Própolis orgânica brasileira na prevenção e tratamento da mucosite oral: estudo in silico de biomoléculas desta própolis com alvos da mucosite oral.

Abstract

Oral mucositis (OM) is an exacerbated mucosal inflammatory process resulting from antineoplastic therapy (e.g. radiotherapy and/or chemotherapy). OM causes ulcerative lesions, erythema, and severe pain, which can affect speech, diet, efficacy, and duration of treatment, prolong hospitalization, decrease quality of life and increase mortality. The mechanism which OM develops is still unclear, so far, it is proposed that there are at least 14 pathways involved in the pathogenesis related to this condition, with the release of reactive oxygen species (ROS). This lack of knowledge and information regarding specific cytokines and chemokines related to this process makes it difficult to develop preventive or therapeutic approaches to OM. Natural products, such as propolis, have been investigated as possible sources of biomolecules for OM attenuation. Propolis is a resinous substance collected from several plants by bees that have antimicrobial, anti- inflammatory, radioprotective, anticancer, antinociceptive potential, among others. Propolis can modulate non-specific immunity, interfering with the production of some pro-inflammatory cytokines and neutralizing the production of ROS. Brazilian organic propolis, especially type 1 (PO1), has a high antioxidant activity and can be an alternative in the treatment of OM. Therefore, the study aims to identify the molecular targets involved in the pathogenesis of OM interacting them with active molecules identified and isolated from PO1, through an in silico study of molecular docking, and assess the bioavailability of the molecules identified in PO1 by Lipinski's 'rule of 5' and gastrointestinal absorption through the SwissADME website. For the study of molecular docking, chemical and structural information of selected OM pathogenesis related targets and molecules identified in PO1 (ligands) were collected, which were selected in the Protein Data Bank (PDB) and PubChem database, respectively. This study adopted two methodological strategies: I- 1-ligand docking and II- Multiple-ligand docking. The AutoDock Vina ® and MGLTools ® software were used to identify and select the most promising binding sites; and the Maestro  software for identifying the most promising binding sites and identifying the residues where interactions between targets and ligands occurred. In strategy I, all seven ligands interacted with all eight targets with binding energy ranging from -1.9 to -8.7 kcal.mol -1 . In strategy II, we observed potential combined activity of all 6 evaluated ligands for all 8 targets, the ligands showed better activity with TNF-a in general. We also observed that the residues from the targets where the ligands interacted were constituents of protease enzymes. We conclude that all ligands identified in PO1 and analyzed in this study promising interacted with all targets, suggesting a possible anti-inflammatory, multi-target, and protease inhibitory activity, and these ligands are suitable molecules for in vitro studies and in vivo.