Ameliorations in dyslipidemia and atherosclerotic plaque by the inhibition of HMG-CoA reductase and antioxidant potential of phytoconstituents of an aqueous seed extract of Acacia senegal (L.) Willd in rabbits

Abstract

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.

Imine Derivatives of Benzoxazole Attenuate High-Fat Diet-Induced Hyperlipidemia by Modulation of Lipid-Regulating Genes

“…HMGCR is a well-known rate-limiting transmembrane enzyme, which is regulated by multiple feedback mechanisms and involved in catalyzing the conversion of HMG-CoA to mevalonate, a precursor of sterols including cholesterol synthesis. , Inhibition of cholesterol biosynthesis by blocking HMGCR in the liver results in the increased clearance of LDL from plasma by multiple methods of reverse cholesterol transport and through activation of sterol regulatory element-binding protein-2 (SREBP-2) . PCSK9, a serine protease, is another target that mediates the absorption of LDL via LDLR, which is principally accountable for eliminating plasma cholesterol.…”

Effects of Dietary Bioactive Lipid Compounds of Acacia nilotica Bark on Productive Performance, Antioxidant Status, and Antimicrobial Activities of Growing Rabbits under Hot Climatic Conditions

“…According to Fran et al [ 22 ], flavonoids (isoflavones) capture radicals before they can damage a cell, quenching active singled oxygen, and decomposing hydrogen peroxide without creating radicals. The Acacia seed extract-treated rabbits had higher levels of antioxidants such as catalase, SOD, and GSH, which are used to scavenge and destroy free radicals, while also having lower levels of free radicals [ 25 ].…”

Molecular Docking Study Reveals α-Santalol from Santalum album Linn. as Promising Inhibitor of CD36 for Atherosclerosis

“…In addition to that, the In Vivo studies demonstrated inhibition of HMG-CoA reductase. Apart from that they also performed an In silico study against HMG-CoA reductase and three compounds of extracts involving linoleic acid, flavan-3-ol, and eicosanoic acid which revealed a potent and strong interaction between the docked complex [15].…”