Evaluation of Withania coagulans-Mediated Titanium Oxide Nanoparticles as Potential Anti-ECC Agents Against Matrix Metalloproteinases MMP-8 and MMP 9 - An In Silico Study

Abstract

Background: Dental caries progression involves degradation of the dentinal collagen matrix mediated by matrix metalloproteinases (MMPs), particularly MMP-8 and MMP-9. Natural phytochemicals with MMP inhibitory potential may provide novel host-modulating strategies for caries prevention. Aim: To evaluate the anti-caries potential of major Withania coagulans phytoconstituents against MMP-8 and MMP-9 through molecular docking and ADMET analysis. Materials and Methods: Four phytochemicals, namely Withanone (CID: 21679027), Withanolide A (CID: 11294368), Withanolide B (CID: 14236711), and Withaferin A (CID: 265237), were retrieved from the PubChem database. Crystal structures of MMP-8 (PDB ID: 1BZS) and MMP-9 (PDB ID: 1GKC) were obtained from the Protein Data Bank. Molecular docking was performed using AutoDock Vina in PyRx, and protein–ligand interactions were analyzed using Discovery Studio Visualizer. Drug-likeness and pharmacokinetic properties were assessed using SwissADME Results: All compounds demonstrated favorable binding affinities toward MMP-8 and MMP-9. Withanolide B exhibited the strongest interaction with MMP-8 (−8.8 kcal/mol), while Withaferin A showed the highest affinity toward MMP-9 (−8.2 kcal/mol). Multiple hydrogen bonds, hydrophobic interactions, and catalytic-site interactions contributed to stable protein–ligand complexes. SwissADME analysis revealed high gastrointestinal absorption, compliance with Lipinski’s Rule of Five, and favorable bioavailability profiles for all compounds. Conclusion: Withania coagulans phytoconstituents demonstrated promising inhibitory potential against MMP-8 and MMP-9 and may serve as novel host-modulating anti-caries agents. Further experimental and clinical validation is required to confirm their therapeutic efficacy....