Integrating <i>In Vivo</i> Model, Molecular Docking and Network Pharmacology to Determine the Mechanism of <i>Theobroma cacao</i> Seed in Treatment of Diarrheal

Abstract

<i>Theobroma cacao</i> is an economically important tropical-fruit tree where chocolate is obtained, and it is used as traditional medicine worldwide against several diseases. In the present study, <i>in vivo</i> model and computational biology approaches were used to elucidate the potential mechanisms of <i>T. cacao</i> in the treatment of diarrhea. The antidiarrheal and intestinal motility activity was conducted using an animal model induced diarrhea with MgSO4. In addition, an OECD acute oral toxicity test was carried out. Prediction analysis of the bioactive effects of <i>T. cacao</i> against diarrhea symptoms were carried out applying functional enrichment analysis, protein-protein interaction, ADME and drug-likeness analysis, and molecular docking. The analysis of the compound-target- pathway-antidiarrheal mechanism relationships was performed in Cytoscape. <i>T. cacao</i> (200 mg/kg) effectively inhibited diarrhea in mice, significantly lowering the diarrheal stools and intestinal motility, without toxicity signs. Gene set enrichment, molecular docking, and network pharmacology revealed 13 <i>T. cacao</i> compounds targeting 12 proteins that regulate 11 signaling pathways related to diarrhea. According to our research results, the <i>T. cacao</i> antidiarrheal effect could be due to the therapeutic action of quercetin, luteolin, and deoxyclovamide compounds on the ABCB1, ABCG2, CYP3A4, EGFR, ERBB2, IL6, SI, and SLC10A2 genes, related to Carbohydrate digestion and absorption, Bladder cancer, Bile secretion and Graft-versus-host disease as the most significant signaling pathways.