Phosphatidylcholine Content Research Articles

Impact of phospholipid digests and bile acid pool variations on the crystallization of atazanavir from supersaturated solutions

Oral delivery of poorly water-soluble drugs (PWSDs), which predominate the development pipeline, poses significant challenges. Weakly basic compounds, such as atazanavir, represent a critical class of PWSDs as even the administration of the crystalline solid may invoke supersaturation during gastric-intestinal transfer. The absorption advantage afforded by this supersaturated state can be offset by inherent metastability and a tendency to revert to the lower energy crystalline state. Therefore, it is important to understand the physiological factors that can affect crystallization to improve in vitro-in vivo predictiveness and to regulate inter-individual responses. The first aim of this study was to elucidate the influence of lyso-phosphatidylcholine (lyso-PC) and sodium oleate on crystallization, as the products of phosphatidylcholine (PC) hydrolysis and the major lipid components of human intestinal fluid (HIF) and updated fasted state simulated intestinal fluid version 3 (FaSSIF-V3). Secondly, as an individual’s bile acid pool is unique, dynamic and related to gut microbiome community structure, it was of interest to investigate the impact of bile acid pool variations on crystallization from supersaturated solutions.To study the effect of PC hydrolysis, media with 2.8 mM sodium glycocholate (GCA) and sodium taurocholate (TCA) (1:1) but varying concentrations of PC, lyso-PC or sodium oleate were prepared. To investigate the influence of inter-individual variations in intestinal bile acid pool size and composition, media simulating the profiles of six healthy Western volunteers were prepared based on previously published data. The crystalline and amorphous solubility of atazanavir, a weakly basic antiretroviral drug, was firstly determined in these media. Nucleation-induction time experiments were then performed at an equivalent extent of supersaturation in each medium (corresponding to the amorphous solubility).At a constant level of GCA/TCA, increasing concentrations of both PC and lyso-PC accelerated crystallization onset; however, this was at least 2-fold more pronounced with lyso-PC at a given molar concentration. The addition of sodium oleate was also observed to induce crystallization. Interestingly, substituting GCA/TCA with the bile salt fraction of other biorelevant media partially circumvented the crystallization-inducing effect of phospholipids and their digests. The presence of dihydroxy bile salts was found to be particularly significant in decelerating the crystallization process. Nucleation-induction times in simulated volunteer pools were found to be dependent upon bile salt concentration, with higher bile salt levels generally prolonging supersaturation. Differences of up to 6-fold were observed.This study demonstrates that the choice of biorelevant medium used to evaluate supersaturating formulations can influence the observed crystallization kinetics. While the presence of lyso-PC and sodium oleate in FaSSIF-V3 medium is more physiologically relevant, further attention should be paid to the bile salt fraction when designing a biorelevant medium for supersaturating formulations. In vivo, inter-individual differences in the amount and types of bile acids and phospholipids present may influence the behaviour of supersaturating formulations.

Molybdenum induces alterations in the glycerolipidome that confer drought tolerance in wheat.

Molybdenum (Mo), which is an essential microelement for plant growth, plays important roles in multiple metabolic and physiological processes, including responses to drought and cold stress in wheat. Lipids also have crucial roles in plant adaptions to abiotic stresses. The aim of this study was to use glycerolipidomic and transcriptomic analyses to determine the changes in lipids induced by Mo that are associated with Mo-enhanced drought tolerance in wheat. Mo treatments increased the transcript levels of genes involved in fatty acid and glycerolipid biosynthesis and desaturation, but suppressed the expression of genes involved in oxylipin production. Wheat plants supplemented with Mo displayed higher contents of monogalactosyldiacyglycerol (MGDG), digalactosyldoacylglycerol (DGDG), phosphatidylglycerol (PG), phosphatidylethanolamine (PE), and phosphatidylcholine (PC) with increased levels of unsaturation. The levels of MGDG, DGDG, PG, and PC increased under PEG-simulated drought (PSD), and the magnitude of the responses varied in the presence and absence of Mo. Mo increased the accumulation of the most abundant glycerolipid species of C36:6, C34:4, and C34:3 by increasing the expression of genes related to desaturation under PSD, and this contributed to maintaining the fluidity of membranes. In addition, Mo attenuated the decreases in the ratios of DGDG/MGDG and PC/PE that were observed under PSD. These changes in lipids in Mo-treated wheat would contribute to maintaining the integrity of membranes and to protecting the photosynthetic apparatus, thus acting together to enhance drought tolerance.

