Protective effect and mechanism insight of purified Antarctic krill phospholipids against mice ulcerative colitis combined with bioinformatics

Antarctic krill oil is functional oil and has a complex phospholipids composition that poses difficulties in elucidating its effect mechanism on ulcerative colitis(UC).The mechanism of UC action was studied by bioinformatics,and the therapeutic effect of Antarctic krill phospholipids(APL)on dextran sulfate sodium(DSS)-induced colitis mice was verified.GO functional enrichment analysis uncovered an enrichment of these genes in the regulation of cell-cell adhesion,membrane region,signaling receptor activator activity,and cytokine activity.Meanwhile,the KEGG results revealed the genes were enriched in the TNF signaling pathway,pathogenic Escherichia coli infection,inflammatory bowel disease and tight junction.Animal experiments showed that APL treatment alleviated the UC symptoms and reduced inflammatory damage.Meanwhile,the expressions of the tight junction(TJ)proteins,ZO-1 and occludin,were restored,and the levels of IL-6 and TNF-αwere reduced.Moreover,Firmicutes/Bacteroidetes ratio in the intestinal microbiota was regulated,and the contents of short-chain fatty acids metabolites were raised.These findings would provide an insight for the beneficial effects of APL and dietary therapy strategies for UC.

Preparation, characterization and evaluation of kaempferol phospholipid complex: Improvement of its solubility and biological effect

Kaempferol(KA),as one of the flavonoids,has extensive pharmacological properties.However,the poor solubility of KA severely limits its clinical application.In our study,the kaempferol phospholipid complex(KA-PC)has been prepared by solvent evaporation for the enhancement of the bioavailability of KA.KA-PC was verified by scanning electron microscope characterization methods.Drug loading,solubility and long-term stability were measured.The characterization results showed that KA-PC was formed through the intermolecular interaction between KA and phospholipids.The solubility of KA-PC in water was 189 times higher than that of KA,and the solubility in n-octanol was also significantly improved.Besides,pharmacodynamic studies showed that KA-PC can significantly reduce the level of serum uric acid in mice without causing renal injury.This study expanded the clinical application of KA by preparing KA-PC.

Availability Test of the Free Phospholipids in the Plasma of Three Species of Freshwater Fish

[Objective] The research aimed to determine the existence of free phospholipids in the plasma of three species of freshwater fish and lay the foundation for discussing the physiological mechanism of coagulation phenomena in three species of freshwater fish.[Method] The activity of heated phospholipids was detected by the availability test of heated rabbit cephalin.Small amount of the platelet-poor plasma of the rabbit Oryctolagus cuniculus,the cell-free plasma of the carp Cyprinus carpio,the crucian Carassi...

Interaction of Soybean Phospholipids Based Lipo-Vesicle and Surfactants of Bile Salts In Vitro

Liposomes were prepared with natural soybean phospholipids by extrusion method after rotating-film evaporating technique. Transmission electron micrography was used to detect the appearances of the prepared liposomes, and the liposome diameter was also measured. The prepared liposomes were sphere in shape with the mean diameter of 217 nm and span of 0.838. The phospholipid bilayer structure, suitable for entrapping various effector molecules, could be seen clearly under transmission electron microscopy. The bile salts of sodium cholate and sodium deoxycholate were used as the surfactants to investigate their interaction with liposomes. The turbidities for the mixture of bile salts and liposomes were evaluated by the visible spectrometry method at the wavelength of 500 nm. And the diameter changes of liposomes were also tested to examine the effect of bile salts on liposomes. At the beginning, the diameters and turbidities of liposomes increased a little as the result of mixed micelles formation during the different stages for the structure changes of surfactant-liposomes micelles. The further added bile salts decreased the diameters and turbidities of liposomes. The liposome suspension underwent several rearrangements before small mixed micelles formed. And the diameter of liposomes changed regularly. The interaction of bile salts and liposomes is important for the further study of the behaviors of liposomes in vivo. The drug loaded and release properties of liposomes can also be well reflected by the interaction of liposomes and surfactants.

