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Gastric ulcers are one of the most prevalent gastrointestinal disorders. The current study investigated the antioxidant and anti-inflammatory effects of selenium (Se) and lecithin (Lec) alone and in combination against ethanol-induced gastric ulcers in mice, and their ability to modulate insulin-like growth factor-1 (IGF-1)/ Phosphatase and tensin homologue deleted on chromosome 10 (PTEN)/ Protein kinase B (Akt)/ Forkhead box O3a (FoxO3a) signaling. The mice were divided into normal, ethanol, Se + ethanol, Lec + ethanol, Se + Lec + ethanol, and omeprazole + ethanol groups. Treatment with the selected doses was continued for 14 days before a single dose of absolute ethanol (5 ml/kg body weight) was administered to induce gastric ulcers in mice. The results showed that pretreatment with Se and Lec combination effectively decreased both the macro- and microscopic gastric lesions and increased the protection index compared to the ethanol group. Remarkably, the Se and Lec combination decreased the levels of reactive oxygen species, malondialdehyde, and cytochrome c and increased glutathione, glutathione peroxidase, and thioredoxin reductase activities in gastric tissues. The Se and Lec combination increased prostaglandin E2 and interleukin-10 levels but decreased tumor necrosis factor-α, interleukin-6 and interleukin-1β levels compared to either treatment alone. Interestingly, this combination decreased the expression of IGF-1, p-Akt, and FoxO3a proteins and increased PTEN expression in gastric tissues. The gastric tissues examination by hematoxylin and eosin staining confirmed these results. Therefore, the Se and Lec combination showed superior protective effects against ethanol-induced gastric ulcers in mice, compared to either treatment alone, through antioxidant, and anti-inflammatory activities, in addition to modulating IGF-1/PTEN/Akt/FoxO3a pathway signaling., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: UV skin exposure is an important matter of public health, as the worldwide rising prevalence of skin cancers indicates. However, a wide majority of commercially available sunscreens are responsible for ocean ecosystem damages such as coral reef degradation and phytoplankton mortality., Aims: To answer the urge for new eco-friendly UV filters, we studied the use of lecithin-based multilamellar liposomes (MLLs) of controlled size and elasticity as a bio-sourced and biodegradable alternative to classic sunscreens. These parameters control allows different skin layers targeting., Methods: The performance of two different MLLs compositions and a commercially available SPF50+ water-resistant liposomal sunscreen was compared on skin explants. SC-MLLs target the stratum corneum and Epi-MLLs the whole epidermis. Preparations were applied prior to skin irradiation. Their efficiencies were evaluated histologically (hematoxylin and eosin staining plus cyclobutane pyrimidine dimer [CPD] immunostaining) and by skin barrier quality assessment (trans-epithelial electrical resistance). Adhesiveness to the skin was also investigated., Results: Altogether, ex vivo results indicate MLLs offer a solar protection as effective as a SPF50+ water-resistant liposomal sunscreen but with a better skin adhesiveness and an improved skin barrier function., Conclusion: Lecithin-based MLLs of controlled physicochemical parameters can be used as a new eco-friendly and water-resistant agent for solar protection. The stratum corneum targeted action of SC-MLLs appears to be more interesting, as SC-MLLs exhibit an overall better performance than Epi-MLLs at a lower cost. The skin barrier improvement showcased could be of interest to people suffering from dry skin or skin barrier impairment related disease., (© 2023 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

We investigated the effect of the rheological properties and composition of lecithin reverse wormlike micelles (LRWs) on the skin permeation of a model of a hydrophilic drug to determine whether LRWs support uniform hydrophilic drug/oil-based formulations and good drug penetrate into skin. Here, we prepared LRWs with D (-)-ribose (RI) or glycerol (GL) as polar compounds, liquid paraffin (LP) or isopropyl myristate (IPM) as oils, and 6-carboxyfluorescein (CF) as a model for a hydrophilic drug, and evaluated the rheological properties and skin penetration characteristics of the preparations. The LRWs showed moderate viscosity at 25 °C, a typical storage temperature, but decreasing viscosity at 32 °C, the surface temperature of human skin, suggesting that the LRWs would penetrate the microstructure of skin (e.g., wrinkles and hair follicles). The highest skin permeability of CF was observed when IPM was used as the oil, suggesting that both the stratum corneum and hair follicle routes are involved in drug permeation. The penetration of CF into hair follicles is influenced not only by the rheology of the formulation but also by the interaction between IPM and sebum in the hair follicles.

I have been studying the improvement of drug solubility using solid dispersion and skin-applied formulations. When preparing solid dispersions using phosphatidylcoline (PC) as a carrier, drug with hydrogen-donating groups interacts with PC to produce amorphous solid dispersions with high drug content; this overcomes improves drug absorption. The drug was solubilized and supersaturated in the oil-based gel formed with hyadrogenated lecithin; this facilitates drug permeation through the skin. The promoting effect differs with the nature of the oil used because of the skin penetration of the oil itself and the accompanying increase in drug solubility and diffusion coefficient in the skin. At actual application volumes of 10 µL/cm 2 or less, the skin penetration of poorly-absorbable drugs depends on the molecular weight and surface tension of the oil. The penetration of the oil vehicle into the upper stratum corneum influences the reach of the drug into the stratum corneum; a high drug concentration near the 7th layer of the stratum corneum promotes migration through the skin by increasing the linear concentration gradient in deeper layers. In addition, we performed a risk assessment, in collaboration with toxicologists, for dermal safety that included the toxicity potential of substances and the parts related to skin transfer.

To explore the potential benefits of dietary phospholipids (PLs) in fish glucose metabolism and to promote feed culture of Chinese perch (Siniperca chuatsi), we set up six diets to feed Chinese perch (initial mean body weight 37.01 ± 0.20 g) for 86 days, including: Control diet (CT), 1% (SL1), 2% (SL2), 3% (SL3), 4% (SL4) soybean lecithin (SL) and 2% (KO2) krill oil (KO) supplemental diets (in triplicate, 20 fish each). Our study found that the SL2 significantly improved the weight gain rate and special growth rate, but the KO2 did not. In addition, the SL2 diet significantly improved feed intake, which is consistent with the mRNA levels of appetite-related genes (npy, agrp, leptin A). Additionally, in the CT and SL-added groups, leptin A expression levels were nearly synchronized with serum glucose levels. Besides, the SL2 significantly upregulated expression levels of glut2, gk, cs, fas and downregulated g6pase in the liver, suggesting that it may enhance glucose uptake, aerobic oxidation, and conversion to fatty acids. The SL2 also maintained the hepatic crude lipid content unchanged compared to the CT, possibly by significantly down-regulating the mRNA level of hepatic lipase gene (hl), and by elevating serum low-density lipoprotein (LDL) level and intraperitoneal fat ratio in significance. Moreover, the serum high-density lipoprotein levels were significantly increased by PL supplementation, and the SL2 further significantly increased serum total cholesterol and LDL levels, suggesting that dietary PLs promote lipid absorption and transport. Furthermore, dietary SL at 1% level could enhance non-specific immune capacity, with serum total protein level being markedly higher than that in the CT group. In conclusion, it is speculated that the promotion of glucose utilization and appetite by 2% dietary SL could be linked. We suggest a 1.91% supplementation of SL in the diet for the best growth performance in juvenile Chinese perch., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Context: Gallic acid (GA) and lecithin showed important roles in antioxidant and drug delivery, respectively. A complex synthesized from GA and soybean lecithin (SL-GAC), significantly improved bioavailability of GA and pharmacological activities. However, the antioxidant activity of SL-GAC and its effect on iron-overload-induced liver injury remains unexplored., Objective: This study investigates the antioxidant properties of SL-GAC in vitro and in mice, and its remediating effects against liver injury by iron-overloaded., Materials and Methods: In vitro , free radical scavenging activity, lipid peroxidation inhibition, and ferric reducing power of SL-GAC were measured by absorbance photometry. In vivo , C57BL/6J mice were randomized into 4 groups: control, iron-overloaded, iron-overloaded + deferoxamine, and iron-overloaded + SL-GAC. Treatments with deferoxamine (150 mg/kg/intraperitioneally) and SL-GAC (200 mg/kg/orally) were given to the desired groups for 12 weeks, daily. Iron levels, oxidative stress, and biochemical parameters were determined by histopathological examination and molecular biological techniques., Results: In vitro , SL-GAC showed DPPH and ABTS free radicals scavenging activity with IC 50 values equal to 24.92 and 128.36 μg/mL, respectively. In C57BL/6J mice, SL-GAC significantly reduced the levels of serum iron (22.82%), liver iron (50.29%), aspartate transaminase (25.97%), alanine transaminase (38.07%), gamma glutamyl transferase (42.11%), malondialdehyde (19.82%), total cholesterol (45.96%), triglyceride (34.90%), ferritin light chain (18.51%) and transferrin receptor (27.39%), while up-regulated the levels of superoxide dismutase (24.69%), and glutathione (11.91%)., Conclusions: These findings encourage the use of SL-GAC to treat liver injury induced by iron-overloaded. Further in vivo and in vitro studies are needed to validate its potential in clinical medicine.

