HMG-CoA Reductase inhibition targeted hypercholesterolemic potential of phytoconstituents of an aqueous shoot extract of Calligonum polygonoides L.: Insight from in vitro, in vivo and in silico assessments

Abstract

Calligonum polygonoides L. is a desertic plant used for the therapeutics of several metabolic disorders and ethnomedicines. Current study was assigned to examine the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibition targeted hypocholesterolemic potential of Calligonum polygonoides L. through in silico, in vitro and in vivo assessments. The LC-MS/MS screening of the aqueous shoot extract showed leading compounds and structural data retrieved from an authentic repository of PubChem. The interactions of HMG-CoA reductase (HMGR) and ligands complex were examined using molecular docking. Significant interaction was shown by dihydrocelastrol with the target enzyme (HMGCR) up to a binding energy of -8.9 Kcal/mol. The assessments of Root Mean Square Deviation, Root Mean Square Fluctuation, radius of gyration, and Solvent Accessible Surface Area along with Molecular Mechanics - Poisson-Boltzmann Surface Area and PCA were examined by GROMACS 2020.2 of best-docked complexes at 100 ns with standards. Consequently, the competent HMGCR inhibition performed by the test extracts up to 75.8% (IC₅₀ = 219.5 µM) through in vitro assessments. Encouragingly, the treatment of test extract showed significant reductions in lipid profile, dyslipidemia indices, and glucose level along with ameliorations in oxidative stress. Subsequently, significant restorations were revealed in the arterial wall of the coronary arteries. Based on the results, it can be concluded that dihydrocelastrol is a potent bioactive phytocompound that can inhibit the HMGCR and significantly reduce hypercholesterolemia.