Natural Compounds AS D2 Receptor Agonist, M4 Receptor Antagonist and ACHE Modulator: Mechanistic and in Silico Modelling Studies
Catalepsy is a behavioural phenomenon where the rodent is not able to change an externally imposed posture, and antipsychotic-induced catalepsy is a rodent model for the motoric side effects often seen when using antipsychotic medication. The present study is focused on the evaluation of methonolic extract of Tagetus patula as anti-catalepsy against haloperidol (1.0 mg/kg, i.p) and Reserpine (5 mg/kg, i.p,) induced catalepsy in mice using levodopa as standard. The biochemical parameters like reduced glutathione (GSH) and catalase were estimated in mice brain in reserpine induced catalepsy. The extract was screened against lipid peroxidation assay and DPPH radical scavenging assay using ascorbic acid as standard. The cataleptic score in haloperidol and reserpine treated groups were found to be higher. But in groups treated with the METP and standard drug (levodopa 25 mg/kg, i.p) the cataleptic score was found to be reduced in both the models. Upon treatment with extract at 200 mg/kg. bd. wt, 400 mg/kg. bd. wt. & levodopa 25 mg/kg, i.p, significant improvement in GSH and catalase levels were observed. The results clearly showed the ability of the extract to scavenge the free radicals in both the assays. In the present study docking studies were performed for natural compounds present in the extract such as Patuletin, Quercetin, δ-elemene, Tagetenone, β-Ocimene, Piperitenone, Tagetone, Limonene, β-ionone, β-caryophyllene and standard drug Levodopa against PDB ID: 3INJ, PDB ID: 1DSG, PDB ID: 6EP4 using schrodinger software. The statistical verification of the model was evaluated with PROCHEK; a structure verification program relies on Ramachandran plot which determines the quality of the predicted structures. The results revealed that Patuletin, Quercetin, Piperitenone, Limonene and δ-elemene had shown highest glide scores which indicates a stronger receptor-ligand binding affinity among the various phytochemical constituents present in the extract. According to Ramachandran plot a good model would be expected to have over 90% in most favoured regions. In our study all the selected protein models have more than 90% favored regions clearly indicating that the selected models are of good quality. From the above it is concluded that the extract possesses anti-cataleptic and anti-oxidant activity.