Seasonal Dynamics of Lipids and Their Fatty Acids in Leaf Buds of Betula pendula Roth and Alnus alnobetula subsp. fruticosa (Rupr.) Raus under Conditions of the Cryolithozone

Absolute and relative content and composition of fatty acids, total lipids, and phospholipids, as principal constituents of cell membranes, were examined on vegetative buds of deciduous trees and shrubs throughout the summer and autumn–winter seasons under climatic conditions of the cryolithozone of Yakutia. Lipid metabolism was found to play an essential role in plants' adaptation to low autumnal and winter temperatures in the permafrost zone of Yakutia. The content of phosphatidylcholine in leaf buds of the birch Betula pendula Roth and the shrub Alnus alnobetula subsp. fruticosa (Rupr.) Raus increased throughout the observation period from 9.9 to 23.4 mg/g dry wt. In the autumn–winter period, the composition of fatty acids in the bud lipids of both species was characterized by a high content of unsaturated C18:2 and C18:3 acids. Biosynthesis of fatty acids in buds of deciduous trees and shrubs at a low temperature was apparently controlled by ω3-desaturase, whose activity elevated the content of α-linolenic acid from 2.9 to 5.7 mg/g in B. pendula and from 1.6 to 4.8 mg/g dry wt in A. alnobetula subsp. fruticosa. The seasonal decrease in air temperature was accompanied by an increase in the unsaturation coefficient (k) from 0.9 to 2.3 in B. pendula and from 1.4 to 1.8 in A. alnobetula subsp. fruticosa. It is proposed that the high content of polyunsaturated fatty acids in the autumn–winter period in vegetative buds of the examined woody plants is determined by a complex of climatic factors of the permafrost zone, such as a sharply contrasting day and night temperatures during plant dormancy, extremely low air temperature in winter (down to –60°С), and a short daylight period at this time of the year.

Associations between cerebrospinal fluid total phosphatidylcholines, neurodegeneration, cognitive decline, and risk of mild cognitive impairment in the Mayo Clinic Study of Aging

It is unclear whether cerebrospinal fluid (CSF) phosphatidylcholines (PCs) are associated with neuroimaging measures of amyloid deposition and neurodegeneration (glucose metabolism, cortical thickness, and hippocampal volume), cognitive decline, or risk of mild cognitive impairment (MCI) among cognitively unimpaired older adults. This study investigated the associations of 19 individual CSF PC concentrations and their total sum with cross-sectional and longitudinal measures of amyloid deposition and neurodegeneration, global and domain-specific cognitive z-scores, and risk of MCI among 655 cognitively unimpaired participants, mean age of 71 years, enrolled in the Mayo Clinic Study of Aging. Neither the CSF total PC concentration nor individual CSF PCs were cross-sectionally or longitudinally associated with neuroimaging measures, cognition, or risk of MCI.

Protective effects of 17-β-oestradiol and phytoestrogen on age-induced oxidative stress and inhibition of surfactant synthesis in rat type II pneumocytes

Epidemiological data suggest protective effects of oestrogen and phytoestrogen on lung tissue. This study aimed to elucidate the role of 17-β-oestradiol and phytoestrogen in age-related inhibition of surfactant synthesis and oxidative stress in rat type II pneumocytes. Forty male and 66 female Wistar rats were used. Female rats were randomly kept intact or ovariectomized at age 12 months. At age 22 months, ovariectomized rats received 17-β-oestradiol, soy extract, or no treatment. Oxidative stress markers CO, NO, cGMP and lipid peroxide (LPO), antioxidant enzymes and phosphatidylcholine (PC) were measured in cultured type II pneumocytes isolated at ages 2, 14, 18, 22 and 24 months. Old, male and ovariectomized rats showed significantly higher CO, NO, cGMP and LPO and lower PC content and antioxidant enzymes. 17-β-oestradiol and phytoestrogen significantly reversed these effects. In conclusion, aging and oestrogen deprivation decreased PC synthesis and altered the redox status in type II pneumocytes, which were partially restored by 17-β-oestradiol or soy supplementation.

