No abstract

Inverse bicontinuous cubic phases of lyotropic liquid crystal self-assembly have received much attention in biomedical, biosensing, and nanotechnology applications. An Ia3d bicontinuous cubic based on the gyroid G-surface can be formed by the Guerbet synthetic glucolipid 2-hexyl-decyl-β-d-glucopyranoside (β-Glc-OC6C10) in excess water. The small water channel diameter of this cubic phase could provide nanoscale constraints in encapsulation of large molecules and crystallization of membrane proteins, hence stresses the importance of water channel tuning ability. This work investigates the swelling behavior of lyotropic self-assembly of β-Glc-OC6C10 which could be controlled and modulated by different surfactants as a hydration-modulating agent. Our results demonstrate that addition of nonionic glycolipid octyl-β-d-glucopyranoside (β-Glc-OC8) at 20 and 25 mol % gives the largest attainable cubic water channel diameter of ca. 62 Å, and formation of coacervates which may be attributed to a sponge phase were seen at 20 mol % octyl-β-d-maltopyranoside (β-Mal-OC8). Swelling of the cubic water channel can also be attained in charged surfactant-doped systems dioctyl sodium sulfosuccinate (AOT) and hexadecyltrimethylammonium bromide (CTAB), of which phase transition occurred from cubic to a lamellar phase. Destabilization of the cubic phase to an inverse hexagonal phase was observed when a high amount of charged lecithin (LEC) and stearylamine (SA) was added to the lipid self-assembly.

The lyotropic phase behavior of four common and easily accessible glycosides, n-octyl α-D-glycosides, namely, α-Glc-OC 8 , α-Man-OC 8 , α-Gal-OC 8 , and α-Xyl-OC 8 , was investigated. The presence of normal hexagonal (H I ), bicontinuous cubic (V I ), and lamellar (L α ) phases in α-Glc-OC 8 and α-Man-OC 8 including their phase diagrams in water reported previously was verified by deuterium nuclear magnetic resonance ( 2 H NMR), via monitoring the D 2 O spectra. Additionally, the partial binary phase diagrams and the liquid crystal structures formed by α-Gal-OC 8 and α-Xyl-OC 8 in D 2 O were constructed and confirmed using small-and wide-angle X-ray scattering and 2 H NMR. The average number of bound water molecules (n b ) per headgroup in the L α phase was determined by the systematic measurement of the quadrupolar splitting of D 2 O over a wide range of molar ratio values (glycoside/ D 2 O), especially at high glucoside composition. The number of bound water molecules bound to the headgroup was found to be around 1.5−2.0 for glucoside, mannoside, and galactoside, all of which possesses four OH groups. In the case of xyloside, which has only three OH groups, the bound water content is ∼2.0. Our findings confirmed that the bound water content of all n-octyl α-Dglycosides studied is lower compared to the number of possible hydrogen bonding sites possibly due to the fact that most of the OH groups are involved in intralayer interaction that holds the lipid assembly together.

Hyperhomocysteinemia has been linked to an increased risk of cardiovascular diseases. High levels of homocysteine (Hcy) promote endoplasmic reticulum (ER) stress that can increase reactive oxygen species (ROS), leading to endothelial dysfunction. Thymoquinone (TQ) is the major active ingredient in Nigella sativa seeds volatile oil and is shown to have a cardioprotective effect. However, no study evaluated the effect of TQ against Hcy-induced endothelial dysfunction. Thus, this study aims to investigate the effects and mechanisms of TQ in reversing Hcy-induced endothelial dysfunction. Isolated aorta from male Sprague-Dawley (SD) rats incubated with Hcy (500 µM) and co-treated with or without TQ (0.1 µM, 1 µM, and 10 µM), 20 µM TUDCA, 100 µM Apocynin or 1 mM Tempol in organ bath to study the vascular function. Additionally, human umbilical vein endothelial cells (HUVECs) were incubated with Hcy (10 mM) and various concentrations of TQ (1 and 10 𝜇M), Tempol (100 𝜇M), Apocynin (100 𝜇M), TUDCA (100 𝜇M) or H2O2 (0.25 mM) to evaluate the cell viability by using a phase contrast microscope and dye exclusion assay. Involvement of ER stress pathway, ROS and NO bioavailability were accessed via immunoassay and fluorescent staining respectively. Molecular docking was performed to evaluate the binding affinity of TQ to GRP78. Our results revealed that Hcy impaired endothelium-dependant relaxation in isolated aorta and induced apoptosis in HUVECs. These effects were reversed by TQ, TUDCA, tempol and apocynin. Treatment with TQ (10𝜇M) also reduced ROS level, improved NO bioavailability as well reduced GRP78 and NOX4 protein in HUVECs. Result from the molecular docking study showed that TQ could bind well to GRP78 through hydrogen bond and hydrophobic interaction with the amino acid at GRP78 ATP binding pocket. Taken together, the present results suggest that TQ preserved endothelial function in rat aorta and reduced apoptosis of HUVECs induced by Hcy through the inhibition of ER stress-mediated ROS and eNOS uncoupling.