The objective of the present research was to develop fluconazole-loaded transferosomal bigels for transdermal delivery by employing statistical optimization (2 3 factorial design-based). Thin-film hydration was employed to prepare fluconazole-loaded transferomal suspensions, which were then incorporated into bigel system. A 2 3 factorial design was employed where ratios of lipids to edge activators, lipids (soya lecithin to cholesterol), and edge activators (sodium deoxycholate to Tween 80) were factors. Ex vivo permeation flux (Jss) of transferosomal bigels across porcine skin was analyzed as response. The optimal setting for optimized formulation (FO) was A= 4.96, B= 3.82, and C= 2.16. The optimized transferosomes showed 52.38 ± 1.76% DEE, 76.37 nm vesicle size, 0.233 PDI, - 20.3 mV zeta potential, and desirable deformability. TEM of optimized transferosomes exhibited a multilamelar structure. FO bigel's FE-SEM revealed a globule-shaped vesicular structure. Further, the optimized transferosomal suspension was incorporated into thyme oil (0.1% w/w)-containing bigel (TO-FO). Ex vivo transdermal fluconazole permeation from different transferosomal bigels was sustained over 24 h. The highest permeation flux (4.101 μg/cm 2 /h) was estimated for TO-FO bigel. TO-FO bigel presented 1.67-fold more increments of antifungal activity against Candida albicans than FO bigel. The prepared thyme oil (0.1% w/w)-containing transfersomal bigel formulations can be used as topical delivery system to treat candida related fungal infections., (© 2023. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

70 kDa heat shock protein Hsp70 (also termed HSP70A1A) is the major stress-inducible member of the HSP70 chaperone family, which is present on the plasma membranes of various tumor cells, but not on the membranes of the corresponding normal cells. The exact mechanisms of Hsp70 anchoring in the membrane and its membrane-related functions are still under debate, since the protein does not contain consensus signal sequence responsible for translocation from the cytosol to the lipid bilayer. The present study was focused on the analysis of the interaction of recombinant human Hsp70 with the model phospholipid membranes. We have confirmed that Hsp70 has strong specificity toward membranes composed of negatively charged phosphatidylserine (PS), compared to neutral phosphatidylcholine membranes. Using differential scanning calorimetry, we have shown for the first time that Hsp70 affects the thermotropic behavior of saturated PS and leads to the interdigitation that controls membrane thickness and rigidity. Hsp70-PS interaction depended on the lipid phase state; the protein stabilized ordered domains enriched with high-melting PS, increasing their area, probably due to formation of quasi-interdigitated phase. Moreover, the ability of Hsp70 to form ion-permeable pores in PS membranes may also be determined by the bilayer thickness. These observations contribute to a better understanding of Hsp70-PS interaction and biological functions of membrane-bound Hsp70 in cancer cells., (© 2023. The Author(s).)

Eulophia macrobulbon (EM) extract-loaded transferosomes represent an advanced approach for enhancing skin permeation of bioactive compounds. The formulations improving skin permeation and characterizations of transferosomes were studied, including morphology, entrapment efficiency (EE), vesicle size, polydispersity index (PDI), zeta potential, and skin permeation in the Strat-M® synthetic membrane. Vesicle size increased with increasing transition temperature (T m ) of phosphatidylcholine and the hydrophilic-lipophilic balance (HLB) of the surfactant used as an edge activator. EM extract-loaded transferosomes with varying amounts of phosphatidylcholine, surfactants, and EM extract showed non-significant differences in EE, PDI, and zeta potential. The results demonstrated that the EM extract-loaded transferosomes improved membrane permeability better than the EM solution. The EM solution exhibited a shorter lag time. Considering the advantages of the EM extract-loaded transferosomes and EM solutions, a combination of both formulations was developed in this study. The results showed that the lag time decreased and membrane permeation increased. This study highlights a novel system combining EM extract-loaded transferosomes and an EM solution, exhibiting considerable improvement in skin permeation and presenting the potential for an efficient transdermal drug delivery system for natural bioactive compounds., Competing Interests: Declaration of Competing Interest The authors have no competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The objective of the study was to examine the effect of soy lecithin (SL) and cholesterol loaded cryclodestrin (CLC) on cryo-survival of sperm cryopreserved in the presence or absence of seminal plasma in Saanen dairy goats. Tris-based dilutions containing various concentrations of SL (0, 0.5%, 1.0% or 2.0%) and CLC (0, 2.0 g/L, 4.0 g/L or 6.0 g/L CLC) were used to cryopreserve Saanen dairy goat sperm. The quality of frozen-thawed sperm, including progressive motility, viability, acrosome and plasma membrane integrity, as well as fertility were detected. Results found that the optimal combination of the two cryoprotectants was 1.0% SL+4.0 g/L CLC, which significantly increased progressive motility, viability, acrosome and plasma membrane integrity of frozen thawed sperm. The impact of the two cryoprotectants in combination was not affected by the presence of seminal plasma. The conception rates obtained after artificial insemination using sperm cryopreserved with and without seminal plasma were 88.89% and 91.67% (P > 0.05), respectively. The respective values for average number of litter sizes were 1.55 ± 0.17 and 1.56 ± 0.21 (P > 0.05). Therefore, this study improved the cryopreservation efficiency of goat semen, enhanced the sperm cryosurvival, and layed a foundation for the wide application of frozen goat semen., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Atorvastatin calcium (AC), a cholesterol-lowering medication, has limited oral bioavailability (14 %) and adverse impacts on the gastrointestinal tract (GIT), liver, and muscle. So, in an effort to improve the poor availability and overcome the hepatotoxicity complications attendant to peroral AC administration, transdermal transfersomal gel (AC-TFG) was developed as a convenient alternative delivery technique. The impact of utilizing an edge activator (EA) and varying the phosphatidylcholine (PC): EA molar ratio on the physico-chemical characteristics of the vesicles was optimized through a Quality by Design (QbD) strategy. The optimal transdermal AC-TFG was tested in an ex-vivo permeation study employing full-thickness rat skin, Franz cell experiments, an in-vivo pharmacokinetics and pharmacodynamics (PK/PD) evaluation, and a comparison to oral AC using poloxamer-induced dyslipidemic Wister rats. The optimized AC-loaded TF nanovesicles predicted by the 2 3 -factorial design strategy had a good correlation with the measured vesicle diameter of 71.72 ± 1.159 nm, encapsulation efficiency of 89.13 ± 0.125 %, and cumulative drug release of 88.92 ± 3.78 % over 24 h. Ex-vivo data revealed that AC-TF outperformed a free drug in terms of permeation. The pharmacokinetic parameters of optimized AC-TFG demonstrated 2.5- and 13.3-fold significant improvements in bioavailability in comparison to oral AC suspension (AC-OS) and traditional gel (AC-TG), respectively. The transdermal vesicular technique preserved the antihyperlipidemic activity of AC-OS without increasing hepatic markers. Such enhancement was proven histologically by preventing the hepatocellular harm inflicted by statins. The results showed that the transdermal vesicular system is a safe alternative way to treat dyslipidemia with AC, especially when given over a long period of time., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The mechanisms underlying late-onset preeclampsia (LOPE) remain unknown. Metabolic disturbances have been implicated as a primary factor in LOPE development. Lipids have been shown to have great clinical value in recent years. This study aimed to use lipidomics to provide evidence for the etiology and potential therapeutic approaches for LOPE. Twenty patients with LOPE and 20 healthy controls were enrolled in this study. Placental lipidomic data were acquired using liquid chromatographymass spectrometry (LC-MS/MS), and the data were analyzed by weighted gene correlation network analysis (WGCNA) and statistical methods. Of 1508 identified lipids, 226 were differentially expressed between the LOPE and control groups. In the LOPE group, the abundance of most unsaturated triglycerides (TG) increased, whereas that of other lipids, including phosphatidylcholine (PC), sphingomyelin, and phosphatidylserine (PS) increased. The WGCNA implied that the correlation network module of lipids was highly related to clinical traits. Pathway analysis revealed that these dysregulated lipids are closely related to glycerophospholipid metabolism. Lipidomics may help identify the pathogenesis underlying placental dysfunction in LOPE patients and provide potential therapeutic targets in the future., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Lecithin nanoliposome (nano-LPO), with its cryoprotective properties, is considered to enhance the performance of a traditional semen cryoprotectant. Objective: To determine the optimal dose of lecithin nano-LPO added to the rooster semen extender. Materials and Methods: Semen samples collected weekly from eight broiler breeder roosters were mixed and aliquoted into five equal subsamples, during the five successive weeks. The subsamples were then diluted with a semen extender containing 0%, 0.5%, 1%, 1.5%, or 2% of lecithin nano-LPO. Post-thawed semen quality attributes, including sperm motility and velocity parameters, plasma membrane functionality, mitochondrial membrane potential (MMP), apoptosis-like changes, and fertility potential, were evaluated. Results: Total motility and velocity parameters, including curvilinear velocity (VCL), straight-line velocity (VSL), average path velocity μm/s (VAP), straightness (STR), linearity (LIN), lateral head displacement (ALH), and wobble (WOB) were quadratically ( p  < 0.01) influenced by graded levels of lecithin nano-LPO, such that the highest values were obtained when 1% of lecithin nano-LPO was used. Treatments had no significant effect on plasma membrane functionality; however, MMP ( p  < 0.08) and percentages of live and dead spermatozoa ( p  < 0.05) quadratically responded to increasing levels of lecithin nano-LPO, where the best outcome was found when about 1% of lecithin nano-LPO was used in the semen extender. The percentage of apoptotic spermatozoa cubically responded to increasing levels of lecithin nano-LPO ( p  ≤ 0.07). No significant trend of fertility rate was found in response to addition of lecithin nano-LPO levels. Conclusions: Supplementing an extender with 1.10% of lecithin nano-LPO is shown to be the optimal dose associated with the most improvement in post-thawed rooster sperm velocity measurements.

