Experimental and theoretical studies of emodin interacting with a lipid bilayer of DMPC

Abstract

Emodin is one of the most abundant anthraquinone derivatives found in nature. It is the active principle of some traditional herbal medicines with known biological activities. In this work, we combined experimental and theoretical studies to reveal information about location, orientation, interaction and perturbing effects of Emodin on lipid bilayers, where we have taken into account the neutral form of the Emodin (EMH) and its anionic/deprotonated form (EM − ). Using both UV/Visible spectrophotometric techniques and molecular dynamics (MD) simulations, we showed that both EMH and EM − are located in a lipid membrane. Additionally, using MD simulations, we revealed that both forms of Emodin are very close to glycerol groups of the lipid molecules, with the EMH inserted more deeply into the bilayer and more disoriented relative to the normal of the membrane when compared with the EM − , which is more exposed to interfacial water. Analysis of several structural properties of acyl chains of the lipids in a hydrated pure DMPC bilayer and in the presence of Emodin revealed that both EMH and EM − affect the lipid bilayer, resulting in a remarkable disorder of the bilayer in the vicinity of the Emodin. However, the disorder caused by EMH is weaker than that caused by EM − . Our results suggest that these disorders caused by Emodin might lead to distinct effects on lipid bilayers including its disruption which are reported in the literature.

Natural Products Isolated from Oriental Medicinal Herbs Inactivate Zika Virus

“…A wide spectrum of biological activities has been described for emodin through different mechanisms of action [27,28,29,32,33] and among these, some are directly related to induced changes of the viral envelopes, such as 95% disruption of the herpes simplex virus type 1 (HSV-1) envelope [30]. The interaction of emodin with phospholipids and its effects in the integrity of vesicles and lipid extracts from Escherichia coli through the perturbation of the physical properties of the bilayer have been reported [31,34], supporting the direct effect of this anthraquinone on biological membranes. Berberine has also been described to act directly on biomembranes [35] or by inducing the increase of membrane permeability [36].…”

Ascorbate-and iron-driven redox activity of Dp44mT and Emodin facilitates peroxidation of micelles and bicelles

“…Many factors dictate the interaction of drugs with the cell membrane, including lipophilicity, size, solubility, charge, etc. [91]. Lipophilicity and charge are key aspects of pharmacopoeia that determine their biological activity [72,76], as discussed for agents of the DpT class, such as Dp44mT [14], and also Emodin [91].…”

“…[91]. Lipophilicity and charge are key aspects of pharmacopoeia that determine their biological activity [72,76], as discussed for agents of the DpT class, such as Dp44mT [14], and also Emodin [91]. The relative lipophilicity of Dp44mT and…”

“…DOPC is a phosphatidylcholine (36:2), which is generally the most abundant phospholipid in animal cell membranes, and thus, provides a physiologically relevant model for the simulation. Molecular dynamics simulations were utilized to assess the interaction of Dp44mT and Emodin with membranes, as they have been extensively implemented to predict drug behavior and activity [91,97,98]. Unfortunately, these types of simulations do not effectively accommodate relatively heavy atoms such as iron, and thus, Dp44mT-Fe complex or potential Emodin-Fe complexes could not be effectively studied using this methodology.…”

Free Energy Computation for an Isomerizing Chromophore in a Molecular Cavity via the Average Solvent Electrostatic Configuration Model: Applications in Rhodopsin and Rhodopsin-Mimicking Systems

“…30−32 The updated ASEC-FEG protocol described below leverages an adaptation of the thermodynamic cycle-based approach previously used to compute the free energy differences of a solute molecule in solution. 33,34 In such an approach, the free energy perturbation (FEP) theory is combined with the hypothetical annihilation of the solute molecule. 35 The same approach has been carefully benchmarked for tautomerization reactions in solution.…”