Differential postprandial incorporation of 20:5n-3 and 22:6n-3 into individual plasma triacylglycerol and phosphatidylcholine molecular species in humans

The mechanisms by which digested fat is absorbed and transported in the circulation are well documented. However, it is uncertain whether the molecular species composition of dietary fats influences the molecular species composition of meal-derived lipids in blood. This may be important because enzymes that remove meal-derived fatty acids from the circulation exhibit differential activities towards individual lipid molecular species. To determine the effect of consuming oils with different molecular compositions on the incorporation of 20:5n-3 and 22:6n-3 into plasma lipid molecular species. Men and women (18–30 years) consumed standardised meals containing 20:5n-5 and 22:6n-3 (total 450 mg) provided by an oil from transgenic Camelina sativa (CSO) or a blended fish oil (BFO) which differed in the composition of 20:5n-3 and 22:6n-3 – containing molecular species. Blood was collected during the subsequent 8 h. Samples were analysed by liquid chromatography-mass spectrometry. The molecular species composition of the test oils was distinct from the composition of plasma triacylglycerol (TG) or phosphatidylcholine (PC) molecular species at baseline and at 1.5 or 6 h after the meal. The rank order by concentration of both plasma PC and TG molecular species at baseline was maintained during the postprandial period. 20:5n-3 and 22:6n-3 were incorporated preferentially into plasma PC compared to plasma TG. Together these findings suggest that the composition of dietary lipids undergoes extensive rearrangement after absorption, such that plasma TG and PC maintain their molecular species composition, which may facilitate lipase activities in blood and/or influence lipoprotein structural stability and function.

Male sterile 305 Mutation Leads the Misregulation of Anther Cuticle Formation by Disrupting Lipid Metabolism in Maize.

The anther cuticle, which is mainly composed of lipid polymers, functions as physical barriers to protect genetic material intact; however, the mechanism of lipid biosynthesis in maize (Zea mays. L.) anther remains unclear. Herein, we report a male sterile mutant, male sterile 305 (ms305), in maize. It was shown that the mutant displayed a defective anther tapetum development and premature microspore degradation. Three pathways that are associated with the development of male sterile, including phenylpropanoid biosynthesis, biosynthesis of secondary metabolites, as well as cutin, suberine, and wax biosynthesis, were identified by transcriptome analysis. Gas chromatography-mass spectrometry disclosed that the content of cutin in ms305 anther was significantly lower than that of fertile siblings during the abortion stage, so did the total fatty acids, which indicated that ms305 mutation might lead to blocked synthesis of cutin and fatty acids in anther. Lipidome analysis uncovered that the content of phosphatidylcholine, phosphatidylserine, diacylglycerol, monogalactosyldiacylglycerol, and digalactosyldiacylglycerol in ms305 anther was significantly lower when compared with its fertile siblings, which suggested that ms305 mutation disrupted lipid synthesis. In conclusion, our findings indicated that ms305 might affect anther cuticle and microspore development by regulating the temporal progression of the lipidome in maize.

