Antagonistic effects of α-tocopherol and ursolic acid on model bacterial membranes

Abstract

α-tocopherol (Toc), the most active component of vitamin E can exert antagonistic effects disabling the therapy of cancers and bacterial infections. Such antagonisms were observed also between Toc and bioactive pentacyclic triterpenes (PT) exhibiting anticancer and antibacterial properties. Both Toc and PT are water-insoluble membrane active substances. Thus, our idea was to emulate their interactions with model Escherichia coli membranes. E. coli inner membranes were selected for the experiments because their lipid composition is quite simple and well characterized and the two main components are phosphatidylethanolamine and phosphatidylglycerol. As a model of E. coli membranes we applied Langmuir monolayers formed by the E. coli total extract of polar lipids (Etotal) as well as by the main lipid components: phosphatidylethanolamine (POPE) and phosphatidylglycerol (ECPG). The antagonistic effects of ursolic acid (Urs) and Toc were investigated with the application of ternary Langmuir monolayers formed by Urs, Toc and one of the phospholipids POPE or ECPG. Our studies indicated that the affinities of Urs and Toc towards the POPE molecule are comparable; whereas there are profound differences in the interactions of Urs and Toc with ECPG. Thus, the model experiments prove that in the case of E. coli membrane, the differences in the interactions between Urs and Toc with the anionic bacterial phosphatidylglycerol can be the key factor responsible for the antagonistic effects observed between PT and Toc in vivo.

Pentacyclic triterpenoid ursolic acid interferes with mast cell activation via a lipid-centric mechanism affecting FcεRI signalosome functions

“…Furthermore, UA reacted specifically with phosphatidylethanolamine phospholipids through hydrogen bonding, disorganizing the membrane interface and thus disrupting the membrane integrity ( 81 ). The combined data suggest that UA, similarly to other triterpenoids and hydrophobic bioactive molecules, incorporates into biological membranes and modulates their fluidity, morphology, and permeability ( 29 , 82 ). Based on the similarity of cholesterol and UA, it is not surprising that chemotaxis of mast cells toward antigen and PGE 2 showed opposite effects when the cells were pretreated with UA or MβCD ( 83 , 84 ).…”

“…The lipid-centric theory postulates that UA, similarly to, for example, anesthetics ( 26 ), dissolves in and interacts with cellular lipids and acts by changing the physical properties and spatial arrangement of plasma membrane components. This theory is supported by X-ray diffraction, differential scanning calorimetry, 31 P NMR, Raman spectroscopy, and fluorescence anisotropy using liposomes of defined lipid composition ( 27 , 28 , 29 , 30 , 31 ).…”

Langmuir films study on lipid-containing artificial tears

“…Before proceeding to the discussion, a consideration is needed. Even though vitamin A [35,36] and vitamin E [37,38] are surface active, their concentration is low in respect to lecithin (PC), in a ratio lower than 3%, and thus the major contribution is due to PC. In references [37,38] it can be 6 seen that the influence of tocopherol (vitamin E) on POPC or E. Coli lipid extracts is small even though tocopherol was present in a molar fraction of 0.25 or 0.20.…”

Antibacterial test and toxicity of plant seed extracts: a review

“…Boulekbache-Makhlouf et al (2013) classified plant extracts on the basis of their MIC values: strong inhibition = MIC < 500 µg/mL; moderate inhibition = 600 µg/mL < MIC < 1500 µg/mL, and low inhibition = MIC > 1600 µg/mL. However, fractionated plant metabolites render lower MIC due to purified extract (McGaw et al, 2002) and elimination of antagonistic antibacterial effect from other components of the complex crude extract composition (Broniatowski et al, 2015).…”