Most antimicrobial peptides (AMPs) damage the cell membrane of bacterial cells and induce rapid leakage of the internal cell contents, which is a main cause of their bactericidal activity. One of the AMPs, magainin 2 (Mag), forms nanopores in giant unilamellar vesicles (GUVs) comprising phosphatidylcholine (PC) and phosphatidylglycerol (PG), inducing leakage of fluorescent probes. In this study, to elucidate the Mag-induced pore formation in lipid bilayer region in E. coli cell membrane, we examined the interaction of Mag with single GUVs comprising E. coli polar lipids (E. coli-lipid-GUVs). First, we investigated the Mag-induced leakage of a fluorescent probe AF488 from single E. coli-lipid-GUVs, and found that Mag caused rupture of GUVs, inducing rapid AF488 leakage. The rate constant of Mag-induced GUV rupture increased with the Mag concentration. Using fluorescence microscopy with a time resolution of 5 ms, we revealed the GUV rupture process: first, a small micropore was observed in the GUV membrane, then the pore radius increased within 50 ms without changing the GUV diameter, the thickness of the membrane at the pore rim concomitantly increased, and eventually membrane aggregates were formed. Mag bound to only the outer monolayer of the GUV before GUV rupture, which increased the area of the GUV bilayer. We also examined the physical properties of E. coli-lipid-GUVs themselves. We found that the rate constant of the constant tension-induced rupture of E. coli-lipid-GUVs was higher than that of PG/PC-GUVs. Based on these results, we discussed the Mag-induced rupture of E. coli-lipid-GUVs and its mechanism., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The utility of andrographolide (AN) in visceral leishmaniasis (VL) and cutaneous leishmaniasis (CL) is limited owing to poor solubility, hindered permeation, and unstable structure under physiological conditions. The present study mainly focuses on synthesizing of andrographolide-Soya-L-α-phosphatidyl choline (ANSPC) complex in ethanol and its characterization using various spectral and analytical techniques. Results from FT-IR, 1 H NMR, ROSEY, and in silico docking techniques suggest ANSPC complex formation due to inter-molecular interaction between the hydrophilic head of SPC and hydroxyl group of AN present at 24th position. ANSPC complex demonstrated the solubility of 113.93 ± 6.66 μg/mL significantly (P < 0.05) greater than 6.39 ± 0.47 μg/mL of AN. The particle size of ANSPC complex was found to be 182.2 ± 2.69 nm. The IC 50 value of AN suspension (PBS, pH ~ 7.4) at 24, 48, and 72 h against Leishmania donovani (L. donovani) was noticed to be 32.76 ± 4.53, 20.87 ± 2.37, and 17.71 ± 3.06 μM/mL, respectively. Moreover, augmented aqueous solubility of ANSPC complex led to significant (P < 0.05) reduction in IC 50 value, i.e., 25.02 ± 4.35, 11.31 ± 0.60, and 8.33 ± 2.71 μM/mL at 24, 48, and 72 h, respectively. The IC 50 values for miltefosine were noted to be 9.84 ± 2.65, 12.13 ± 7.26, and 6.56 ± 0.61 μM/mL at similar time periods. Moreover, ANSPC complex demonstrated augmented cellular uptake at 24 h as compared to 6 h in L. donovani. We suppose that submicron size and phospholipid-mediated complexation might have endorsed the permeation of ANSPC complex across the plasma membrane of L. donovani parasite by transport mechanisms such as P-type ATPase. ANSPC complex warrants further in-depth in vivo studies under a set of stringent parameters for translating the product into a clinically viable form., (© 2023. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Brucine, one of the natural medications obtained from Nux vomica seeds, is used as an anti-inflammatory drug. Several investigations were performed to overcome its drawbacks, which will affect significantly its pharmaceutical formulation. The goal of the current investigation was to design, optimize, and evaluate the anti-inflammatory performance of BRU ethosomal gel. Brucineethosomal formulations were prepared using thin film hydration method and optimized by central composite design approach using three independent variables (lecithin concentration, cholesterol concentration, and ethanol percentage) and three response variables (vesicular size, encapsulation efficiency, and skin permeation). The optimized formulation was examined for its stability and then incorporated into HPMC gel to get BRU ethosomal gel. The obtained BRU-loaded ethosomal gel was evaluated for its physical properties, in vitro release, and ex vivo permeation and skin irritation. Finally, carrageenan-induced rat hind paw edema test was adopted for the anti-inflammatory activity. The developed BRU ethosomal gel exhibited good physical characteristics comparable with the conventional developed BRU gel. In vitro release of BRU from ethosomal gel was effectively extended for 6 h. Permeation of BRU from ethosomes was significantly higher than all formulations (p < 0.05), since it recorded steady state transdermal flux value 0.548 ± 0.03 μg/cm 2  h with enhancement ratio 2.73 ± 0.23. Eventually, BRU ethosomal gel exhibited potent anti-inflammatory activity as manifested by a significant decrease in rat hind paw inflammation following 24 h. In conclusion, the study emphasized the prospective of ethosomal gel as a fortunate carrier for intensifying the anti-inflammatory effect of Brucine., (© 2021. American Association of Pharmaceutical Scientists.)

Background: α-cyclodextrin (α-CD) is one of the dietary fibers that may have a beneficial effect on cholesterol and/or glucose metabolism, but its efficacy and mode of action remain unclear., Methods: In the present study, we examined the anti-hyperglycemic effect of α-CD after oral loading of glucose and liquid meal in mice., Results: Administration of 2 g/kg α-CD suppressed hyperglycemia after glucose loading, which was associated with increased glucagon-like peptide 1 (GLP-1) secretion and enhanced hepatic glucose sequestration. By contrast, 1 g/kg α-CD similarly suppressed hyperglycemia, but without increasing secretions of GLP-1 and insulin. Furthermore, oral α-CD administration disrupts lipid micelle formation through its inclusion of lecithin in the gut luminal fluid. Importantly, prior inclusion of α-CD with lecithin in vitro nullified the anti-hyperglycemic effect of α-CD in vivo, which was associated with increased intestinal mRNA expressions of SREBP2-target genes (Ldlr , Hmgcr , Pcsk9 , and Srebp2 )., Conclusions: α-CD elicits its anti-hyperglycemic effect after glucose loading by inducing lecithin inclusion in the gut lumen and activating SREBP2, which is known to induce cholecystokinin secretion to suppress hepatic glucose production via a gut/brain/liver axis.

The actinomycete Lentzea aerocolonigenes produces the antitumor antibiotic rebeccamycin. In previous studies the rebeccamycin production was significantly increased by the addition of glass beads during cultivation in different diameters between 0.5 and 2 mm and the induced mechanical stress by the glass beads was proposed to be responsible for the increased production. Thus, this study was conducted to be a systematic investigation of different parameters for macroparticle addition, such as bead diameter, concentration, and density (glass and ceramic) as well as shaking frequency, for a better understanding of the particle-induced stress on L. aerocolonigenes. The induced stress for optimal rebeccamycin production can be estimated by a combination of stress energy and stress frequency. In addition, the macroparticle-enhanced cultivation of L. aerocolonigenes was combined with soy lecithin addition to further increase the rebeccamycin concentration. With 100 g L -1 glass beads in a diameter of 969 µm and 5 g L -1 soy lecithin a concentration of 388 mg L -1 rebeccamycin was reached after 10 days of cultivation, which corresponds to the highest rebeccamycin concentrations achieved in shake flask cultivations of L. aerocolonigenes stated in literature so far., (© 2021 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals LLC.)