IN VITRO STUDY OF A TRANSFERSOMAL GEL PREPARATION CONTAINING LYNESTRENOL AS A TRANSDERMAL DRUG DELIVERY SYSTEM

Objective: Lynestrenol, a progestin hormone derivative, can suppress the productions of endogenous estrogen and progesterone hormones (ovaries)to prevent ovulation. In this study, lynestrenol was included in various transfersomal gel preparations for its transdermal delivery into fat (F)-andnon-fat (NF)-containing skin tissues.Methods: Lynestrenol transfersome vesicles were prepared by encapsulating the drug in varied concentrations of phosphatidylcholine and Tween80 using lipid film hydration method. Transfersomes were produced in the form of gel preparations at a dose of 0.15 mg/week and evaluated fortheir particle size, percentage of entrapment efficiency, and particle polydispersity. We performed in vitro evaluations of the formulation variants F0(lynestrenol gel control) and F1 and F2 (lynestrenol transfersome gels) with variations in their phosphatidylcholine and Tween 80 content. We thenperformed an in vitro evaluation using the Franz diffusion cell (FDC) method for 12 h using all three formulations on F and NF-containing rat skin.Results: The FDC results demonstrated that lynestrenol was deposited into fat tissue and increased concentrations of Tween 80 (edge activator)increased lynestrenol delivery into this tissue. In addition, the percentages of drug penetration from NF rat skin treated with F0, F1, and F2 gels were19.56%, 20.13%, and 20.56%, respectively, and those from F rat skin were 17.16%, 17.38%, and 17.50%, respectively.Conclusion: In vitro evaluation using the FDC method indicates that transdermal drug delivery through to fat tissues using transfersomes is apromising method for lynestrenol delivery.

Lipid Composition of Three Bermudagrasses in Response to Chilling Stress

Cell and plastid membranes play a critical role in plant response to chilling stress. Fall color retention (chilling tolerance) of bermudagrass (Cynodon sp.) is known to vary with cultivar and management practices. A growth chamber study was conducted to characterize the lipid composition of three bermudagrasses in response to chilling stress. The grasses selected were ‘Tahoma 31’ (chilling-sensitive) and ‘Tifway’ (chilling-tolerant) interspecific hybrid bermudagrass (C. dactylon × C. transvaalensis) and ‘Celebration’ common bermudagrass (C. dactylon), which served as an internal standard. Plants were subjected to simulated fall conditions defined as an 8/2 °C (day/night) temperature regime with 10-hour photoperiod and evaluated for chilling response for 42 days before allowing plants to enter an apparent dormancy. Plant leaves were sampled for lipidomics analysis at 0, 14, and 42 days of chilling treatment (DOT) and again after 40 days of recovery from dormancy (during which temperatures were adjusted to mimic average spring conditions for Oklahoma). ‘Tifway’ demonstrated the lowest electrolyte leakage (EL) and visual discoloration at 42 DOT, while ‘Tahoma 31’ had the greatest EL and discoloration on the same date, and ‘Celebration’ was intermediate of the two. Prolonged exposure to chilling stress generally increased digalactosyldiacylglycerol and phosphatidylcholine (PC) content and decreased monogalactosyldiacylglycerol (MGDG) content, with ‘Tahoma 31’ showing the greatest increase in PC and decrease in MGDG. The double bond index, an indicator of fatty acid unsaturation, was greatest in ‘Tifway’ at 42 DOT. Each cultivar increased in fatty acid unsaturation, with Tifway demonstrating the greatest increase in MGDG unsaturation. Multivariate discriminant analysis identified six individual lipid species that contributed most to the cultivar response to chilling. These findings suggest unsaturation level of plastid lipids, particularly MGDG, is important for chilling tolerance and therefore fall color retention of bermudagrass. Furthermore, this study provides evidence that chilling tolerance can be negatively associated with freezing tolerance in bermudagrass.

Monocytes present age‐related changes in phospholipid concentration and decreased energy metabolism

Age‐related changes at the cellular level include the dysregulation of metabolic and signaling pathways. Analyses of blood leukocytes have revealed a set of alterations that collectively lower their ability to fight infections and resolve inflammation later in life. We studied the transcriptomic, epigenetic, and metabolomic profiles of monocytes extracted from younger adults and individuals over the age of 65 years to map major age‐dependent changes in their cellular physiology. We found that the monocytes from older persons displayed a decrease in the expression of ribosomal and mitochondrial protein genes and exhibited hypomethylation at the HLA class I locus. Additionally, we found elevated gene expression associated with cell motility, including the CX3CR1 and ARID5B genes, which have been associated with the development of atherosclerosis. Furthermore, the downregulation of two genes, PLA2G4B and ALOX15B, which belong to the arachidonic acid metabolism pathway involved in phosphatidylcholine conversion to anti‐inflammatory lipoxins, correlated with increased phosphatidylcholine content in monocytes from older individuals. We found age‐related changes in monocyte metabolic fitness, including reduced mitochondrial function and increased glycose consumption without the capacity to upregulate it during increased metabolic needs, and signs of increased oxidative stress and DNA damage. In conclusion, our results complement existing findings and elucidate the metabolic alterations that occur in monocytes during aging.

