Exploration of the potential mechanisms of compounds from Rheum palmatum L．against Chronic Obstructive Pulmonary Disease: a network pharmacology study

Background: Rheum palmatum L． (RpL) is a traditional Chinese medicine commonly used in clinical. However, there was no systematic research to elucidate the mechanisms of RpL acting on COPD.

Objective: To explore the potential mechanisms against COPD based on network pharmacology.

Method: The active compounds of RpL were retrieved from TCMSP database, and their corresponding targets were obtained through TCMSP and STITCH databases. COPD-related targets were identified from the TTD, GeneCards and MalaCards database. Drug-disease genes were obtained through intersection analysis, and the correlation between these genes and COPD was analyzed. After that, a protein-protein interaction network was constructed and enrichment analysis was performed. Then, key targets were obtained according to the network topology attributes analysis. Finally, the Auto dock vina 1.1.2 was used for molecular docking to verify the binding ability between the active compounds and key targets.

Results: There were 8 active compounds and 90 corresponding targets were identified in RpL. A total of 4502 COPDrelated targets were obtained from databases. After cross-analysis, 81 drug-disease targets were obtained. Drug-disease targets mainly regulated apoptosis and inflammatory responses and participated in related signal pathways. Besides, 28 key genes were obtained from the network topology analysis. TP53, TNF, NFKB1, VEGFA, MMP9, and MMP1 were selected to dock with the compounds. The results of molecular docking showed that the above targets have different affinities with the 8 active compounds of RpL.

Conclusion: The mechanisms of RpL acting on COPD were mainly related to the regulation of apoptosis, inflammatory response, and airway remodeling.

Keywords: Chronic Obstructive Pulmonary Disease; Rheum palmatum L．; molecular docking; network pharmacology.