This study investigates whether lecithin could fasten lipolysis through the alleviation of protein aggregation in an infant formula emulsion model. Our previous study reported low intestinal digestion of infant formula could be due to the aggregation of proteins that slow lipid digestion. The emulsion contained lipids droplets simulating the fatty acid composition in breast milk, different levels of lecithin and milk protein. The interphase proteins were replaced with lecithin in a dose-dependent manner. The results showed the addition of 5% and 7% lecithin improves the physical stability, narrows the range of particle size, reduces the mean particle size and increases the zeta potential. The 5% lecithin emulsion showed the highest rate and extent of lipid and protein digestion. These positive effects were caused by lecithin through stabilizing the emulsion and suppressing droplet flocculation after digestion. Lecithin promotes lipid digestion and may improve the "insufficient fat supply" in infant formula., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Lecithin:cholesterol acyltransferase protein (LCAT) promotes the esterification reaction between cholesterol and phospholipid-derived acyl chains. Positive allosteric modulators have been developed to treat LCAT deficiencies and, plausibly, also cardiovascular diseases in the future. The mechanism of action of these compounds is poorly understood. Here computational docking and atomistic molecular dynamics simulations were utilized to study the interactions between LCAT and the activating compounds. Results indicate that all drugs bind to the allosteric binding pocket in the membrane-binding domain in a similar fashion. The presence of the compounds in the allosteric site results in a distinct spatial orientation and sampling of the membrane-binding domain (MBD). The MBD's different spatial arrangement plausibly affects the lid's movement from closed to open state and vice versa, as suggested by steered molecular dynamics simulations., Competing Interests: The authors have declared that no competing interests exist.

A 70-day experiment was carried out to assess the effect of different levels (0, 1 and 2%) of soy lecithin in the diet on growth, survival, antioxidant defense markers, immune gene expression and thermal tolerance limits of golden mahseer, Tor putitora fry. Percentage weight gain, specific growth rate (SGR %) and survival of mahseer fed lecithin supplemented diets were not significantly different from those of the control group. Also, the mRNA expression levels of different immune related genes such as tnfα, il-1β, il-10, complement-3, interferon-gamma (ifnγ) and tlr4 were unaffected by dietary lecithin supplementation. Nevertheless, superoxide dismutase (SOD) activity was significantly greater in the lecithin-fed groups than the control fish. The glutathione-S-transferase (GST) activity was exceptionally high in the 2% lecithin supplemented group compared to the rest two groups. This increase in antioxidant status with dietary lecithin supplementation, however, was not reflected in the whole body malonaldehyde (MDA) levels, as it did not vary significantly among the dietary groups. Importantly, dietary inclusion of soy lecithin significantly increased upper thermal tolerance limits as evidenced by higher CT max and LT max values. Likewise, golden mahseer fry fed with lecithin supplemented diets (both 1 and 2%) registered significantly lower critical and lethal thermal minimum (CT min and LT min ) values than the control group, indicating higher cold tolerance capacity. Our results thus demonstrate that the dietary inclusion of soy lecithin could enhance the upper and lower thermal tolerance limits and antioxidant status of golden mahseer fry and failed to enhance immune related gene expression., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

An experiment was performed to assess the inclusion of soybean lecithin (SL) in the replacement of soybean oil (SO), for grower and finisher broiler chicken diets (up to 15 d of life), and its effects on performance, fatty acid (FA) absorption, gut health, and saturation degree of the abdominal fat pad (AFP). A total of 1,440 female Ross-308 chickens were distributed in 60 pens and were fed 5 experimental diets. The control diet (T1) was supplemented with SO (grower and finisher diets at 2.00%), and 4 levels of SL were included in replacement: T2 (0.25% in grower and 0.50% in finisher diets), T3 (0.50% in grower and 1.00% in finisher diets), T4 (0.75% in grower and 1.50% in finisher diets), and T5 (1.00% in grower and 2.00% in finisher diets). At day 39, titanium dioxide was added to finisher diets at 5 g/kg to perform a digestibility balance. At day 46, AFP, tissue, and gut digesta samples were collected to characterize FA digestibility, adipose saturation degree, microbial groups, and histomorphometry. No effects were associated with SO replacement by SL on performance (P > 0.05), ileal digestibility of total, saturated and monounsaturated FA (P > 0.05), nor jejunal morphology (P > 0.05). Total replacement of SO by SL reduced ileal absorption of polyunsaturated FA (P < 0.02) and increased jejunal Lactobacillus spp. counts (P = 0.049). Higher levels of SL inclusion (T4 and T5) lowered polyunsaturated FA concentration of the AFP (P = 0.002) and, thus, slightly reduced its unsaturated-to-saturated FA ratio (P = 0.005). Soybean lecithin inclusion did not modify performance parameters, total FA absorption, nor jejunal morphology, however caused changes on polyunsaturated FA absorption, jejunal microbiota, and saturation degree of the AFP. The study demonstrates that soybean lecithin can be included, in combination with or in replacement of soybean oil, as an alternative energy source for grower (up to a 1%) and finisher broiler diets (up to 2%)., (Copyright © 2020. Published by Elsevier Inc.)

Phospholipase A 2 (PLA 2 ) from Streptomyces violaceoruber is a lipolytic enzyme used in a wide range of industrial applications including production of lysolecithins and enzymatic degumming of edible oils. We have therefore investigated expression and secretion of PLA 2 in two workhorse microbes, Pichia pastoris and Escherichia coli . The PLA 2 was produced to an activity of 0.517 ± 0.012 U/ml in the culture broth of the recombinant P. pastoris . On the other hand, recombinant E. coli BL21 star (DE3), overexpressing the authentic PLA 2 (P-PLA2), showed activity of 17.0 ± 1.3 U/ml in the intracellular fraction and 21.7 ± 0.7 U/ml in the culture broth. The extracellular PLA 2 activity obtained with the recombinant E. coli system was 3.2-fold higher than the corresponding value reached in a previous study, which employed recombinant E. coli BL21 (DE3) overexpressing codon-optimized PLA2. Finally, we observed that the extracellular PLA 2 from the recombinant E. coli P-PLA 2 culture was able to hydrolyze 31.1 g/l of crude soybean lecithin, an industrial substrate, to a conversion yield of approximately 95%. The newly developed E. coli -based PLA 2 expression system led to extracellular production of PLA 2 to a productivity of 678 U/l·h, corresponding to 157-fold higher than that obtained with the P. pastoris -based system. This study will contribute to the extracellular production of a catalytically active PLA 2 .

Passive gastrointestinal absorption and membrane retention of twelve esters of (S,S)-ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid (EDCP) and (S,S)-1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid (PDCP), as well as of these two non-esterified acids were estimated using PAMPA test. Artificial PAMPA membrane used in this study for the simulation of gastrointestinal barrier was solution of egg lecithin in dodecane (1 % w/v). All tested compounds belong to class III (high membrane retention and low permeation), whereas EDCP, dipentyl ester of PDCP (DPE-PDCP) and diisopentyl ester of PDCP (DIPE-PDCP) belong to class I (negligible membrane retention and low permeation). Finally, quantitative structure - permeability and structure - retention relationships models were created in order to find quantitative relationships between physico-chemical properties of tested compounds and PAMPA membrane permeability/membrane retention parameters. Statistically the most reliable models were analysed and used for the design of new compounds for which favourable membrane permeability and retention can be expected., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Surfactants are important ingredients in pharmaceutical and cosmetic formulations, as in creams, shampoos or shower gels. As conventional emulsifiers such as sodium dodecyl sulfate (SDS) have fallen into disrepute due to their skin irritation potential, the naturally occurring lecithins are being investigated as a potential alternative. Thus, lecithin-based nanoemulsions with and without the drug curcumin, known for its wound healing properties, were produced and characterised in terms of their particle size, polydispersity index (PDI) and zeta potential and compared to SDS-based formulations. In vitro toxicity of the produced blank nanoemulsions was assessed with primary human keratinocytes and fibroblasts using two different cell viability assays (BrdU and EZ4U). Further, we investigated the penetration profiles of the deployed surfactants and oil components using combined ATR-FTIR/tape stripping experiments and confirmed the ability of the lecithin-based nanoemulsions to deliver curcumin into the stratum corneum in tape stripping-UV/Vis experiments. All manufactured nanoemulsions showed droplet sizes under 250 nm with satisfying PDI and zeta potential values. Viability assays with human skin cells clearly indicated that lecithin-based nanoemulsions were superior to SDS-based formulations. ATR-FTIR tests showed that lecithin and oil components remained in the superficial layers of the stratum corneum, suggesting a low risk for skin irritation. Ex vivo tape stripping experiments revealed that the kind of oil used in the nanoemulsion seemed to influence the depth of curcumin penetration into the stratum corneum., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Scavenger receptor class B type I (SR-BI) mediates the selective uptake of cholesteryl esters (CE) from high-density lipoproteins (HDL). An impaired SR-BI function leads to hyperalphalipoproteinemia with elevated levels of cholesterol transported in the HDL fraction. Accumulation of cholesterol in apolipoprotein B (apoB)-containing lipoproteins has been shown to alter skin lipid composition and barrier function in mice. To investigate whether these hypercholesterolemic effects on the skin also occur in hyperalphalipoproteinemia, we compared skins of wild-type and SR-BI knockout (SR-BI - / - ) mice. SR-BI deficiency did not affect the epidermal cholesterol content and induced only minor changes in the ceramide subclasses. The epidermal free fatty acid (FFA) pool was, however, enriched in short and unsaturated chains. Plasma CE levels strongly correlated with epidermal FFA C18:1 content. The increase in epidermal FFA coincided with downregulation of cholesterol and FFA synthesis genes, suggesting a compensatory response to increased flux of plasma cholesterol and FFAs into the skin. Importantly, the SR-BI - / - epidermal lipid barrier showed increased permeability to ethyl-paraminobenzoic acid, indicating an impairment of the barrier function. In conclusion, increased HDL-cholesterol levels in SR-BI - / - mice can alter the epidermal lipid composition and lipid barrier function similarly as observed in hypercholesterolemia due to elevated levels of apoB-containing lipoproteins., (Copyright © 2019 The Author(s). Published by Elsevier B.V. All rights reserved.)

