Integrating In-silico with In-vitro Studies of Rutin as an Anti Hypertensive

Abstract

Rutin was evaluated for its antihypertensive effect by In vitro ACE inhibitory activity using Captopril as standard. For molecular docking the proteins namely PDB ID: 1UZE, 1O86, 2XY9 and 3L3N are selected and modelled. The abilities of the 3D model were assessed via the PROCHECK database and considered with the Ramachandran plot. The G-score of rutin was found to be more than the glide score of standard drug captopril affirming that the compound had similar affinity to impasse to the proteins. Proteins with PDB ID 1UZE, 1O86, 2XY9, and 3L3N showed more than 90% favoured area which evidently specifies that the designated protein in the current research is of noble eminence. ADME (Absorption, Distribution, Metabolism and Excretion outcome shown the three violations of rutin out of the five and the Captopril has got zero violations which noticeably shown the possibility for its greater oral bioavailability. The results of bioactive score revealed that rutin and captopril showed moderately active against GPCR ligand, ion channel modulator, kinase inhibitor and nuclear receptor but both rutin and the standard captopril were found to be highly dynamic counter to protease inhibitor and enzyme inhibitor. The PASS results clearly stated that rutin and captopril as cardio protectant, vasoprotector, vasodilator, antihypertensive. Rutin was predicted with hepatoxicity and nephrotoxicity while captopril was predicted with myocardial infarction, hepatotoxicity and nephrotoxicity. The direct targets of rutin have interventions with Cytochrome P4503A, Carbonic anhydrase II, Sodium /glucose cotransporter/2 and TNF-alpha for direct targets. The possible targets were with vascular endothelial growth factor receptor 1, and Sodium /glucose cotransporter/2. In vitro ACE inhibition assay demonstrated that rutin has shown antihypertensive activity by inhibiting angiotensin converting enzyme. From the above results the mechanism of action of rutin was validated through in silico interactions with the suitable PDB’s from MCULE software.