Curcumin targets Enterococcus faecalis virulence by inhibiting the enterococcal surface protein, offering a potential treatment for endodontic diseases

Nezar Boreak, Abdullah S Almuqbil, Wejdan Hakami, Saad Alshahrani, Aisha Alshehri, Aishah Haqawi, Noha Kh Mokli, Dimah Salem Saleh, Nardeen Hakami, Lamis Muthaffar, Alhussain Ahmad Thubab

Abstract


Background: The present study explores the inhibitory effect of curcumin on the Enterococcal Surface Protein (ESP) of Enterococcus faecalis (E. faecalis), a key pathogen in endodontic and post-endodontic diseases.

Methods: The 3D structure of ESP was modeled using SWISS-MODEL, and structural cavities were identified via CB-Dock2. Molecular docking was performed with DockingServer. ADMET properties were predicted using pkCSM, while curcumin’s biological activity and potential macromolecular targets were assessed using PASS Online and SwissTargetPrediction, respectively. Cytotoxicity of curcumin on HEK293 cells was evaluated by MTT assay.

Results: Curcumin demonstrated good binding affinity (-11.06 kcal/mol) with ESP, supported by HBPlot analysis and SeamDock validation (-10.5 kcal/mol). Curcumin's deep binding within ESP's cavity suggests its potential to disrupt E. faecalis colonization and biofilm formation, offering a novel therapeutic strategy. ADMET predictions revealed favourable pharmacokinetic properties, including high intestinal absorption (82.19%) and no hepatotoxicity, positioning curcumin as a safe and effective candidate. PASS analysis highlighted curcumin's diverse biological activities, such as antioxidant, anti-inflammatory, and enzyme inhibitory effects, aligning with its therapeutic potential. SwissTargetPrediction further identified potential protein targets, including transcription factors and kinases, broadening its applicability. Concentration- and time-dependent assays confirmed curcumin's non-toxic nature toward normal HEK293 cells, highlighting its safety profile.

Conclusion: In conclusion, these findings collectively demonstrate curcumin's potential as a therapeutic agent for endodontic diseases, leveraging its ability to target E. faecalis virulence while addressing inflammation and oxidative stress.

 

Keywords: Biofilm formation; Curcumin; Enterococcus faecalis; Endodontic diseases; Molecular docking; Post-endodontic diseases


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DOI: http://dx.doi.org/10.62940/als.v12i4.3808

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