Vegetable lecithins, widely used in the food industry as emulsifiers, are a mixture of naturally occurring lipids containing more than 50% of phospholipids (PL). PL exert numerous important physiological effects. Their amphiphilic nature notably enables them to stabilise endogenous lipid droplets, conferring them an important role in lipoprotein transport, functionality and metabolism. In addition, beneficial effects of dietary lecithin on metabolic disorders have been reported since the 1990s. This review attempts to summarize the effects of various vegetable lecithins on lipid and lipoprotein metabolism, as well as their potential application in the treatment of dyslipidemia associated with metabolic disorders. Despite controversial data concerning the impact of vegetable lecithins on lipid digestion and intestinal absorption, the beneficial effect of lecithin supplementation on plasma and hepatic lipoprotein and cholesterol levels is unequivocal. This is especially true in hyperlipidemic patients. Furthermore, the immense compositional diversity of vegetable lecithins endows them with a vast range of biochemical and biological properties, which remain to be explored in detail. Data on the effects of vegetable lecithins alternative to soybean, both as supplements and as ingredients in different foods, is undoubtedly lacking. Given the exponential demand for vegetable products alternative to those of animal origin, it is of primordial importance that future research is undertaken in order to elucidate the mechanisms by which individual fatty acids and PL from various vegetable lecithins modulate lipid metabolism. The extent to which they may influence parameters associated with metabolic disorders, such as intestinal integrity, low-grade inflammation and gut microbiota must also be assessed., Competing Interests: Declaration of competing interest C.V. and L.C. are employees of ITERG. C.R. is a PhD student hired by ITERG (CIFRE doctoral grant). M.-C.M. received research fundings for other topics from Sodiaal-Candia R&D, the Centre National Interprofessionnel de l’Economie Laitière (CNIEL, French Dairy Interbranch Organization) and Nutricia Research and has consultancy activities for food & dairy companies. These activities had no link with the present review. M.-C. M. is an external expert member of the Scientific Committee of ITERG. All authors are members of UMT ACTIA BALI (BioAvailability of Lipids and Intestine)., (Copyright © 2019 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)

Two experiments were conducted to evaluate the use of crude soybean lecithin (L) as an alternative energy source in broiler feeding and to study its influence on performance, fatty acid (FA) digestibility between 9 to 11 D and 36 to 37 D, feed AME content, and the FA profile of the abdominal fat pad (AFP). A basal diet was supplemented at 3% with soybean oil (S; experiment 1) or a monounsaturated vegetable acid oil (A; experiment 2) and increasing amounts of L (1, 2, and 3%) were included in replacement. The inclusion of L did not modify performance results (P > 0.05). In starter diets, the replacement of S by L reduced feed AME content (P < 0.001) and lowered PUFA digestibility (P = 0.028), whereas in the grower-finisher phase, a blend of 2% of S and 1% of L did not modify feed AME content or FA digestibility. When L was included instead of A, no effects on feed AME value and total FA digestibility (P > 0.05) were shown in the starter phase, whereas in grower-finisher diets, a blending of 2% of A and 1% of L enhanced feed AME content (P < 0.001) and total FA digestibility (P = 0.001). The FA profile of the AFP reflected the FA composition of the diets. Crude soybean lecithin represents an alternative energy source for broiler chickens, and it can be used in growing-finishing diets in replacement of 1% S. The best option to include both alternative fats (L and A) was 2% of L with 1% of A in starter diets and 1% of L with 2% of A in grower-finisher diets because they showed positive synergic effects. The results suggest that dietary FA profile have a bigger impact on the AFP saturation degree than the different dietary lipid molecular structures., (© 2019 Poultry Science Association Inc.)

Organophosphorus compounds (OP) are stable P source in nature, and can increase eutrophication risk in waterbodies. Lecithin was the most difficult OP to be broken down. In this study, two typical phosphate-solubilizing microorganisms, Aspergillus niger and Acinetobacter sp., were applied to evaluate their ability to decompose both inorganic phosphates and lecithin. A. niger and Acinetobacter sp. could solubilize calcium phosphates by secreting various organic acids, e.g., oxalic and formic acids. The fungus, A. niger, shows significantly higher ability of solubilizing these inorganic phosphates than Acinetobacter sp., primarily due to its secretion of abundant oxalic acid. However, the bacterium, Acinetobacter sp., could secrete more acid phosphatase than A. niger for lecithin decomposition, i.e., 9300 vs. 8500 μmol L -1 h -1 . Moreover, after addition of CaCl 2 , the released P from lecithin was transformed to stable chlorapatite in the medium. To the contrast, Ca cations inclined to form calcium oxalate (rather than stable phosphate mineral) after the incubation of A. niger, as it induced relatively acidic environment after breaking down lecithin. Therefore, this work sheds light on the bright future of applying bacteria and Ca cations in OP pollutant management.

A feeding experiment was conducted to evaluate the effects of dietary soybean lecithin (SBL) supplementation on performance, hemato-immunological parameters, lipid biochemistry, antioxidant status, digestive enzymes activity and intestinal histomorphometry of Caspian brown trout, Salmo trutta caspius in the pre-spawning stage. The basal diet was supplemented with 0% (control), 3%, 6%, 9% and 12% of SBL to obtain five experimental diets. Fish with an average weight of 350 ± 10 g were randomly distributed among five experimental groups and fed for 90 days. Dietary SBL resulted in better performance including specific growth rate (SGR), weight gain (WG) and feed conversion ratio (FCR) (p < 0.05). Among the different hemato-immunological parameters, white blood cell counts (WBC), lysozyme, alternative complement activity (ACH50) and total immunoglobulin (IgM) content of serum were significantly increased with dietary SBL inclusion (p < 0.05). For antioxidant enzymes, glutathione S-transferase (GST) and catalase (CAT) showed significant differences among various experimental diets (p < 0.05). Furthermore, digestive enzymes activity including alkaline protease, lipase and amylase were increased in those fish received SBL supplemented diets (p < 0.05). Our results revealed that the dietary SBL improved some physiological responses of the fish and indicate 6-9% dietary SBL supplementation would improve the physiological competence of the pre-spawning Caspian brown trout breeders., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The aim of this study was to evaluate the quality of ram semen after cryopreservation with different levels of fennel (Foeniculum vulgare) extract (0 (F0), 5 (F5), 10 (F10) and 15 (F15) mg/L) and sperm concentrations (200 (C200) and 400 (C400) × 10 6 sperm/mL) in a soy lecithin (SL)-based extender. Twenty ejaculates were collected from four ghezel rams and diluted with eight sperm concentrations/fennel combinations: F0C200, F5C200, F10C200, F15C200, F0C400, F5C400, F10C400 and F15C400. Sperm motility, abnormality, plasma membrane, viability, mitochondrial activity, lipid peroxidation (LPO), mitochondrial activity and apoptotic changes were evaluated after freeze-thawing process. It was observed that F10C400 significantly improved total and progressive motility, VSL, membrane integrity of post-thawed ram sperm. MDA level was lower in F5C200 and F10C400 compared to other treatments. The higher percentage of live sperm and the lower percentage of apoptotic sperm were obtained in F10C200 compared to F0C200, F5C200 F15C400, F0C400, F5C400 and F15C400. Extender F10C200 resulted in the highest mitochondria activity compared to the rest of the extenders except F10C400. We conclude that a combination of 10 mg/mL fennel (Foeniculum vulgare) extract and sperm concentration of 200 × 10 6 sperm/mL can improve the ram semen quality cryopreserved in a soybean lecithin based extender., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Application of agro-industrial by-products for the production of lactic acid was studied in this paper. Brewer's spent grain (BSG), malt rootlets (MR), brewer's yeast (BY), and soy lecithin (SL) were used as raw materials in L-(+)-LA fermentation by free and immobilized Lactobacillus rhamnosus ATCC 7469. The BSG, solid remains after BSG and MR hydrolysis (BSGMRSR), and MR were evaluated as carriers for batch and repeated batch fermentations with immobilized cells. During batch fermentations with immobilized cells, high cell viability (10 to 11 log CFU/g) was achieved on all carriers. In batch fermentation with BSG as a carrier, the highest LA yield of 93.79% and volumetric productivity of 1.15 g/L/h were obtained. Furthermore, very high LA yield (95.46%), volumetric productivity (1.98 g/L/h) and L. rhamnosus viability (11.5 log CFU/g) were achieved in repeated batch fermentations with the cells immobilized on this carrier. The immobilized cells showed high survival rate (94-95%) during exposure to simulated gut condition. Based on the analysis of BSGMRSR, and BY solid remains, and on in vitro evaluation of the probiotic characteristics of immobilized cells, it was observed that they could satisfy the recommendations for high-quality feed preparation.

