In Silico Investigations on the Probable Macromolecular Drug Targets Involved in the Anti-Schizophrenia Activity of Terminalia bellerica

Background: Schizophrenia is a severe mental disorder that affects around 1% of the population worldwide. The available antipsychotics alleviate the positive symptoms of the illness. However, their effect on the negative and cognitive symptoms is limited. The fruit powder of Terminalia bellerica has been found to possess antipsychotic activity, which might be useful in treating the symptoms of schizophrenia. Objective: The present study was performed to evaluate the affinity of the active constituents of Terminalia bellerica towards macromolecular drug targets involved in the pathophysiology of schizophrenia and, thereby, determine the structural features of the ligands involved in the interactions with the proposed targets. Methods: A molecular docking study was carried out on ten active constituents of Terminalia bellerica with four-drug targets involved in the aetiology of schizophrenia. These targets are dopamine, N-methyl- D-aspartate, Gamma-aminobutyric acid, and phosphodiesterase 10A receptors. The binding interactions between the target proteins and the ligands with the highest affinities were studied thoroughly. Results: β-sitosterol, ellagic acid, and quercetin displayed high binding affinity toward all the macromolecular drug targets. Results: β-sitosterol, ellagic acid, and quercetin displayed high binding affinity toward all the macromolecular drug targets. β-sitosterol possesses a high binding affinity for the dopamine receptor, while quercetin has high binding affinities for both dopamine and N-methyl-D-aspartate receptor. On the other hand, ellagic acid formed stronger binding interactions with Gamma-aminobutyric acid and phosphodiesterase 10A. Conclusion: Terminalia bellerica can serve as a new anti-psychotic drug from natural sources with more promising development.