In Silico Comparison of Two Herbal Acetylcholinesterase Inhibitors with Tacrine by Docking Method

Background and Aim : Acetylcholinesterase (AchE) has been shown as the most important target to improve the Alzheimer’s disease (AD) symptoms due to the findings about cholinergic deficiency in AD. Accordingly, AchE inhibitors are the well-known strategy in treatment of AD. In this regard, usage of herbal based medications in treatment of AD has been started. Silybum marianum (L.) Gaertn is a familiar plant in traditional medicine, commonly for treatment of liver disorders. Silymarin is the main active component of this plant, and it may be useful in memory disorders as AD. Rosmarinic acid is one of the main polyphenolic substances, existing in rosemary and other culinary plants, with pharmacologic properties. Hence, in this study we intended to compare the AchE inhibitory effects of silymarin and rosmarinic acid with tacrine, the known cholinesterase inhibitor, by docking method.Methods : Protein structure of human AchE was picked from Protein Data Bank with PDB ID: 6O4W. As human AchE (PDB ID: 6O4W) had dimeric structure, the chain A was selected for docking process. The molecular structures of tacrine (CID: 1935), rosmarinic acid (CID: 5315615) and silymarin (CID: 7073228) were took from PubChem. Chimera 1.8 was used for protein editing and making the pdb files. Also, MGLTools 1.5.6, AutoDockTools-1.5.6 and AutoDock4 were applied to complete docking process.Results : The inhibition constants (Kis) of silymarin, rosmarinic acid and tacrine in interaction with AchE (chain A) were 213.74 pM, 710.91 pM and 741.85 nM, respectively.Conclusion : The docking results revealed that silymarin and rosmarinic acid presented much lower Kis than tacrine. Therefore, silymarin and rosmarinic acid seem to show higher affinity in interaction with human AchE in comparison with tacrine. Because tacrine is a potent inhibitor of AchE with potential of hepatotoxicity because of butyrylcholinesterase inhibitory effect, it seems that AchE inhibitory effect of silymarin and rosmarinic acid (in pico molar concentration) may be more effective than tacrine. Furthermore, there are experiments about effective inhibition of amyloid β-protein formation, one of the most significant lesions in pathogenesis of AD, by silymarin. Also, there is evidence on suppression of AD development by rosmarinic acid via reducing β-amyloid aggregation by increasing monoamine secretion. Amazingly, the in silico result of this study is in accordance with the other studies about good inhibitory effect of silymarin and rosmarinic acid on AchE and butyrylcholinesterase. Thus, the in silico evaluation of the inhibitory effects of silymarin and rosmarinic acid on AchE in comparison with tacrine might once more reveal the pharmacologic potential of these two herbal constituent in treatment of AD. Obviously, the evaluation of the affinity of silymarin and rosmarinic acid with butyrylcholinesterase is necessary to clarify the possible side effects.

کلیدواژه ها:

tacrine ، rosmarinic acid ، silymarin ، acetylcholinesterase ، docking