Changes of Tumor Necrosis Factor, Surfactant Protein A, and Phospholipids in Bronchoalveolar Lavage Fluid in the Development and Progression of Coal Workers’ Pneumoconiosis

Objective To evaluate the alterations of biomarkers in the development and progression of coal workers＇ pneumoconiosis （CWP）. Methods The type and number of cells, and the levels of tumor necrosis factor-alpha （TNF-α）, pulmonary surfactant protein, phospholipids and fibronectin in bronchoalveolar lavage fluid were assayed in 14 health active coal miners, 21 coal miners without CWP and 13 miners with CWP of 0/1 to 1/1. Results Compared to active coal miners without CWP （8,23μg/mL）, TNF-α concentration was gradually decreased when dust exposure was stopped （5.90 μg/mL）. Elevated surfactant protein A （SP-A） level and phosphatidylglycerol （PG） to phosphatidylinositol （PI） ratio were found in miners actively exposed to coal dust （6528 μg/mL for SP-A and 10. for PG/P1）, and both parameters decreased when CWP progressed from CWP （0/1） （3419μg/mL for SP-A and 5.9 for PG/PI） to CWP （1/1） （1654 μg/mL for SP-A and 5.5 for PG/PI）. Conclusion Biomarkers in bronchoalveolar lavage fluid can be used to screen coal miners at high risk of developing coal workers＇ pneumoconiosis.

A review on phospholipids and their main applications in drug delivery systems

Phospholipids have the characteristics of excellent biocompatibility and a especial amphiphilicity.These unique properties make phospholipids most appropriate to be employed as important pharmaceutical excipients and they have a very wide range of applications in drug delivery systems.The aim of this review is to summarize phospholipids and some of their related applications in drug delivery systems,and highlight the relationship between the properties and applications,and the effect of the species of phospholipids on the efficiency of drug delivery.We refer to some relevant literatures,starting from the structures,main sources and properties of phospholipids to introduce their applications in drug delivery systems.The present article focuses on introducing five types of carriers based on phospholipids,including liposomes,intravenous lipid emulsions,micelles,drug-phospholipids complexes and cochleates.

Long-Term Effects of Docosahexaenoic Acid-Bound Phospholipids and the Combination of Docosahexaenoic Acid-Bound Triglyceride and Egg Yolk Phospholipid on Lipid Metabolism in Mice

The bioavailability of docosahexaenoic acid(DHA) and eicosapentaenoic acid(EPA) depends on their chemical forms. This study investigated the long-term effects of DHA-bound triglyceride(TG-DHA), DHA-bound phospholipid(PL-DHA), and the combination of TG-DHA and egg yolk phospholipid(Egg-PL) on lipid metabolism in mice fed with a high-fat diet(fat levels of 22.5%). Male C57BL/6J mice were fed with different formulations containing 0.5% DHA, including TG-DHA, PL-DHA, and the combination of TG-DHA and Egg-PL, for 6 weeks. Serum, hepatic, and cerebral lipid concentrations and the fatty acid compositions of the liver and brain were determined. The concentrations of serum total triglyceride(TG), total cholesterol(TC), high-density lipoprotein cholesterol(HDL-c), and hepatic TG in the PL-DHA group and the combination group were significantly lower than those in the high-fat(HF) group(P < 0.05). Atherogenic index(AI) of the PL-DHA group was significantly lower than that of the combination group(P < 0.05). Hepatic TC level in the combination group was significantly lower than that in the HF group(P < 0.05), but no significant difference was observed between the combination group and the PL-DHA group. Both the PL-DHA and the combination groups showed significantly increased DHA levels in the liver compared with the HF group(P < 0.05). However, there were no obvious increases in the cerebral DHA levels in all DHA diet groups. These results suggest that PL-DHA was superior to the combination of TG-DHA and Egg-PL in decreasing the AI. Long-term dietary supplementation with low amount of DHA(0.5%) may improve hepatic DHA levels, although cerebral DHA levels may not be enhanced.

Mucin and phospholipids determine viscosity of gallbladder bile in patients with gallstones

AIM: An increased viscosity of gallbladder bile has been considered an important factor in the pathogenesis of gallstone disease. Besides lipids and proteins, mucin has been suggested to affect the viscosity of bile. To further clarify these issues we compared mucin, protein and the lipid componEnts of hepatic and gallbladder bile and its viscosity in patients with gallstones. METHODS: Viscosity of bile (mPa.s) was measured using rotation viscosimetry in regard to the non Newtonian property of bile at low shear rates. RESULTS: Biliary viscosity was markedly higher in gallbladder bile of patients with cholesterol (5.00 +/- 0.60 mPa.s, mean +/- SEM, r= 28) and mixed stones (3.50 +/- 0.68 mPa.s; r= 8) compared to hepatic bile (0.92 +/- 0.06 mPa.s, r= 6). A positive correlation between mucin and viscosity was found in gallbladder biles (r = 0.65; P 【 0.001) but not in hepatic biles. The addition of physiologic and supraphysiologic amounts of mucin to gallbladder bile resulted in a dose dependent non linear increase of its viscosity. A positive correlation was determined between phospholipid concentration and viscosity (r = 0.34, P 【 0.005) in gallbladder biles. However, no correlation was found between total protein or the other lipid concentrations and viscosity in both gallbladder and hepatic biles. CONCLUSION: The viscosity of gallbladder bile is markedly higher than that of hepatic bile in patients with gallstones. The concentration of mucin is the major determinant of biliary viscosity and may contribute by this mechanism to the role of mucin in the pathogenesis of gallstones.

