Utilizing Cinnamomum verum (a culinary spice), as a functional food ingredient ameliorating hypercholesterolemia: In-vivo, in-vitro, and in-silico multi-model analysis

Hypercholesterolemia involves elevated levels of total cholesterol (T.C.), low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), and reduced high-density lipoprotein (HDL), linked to sedentary lifestyles, irregular eating habits, high-fat diets, type 2 diabetes, and various hereditary and environmental factors. It poses significant health risks, including high blood pressure, atherosclerosis, fatty liver, and cardiovascular disease. This study aimed to evaluate the lipid-lowering effects of ethanolic extract of Cinnamon in hypercholesterolemia-induced rats using in-vivo, in-vitro, and in-silico approaches. In the present work, thirty female Albino rats were divided into six groups: Group I (basal diet), Group II (high-fat diet), Group III (statin treatment), and Groups IV-VI (high-fat diet with different doses of cinnamon extract). Serum lipid profiles were measured after four weeks of treatment. In-vitro HMG-CoA reductase inhibition was assessed. In-silico studies, including molecular docking, ADME analysis, toxicity prediction, and molecular dynamics (M.D.) simulations, were conducted. DFT studies with MESP/HOMO/LUMO analysis provided electronic property insights. High-fat diet increased body weight and serum lipid levels in rats. Cinnamon extract significantly reduces body weight and serum LDL, VLDL, and triglycerides while increasing HDL levels. Histopathology showed reduced fat accumulation and normal liver morphology in cinnamon-treated groups. In-vitro analysis revealed significant HMG-CoA reductase inhibition by cinnamon extract. In-silico docking confirmed strong binding affinities of cinnamon compounds to HMG-CoA reductase. ADME analysis and toxicity prediction indicated favorable pharmacokinetics. MD simulations showed stable ligand-protein complexes, and DFT studies highlighted the electronic properties of active compounds. To conclude, the cinnamon ethanolic extract demonstrated effective lipid-lowering properties in hypercholesterolemic rats, supported by in-vitro and in-silico analyses, suggesting its potential as a therapeutic agent for hypercholesterolemia. Further research is needed to explore underlying mechanisms and clinical outcomes.