Targeting Hepatic Glutaminase 1 Ameliorates Non-alcoholic Steatohepatitis by Restoring Very-Low-Density Lipoprotein Triglyceride Assembly

Non-alcoholic steatohepatitis (NASH) is characterized by the accumulation of hepatic fat in an inflammatory/fibrotic background. Herein, we show that the hepatic high-activity glutaminase 1 isoform (GLS1) is overexpressed in NASH. Importantly, GLS1 inhibition reduces lipid content in choline and/or methionine deprivation-induced steatotic mouse primary hepatocytes, in human hepatocyte cell lines, and in NASH mouse livers. We suggest that under these circumstances, defective glutamine fueling of anaplerotic mitochondrial metabolism and concomitant reduction of oxidative stress promotes a reprogramming of serine metabolism, wherein serine is shifted from the generation of the antioxidant glutathione and channeled to provide one-carbon units to regenerate the methionine cycle. The restored methionine cycle can induce phosphatidylcholine synthesis from thephosphatidylethanolamine N-methyltransferase-mediated and CDP-choline pathways as well as by base-exchange reactions between phospholipids, thereby restoring hepatic phosphatidylcholine content and very-low-density lipoprotein export. Overall, we provide evidence that hepatic GLS1 targeting is a valuable therapeutic approach in NASH.

Sex-specific perturbation of complex lipids in response to medium-chain fatty acids in very long-chain acyl-CoA dehydrogenase deficiency.

Very-long-chain acyl-CoA dehydrogenase deficiency (VLCAD) is the most common defect of long-chain fatty acid β-oxidation. The recommended treatment includes the application of medium-chain triacylglycerols (MCTs). However, long-term treatment of VLCAD-/- mice resulted in the development of a sex-specific metabolic syndrome due to the selective activation of the ERK/mTORc1 signalling in females and ERK/peroxisome proliferator-activated receptor gamma pathway in males. In order to investigate a subsequent sex-specific effect of MCT on the lipid composition of the cellular membranes, we performed lipidomic analysis, SILAC-based quantitative proteomics and gene expression in fibroblasts from WT and VLCAD-/- mice of both sexes. Treatment with octanoate (C8) affected the composition of complex lipids resulting in a sex-specific signature of the molecular profile. The content of ceramides and sphingomyelins in particular differed significantly under control conditions and increased markedly in cells from mutant female mice but remained unchanged in cells from mutant males. Moreover, we observed a specific upregulation of biosynthesis of plasmalogens only in male mice, whereas in females C8 led to the accumulation of higher concentration of phosphatidylcholines and lysophosphatidylcholines. Our data on membrane lipids in VLCAD after supplementation with C8 provide evidence of a sex-specific lipid perturbation. We hypothesize a likely C8-induced pro-inflammatory response contributing to the development of a severe metabolic syndrome in female VLCAD-/- mice on long-term MCT supplementation.

