Potential of fenugreek (Trigonella foenum-graecum L.) metabolites as dental residual ridge resorption inhibitors through estrogen receptor signaling: In silico study

Abstract

Context: Edentulism is a global health burden with long-life disabilities. Dental implant procedures are frequently constrained to alveolar residual ridge resorption. The resorption is strongly correlated with an imbalance of osteoblast-osteoclast activities. Estrogen well established maintain bone homeostasis. Fenugreek (Trigonella foenum-graecum L.) is a promising drug candidate to promote estrogenic activity and resist residual ridge resorption. Aims: To evaluate the drug-likeness, pharmacokinetic, toxicity as well as molecular interaction prediction between T. foenum-graecum metabolite compounds and estrogen receptor-α (ESRα)/estrogen receptor-ß (ESRß). Methods: The drug-likeness was evaluated using Lipinski's rule of five. A web server (PkCSM) was used to predict the pharmacokinetics and toxicity. The metabolites were retrieved from the Kanaya database. The biological activity prediction was performed using PASS Online. The ligands’ structures were downloaded from PubChem National Centre for Biotechnology Information database. Proteins were obtained from Protein Data Bank. Molecular docking prediction was carried out using PyRx software and visualized using Discovery Studio Software. Results: Quercetin, naringenin, luteolin, and kaempferol displayed the highest biological activity of estrogen agonist, anti-inflammatory, and tumor necrosis factor (TNF) expression inhibitor. Four metabolites exhibited the potential to be developed as oral drugs with good absorption in gastrointestinal, moderate tissue distribution, and safe for liver tissue. Quercetin and kaempferol showed the most negative value of binding affinity. Quercetin formed three hydrogen bonds and eight hydrophobic bonds with ESRα. Luteolin had three hydrogen bonds and five hydrophobic bonds on ESRβ. Conclusions: Metabolites present in T. foenum-graecum, like quercetin, naringenin, luteolin, and kaempferol, were potential drug candidates that could act as estrogen agonists to inhibit the dental residual ridge resorption.