Expanding the Knowledge of the Molecular Effects and Therapeutic Potential of Incomptine A for the Treatment of Non-Hodgkin Lymphoma: In Vivo and Bioinformatics Studies, Part III

<b>Background/Objectives</b>: Non-Hodgkin lymphoma (NHL) is a group of blood cancers that arise in the lymphatic nodes and other tissues after an injury to the DNA of B/T lineage and NK lymphocytes. Recently, we reported that incomptine A (<b>IA</b>) has in vivo antilymphoma properties. This research aimed to evaluate the effects of <b>IA</b> in the treatment of NHL using antilymphoma activity, Tandem Mass Tag (TMT), and bioinformatics approaches. <b>Methods</b>: The antilymphoma activity of <b>IA</b> was tested on male Balb/c mice inoculated with U-937 cells. Also, TMT, gene ontology enrichment, Reactome pathway, Kyoto Encyclopedia of Gene and Genomes pathway, molecular docking, toxicoinformatic, and pharmaceutical analyses were performed. <b>Results</b>: By TMT analysis of the altered levels of proteins present in the lymph nodes of Balb/c mice with NHL and treated with <b>IA</b>, we identified 106 significantly differentially expressed proteins (DEPs), including Il1rap, Ifi44, Timd4, Apoa4, and Fabp3 as well as Myh3, Eno 2, and H4c11. Among these, the Fhl1 result was the most important cluster altered and a potential core target of <b>IA</b> for the treatment of NHL. Network pharmacology studies have revealed that DEPs are associated with processes such as muscle contraction, glycolysis, hemostasis, epigenetic regulation of gene expression, transport of small molecules, neutrophil extracellular trap formation, adrenergic signaling in cardiomyocytes, systemic lupus erythematosus, alcoholism, and platelet activation, signaling, and aggregation. Computational studies revealed strong binding affinities with six proteins associated with cancer, positive pharmacokinetic properties, and no toxicity. <b>Conclusions</b>: Our contribution suggests that <b>IA</b> may be a compound with potential therapeutic effects against NHL.