Advances in studies of phospholipids as carriers in skin topical application

Objective： This article provides an overview of characteristics of phospholipids, the characteristics and influential factors of liposome and microemulsion as carriers for skin delivery of drugs, and the latest advances of the phospholipids carriers in transdermal delivery systems. The perspective is that phospholipids carriers may be capable of a wide range of applications in the transdermal delivery system.

Analysis of phospholipids in microalga Nitzschia closterium by UPLC-Q-TOF-MS

Precise structural identification of phospholipids in the microalga Nitzschia closterium has been established using ultra performance liquid chromatography-electrospray ionization-quadrupole-time of flight-mass spectrometry (UPLC-ESI-Q-TOF-MS) for direct analysis of total lipid extracts.Mass spectrometry was performed in reflective time-of-flight using electron spraying ionization in negative mode.Phospholipid molecular species identification was based on the characteristic product ions and neutral loss yielded by different phospholipids under ESI-MS/MS mode.The molecular species were confirmed by the carboxylate anions produced by phospholipids in negative mode;the regiospecificity of the two acyl chains was determined from the ratio of sn-1 to sn-2 carboxylate anion abundances.As a result,18 lipid molecular species were identified for the first time in this microalga,comprising seven phosphatidylcholines (PC),two phosphatidylethanolamines (PE),two phosphatidylinositols (PI),and seven phosphatidylglycerols (PG).Lipid standards of PC,PE,PI,and PG were added to the total lipids as internal standards for semiquantitative analysis,revealing concentrations of phospholipids in this species between 0.09 and 3.37 nmol/mg.This method can produce a full structural profile of intact phospholipid molecular species and can be used for study of the physiological and ecological functions of lipids by monitoring their individual changes over time.

An Effective Extract Method of Phospholipids from Antarctic Krill <em>Euphausea superba</em>

Phospholipids are one of the major bioactive ingredients of Antarctic krill Euphausea superba. A feasible and effective extraction method of Antarctic krill oil was investigated and modified by orthogonal test which the ratio of solid to liquid was 1:2.5, extraction time was 5 min, ratio of ethyl acetate (EA) and n-butanol (BuOH) was 1:1. With this method, the extract of krill oil has a higher phospholipids content of 27.7% - 42.3%, together with total oil yields of 4.15% - 6.18%.

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.

Hexagonal arrangement of phospholipids in bilayer membranes

The phospholipid membrane plays a key role in myriad biological processes and phenomena, and the arrangement structure of membrane determines its function. However, the molecular arrangement structure of phospholipids in cell membranes is difficult to detect experimentally. On the basis of molecular dynamic simulations both in a non-destructive way and at native environment, we observed and confirmed that the phospholipids self-assemble to a hexagonal arrangement structure under physiological conditions. The underlying mechanism was revealed to be that there are hexagonal arrangement regions with a lower free energy around each lipid molecule. The findings potentially advance the understanding of biological functions of phospholipid bilayers.

The Modulation Effect of Triglyceride Type and Phospholipids Type ω-3 LCPUFA on Mice Gut Microbiota

The evaluation from prospective cohort studies on the dietary ω-3 long-chain polyunsaturated fatty acid (LCPUFA) supplementation and nutritional value is consistent. However, the effect of different types of ω-3 long-chain PUFA (ω-3 LCPUFA) on microbiota in intestine is inconsistent. In this study, the mice were divided into three groups (N, PL, FO), with AIN-93M (N), AIN-93M + Phospholipids type ω-3 LCPUFA (PL) and AIN-93M + triglyceride type ω-3 LCPUFA (FO), respectively. Denaturing Gradient Gel Electrophoresis (DGGE) was used to detect the structure of intestinal microbiota. The data showed that the composition of gut microbiota was changed by treating with the two types of ω-3 LCPUFA. The results revealed that gut microbiota’ enrichment in FO group was decreased while in PL group was increased. The data also showed that the histological morphology of the small intestine in treated mice was improved especially in group PL, which was much more significant and suggested that Phospholipids type ω-3 LCPUFA is beneficial to intestinal health.