Background and Objectives: The importance of quercetin and flavonoids in the diet and as food supplements is well known, and literature studies support their potential use to treat several human diseases. Many beneficial properties have been described for quercetin, so much effort has been directed into overcoming the major drawbacks of this natural compound-its poor solubility and low oral absorption. The aims of this study were to compare a new food-grade lecithin-based formulation of quercetin, Quercetin Phytosome ® , to unformulated quercetin in terms of solubility in simulated gastrointestinal fluids and oral absorption in a randomized crossover pharmacokinetic study of healthy volunteers., Methods: The solubility of the new formulation was determined by in vitro incubation in simulated gastrointestinal fluids, and quercetin was detected by ultra performance liquid chromatography. A single-dose, randomized, six-sequence/three-period crossover clinical trial (3 × 3 × 3 crossover design) with a balanced carryover effect was conducted in healthy volunteers under fasting conditions. Twelve healthy volunteers of both sexes with an age range of 18-50 years were recruited; one dose of quercetin and two different doses of Quercetin Phytosome were administered orally as film-coated tablets. Pharmacokinetic samples were collected at twelve time points (from 0 h to 24 h) after administration, and quercetin levels were measured by HPLC/MS/MS. Data were analyzed using the Phoenix WinNonlin (v.6.4) software package, and the most significant pharmacokinetic parameters were calculated. Statistical analysis involved performing a two-way ANOVA with repeated measures followed by post hoc analysis (Tukey's test)., Results: Significant improvements in both in vitro solubility and oral absorption (in terms of both exposure and maximum concentration achieved) by healthy volunteers in a human clinical study were obtained with the Quercetin Phytosome formulation as compared to unformulated quercetin., Conclusions: A more soluble formulation of quercetin based on lecithin, Quercetin Phytosome, has recently been developed, and was found to facilitate the attainment of very high plasma levels of quercetin-up to 20 times more than usually obtained following a dose of quercetin-when the novel formulation was administered orally in human volunteers, and it did not have any notable side effects. These results suggest that Quercetin Phytosome allows the oral administration of quercetin in a safe and bioavailable manner, thus facilitating the effective utilization of this natural compound to treat various human diseases.

During the last decade a special interest has been focused on studying the relationship between the composition and structure of emulsions and the extent of lipolysis, driven by the necessity of modulate lipid digestion to decrease or delay fats absorption or increase healthy fat nutrients bioavailability. Because bile salts (BS) play a crucial role in lipids metabolism, understanding how typical food emulsifiers affect the structures of BS under duodenal conditions, can aid to further understand how to control lipids digestion. In the present work the BS-binding capacity of three emulsifiers (Lecithin, Tween 80 and β-lactoglobulin) was studied under duodenal conditions. The combination of several techniques (DLS, TEM, ζ-potential and conductivity) allowed the characterization of molecular assemblies resulting from the interactions, as modulated by the relative amounts of BS and emulsifiers in solution., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Micellar liquid chromatography is a popular method used in the determination of a compound's lipophilicity. This study describes the use of the obtained micelle-water partition coefficient (log P mw ) by such a method in the prediction of human intestinal absorption (HIA). As a result of the close resemblance of the novel composition of the micellar mobile phase to that of physiological intestinal fluid, prediction was deemed to be highly successful. The unique micellar mobile phase consisted of a mixed micellar mixture of lecithin and six bile salts, i.e. a composition matching that found in the human intestinal environment, prepared in ratios resembling those in the intestine. This is considered to be the first method to use a physiological mixture of biosurfactants in the prediction of HIA. As a result, a mathematical model with high predictive ability (R 2 PRED  = 81%) was obtained using multiple linear regression. The micelle-water partition coefficient (log P mw ) obtained from micellar liquid chromatography was found to be a successful tool for prediction where the final optimum model included log P mw and polar surface area as key descriptors with high statistical significance for the prediction of HIA. This can be attributed to the nature of the mobile phase used in this study which contains the lecithin-bile salt complex, thus forming a bilayer system and therefore mimicking absorption across the intestinal membrane., (© 2018 The Authors. Biomedical Chromatography published by John Wiley & Sons, Ltd.)

The present study aimed to demonstrate that Sideral ® RM (SRM, Sucrosomial ® Raw Material Iron) is transported across the excised intestine via a biological mechanism, and to investigate the effect that this transport route may produce on oral iron absorption, which is expected to reduce the gastrointestinal (GI) side effects caused by the bioavailability of non-absorbed iron. Excised rat intestine was exposed to fluorescein isothiocyanate (FITC)-labeled SRM in Ussing chambers followed by confocal laser scanning microscopy to look for the presence of fluorescein-tagged vesicles of the FITC-labeled SRM. To identify FITC-labeled SRM internalizing cells, an immunofluorescence analysis for macrophages and M cells was performed using specific antibodies. Microscopy analysis revealed the presence of fluorescein positive particulate structures in tissues treated with FITC-labeled SRM. These structures do not disintegrate during transit, and concentrate in macrophage cells. Iron bioavailability was assessed by determining the time-course of Fe 3+ plasma levels. As references, iron contents in liver, spleen, and bone marrow were determined in healthy rats treated by gavage with SRM or ferric pyrophosphate salt (FP). SRM significantly increased both area under the curve (AUC) and clearance maxima (C max ) compared to FP, thus increasing iron bioavailability (AUC rel = 1.8). This led to increased iron availability in the bone marrow at 5 h after single dose gavage.

Felodipine has a very low bioavailability due to first-pass metabolism. The aim of this study was to enhance its bioavailability by transdermal application. Felodipine-loaded transferosomes were prepared by thin-film hydration using different formulation variables. An optimized formula was designed using statistical experimental design. The independent variables were the used edge activator, its molar ratio to phosphatidylcholine, and presence or absence of cholesterol. The responses were entrapment efficiency of transferosomes, their size, polydispersity index, zeta potential, and percent drug released after 8 h. The optimized formula was subjected to differential scanning calorimetry studies and its stability on storage at 4°C for 6 months was estimated. This formula was improved by incorporation of different permeation enhancers where ex vivo drug flux through mice skin was estimated and the best improved formula was formulated in a gel and lyophilized. The prepared gel was subjected to in vivo study using Plendil® tablets as a reference. According to the calculated desirability, the optimized transferosome formula was that containing sodium deoxycholate as edge activator at 5:1 M ratio to phosphatidylcholine and no cholesterol. The thermograms of this formula indicated the incorporation of felodipine inside the prepared vesicles. None of the tested parameters differed significantly on storage. The lyophilized gel of labrasol-containing formula was chosen for in vivo study. The relative bioavailability of felodipine from the designed gel was 1.7. In conclusion, topically applied lyophilized gel containing felodipine-loaded transferosomes is a promising transdermal delivery system to enhance its bioavailability.

Objective: The goal of this study is to improve the transdermal delivery of phosphatidylcholine (PC) via constructing a novel nanolipid vesicular system (NLVS) with high level of permeability through the stratum corneum (SC)., Significance: In our study, a novel drug free NLVS was developed. The system depends on PC boundary cartilage lubrication to relieve osteoarthritic pain without developing gastrointestinal problems associated with anti-inflammatory drug., Materials and Methods: A full two-level (2 3 ) factorial design is applied to optimize the quality of the prepared NLVS. The selected independent variables are the concentration of PC, the concentration of edge activator (EA), and EA type. The developed NLVS was evaluated for in-vitro, ex-vivo as well as in-vivo efficacy in rat animal model., Results: Based on the factorial design, the selected formulation variables significantly affect the tested responses. The prepared NLV formulations have a particle size (PS)in the range of 10.34 to 496.3 nm, polydispersity index (PdI) values less than one, and negative zeta potential (ZP) range of -1.42 to -32.01 mV. In-vitro and ex-vivo study results reveal that the designed NLVS is effective in sustaining PC release and enhancing its transdermal permeation over 24 h. The optimal permeation flux through ex-vivo study is 0.415 mg/cm 2 /h following zero-order kinetics. Moreover, in-vivo study of the optimized formulations demonstrated remarkable reduction in inflammatory mediators associated with osteoarthritis (OA)., Conclusion: The results indicate that the optimized drug free NLVS significantly augment transdermal delivery of PC and have a potential role in treatment of OA without the risk of systemic side effects.

