The aim of this study was to evaluate hypocholesterolemic potential of phytoconstituents of ethanolic seed extract of cumin (Cuminum cyminum L.) by assessments of interaction capabilities with 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMG-CoA) reductase through in vivo and in silico assessments along with screening of phytoconstituents of the test extract. The phytoconstituents of the test extract were identified by Gas chromatography-mass spectrometry (GC-MS)/MS examinations. The hypercholesterolemic rabbit animal model was used for in vivo study and further examined the lipid profile and atherogenic indices. The treatments of the test extract and standard drug (atorvastatin) caused significant reductions in dyslipidemia indices, that is, atherogenic index of plasma (AIP), Casteli Risk Index-I (CRI-I), CRI-II and atherogenic coefficient (AC). Accordingly, the molecular docking showed significant interactions between the cuminaldehyde and HMG-CoA reductase compared to the other phytoconstituents. Further, molecular dynamics (MD) validated the interaction capabilities through assessments of N-Substance, V-Volume, T-Temperature (NVT), N-Substance, P-Pressure, T-Temperature (NPT), Root Mean Score Deviation (RSMD), Root Mean Score Fluctuation (RSMF), radius of gyration, system density, and potential energy along with locality assessment of complex interactions evaluated by angle distribution, average angle interaction, free energy of solvation, and solvent accessible surface area (SASA). Subsequently, the absorption, distribution, metabolism, excretion and toxicity (ADMET) predictions revealed the druggability and bioavailability criteria of the leading identified compounds. On the basis of results obtained, it can be concluded that small phytochemical molecules of test extract of cumin (Cuminum cyminum L.) have capabilities to inhibit the HMG-CoA reductase and ameliorate the dyslipidemia indices.

Objective: The present study is related with the assessment of anti-atherosclerotic efficacy of 70% EtOH extract of cumin seed in diet-induced hyperlipidemic rabbits.Methods: Rabbits were rendered hyperlipidemic by oral administration of cholesterol for 15 days. Then, the animals were treated with 70% EtOH (ethanolic extract) of cumin seed extract for 45 days (Group III). Another set of animals was treated with atorvastatin, the standard drug for 45 days. At the end of experimental period, the serum biochemical, hematological, and histological analysis of thoracic aorta was done.Results: The cumin seed extract showed contain hypolipidemic effect by reducing plasma cholesterol, low-density lipoproteins, and triglycerides level. While toxicological studies suggest no adverse effect on renal and liver function tests, hematological parameters were also observed in a normal range. Histological analysis showed that cholesterol administration caused a narrowing of the aortal lumen while treatment with 70% EtOH and atorvastatin decreased the plaque size and restored the luminal size of the aorta to normal.Conclusion: The present study suggests that commonly used culinary spice cumin seed possesses hypolipidemic and cardioprotective effect with a positive effect on serum biochemistry, histology, and hematology.