Metabolome profiling in skeletal muscle to characterize metabolic alterations in over-conditioned cows during the periparturient period

The transition from late gestation to early lactation is associated with extensive changes in metabolic, endocrine, and immune functions in dairy cows. Skeletal muscle plays an important role in maintaining the homeorhetic adaptation to the metabolic needs of lactation. The objective of this study was to characterize the skeletal muscle metabolome in the context of the metabolic changes that occur during the transition period in dairy cows with high (HBCS) versus normal body condition (NBCS). Fifteen weeks antepartum, 38 pregnant multiparous Holstein cows were assigned to 1 of 2 groups, which were fed differently to reach the targeted BCS and back fat thickness (BFT) until dry-off at -49 d before calving (HBCS: >3.75 and >1.4 cm; NBCS: <3.5 and <1.2 cm). During the dry period and the subsequent lactation, both groups were fed identical diets. The differences in both BCS and BFT were maintained throughout the study. The metabolome was characterized in skeletal muscle samples (semitendinosus muscle) collected on d -49, 3, 21, and 84 relative to calving using a targeted metabolomics approach (AbsoluteIDQ p180 kit; Biocrates Life Sciences AG, Innsbruck, Austria), which allowed for the quantification of up to 188 metabolites from 6 different compound classes (acylcarnitines, amino acids, biogenic amines, glycerophospholipids, sphingolipids, and hexoses). On d -49, the concentrations of citrulline and hydroxytetradecadienyl-l-carnitine in muscle were higher in HBCS cows than in NBCS cows, but those of carnosine were lower. Over-conditioning did not affect the muscle concentrations of any of the metabolites on d 3. On d 21, the concentrations of phenylethylamine and linoleylcarnitine in muscle were lower in HBCS cows than in NBCS cows, and the opposite was true for lysophosphatidylcholine acyl C20:4. On d 84, the significantly changed metabolites were mainly long-chain (>C32) acyl-alkyl phosphatidylcholine and di-acyl phosphatidylcholine, along with 3 long-chain (>C16) sphingomyelin that were all lower in HBCS cows than in NBCS cows. These data contribute to a better understanding of the metabolic adaptation in skeletal muscle of dairy cows during the transition period, although the physiological significance and underlying molecular mechanisms responsible for the regulation of citrulline, hydroxytetradecadienyl-l-carnitine, carnosine, and phenylethylamine associated with over-conditioning are still elusive and warrant further investigation. The changes observed in muscle lysophosphatidylcholine and phosphatidylcholine concentrations may point to an alteration in phosphatidylcholine metabolism, probably resulting in an increase in membrane stiffness, which may lead to abnormalities in insulin signaling in the muscle of over-conditioned cows.

The kinetics of photostabilization of cyanocobalamin in liposomal preparations

AbstractCyanocobalamin (B12) is a photosensitive vitamin, and its photodegradation to hydroxocobalamin (B12b) in liposomes has been investigated. The values of apparent first‐order rate constants (kobs) for the photodegradation of B12 in liposomes (nine preparations) are in the range of (0.52‐2.24) × 10–3 min–1, compared to 3.21 × 10–3 min–1 for B12 in aqueous solution (pH 5.0). The entrapment efficiency of B12 in liposomes is 26.4‐38.8%. The values of kobs show a linear relation with phosphatidylcholine (PC) content in liposomes, indicating the influence of PC in inhibiting the rate of photolysis of B12. The value of the bimolecular rate constant for photochemical interaction of B12 and PC is 0.32 M–1 min–1, indicating the stabilizing effect of PC on the photolysis of B12. The ratio of B12 stabilization in liposomal preparations is in the range 2‐6 compared to that of the unentrapped vitamin The stabilization of B12 is mediated by a photoinduced charge‐transfer B12‐PC complex that leads to the reduction of B12 to B12r, which is then oxidized to B12b that has low susceptibility to photolysis. The extent of stabilization of B12 probably depends on the degree of interaction between the two compounds under the reaction conditions, indicated by the loss of B12 fluorescence.

Association of α/β-Hydrolase D16B with Bovine Conception Rate and Sperm Plasma Membrane Lipid Composition.