Oral absorption of hyaluronic acid and phospholipids complexes in rats

AIM： To prepare a complex of hyaluronic acid （HA） and phospholipids （PL）, and study the improvement effect of PL on the oral absorption of HA. METHODS： The complex of HA-PL （named Haplex） was prepared by film dispersion and sonication method, its physico-chemical properties were identified by infrared spectra and differential scanning calorimetry （DSC）. The oral absorption of Haplex was studied. Thirty-two healthy rats were divided into 4 groups randomly： （1） a normal saline （NS） control group; （2） an HA group; （3） a mixture group and （4） a Haplex group. After intragastric administration, the concentration of HA in serum was determined. RESULTS： The physico-chemical properties of Haplex were different from HA or PL or their mixture. After Haplex was administered to rats orally, the serum concentration of HA was increased when compared with the mixture or HA control groups from 4 h to 10 h （P 〈 0.05）. The AAUCo-12, of Haplex was also greater than that of the other three groups （P 〈 0.05）. CONCLUSION： The method of film dispersion and sonication can prepare HA and PL complex, and PL can enhance the oral absorption of exogenous HA.

Oxidized phospholipids and lipoprotein-associated phospholipase A_2 as important determinants of Lp(a) functionality and pathophysiological role

Lipoprotein（a） [Lp（a）] is composed of a low density lipoprotein（LDL）-like particle to which apolipoprotein（a）[apo（a）] is linked by a single disulfide bridge. Lp（a） is considered a causal risk factor for ischemic cardiovascular disease（CVD） and calcific aortic valve stenosis（CAVS）. The evidence for a causal role of Lp（a） in CVD and CAVS is based on data from large epidemiological databases, mendelian randomization studies, and genome-wide association studies. Despite the well-established role of Lp（a） as a causal risk factor for CVD and CAVS, the underlying mechanisms are not well understood. A key role in the Lp（a） functionality may be played by its oxidized phospholipids（OxPL） content. Importantly, most of circulating OxPL are associated with Lp（a）; however, the underlying mechanisms leading to this preferential sequestration of OxPL on Lp（a） over the other lipoproteins,are mostly unknown. Several studies support the hypothesis that the risk of Lp（a） is primarily driven by its OxPL content.An important role in Lp（a） functionality may be played by the lipoprotein-associated phospholipase A_2（Lp-PLA_2）,an enzyme that catalyzes the degradation of OxPL and is bound to plasma lipoproteins including Lp（a）. The present review article discusses new data on the pathophysiological role of Lp（a） and particularly focuses on the functional role of OxPL and Lp-PLA_2 associated with Lp（a）.

Essential phospholipids for nonalcoholic fatty liver disease associated with metabolic syndrome: A systematic review and network meta-analysis

BACKGROUND Essential phospholipids(EPL)are used for the supportive treatment of nonalcoholic fatty liver disease(NAFLD),but data are mostly from small-scale studies.AIM To evaluate the efficacy of EPL treatment in adult patients with NAFLD and type 2 diabetes and/or obesity.METHODS The MEDLINE,PubMed,Embase,and Cochrane databases were searched up to March 2019 for clinical trials and comparative observational studies.Eligible studies were those published in English or Chinese that enrolled adult patients(≥18 years)with NAFLD and type 2 diabetes mellitus and/or obesity receiving EPL as monotherapy or as add-on therapy to existing therapy,and that included at least one of the efficacy outcomes of interest.A variety of studies were identified;thus,direct,indirect and cohort meta-analyses were performed.Mean difference(MD)and 95%confidence interval(CI)were calculated for continuous variables,and relative risk with 95%CI for disease response and recovery.A random-effects model was used to address between-study heterogeneity.RESULTS Ten studies met the inclusion criteria(n=22-324).EPL treatment duration ranged from 4 to 72 wk.In the direct meta-analysis(four randomized controlled trials),compared with antidiabetic therapy alone,EPL plus antidiabetic therapy was associated with a significantly greater reduction in[alanine aminotransferase(ALT);MD:11.28 U/L(95%CI:-17.33,-5.23),P=0.0003],triglyceride[MD:-49.33 mg/dL(95%CI:-66.43,-32.23),P<0.0001]and total cholesterol levels[MD:-29.74 mg/dL(95%CI:-38.02,-21.45),P<0.0001].There was also a significant increase in the rate of overall improvement[relative risk 1.50(95%CI:1.26-1.79),P<0.0001],and risk of no disease(P=0.0091),and a reduction in moderate disease(P=0.0187);there were no significant differences in severe disease,mild disease,or significant improvement.In the cohort meta-analysis of three non-randomized clinical trials,the MD in ALT levels was-16.71 U/L(95%CI:-24.94,-8.49)and 23%of patients had improved disease.In the cohort meta-analysis of five randomized trials,MD in ALT levels was–28.53 U/L(95%CI:-35.42,-21.65),and 87%(95%CI:81%,93%)and 58%(95%CI:46%,70%)of patients showed clinical improvement and significant clinical improvement.CONCLUSION This analysis provides evidence for a benefit of EPL in patients with NAFLD and diabetes and/or obesity.Further large-scale trials are warranted.