Melanoma is the deadliest type of skin cancer. CD20+ melanoma stem cells (CSCs) are pivotal for metastasis and initiation of melanoma. Therefore, selective elimination of CD20+ melanoma CSCs represents an effective treatment to eradicate melanoma. Salinomycin has emerged as an effective drug toward various CSCs. Due to its poor solubility, its therapeutic efficacy against melanoma CSCs has never been evaluated. In order to target CD20+ melanoma CSCs, we designed salinomycin-loaded lipid-polymer nanoparticles with anti-CD20 aptamers (CD20-SA-NPs). Using a single-step nanoprecipitation method, salinomycin-loaded lipid-polymer nanoparticles (SA-NPs) were prepared, then CD20-SA-NPs were obtained through conjugation of thiolated anti-CD20 aptamers to SA-NPs via a maleimide-thiol reaction. CD20-SA-NPs displayed a small size of 96.3 nm, encapsulation efficiency higher than 60% and sustained drug release ability. The uptake of CD20-SA-NPs by CD20+ melanoma CSCs was significantly higher than that of SA-NPs and salinomycin, leading to greatly enhanced cytotoxic effects in vitro, thus the IC 50 values of CD20-SA-NPs were reduced to 5.7 and 2.6 μg/mL in A375 CD+20 cells and WM266-4 CD+ cells, respectively. CD20-SA-NPs showed a selective cytotoxicity toward CD20+ melanoma CSCs, as evidenced by the best therapeutic efficacy in suppressing the formation of tumor spheres and the proportion of CD20+ cells in melanoma cell lines. In mice bearing melanoma xenografts, administration of CD20-SA-NPs (salinomycin 5 mg·kg -1 ·d -1 , iv, for 60 d) showed a superior efficacy in inhibition of melanoma growth compared with SA-NPs and salinomycin. In conclusion, CD20 is a superior target for delivering drugs to melanoma CSCs. CD20-SA-NPs display effective delivery of salinomycin to CD20+ melanoma CSCs and represent a promising treatment for melanoma.

The transdermal delivery of 2 fluorescent probes with similar molecular weight but different lipophilicity, into and through the skin from 2 commercially available transdermal bases, pluronic lecithin organogel, and Lipoderm ® has been evaluated. First, in vitro penetration of fluorescein sodium and fluorescein (free acid) through porcine skin was evaluated. Retention and depth distribution profiles in skin were obtained by tape stripping and then followed by optical sectioning using multiphoton microscopy. The results showed that Lipoderm ® led to an enhanced penetration of the hydrophilic compound, fluorescein sodium. For the lipophilic compound fluorescein (free acid), Lipoderm ® performed similar to pluronic lecithin organogel base, where minimal drug was detected in either receptor phase. The skin retention and depth distribution results also showed that the hydrophilic fluorescein sodium had high skin retention with Lipoderm ® , whereas fluorescein (free acid) had very low penetration and retention with increasing skin depth. Moreover, optical sectioning by multiphoton microscopy revealed an uneven distribution of probes across the skin in the x-y plane for both transdermal bases. This work showed that a hydrophilic compound has significantly increased skin penetration and retention when formulated with Lipoderm ® , and the skin retention of the probe was the main determinant of its skin flux., (Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

The effect of the antimicrobial compound triclosan (5-chloro-2'-(2,4-dichlorophenoxy)phenol) on the permeability of lecithin liposomes and rat liver mitochondria was studied. It was found that triclosan was able to increase nonspecific permeability of liposomes in a dose-dependent manner, which was detected by the release of the fluorescent probe sulforhodamine B (SRB) from vesicles. A partial release of SRB occurs instantly at the moment of triclosan addition, which is followed by a slow leakage of the dye. The triclosan-induced release of SRB from liposomes grew as pH of the medium was decreased from 9.5 to 7.5. As revealed by the laurdan generalized polarization (GP) technique, triclosan increased laurdan GP in lecithin liposomes, indicating a decrease in membrane fluidity. Measurements of GP as a function of fluorescence excitation wavelength gave an ascending line for triclosan-containing liposomes, which can be interpreted as phase heterogeneity of the lipid/triclosan system. Dynamic light scattering experiments also showed that at a high triclosan-to-lipid molar ratio (~0.5), a population of smaller light-scattering particles (~0.4 of the size of liposomes) appear in the system. Experiments with rat liver mitochondria demonstrated that triclosan (10-70μM) induced a high-amplitude cyclosporin А-insensitive swelling of the organelles accompanied the release of cytochrome c. On the basis of the results obtained, possible mechanisms of the toxic effect of triclosan in eukaryotic cells are discussed., (Copyright © 2017 Elsevier B.V. All rights reserved.)

ApoA-I activates LCAT that converts lipoprotein cholesterol to cholesteryl ester (CE). Molecular dynamic simulations suggested earlier that helices 5 of two antiparallel apoA-I molecules on discoidal HDL form an amphipathic tunnel for migration of acyl chains and unesterified cholesterol to the active sites of LCAT. Our recent crystal structure of Δ(185-243)apoA-I showed the tunnel formed by helices 5/5, with two positively charged residues arginine 123 positioned at the edge of the hydrophobic tunnel. We hypothesized that these uniquely positioned residues Arg123 are poised for interaction with fatty acids produced by LCAT hydrolysis of the sn-2 chains of phosphatidylcholine, thus positioning the fatty acids for esterification to cholesterol. To test the importance of Arg123 for LCAT phospholipid hydrolysis and CE formation, we generated apoA-I[R123A] and apoA-I[R123E] mutants and made discoidal HDL with the mutants and WT apoA-I. Neither mutation of Arg123 changed the particle composition or size, or the protein conformation or stability. However, both mutations of Arg123 significantly reduced LCAT catalytic efficiency and the apparent V max for CE formation without affecting LCAT phospholipid hydrolysis. A control mutation, apoA-I[R131A], did not affect LCAT phospholipid hydrolysis or CE formation. These data suggest that Arg123 of apoA-I on discoidal HDL participates in LCAT-mediated cholesterol esterification., (Copyright © 2018 by the American Society for Biochemistry and Molecular Biology, Inc.)

Phosphatidylserine (PS) is useful as the additive in industries for memory improvement, mood enhancement and drug delivery. Conventionally, PS was extracted from soybeans, vegetable oils, egg yolk, and biomass; however, their low availability and high extraction cost were limiting factors. Phospholipase D (PLD) is a promising tool for enzymatic synthesis of PS due to its transphosphatidylation activity. In this contribution, a new and uncharacterized PLD was first obtained from GenBank database via genome mining strategy. The open reading frame consisted of 1614 bp and potentially encoded a protein of 538-amino-acid with a theoretical molecular mass of 60 kDa. The gene was successfully cloned and expressed in Escherichia coli. Its enzymatic properties were experimentally characterized. The temperature and pH optima of PLD were determined to be 60°C and 7.5, respectively. Its hydrolytic activity was improved by addition of Ca 2+ at 5 mM as compared with the control. The enzyme displayed suitable transphosphatidylation activity and PS could be synthesized with L-serine and soybean lecithin as substrates under the catalysis of PLD. This PLD enzyme might be a potential candidate for industrial applications in PS production. To the best of our knowledge, this is the first report on genome mining of PLDs from GenBank database.

A study was conducted to determine the AMEn contents of fat by-products from the soybean oil industry for broiler chickens. A total of 390 slow-feathering Cobb × Cobb 500 male broilers were randomly distributed into 13 treatments having 6 replicates of 5 birds each. Birds were fed a common starter diet from placement to 21 d. Experimental corn-soy diets were composed of four fat sources, added at 3 increasing levels each, and were fed from 21 to 28 d. Fat sources utilized were acidulated soybean soapstock (ASS), glycerol (GLY), lecithin (LEC), and a mixture (MIX) containing 85% ASS, 10% GLY and 5% LEC. A 4 × 3 + 1 factorial arrangement was used with 4 by-products (ASS, GLY, LEC, or MIX), 3 inclusion levels and 1 basal diet. Each of the four fat by-product sources was included in the diets as follow: 2% of by-products (98% basal + 2% by-product), 4% (96% basal + 4% by-product), or 6% (94% basal + 6% by-product). Birds were submitted to 94, 96, 98, and 100% of ad libitum feed intake; therefore, the differences in AMEn consumption were only due to the added by-product. Total excreta were collected twice daily for 72 h to determine apparent metabolizable energy contents starting at 25 d. The AMEn intake was regressed against feed intake and the slope was used to estimate AMEn values for each fat source. Linear regression equations (P < 0.05) estimated for each by-product were as follow: 7,153X - 451.9 for ASS; 3,916X - 68.2 for GLY; 7,051X - 448.3 for LEC, and 8,515X - 622.3 for MIX. Values of AMEn were 7,153, 3,916, 7,051, and 8,515 kcal/kg DM for ASS, GLY, LEC, and MIX, respectively. The present study generated AMEn for fat by-products data that can be used in poultry feed formulation. It also provides indications that, by adding the 3 by-products in the proportions present in the MIX, considerable economic advantage can be attained., (© 2017 Poultry Science Association Inc.)

