Investigate Inhibitory Effects of Ginger polyphenols compare to Simvastatin towards HMG-CoA reductase: An Integrated Molecular Docking and Molecular dynamic simulation

Abstract

Diabetes is an increasing problem in Ethiopia, affecting up to 6.5% of Ethiopian adults. There are serious complications associated with diabetes including macrovascular and microvascular. Controlling Lipid profiles and blood glucose significantly reduces the risk of complications. Statins are the only current treatment for both type 1 diabetes and Type 2 diabetes dyslipidemia. HMG-CoA reductase plays a central role in the production of cholesterol which, associated with cardiovascular disease (CVD). Statins have been found to reduce cardiovascular disease and mortality in those who are at high risk. Nonetheless, it has adverse effect, such as drug-related hypoglycemia and high cost. These situations lead to develop suitable phytotherapeutic agents with less frequent side effects. Ginger (Zingiber officinale) is widely consumed as a spice, and numerous studies suggest that ginger may have beneficial effects for diabetes and dyslipidemia. But, further studies are needed to investigate effects of binding affinity and binding site residues for major ginger extract polyphenols towards target HMG-CoA reductase. In this study, ADMET web server, Auto-Dock 5.4 and Gromacs 2020 were used. Out of eleven major gingers polyphenols screened three selected based on docking energy compare to Simvastatin for MD simulation. The predicted binding affinity for 6-paradol, 6-shogaol and gingerdione were -8.51, -6.93, -9.24 kcal/mol, respectively. The results of molecular dynamic simulation are consistence with docking. The predicted ligand binding site residues are Arg641, Gly808, Arg641, Met781, Ser794 and Arg595. In conclusion, 6-paradol, 6-shogaol and gingerdione could be possible therapy because, of interactions with target HMG-CoA reductase. Therefore, further wet lab study will be needed, for the better understanding of the mechanism of action of ginger extract by which it modulates liver and kidney vivo condition.