Salts Influence Cathechins and Flavonoids Encapsulation in Liposomes: A Molecular Dynamics Investigation

Abstract

Cathechins and flavonoids are responsible of numerous health benefits. Two of the most representatives' compounds for their antioxidant and therapeutic effects are Epigallocatechin 3-Gallate (EGCG), from green tea extracts, and morelloflavone (MF), from Garcinia dulcis. Here we explore, by atomistic Molecular Dynamics simulations, how EGCG and MF interact with lipid bilayers and we show the salts' influence on their encapsulation degree in neutral liposomes. As a result, we found out that EGCGs naturally bind to the hydrophilic regions of phospholipids, positioning themselves mostly at the interface between water and lipid phases. The presence of a salt clearly influences the EGCG molecules' absorption and the total effect depends strongly on the salt nature and concentration. Beside, for MF, we observed a high stability of the intermolecular MFs aggregates in water that strongly penalizes the flavonoid's interaction with the lipid polar heads. However, salts can influence MF's liposomal penetration, even if they are not able to promote completely its absorption inside the bilayer. For both compounds, the increase of penetration is more marked in presence of magnesium chloride, whilst calcium chloride showed the opposite effect.

Liposomal Formulations for an Efficient Encapsulation of Epigallocatechin-3-Gallate: An In-Silico/Experimental Approach

“…Because of its water solubility, EGCG tends to diffuse into the aqueous phase during the emulsion process; in order to improve the encapsulation efficiency it is consequently important to employ liposome formulations able to enhance the interaction of the molecule with the lipid matrix. Starting from our previous results [ 26 ], we proceeded to investigate the effect of divalent salts on the encapsulation efficiency in these new liposomal vectors, employing increasing quantities of MgCl 2 and CaCl 2 (1:1, 3:1, 5:1 and 6:1 salt and EGCG molar ratio) that can interact not only with neutral and charged phospholipids by Coulombic forces but also with the phenolic and aromatic groups of EGCG. Our experimental results suggest the existence of substantial differences in the Ca 2+ and Mg 2+ interaction with lipids and EGCGs at level of the molecular scale organization of the lipid bilayer ( Table 1 ).…”

“…In a previous work [ 26 ], we already used an in silico approach to study the influence of salt addition in EGCG and morelloflavone (MF) interaction with 1-palmitoyl-2-oleoylphosphatidyl-choline (POPC) liposomes. Starting from these results, in this work we focused on the influence of lipid matrix composition on promoting EGCG interaction at the bilayer surface.…”

A Comprehensive In Silico Method to Study the QSTR of the Aconitine Alkaloids for Designing Novel Drugs

“…During the MD simulation, minimization and equilibration of original and docked proteins occurred in a 15 Å3 size water box. A CHARMM 22 force field file was applied for energy minimization and equilibration with Gasteiger–Huckel charges using Boltzmann initial velocity [ 93 , 94 ]. Integrator parameters also included 2 fs/step for all rigid bonds and nonbonded frequencies were selected for 1 Å and full electrostatic evaluations for 2 Å were used with 10 steps for each cycle [ 93 ].…”

“…Integrator parameters also included 2 fs/step for all rigid bonds and nonbonded frequencies were selected for 1 Å and full electrostatic evaluations for 2 Å were used with 10 steps for each cycle [ 93 ]. The particle mesh Ewald method was used for electrostatic interactions of the simulation system periodic boundary conditions with grid dimensions of 1.0 Å [ 94 ]. The pressure was maintained at 101.325 kPa using the Langevin piston and the temperature was controlled at 310 K using Langevin dynamics.…”

Redox Properties and Interchromophoric Electronic Interactions in Isoalloxazine−Anthraquinone Dyads

“…The large variability in the redox potentials and activity of the flavin in different enzymes,,,, mostly depends by the role of the environment that surrounds the isoalloxazine system, as evidenced by many studies in the literature where this aspect has been thoroughly investigated. Amongst the interactions studied the most interesting includes hydrogen bonding,, aromatic π‐π stacking, steric effects, change transfer interactions and complexation with metal ions …”