fa عمومى General پژوهشي Research <div class="rounded" style="background: rgb(238, 238, 238); border: 1px solid rgb(204, 204, 204); padding: 5px 10px; text-align: justify;"><span style="line-height:2;"><span style="font-family:Times New Roman;"><span style="font-size:14px;"><span style="color:#2980b9;"><b>Background and Objective</b>:</span> Periodontitis is a major chronic inflammatory disease of the oral tissues, which is driven by a complex interplay between dysbiotic plaque biofilms and the host immune response. Receptor activator of nuclear factor-&kappa;B ligand (RANKL) plays a significant role in the RANK/RANKL/osteoprotegerin pathway, leading to bone resorption and periodontitis. Therefore, RANKL is a promising therapeutic target for the treatment and prevention of periodontitis. This study aimed to evaluate the potential of a series of cinnamic acids to inhibit the RANKL functional inhibitory residues (FIR).<br> <span style="color:#2980b9;"><b>Methods</b>:</span> Molecular docking analysis was conducted using AutoDock 4.0 to estimate the binding affinities of ten cinnamic acids to the RANKL FIR (PDB: 3URF). The specific binding modes and molecular interactions were subsequently analyzed and visualized using Discovery Studio Visualizer.<br> <span style="color:#2980b9;"><b>Results</b>:</span> Three cinnamic acids showed strong binding affinities, namely cynarin, chlorogenic acid (CGA), and rosmarinic acid, with binding free energy values (&Delta;Gbinding) below -10 kcal/mol. The most potent inhibitor among these compounds was identified as cynarin, with an inhibition constant in the picomolar range (ki=9.53 pM). The most extensive hydrogen bonding was observed with cynarin, as indicated by interaction profiling, with five H-bonds formed.<br> <span style="color:#2980b9;"><b>Conclusion</b>: </span>The findings suggest cynarin, CGA, and rosmarinic acid as promising natural compounds for RANKL inhibition. Therefore, these compounds are positioned as potential candidates for novel therapeutic strategies aimed at preventing periodontitis progression.</span></span></span></div> Bone resorption, Cinnamica acid, Drug, Inhibitor, Periodontitis, Receptor activator of nuclear factor-κB ligand (RANKL) 0 0 http://ajpr1.umsha.ac.ir/browse.php?a_code=A-10-2-7&slc_lang=fa&sid=1 Parzhin Moradi 100319475328460038 100319475328460038 No Department of Orthodontics, School of Dentistry, Hamadan University of Medical Sciences, Hamadan, Iran Mahnaz Rezaei 100319475328460039 100319475328460039 No Department of Orthodontics, School of Dentistry, Hamadan University of Medical Sciences, Hamadan, Iran Amir Taherkhani 100319475328460040 100319475328460040 Yes Research Center for Molecular Medicine, Institute of Cancer, Hamadan University of Medical Sciences, Hamadan, Iran Fatemeh Ghaemi Panahian 100319475328460041 100319475328460041 No Department of Restorative Dentistry, School of Dentistry, Dental Research Center, Hamadan University of Medical Sciences, Hamadan, Iran Shiva Shayesteh 100319475328460042 100319475328460042 No Department of Periodontics, School of Dentistry, Hamadan University of Medical Sciences, Hamadan, Iran