High Density Lipoprotein Phospholipids as a Marker of Coronary Heart Disease of Shen-Yang Deficiency Syndrome

Objective: To seek a new biochemical index for diagnosis of coronary heart disease (CHD) of shen-Yang deficiency syndrom (CHD-SYD). Methods: Sixty-one patients with CHD were divided into 3 groups according to their TCM Syndrome type, 10 patients in the group without Xin-Qi deficiency (Group A), 25 in the group with Xin-Qi deficiency but without Shen-Yang deficiency (Group B) and 26 in the group both with Xin-Qi deficiency and Shen-Yang deficiency (Group C). Levels of 17-hydroxy-corticoste-roid in urine (urinary 17-OHCS) per 24 hrs, and serum level of high density lipoprotein cholesterol (HDL-C) and high density lipoprotein phospholipid (HDL-PL) in them were determined in synchrostep and compared with those in the control group of 23 healthy aged persons, urinary 17-OHCS per 24 hrs was taken as the diagnostic standard to screen a new index for diagnosis of Shen-Yang deficiency Syndrome, and preliminary appraisal to the index was made. Results: Serum HDL-PL in the CHD-SYD patients( Group C) was 616+157 mg/L, which was obviously lower than that in the patients of Group A and B. With low HDL-PL(<650 mg/L) used as the index to diagnose CHD-SYD, the sensitivity was 73%, the specificity 86% and the accuracy 80%. Conclusion: HDL-PL <650 mg/L could be adopted as an index for CHD-SYD diagnosis, which is simple and practical.

Optimization of High EPA Structured Phospholipids Synthesis from （u-3 Fatty Acid Enriched Oil and Soy Lecithin

The molecular structure of phospholipids can be changed enzymatically to obtain different tailor-made phospholipids. Incorporation of ω-3 fatty acids into phospholipids structure increased their oxidative stability, suggesting more health beneficial phospholipids. This study aimed to optimize eicosapentaenoic acid （EPA） incorporation into phospholipids structure by acidolysis reaction using free lipase （EC 3.1.1.3） from Rhizomucor miehei. Deoiled soy lecithin from anjasmoro variety was used as phospholipids source, while ω-3 fatty acid enriched oil was used as acyl source. Oil enriched with ω-3 fatty acids was obtained from low temperature solvent crystallization of lemuru （Sardinella longiceps） by-product. Response surface methodology （RSM） was used in this study to determine the relationship between the three factors （enzyme concentration, reaction time and substrate ratio） and their effects on EPA incorporation into soy lecithin structure. The results showed that the relation between EPA content with three factors （reaction time, enzyme concentration and substrate ratio） was quadratic. The significant factors were substrate ratio and reaction time. Optimum conditions at a ratio of 3.77：1 between ω-3 fatty acids enriched oil and soy lecithin, 30% lipase concentration, and 24.08 h reaction time, gave 22.81% of EPA content of structured phospholipids.

Effect of pineapple peel extract on total phospholipids and lipid peroxidation in brain tissues of rats

Objective:To investigate the ability of the methanolic extract of pineapple peel to attenuate alcohol-induced changes in total phospholipids and lipid peroxidation in brain tissues. Methods:Oxidative stress was induced by oral administration of ethanol(20%w/v) at a dosage of 5 mL/kg bw in rats.After 28 days of treatment,the rats were fasted overnight and sacrificed by cervical dislocation.Brain tissues were assayed for total phospholipid(TP) content and malondialdehyde(MDA).Results:Administration of alcohol significantly caused a reduction in TP content.Treatment with pineapple peel extract significantly increased the TP content. Significant high levels of MDA was observed in alcohol-fed rats,treatment with pineapple peel extract significantly reduced the MDA levels.Conclusions:Results obtained from this study indicates that pineapple peel extract protects against alcohol-induced changes in total phospholipids and lipid peroxidation in brain tissues.