Molecular Docking Investigation of Dioscorea alata Compounds Binding to CCKBR, CHRM3, CHRM5, and H2R for Gastric Ulcer Treatment

Abstract

Gastric ulcer is a pathological condition characterized by damage to the mucosal and submucosal tissue layers of the stomach. The main proteins targeted in the treatment of gastric ulcers are CCKBR, CHRM3, CHRM5, and H2R because of their roles in the regulation of gastric acid secretion. Dioscorea alata (DA) is known to contain various active compounds with high sapogenin, diosgenin, and dioscorin content, in addition to its carbohydrate content. We investigated the potential of DA compounds to bind to these proteins in silico. Compound and protein structures were retrieved from PubChem (https://pubchem.ncbi.nlm.nih.gov), ChemSpider (http://www.chemspider.com), and the RCSB PDB (https://rcsb.org). Proteins and compounds are prepared first, and then docked to obtain the interactions that might form, and finally visualized to observe the interactions that have been constructed. The results showed that diosgenin and prosapogenin have potential as inhibitors of CCKBR and CHRM5, and diosgenin and dimethyl batatasin IV have potential as inhibitors of CHRM3 and H2R. We conclude that diosgenin, prosapogenin, and dimethyl batatasin IV in DA compounds have the potential to inhibit CCKBR, CHRM3, CHRM5, and H2R for gastric ulcer treatment. It is necessary to further study the effect of Dioscorea alata in vitro through a gastric ulcer model study. HIGHLIGHTS Dioscorea alata (DA) is known to contain various active compounds with high sapogenin, diosgenin, and dioscorin content in addition to its carbohydrate content Gastritis (gastric ulcer) is a pathological condition characterized by damage to the mucosal and sub-mucosal tissue layers of the stomach. The main proteins targeted in the treatment of gastric ulcers are CCKBR, CHRM3, CHRM5, and H2R because of their roles in the regulation of gastric acid secretion We performed an in-silico study to investigate the potential of DA compounds to inhibit these proteins. Compound and protein structures were retrieved from PubChem, ChemSpider, and the RCSB PDB. Proteins were prepared with Swiss PDB viewer v. 4.10. Compounds were prepared with Open Babel in Cytoscape v.3.9.1. Docking was done with AutoDock Vina in PyRx v.0.9.7. Visualization was done with Discovery Studio v. 19.1 We determined that several DA compounds have the potential to act as inhibitors of CCKBR, CHRM3, CHRM5, and H2R by reviewing the predicted binding energy, competitive properties based on literature studies and the bioactivity and molecular docking analysis. The results of this study are expected to be the basis for further gastric ulcer treatment research GRAPHICAL ABSTRACT