Molecular Mechanisms of Persicaria hydropiper (L.) Delarbre against Trypanosoma brucei

Background:: Persicaria hydropiper (L.) Delarbre (P. hydropiper) has long been used for the treatment of parasitic diseases by the Chinese ethnic minority “Tujia” people residing in the mountainous area of southwestern China. Objectives:: Our previous experiments have demonstrated remarkable pharmacological effects of P. hydropiper against Trypanosoma brucei (T. brucei). The present study aimed to investigate the molecular mechanisms underlying the anti-trypanosomiasis activity of P. hydropiper Methods:: Thirty-nine common targets of P. hydropiper and trypanosomiasis were obtained from the databases, and these common targets were uploaded to the STRING database to obtain a protein- protein interaction network diagram. Then, the hub genes of these common targets were screened using the CytoHubba. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted by the Metascape. Subsequently, the LeDock was used for molecular docking verification between the hub gene, antitrypanosomiasis targets, and P. hydropiper. Finally, the most effective compound in P. hydropiper revealed by the docking results was used for the verification of the antitrypanosomiasis ability by western blotting analyses. Results:: Enrichment analysis indicated that the anti-trypanosomiasis of P. hydropiper was more frequently involved in mediating inflammation, probably by targeting interleukin-6 (IL-6), tumor necrosis factor (TNF), interleukin-10 (IL-10), and matrix metalloprotein-9 (MMP-9). Molecular docking demonstrated that the bioactive compound quercitrin in P. hydropiper exhibited the most stable binding mode with the trypanosomiasis target, and the compound previously confirmed to inhibit T. brucei, vanicoside F, exhibited the highest stability with ornithine decarboxylase (ODC) and cysteine protease (CYP). The western blotting results showed that quercitrin significantly suppressed lipopolysaccharide (LPS)-induced inflammation (mimicking T. brucei infection) and decreased expression of IL-10. Conclusion:: Our study demonstrated that P. hydropiper acts on T. brucei via the characteristics of multiple targets and pathways with several components through network pharmacology and is thus a potential candidate to be developed as a novel anti-trypanosomiasis drug.