Multiple Ligand Simultaneous Docking Analysis of Epigallocatechin-O-Gallate (Green Tea) and Withaferin A (Ashwagandha) Effects on Skin-Aging Related Enzymes

Abstract

Phytoconstituents epigallocatechin gallate and withaferin A, found in Camellia sinensis (Kangra green tea) and Withania sominifera (Ashwagandha) respectively, were explored for their binding affinity towards various enzymes involved in the skin-aging process. Epigallocatechin gallate and withaferin A were analyzed for their physiochemical properties, drug-likeness and human intestinal absorptivity using Data Warrior, Molsoft and SwissADME (boiled egg model) respectively. Molecular docking analysis for different enzymes involved in aging (collagenase, elastase and hyaluronidase), antioxidant enzymes (superoxide dismutase, glutathione-s-transferase, glutathione peroxidase and catalase) and mitochondrial enzymes (nicotinamide adenine dinucleotide (NAD)+hydrogen (H) dehydrogenase, succinate dehydrogenase, cytochrome c oxidase and adenosine triphosphate synthase) was carried out for epigallocatechin gallate alone (1), withaferin A alone (2), epigallocatechin gallate and withaferin A in combination (3) and a reference molecule. Autodock Vina was employed to carry out individual molecular docking as well as multiple ligand simultaneous docking. The results were analyzed in terms of binding energy and different interacting residues. Interestingly, (3) displayed a higher binding affinity towards all the aging and antioxidant enzymes as compared to (1), (2) and the references. Moreover, the combination of the constituents exhibited better binding for most of the mitochondrial enzymes. Additionally, molecular dynamics simulations were performed to estimate stability and flexibility of best complexes, while collagenase activity colorimetric assay was carried out to study the effects of (1), (2) and (3) on collagenase. The in vitro analysis indicated a 1.5 times increase in collagenase inhibition upon using (3) as compared to ascorbic acid (standard). Overall, the results indicate that epigallocatechin gallate and withaferin A, in combination, may potentially inhibit skin-aging, while enhancing antioxidant effects of various enzymes, and warrant further experimental validation.