The assigned work was aimed to examine the capability of phytoconstituents of an aqueous seed extract of Acacia senegal (L.) Willd to inhibit HMG-CoA reductase and regression of the atherosclerotic plaque. The chemical fingerprinting of the test extract was assessed by LC-MS/MS. Consequently, the analyses of in-vitro, in-vivo, and in-silico were executed by using the standard protocols. The in-vitro assessment of the test extract revealed 74.1% inhibition of HMG-CoA reductase. In-vivo assessments of the test extract indicated that treated hypercholesterolemic rabbits exhibited a significant (P≤0.001) amelioration in the biomarker indices of the dyslipidaemia i.e., atherogenic index, Castelli risk index(I&II), atherogenic coefficient along with lipid profile. Subsequently, significant reductions were observed in the atherosclerotic plaque and antioxidant levels. The in-silico study of molecular docking shown interactions capabilities of the leading phytoconstituents of the test extract i.e., eicosanoic acid, linoleic acid, and flavan-3-ol with target protein of HMG-CoA reductase. The values of RSMF and potential energy of top docked complexes were show significant interactions. Accordingly, the free energy of solvation, interaction angle, radius of gyration and SASA were shown significant stabilities of top docked complex. The cumulative data of results indicate phytoconstituents of an aqueous seed extract of Acacia senegal have capabilities to inhibit the HMG-CoA reductase and improve the levels of antioxidants.

The current study was carried out to evaluate the potential of curcumin against the progression of atherosclerosis and cholesterol biosynthesis by incorporating the combined data of in-vivo assessments and integrative omics examinations. The high fat diet and supplementation of cholesterol powder caused significant alterations in the lipid profile as well as hypercholesterolemia indices. The induced hypercholesterolemia promoted progression of atherosclerotic plaque with the occurrence of foam cells in a bulged structure. Simultaneously, the treatments of curcumin and atorvastatin caused significant reductions in total cholesterol, low density lipoprotein cholesterol, and very low-density lipoprotein cholesterol, as well as hypercholesterolemia indices of Castelli Risk Index-I and II and atherogenic indices. Accordingly, the treatments of curcumin and atorvastatin caused significant regressions in atherogenic plaque area, total wall area, and increased lumen volume. Subsequently, molecular docking showed significant interactions of curcumin and atorvastatin with β-Hydroxy β-methylglutaryl-CoA reductase, which were depicted by bonding energy, number of H-bonds, and bond length. Accordingly, the absorption, distribution, metabolism, excretion, and toxicity and toxicity data revealed significant druggability of curcumin along with supportive analysis of Brain Or IntestinaL EstimateD-Egg prediction of gastrointestinal absorption. Thus, it can be illustrated that curcumin has significant potential to promote regression in atherosclerotic plaque and subside the cholesterol biosynthesis by inhibition of HMG-CoA reductase, as indicated by the outcomes.

No abstract

No abstract

Background: The HMG-CoA inhibitor are used to control adverse cardiovascular event caused by Hypercholesterolemia and dyslipidaemia. The current study was aimed to evaluate the ability of phytoconstituents of an aqueous seed extract of Acacia senegal (L.) Willd to inhibit HMG-CoA reductase and regress the formation of atherosclerotic plaque. Methods: The chemical fingerprinting of the test extract was assessed by LC-MS. Consequently, the assessments of in-vitro, in-vivo, and in-silico were performed by following the standard methods.Results: The in-vitro assessment of the test extract revealed 74.1 % inhibition potential of HMG-CoA reductase. In-vivo evaluations of the test extract indicated that treated hypercholesterolemic rabbits exhibited a significant (𝑃 ≤ 0.001) ameliorations in the biomarker indices of the dyslipidaemia, such as the atherogenic index, Castelli risk index (I&II), atherogenic coefficient along with lipid profile. Concomitantly, significant reductions were observed in the atherosclerotic plaque area and antioxidants. The in-silico study of molecular docking shown interactions capabilities of key phytoconstituents of the test extract with target protein of HMG-CoA reductase which further validated by the molecular dynamics through potentail energy, NPT, NVT, RSMD and others. Subsequently, the ADMET analysis shown ideal druggability. Conclusion: The results indicate that phytoconstituents of an aqueous seed extract of Acacia senegal (L.) Willd. could inhibit HMG-CoA reductase and improve the levels of antioxidants activity that may reduce symptoms associated with hypercholesterolemia.