Barbiturates* ; Brain* ; Membranes* ; Phospholipids*

Barbiturates* ; Brain* ; Cholesterol* ; Membranes* ; Phospholipids*

AIMTo investigate the interaction between drugs and ordered phospholipid membrane using immobilized artificial membrane chromatography (IAMC).

METHODSIAMC was used to determine the interaction drugs with phospholipid membrane, expressed as membrane affinity (lg kIAM). An n-octanol/buffer system was also employed as the reference hydrophobicity (lg Do/w,7.4).

RESULTSWithin the range of used acetonitrile percentages (phi) 0-30% in mobile phase, retention index (lg kIAM) showed excellent correlation with phi. Intercepts of fitted straight lines between lg kIAM and phi were comparable but slopes were much different for the three organic modifiers (acetonitrile, ethanol and methanol). Effects by adding CH2 substituent on lipophilicity difference (delta lg kIAM and delta lg Do/w,7.4) were similar for p-hydroxyl benzoic methyl ester to butyl ester, whereas different for p-hydroxylbenzoic acid to methyl ester.

CONCLUSIONIAMC system is a convenient, efficient and rapid tool for determining membrane interaction.

To prepare composite phospholipid liposomes containing total alkaloids of Strychnos nux-vomica with hydrogenated soybean phosphatidylcholine (HSPC) and 1, 2-dipalmitoyl-sn-glycero-3-phosphacholine (DPPC), and compare with normal DPPC thermosensitive liposomes for thermosensitive release property. Total alkaloids were extracted from S. nux-vomica with the impregnation method and further purified. Liposomes containing total alkaloids, thermosensitive liposomes and conventional thermosensitive liposomes without thermosensitive release property were prepared by ammonium sulfate transmembrane gradients and stealth liposome technique. Their encapsulation efficiency (EE), grain size, zeta potential and drug release behavior were compared. Their EEs and zeta potentials were almost identical; but the grain sizes of composite phospholipid liposomes and thermosensitive liposomes were significantly smaller than conventional liposomes. After comparing release behaviors of the three liposomes at 37, 43 degrees C, we found that the release of composite phospholipid liposomes was significantly lower than that of thermosensitive liposomes at 37 degrees C, but higher than that of thermosensitive liposomes at 43 degrees C. Meanwhile, conventional liposomes, with a very high phase-transition temperature, showed only slight release behavior at both temperatures. The study results showed that composite phospholipid liposomes had a better thermosensitive release behavior when the dosage of lysophosphatidic was reduced by 2. 5 times.
Alkaloids ; chemistry ; Liposomes ; chemistry ; Phospholipids ; chemistry ; Strychnos nux-vomica ; chemistry

The purpose of this study was to investigate the preparation and characteristics of curcumin phospholipid complex, including the effects of reaction time, reaction solvent, reaction concentration and reaction temperature. Preparation technology resulted in that 0.5 g curcumin and 10 g soy phospholipid dissolved in 100 mL anhydrous alcohol, were stirred 1 h in 50 degrees C waterbath, then steamed alcohol in decompression, collected solid residue and vacuum dried for 12 h. The physicochemical properties for the new complex including IR spectrometer, mass spectrograph and HNMR equipment were detected. As a result, the formation of the complex is based on the reaction between phospholipid polar group rounding phosphorus atom and curcumin. This result gave the evidence for the formation mechanism of phospholipid complex.
Curcuma ; chemistry ; Drugs, Chinese Herbal ; chemistry ; Phospholipids ; chemistry

OBJECTIVE: To construct protein functional network according to the physiological process in vivo and functionally based distinct families, to understand biological functions, and to make wise decisions. METHODS: We described here a very effective strategy combining with multiple-docking and protein-ligand binding-affinity fingerprint method to generate bio-functional network and pathway and reveal the protein "unknown" functions and their relationship. RESULTS: Totally 27 sets of proteins and 28 bio-active molecules were used to reconstruct the possible phospholipids metabolic network by computational simulation strategy. The protein-ligand network reconstruction and pathway based drug design showed that the direct interaction investigation might be effective in complex biological system study. CONCLUSION Even for weak and moderate interactions in the real biology system, the relationship between each other can be achieved by fingerprint analysis based on multiple-docking data. The results of these calculations give valuable insight into the pathway and the function relationship among these proteins. This method can be a very useful tool for protein classification, target selection, and inhibitor design.
Ligands ; Molecular Docking Simulation ; Phospholipids ; metabolism ; Proteins ; chemistry