This study aimed to determine the effects of supplementing the diet of adult Nile tilapia Oreochromis niloticus with phosphatidylcholine (PC) on growth performance, body composition, fatty acid composition and gene expression. Genetically Improved Farmed Tilapia fish with an initial body weight of 83·1 (sd 2·9) g were divided into six groups. Each group was hand-fed a semi-purified diet containing 1·7 (control diet), 4·0, 6·5, 11·5, 21·3 or 41·0 g PC/kg diet for 68 d. Supplemental PC improved the feed efficiency rate, which was highest in the 11·5 g PC/kg diet. Weight gain and specific growth rate were unaffected. Dietary PC increased PC content in the liver and decreased crude fat content in the liver, viscera and body. SFA and MUFA increased and PUFA decreased in muscle with increasing dietary PC. Cytoplasmic phospholipase A 2 and secreted phospholipase A 2 mRNA expression were up-regulated in the brain and heart in PC-supplemented fish. PC reduced fatty acid synthase mRNA expression in the liver and visceral tissue but increased expression in muscle. Hormone-sensitive lipase and lipoprotein lipase expression increased in the liver with increasing dietary PC. Growth hormone mRNA expression was reduced in the brain and insulin-like growth factor-1 mRNA expression in liver reduced with PC above 6·5 g/kg. Our results demonstrate that dietary supplementation with PC improves feed efficiency and reduces liver fat in adult Nile tilapia, without increasing weight gain, representing a novel dietary approach to reduce feed requirements and improve the health of Nile tilapia.

To investigate the etiopathogenesis of fatty liver hemorrhagic syndrome (FLHS) and the protective effects of soybean lecithin against FLHS in laying hens, 135 healthy 300-day-old Hyline laying hens were randomly divided into groups: control (group 1), diseased (group 2), and protected (group 3). Each group contained 45 layers with 3 replicates. The birds in these 3 groups were fed a control diet, a high-energy/low-protein (HELP) diet or the HELP diet supplemented with 3% soybean lecithin instead of maize. The fat percent in the liver was calculated. Histopathological changes in the liver were determined by staining, and the mRNA expression levels of apolipoproteinA I (apoA I) and apolipoprotein B100 (apoB100) in the liver were determined by RT-PCR. The results showed that the fat percent in the liver of group 2 was much higher (P < 0.01) than that of group 1 and group 2 on d 30 and 60. The histology of the liver in group 2 on d 30 and 60 displayed various degrees of liver lesions, while the hepatocytes showed a normal structure in group 3 with mild microvesicular steatosis in the liver cell on d 30 and 60. The mRNA expression levels of apoA I and apoB100 in the livers were variable throughout the experiment. The expression level of apoA I in group 2 significantly decreased on d 60 (P < 0.05); the expression level of apoB100 slightly increased on d 30 in group 2, while it sharply decreased on d 60. Compared to group 1, the expression level of apoB100 showed no significant difference in group 3 (P < 0.05). This study indicated that FLHS induced pathological changes and abnormal expression of apoA I and apoB100 in the livers of laying hens and that soybean lecithin alleviated these abnormal changes., (© 2017 Poultry Science Association Inc.)

Context: Atorvastatin calcium (ATV), a cholesterol-lowering agent, suffers from poor systemic availability (14%) after oral administration in addition to other side effects on the gastrointestinal tract, liver and muscle., Objective: The goal of the present investigation was to improve ATV bioavailability and overcome complications attendant with peroral administration by developing a new nanovesicular system encapsulating ATV for its delivery via the transdermal route., Methods: The vesicular systems were prepared by incorporating different polyethylene glycol fatty acid esters such as Labrasol, Cremophor EL, Gelucire 44/14 and Tween 80 as edge activators (EAs) in the lipid bilayer. The effect of the phosphatidylcholine (PC):EA molar ratio on the physicochemical properties of the vesicles was investigated. The pharmacokinetic studies of the optimized formulation were evaluated in rats. The optimized formulation was tested in poloxamer 407-induced hyperlipidemic rats. The plasma lipid profile, activity of liver enzymes, and oxidative stress parameters were measured using commercially available kits., Results: The results revealed high ATV entrapment efficiency (EE%) ranging from 55.62 to 83.91%. The formulations that contained Labrasol showed the highest EE%. The mean diameter of the vesicles was in the range of 186-583nm. T8 containing Gelucire 44/14 as an EA in the molar ratio of 15:1 (PC:EA) gave the smallest size and exhibited the best permeation parameters across the skin. The pharmacokinetic studies revealed that about three times statistically significant (p<0.05) improvement in bioavailability, after transdermal administration of nanotransfersomal ATV gel compared to oral ATV suspension. The transdermal vesicular system exhibited a significant decrease in plasma total cholesterol, triglycerides and LDL cholesterol comparable to oral ATV. Additionally, it lowered the malondialdehyde levels in plasma and abolished the increase in liver enzyme activity., Conclusion: The results obtained suggest that the proposed transdermal vesicular system can serve as a promising alternative means for delivery of ATV., (Copyright © 2017. Published by Elsevier B.V.)

This research studied the enzymatic modification of egg yolk phospholipids and its effect on physicochemical properties. Egg yolk lipids were extracted with food grade ethanol and egg phospholipids (ePL) produced by deoiling with acetone. Vegetable oils were used to interesterify ePL utilizing Lipozyme®: sn-1,3 specific lipase. The enzymatic interesterification resulted in a single phase liquid product, whereas simple blending of the ePL and vegetable oil resulted in a product with two phases. In addition solid fat content decreased by 50% at -10°C and 94% at 35°C when compared with egg yolk lipids extract. A decrease in melting temperature resulted from the interesterification process. Interesterification improved emulsion stability index when used as an emulsifier in oil-in-water emulsion and compared to the native and soy lecithin. Enzyme reusability test showed retention of 63% activity after 10 cycles. Overall, the properties of native egg phospholipids were significantly enhanced in a potentially useful manner through interesterification., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Lecithin, a naturally small molecular surfactant, which is widely used in the food industry, can delay aging, enhance memory, prevent and treat diabetes. The interaction between zein and soy lecithin with different mass ratios (20:1, 10:1, 5:1, 3:1, 2:1, 1:1 and 1:2) in ethanol-water solution and characterisation of zein and lecithin composite colloidal nanoparticles prepared by antisolvent co-precipitation method were investigated. The mean size of zein-lecithin composite colloidal nanoparticles was firstly increased with the rise of lecithin concentration and then siginificantly decreased. The nanoparticles at the zein to lecithin mass ratio of 5:1 had the largest particle size (263 nm), indicating that zein and lecithin formed composite colloidal nanoparticles, which might aggregate due to the enhanced interaction at a higher proportion of lecithin. Continuing to increase lecithin concentration, the zein-lecithin nanoparticles possibly formed a reverse micelle-like or a vesicle-like structure with zein in the core, which prevented the formation of nanoparticle aggregates and decreased the size of composite nanoparticles. The presence of lecithin significantly reduced the ζ-potential of zein-lecithin composite colloidal nanoparticles. The interaction between zein and lecithin enhanced the intensity of the fluorescence emission of zein in ethanol-water solution. The secondary structure of zein was also changed by the addition of lecithin. Differential scanning calorimetry thermograms revealed that the thermal stability of zein-lecithin nanoparticles was enhanced with the rise of lecithin level. The composite nanoparticles were relatively stable to elevated ionic strengths. Possible interaction mechanism between zein and lecithin was proposed. These findings would help further understand the theory of the interaction between the alcohol soluble protein and the natural small molecular surfactant. The composite colloidal nanoparticles formed in this study can broaden the application of zein and be suitable for incorporating water-insoluble bioactive components in functional food and beverage products., Competing Interests: The authors have declared that no competing interests exist.

Background: The present study was undertaken to gain knowledge on the role of bile components and lecithin on development of aberrations in digestive functions which seemingly have increased in Atlantic salmon in parallel with the increased use of plant ingredients in fish feed. Post smolt Atlantic salmon were fed for 77 days one of three basal diets: a high fish meal diet (HFM), a low fishmeal diet (LFM), or a diet with high protein soybean meal (HPS). Five additional diets were made from the LFM diet by supplementing with: purified taurocholate (1.8 %), bovine bile salt (1.8 %), taurine (0.4 %), lecithin (1.5 %), or a mix of supplements (suppl mix) containing taurocholate (1.8 %), cholesterol (1.5 %) and lecithin (0.4 %). Two additional diets were made from the HPS diet by supplementing with: bovine bile salt (1.8 %) or the suppl mix. Body and intestinal weights were recorded, and blood, bile, intestinal tissues and digesta were sampled for evaluation of growth, nutrient metabolism and intestinal structure and function., Results: In comparison with fish fed the HFM diet fish fed the LFM and HPS diets grew less and showed reduced plasma bile salt and cholesterol levels. Histological examination of the distal intestine showed signs of enteritis in both LFM and HPS diet groups, though more pronounced in the HPS diet group. The HPS diet reduced digesta dry matter and capacity of leucine amino peptidase in the distal intestine. None of the dietary supplements improved endpoints regarding fish performance, gut function or inflammation in the distal intestine. Some endpoints rather indicated negative effects., Conclusions: Dietary supplementation with bile components or lecithin in general did not improve endpoints regarding performance or gut health in Atlantic salmon, in clear contrast to what has been previously reported for rainbow trout. Follow-up studies are needed to clarify if lower levels of bile salts and cholesterol may give different and beneficial effects, or if other supplements, and other combinations of supplements might prevent or ameliorate inflammation in the distal intestine.