We have identified a Holstein sire named Tarantino who had been approved for artificial insemination that is based on normal semen characteristics (i.e., morphology, thermoresistance, motility, sperm concentration), but had no progeny after 412 first inseminations, resulting in a non-return rate (NRdev) of −29. Using whole genome association analysis and next generation sequencing, an associated nonsense variant in the α/β-hydrolase domain-containing 16B gene (ABHD16B) on bovine chromosome 13 was identified. The frequency of the mutant allele in the German Holstein population was determined to be 0.0018 in 222,645 investigated cattle specimens. The mutant allele was traced back to Whirlhill Kingpin (bornFeb. 13th, 1959) as potential founder. The expression of ABHD16B was detected by Western blotting and immunohistochemistry in testis and epididymis of control bulls. A lipidome comparison of the plasma membrane of fresh semen from carriers and controls showed significant differences in the concentration of phosphatidylcholine (PC), diacylglycerol (DAG), ceramide (Cer), sphingomyelin (SM), and phosphatidylcholine (-ether) (PC O-), indicating that ABHD16B plays a role in lipid biosynthesis. The altered lipid contents may explain the reduced fertilization ability of mutated sperms.

Changes of lipid metabolism of Arabidopsis thalianain response to oligochitosan treatment

Lipids are vital cellular constituents in plant, and lipid peroxidation metabolites are critical defence substances in plants. In this study, mass spectrometry along with projections to latent structures discriminant analysis (PLS-DA) was used to detect lipid metabolism changes in Arabidopsis thaliana in response to oligochitosan (an effective resistance elicitor for the control of plant diseases). The PLS-DA showed that lipid metabolites of Arabidopsis thaliana were influenced by oligochitosan treatment. The total content of oxylipin containing monogalactosyldiacylglycerols, oxylipin-containing digalactosyldiacylglycerols, and oxylipin-containing phosphatidylglycerols increased firstly (after 1 h), and then decreased with the increase of oligochitosan treatment duration. In contrast, the total content of monogalactosyldiacylglycerols, phosphatidylcholines, phosphatidyl-ethanolamine, and phosphatidylglycerols decreased firstly, and then increased with the increase of oligochitosan treatment duration. The amounts of free fatty acids (C16:2, C16:3, C18:2, and C18:3) were lower after treatment with oligochitosan for 1, 3, and 6 h than in the control, while the production of volatile organic compounds such as 2-hexenal (except for 3 h) and nonanal was higher than in the control. In conclusion, lipid metabolites of Arabidopsis thaliana were influenced by oligochitosan treatment, and the synthesized lipids and oxylipin-containing lipids were remodelled and free fatty acids was metabolized to volatile organic compounds.

Formulation and optimization of ethosomes loaded with ropinirole hydrochloride: Application of quality by design approach

The objective of the present study was to formulate and understand ethosomal formulations of Ropinirole (ROP) using quality by design (QbD) approach. To assess the effect of independent variable such as soya phosphatidyl choline and ethanol concentration on dependable variable such as vesicle size and percentage entrapment efficiency, a 32 factorial design were employed. Ethosomes were prepared by cold method and evaluated for the following parameter; vesicle size, zeta potential, polydispersity index and percentage entrapment efficiency. In vitro drug release of optimized formulation was performed and compare with pure drug solution. Based on QbD approach, design space (DS) was optimized with a combination of selected variables with entrapment efficiency > 50% w/w and a particle size < 400 nm. The results of multivariate regression analysis illustrated that vesicle size and % entrapment efficiency of ethosomes were affected by ethanol concentration and phosphatidyl choline amount. The optimized formulation had ethanol concentration of 49.9% and Soya phosphatidyl choline amount 380 mg with vesicle size of 320.45 nm and entrapment efficiency of 65.69 ± 3.5%. In vitro drug release after 24 h from optimized formulation was found to be 64.8% when compared to pure drug which released 99.2% within 2 h. The conclusion of the study substantiates that by using a QbD approach, the effect of formulation variation in responses can be easily found based on the knowledge gained by regression analysis, the concept of ‘‘desirability function”.