Human secreted phospholipase A2 GIIE (hGIIE) is involved in inflammation and lipid metabolism due to its ability of hydrolyzing phospholipids. To reveal the mechanism of substrate head-group selectivity, we analyzed the effect of mutation of hGIIE on its activity and selectivity. hGIIE structural analysis showed that E54 might be related to its substrate head-group selectivity. According to the sequence alignment, E54 was mutated to alanine, phenylalanine, and lysine. Mutated genes were cloned and expressed in Pichia pastoris X33, and the enzymes with mutations were purified with 90% purity by ion exchange and molecular size exclusion chromatography. The enzymatic activities were determined by isothermal microthermal titration method. The Km of mutant E54K towards 1,2-dihexyl phosphate glycerol decreased by 0.39-fold compared with that of wild type hGIIE (WT), and the Km of E54F towards 1,2-dihexanoyl-sn-glycero-3-phosphocholine increased by 1.93-fold than that of WT. The affinity of mutant proteins with phospholipid substrate was significantly changed, indicating that E54 plays an important role in the substrate head-group selectivity of hGIIE.
Humans ; Kinetics ; Mutation ; Phospholipases A2, Secretory ; Phospholipids ; Saccharomycetales ; Substrate Specificity

Phospholipids are important components of biomembrane and lipoproteins. Phospholipids can be oxidized by free radicals/nonradicals and enzymes to form oxidized phospholipids (OxPLs), which can lead to further generation of oxidation products with different biological activities. Clinical evidence shows that OxPLs are constantly generated and transformed during the pathogenesis of atherosclerosis and accumulated at the lesion sites. OxPLs are highly heterogeneous mixtures that can influence the progress of atherosclerosis through a variety of related receptors or signaling pathways. This review summarizes the process of phospholipid oxidation, the related products, the interaction of OxPLs with endothelial cells, monocytes/macrophages, smooth muscle cells, platelets and lipoproteins involved in the pathological process of atherosclerosis, and the progress of the researches using OxPLs as a target to inhibit atherosclerosis in recent years.
Atherosclerosis ; Endothelial Cells ; Humans ; Myocytes, Smooth Muscle ; Oxidation-Reduction ; Phospholipids

Long-chain acyl-coenzyme A (CoA) synthase 4 (ACSL4) is an enzyme that esterifies CoA into specific polyunsaturated fatty acids, such as arachidonic acid and adrenic acid. Based on accumulated evidence, the ACSL4-catalyzed biosynthesis of arachidonoyl-CoA contributes to the execution of ferroptosis by triggering phospholipid peroxidation. Ferroptosis is a type of programmed cell death caused by iron-dependent peroxidation of lipids; ACSL4 and glutathione peroxidase 4 positively and negatively regulate ferroptosis, respectively. In addition, ACSL4 is an essential regulator of fatty acid (FA) metabolism. ACSL4 remodels the phospholipid composition of cell membranes, regulates steroidogenesis, and balances eicosanoid biosynthesis. In addition, ACSL4-mediated metabolic reprogramming and antitumor immunity have attracted much attention in cancer biology. Because it facilitates the cross-talk between ferroptosis and FA metabolism, ACSL4 is also a research hotspot in metabolic diseases and ischemia/reperfusion injuries. In this review, we focus on the structure, biological function, and unique role of ASCL4 in various human diseases. Finally, we propose that ACSL4 might be a potential therapeutic target.
Humans ; Ferroptosis ; Apoptosis ; Phospholipids/metabolism* ; Nitric Oxide Synthase

Pulmonary surfactant instillation is the treatment of choice in neonatal respiratory distress syndrome. The development of artificial surfactant has three decades of history. Animal-derived artificial surfactant is used in most countries and consists of 80% phospholipids and glycerol. 10% of the formulation is comprised of surfactant proteins, which have the critical role in surfactant function of lowering surface tension in the alveoli. Synthetic surfactants are made using synthetic peptide analogues as the surfactant protein counterparts. These are not the same as the human surfactant protein sequences; however, researchers are attempting to find the ideal synthetic peptide sequence for use in synthetic surfactants. Prophylactic and rescue surfactant therapy are two main therapeutic options. A recent recommendation emphasizes the importance of rescue therapy with continuous positive nasal airway pressure, rather than prophylactic use immediate after birth. This article briefly reviews the history and physiology of surfactant use, as well as clinical practice of surfactant and future studies.
Glycerol ; Humans ; Parturition ; Phospholipids ; Physiology ; Pulmonary Surfactants* ; Respiratory Distress Syndrome, Newborn ; Surface Tension ; Surface-Active Agents