordii (TW), as a traditional Chinese medicine (TCM), has been widely used in anti-inflammation, anticancer, and other fields. However, the potential of TW in treating PAH is currently unclear. Methods. Active ingredients and their corresponding genes were harvested from the Traditional Chinese Medicine Database and Analysis Platform (TCMSP), CTD, and STITCH. Meanwhile, genes associated with PAH were adopted from OMIM and GeneCards databases. Through Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analyses, potential targeting KEGG pathways and functions were further collected. Then, STRING was used to generate the protein-protein interaction (PPI) network. The “ingredients-targets-pathway” network was built by Cystoscope. Finally, the binding between active ingredients of TW and corresponding targets of PAH was identified via molecular docking technology and surface plasmon resonance (SPR) experiments. Results. The network pharmacology analysis revealed 36 active ingredients in TW and 150 potential targets related to the treatment of PAH with TW. Moreover, GO enrichment analysis showed that the key function in molecular function (MF) was related to enzyme binding, the key function in biological process (BP) was related to cellular response to organic substance, and the key function in cellular component (CC) was related to KEGG enrichment analysis and found that it was closely related to the IL-17 signaling pathway, TNF signaling pathway, Toll-like receptor signaling pathway, and apoptosis. At last, molecular docking results revealed that the main active ingredients of TW had a strong binding ability with the PAH target protein. In addition, the SPR experiment revealed that kaempferol was combined with the CASP3 protein rather than PARP1, while triptolide was combined with PARP1 rather than the CASP3 protein. Conclusion. TW may have therapeutic effects on PAH through multitargets and multimethods, which provide a scientific basis for further elaborating the mechanism of Tripterygium wilfordii in the treatment of PAH.

Mechanisms of cordycepin in the treatment of pulmonary arterial hypertension in rats based on metabonomics and transcriptomics

“…Additionally, molecular docking studies have demonstrated that Cordycepin can effectively bind to P53 and P21 proteins, supporting its potential mechanism of action in treating PAH (Fig. 11) 37 .…”

Expression Profiles of circRNAs and Identification of hsa_circ_0007608 and hsa_circ_0064656 as Potential Biomarkers for COPD-PH Patients

“…[15][16][17] Likewise, researchers have tried to apply bioinformatics analysis in the study of PH to elucidate the potential functions of circRNAs related to PH, mostly based on databases and animal experiments. [18][19][20][21][22][23][24][25][26][27][28] However, few studies have utilized clinical samples diagnosed by RHC, and researches for COPD-PH are even fewer. To the best of our knowledge, the present study is the first to profile circRNA expression of lung tissues from COPD patients with mean pulmonary artery pressure (mPAP)≥20 mmHg measured by right heart catheterization (RHC).…”