Crosslink among phosphatidylinositol-3 kinase/Akt, PTEN and STAT-5A signaling pathways post liposomal galactomannan hepatocellular carcinoma therapy

Liposomal drug-delivery systems (LDDs) provide a promising opportunity to precisely target organs, improve drug bioavailability and reduce systemic toxicity. On the other hand, PI3K/Akt signaling pathways control various intracellular functions including apoptosis, invasion and cell growth. Hyper activation of PI3K and Akt is detected in some types of cancer that posses defect in PTEN. Tracking the crosstalk between PI3K/Akt, PTEN and STAT 5A signaling pathways, in cancer could result in identifying new therapeutic agents. The current study, identified an over view on PI3K/Akt, PTEN and STAT-5A networks, in addition to their biological roles in hepatocellular carcinoma (HCC). In the current study galactomannan was extracted from Caesalpinia gilliesii seeds then loaded in liposomes. Liposomes were prepared employing phosphatidyl choline and different concentrations of cholesterol. HCC was then induced in Wistar albino rats followed by liposomal galactomannan (700 ± 100 nm) treatment. Liver enzymes as well as antioxidants were assessed and PI3K/Akt, PTEN and STAT-5A gene expression were investigated. The prepared vesicles revealed entrapment efficiencies ranging from 23.55 to 69.17%, and negative zeta potential values. The optimum formulation revealed spherical morphology as well as diffusion controlled in vitro release pattern. Liposomal galactomannan elucidated a significant reduction in liver enzymes and MDA as well as PI3K/Akt, PTEN and STAT 5A gene expression. A significant elevation in GST and GSH were deduced. In conclusion, Liposomal galactomannan revealed a promising candidate for HCC therapy.

Significance of bilayer-forming phospholipids for skeletal muscle insulin sensitivity and mitochondrial function.

Phosphatidylcholine (PC) and phosphatidylethanolamine (PE), which make up the bulk of mammalian cell membrane phospholipids, are recognized for their importance in metabolic health. Perturbations in the ratio of PC:PE can affect membrane integrity and function, which thus have serious health consequences. Imbalance in the hepatic PC and PE membrane content can be linked to metabolic disturbances such as ER stress, fatty liver and insulin resistance. Given that impaired insulin sensitivity underlies the pathology of many metabolic disorders and skeletal muscle is a significant regulator of energy metabolism, it is likely that aberrant phospholipid metabolism in skeletal muscle affects whole-body insulin sensitivity. Sarco/endoplasmic reticulum Ca 2+ ATPase (SERCA) activity and mitochondrial function respond to alterations in PC:PE ratio and are associated with glucose homeostasis. Moreover, PC and PE content within the mitochondrial membrane influence mitochondrial respiration and biogenesis and thus, metabolic function. As skeletal muscle phospholipids respond to stimuli such as diet and exercise, understanding the implications of imbalances in PC:PE ratio is of great importance in the face of the rising epidemic of obesity related diseases. This review will summarize the current state of knowledge signifying the links between skeletal muscle PC:PE ratio and insulin sensitivity with respects to PC and PE metabolism, SERCA activity, mitochondrial function and exercise.

Effect of chitosan coatings incorporated with antioxidant of bamboo leaves and potassium sorbate on lipid oxidation and hydrolysis of scallop (Chlamys farreri) during refrigerated storage

Nutrient loss, caused by lipid oxidation and hydrolysis, occurs in the scallop adductor muscle during refrigerated storage. To retard this process, chitosan coating with inclusion of antioxidant of bamboo leaves (AOB) and potassium sorbate (PS) were used. Results indicated the coatings employed could significantly inhibit the increases in total number of colonies, total volatile basic nitrogen, peroxide value, thiobarbituric acid-reactive substances, lipase activity and free fatty acid content as well as the decrease in contents of triacylglycerols, phosphatidylcholine, phosphatidylethanolamine and polyunsaturated fatty acids (PUFA) in the scallop adductor muscle during refrigerated storage. After 8 days, the contents of PUFA, eicosapentaenoic acid and docosahexenoic acid in the control adductor muscle decreased by 46.91, 47.46 and 45.50%, respectively, while the corresponding values were 35.93-36.68, 34.01-36.45 and 32.73-37.50%, respectively, for AOB- and PS-coated adductor muscles. Therefore, chitosan coatings incorporated with AOB and PS could retard nutrient loss by inhibiting lipid oxidation and hydrolysis.