In Silico Interaction of the Active Compounds of Scurrula Atropurpurea with the RANK/RANKL/OPG System in Diabetoporosis

Abstract

Introduction: Diabetoporosis is a very complex health problem in Indonesia. One approach to the problem is through native Indonesian herbal medicine. The application of Scurrula atropurpurea in the treatment of diabetoporosis has not been revealed, so preliminary in silico study needs to be done. Aim: The purpose of the present study was to analyze the interaction between the active compound of Scurrula atropurpurea and the RANKL/RANK/OPG system in the pathomechanism of osteoporosis in diabetes mellitus. Methods: The procedures of the study included the search for the constituent amino acid of the RANK/RANKL/OPG system, the search for the structure of the active component of Scurrula atropurpurea , 3D modeling of protein structure, protein-ligand docking and visualization, and analysis of protein-ligand bonding interactions. Results: Those bond energies were RANKL-aviculin (–274.96 kJ/mol), RANKL-rutin (–263.12 kJ/mol), RANKL-quercitrin (–256.98 kJ/mol), RANKL-quercetin (–226,50 kJ/mol), RANKL-kaempferol (–221,65 kJ/mol), RANKL-catechin (–214,85 kJ/mol), RANKL-epicatechin (–211.66 kJ/mol), RANKL-caffeine (-171.73 kJ/mol), and RANKL-theobromine (-161.14 kJ/mol). The bond energies were RANK-rutin (-719.26 kJ/mol), RANK-catechin (-680.15 kJ/mol), RANK-caffeine (-654.48 kJ/mol), RANK-theobromine (-651.77 kJ/mol), RANK-quercitrin (-650.68 kJ/mol), RANK-kaempferol (-643.03 kJ/mol), RANK-epicatechin (-641.86 kJ/mol), RANK-quercetin (-641.76 kJ/mol), and RANK-aviculin (-628.62 kJ/mol). Those bond energies were OPG-epicatechin (-590.09 kJ/mol), OPG-theobromine (-578.08 kJ/mol), OPG-caffeine (-568.88 kJ/mol), RANKL-catechin (-560.63 kJ/mol), OPG-quercitrin (-554.50 kJ/mol), OPG-rutin (-547.91 kJ/mol), OPG-quercetin (-545.75 kJ/mol), OPG-kaempferol (-544.48 kJ/mol), and OPG-aviculin (-539.15 kJ/mol). Conclusion: The nine active ingredients of Scurrula atropurpurea do not interfere with the physiological function of RANKL to interact with RANK. The initial interaction of RANK with catechin or rutin will facilitate the bond of RANK to RANKL. When forming a complex with OPG, epicatechin will facilitate its interaction with RANKL.

Antiosteoporosis Studies of 20 Medicine Food Homology Plants Containing Quercetin, Rutin, and Kaempferol: TCM Characteristics, In Vivo and In Vitro Activities, Potential Mechanisms, and Food Functions

“…On the other hand, the research in silico interaction of rutin with the RANK/RANKL system in diabetoporosis showed that the initial interaction of RANK with rutin will facilitate the bond of RANK to RANKL. This is in contrast to previous findings that rutin decreases the activity of RANKL [ 99 ].…”