Effects of ursolic acid on the structural and morphological behaviours of dipalmitoyl lecithin vesicles

Abstract

Effects of ursolic acid on the structural and morphological characteristics of dipalmitoyl lecithin(DPPC)-water system was studied by using differential scanning calorimetry (DSC), small- and wide-angle X-ray scattering (SWAXS), freeze-fracture method combined with transmission electron-microscopy (FF-TEM) and infrared spectroscopy (FT-IR). The surface of the uncorrelated lipid system is rippled or grained and a huge number of small, presumably unilamellar vesicles are present if the UA/DPPC molar ratio is 0.1 mol/mol or higher. Besides the destroyed layer packing of regular multilamellar vesicles, non-bilayer (e.g. cubic or hexagonal) local structures are evidenced by SAXS and FF-TEM methods. The ability of UA to induce non-bilayer structures in hydrated DPPC system originates from the actual geometry form of associated lipid and UA molecules as concluded from the FT-IR measurements and theoretical calculations. Beside numerous beneficial e.g. chemopreventive and chemotherapeutic effect of ursolic acid against cancer, their impact to modify the lipid bilayers can be utilized in liposomal formulations.

Giant Plasma Membrane Vesicles: An Experimental Tool for Probing the Effects of Drugs and Other Conditions on Membrane Domain Stability

“…These membranes undergo a main chain melting transition between a liquid phase and gel or solid phases, whose properties have been extensively studied by a variety of experimental methods. In all cases, incorporating hydrophobic general anesthetics into single component membranes lowers the main chain transition temperature (T M ) and disorders lipid chains (makes their motions more isotropic) at fixed temperature (Shieh, Ueda, Lin and Eyring 1976; Kamaya, Ueda, Moore and Eyring 1979; Miller, Firestone, Alifimoff and Streicher 1989; Heimburg and Jackson 2007; Lorincz, Mihaly, Nemeth, Wacha and Bota 2015). These molecules also can impact the lateral pressure profiles, bending rigidity, and water permeability of simple membranes (Trudell, Payan, Chin and Cohen 1975; Mountcastle, Biltonen and Halsey 1978; Gruner and Shyamsunder 1991; Jorgensen, Ipsen, Mouritsen, Bennett and Zuckermann 1991; Jorgensen, Ipsen, Mouritsen and Zuckermann 1993).…”

Effect of Ursolic and Oleanolic Acids on Lipid Membranes: Studies on MRSA and Models of Membranes

“…demonstrated by using FTIR and DPPC, a broadening gel-to-liquid crystalline phase with the phase transition temperature shifted towards higher values and an increase of gauche isomers of acyl chains above Tm upon the presence of UA. The mechanism is likely different to that of cholesterol since cholesterol, in contrast with UA, abolished completely the main transition and the hidden formation of gauche conformers [ 55 ]. Differences in the effect induced by UA and OA could result in differences in the propensity of UA and OA to induce interdigitated lipid structure at low temperatures, as observed for membrane-active peptides.…”

“…The cis junction results in a non-planarity of UA and OA (as opposed to compounds with a lupeol skeleton). Their configuration originated from the van der Waals type interaction between the ester group of the lipid and the –OH group of UA and OA [ 55 ]. Ursanes and oleananes differ only in the location of one methyl group [ 58 ] and thus in number and location of chiral centers [ 60 ].…”

“…The reduction in the size of the headgroup hydration shell, compounded by the loss of counter ions, increases the tendency of the lipid ion pairs to adopt a packing geometry with increased negative curvature, thus resulting in the formation of an inverted hexagonal phase. This process could be reinforced by pentacyclic triterpenes as demonstrated for OA in hydrated DPPC system [ 55 ] and UA in DPPC and DPPC:Chol model [ 18 ]. In the temperature domain of the gel phase, the geometrical form of lipids associated with UA turns into conical form and the self-assembly results in the hexagonal structure.…”

Pentacyclic triterpenes modulate liposome membrane fluidity and permeability depending on membrane cholesterol content

“…Using X-ray diffraction and infrared spectroscopy, Lorincz et al (2015) showed that ursolic acid, a derivative of OA, promoted the formation of non-layered (e.g. cubic or hexagonal) structures for DPPC liposomes containing 10% of ursolic acid, and this was accompanied with a significant expansion in the acyl chain cross-sectional area of a lipid molecule (Lőrincz et al, 2015). Given that OA and ER shared the same TTP In addition, the width of liposome size distribution expressed by the "span factor" was calculated according to Eq.…”