ABSTRACT
The alarming increase in multidrug resistance, which includes Bedaquiline and Delamanid, stumbles success in Tuberculosis treatment outcome. Mycobacterium tuberculosis gains resistance to rifampicin, which is one of the less toxic and potent anti-TB drugs, through genetic mutations predominantly besides efflux pump mediated drug resistance. In recent decades, scientific interventions are being carried out to overcome this hurdle using novel approaches to save this drug by combining it with other drugs/molecules or by use of high dose rifampicin. This study reports five small molecules namely Ellagic acid, Methyl Stearate, Myoinositol, Rutin, and Shikimic acid that exhibit synergistic inhibitory activity with rifampicin against resistant TB isolates. In-silico examinations revealed possible blocking of Rv1819c-an ABC transporter efflux pump that was known to confer resistance in M. tuberculosis to rifampicin. The synergistic anti-TB activity was assessed using a drug combination checkerboard assay. Efflux pump inhibition activity of ellagic acid, myoinositol, and methyl stearate was observed through ethidium bromide accumulation assay in the drug-resistant M. tuberculosis clinical strains and recombinant Mycobacterium smegmatis expressing Rv1819c in coherence with the significant reduction in the minimum inhibitory concentration of rifampicin. Cytotoxicity of the active efflux inhibitors was tested using in silico and ex vivo methods. Myoinositol and methyl stearate were completely non-toxic to the hematological and epithelial cells of different organs under ex vivo conditions. Based on these findings, these molecules can be considered for adjunct TB therapy; however, their impact on other drugs of anti-TB regimen needs to be tested.
Subject(s)
Mycobacterium tuberculosis , Tuberculosis, Multidrug-Resistant , Humans , Rifampin/pharmacology , Stearates/therapeutic use , Inositol , Ellagic Acid , Tuberculosis, Multidrug-Resistant/drug therapy , Antitubercular Agents/pharmacology , Microbial Sensitivity TestsABSTRACT
Thermal decomposition is a very efficient synthesis strategy to obtain nanosized metal oxides with controlled structures and properties. For the iron oxide nanoparticle synthesis, it allows an easy tuning of the nanoparticle's size, shape, and composition, which is often explained by the LaMer theory involving a clear separation between nucleation and growth steps. Here, the events before the nucleation of iron oxide nanocrystals are investigated by combining different complementary in situ characterization techniques. These characterizations are carried out not only on powdered iron stearate precursors but also on a preheated liquid reaction mixture. They reveal a new nucleation mechanism for the thermal decomposition method: instead of a homogeneous nucleation, the nucleation occurs within vesicle-like-nanoreactors confining the reactants. The different steps are: 1) the melting and coalescence of iron stearate particles, leading to "droplet-shaped nanostructures" acting as nanoreactors; 2) the formation of a hitherto unobserved iron stearate crystalline phase within the nucleation temperature range, simultaneously with stearate chains loss and Fe(III) to Fe(II) reduction; 3) the formation of iron oxide nuclei inside the nanoreactors, which are then ejected from them. This mechanism paves the way toward a better mastering of the metal oxide nanoparticles synthesis and the control of their properties.
Subject(s)
Metal Nanoparticles , Oxides , Culture Media , Ferric Compounds/chemistry , Iron , Metal Nanoparticles/chemistry , Oxides/chemistry , StearatesABSTRACT
Sunflower oil oleogels consisting of 3% and 8% polyglycerol stearate (PGSO) were studied as an alternative frying media for onion rings. The physicochemical properties and thermo-rheological characteristics of oleogels were provided. The sensorial quality and texture profiles of onion rings fried in oleogels were compared with those fried in control sunflower oil. Free fatty acids at the end of 6 h were determined, and decreasing trend was reported in order as PGSO-8, control (sunflower) oil, and PGSO-3. The oxidation induction time for PGSO-8 was significantly lower (1.46 min) than those of the control and PGSO-3 samples following frying. Compared to the control group, the onion ring samples fried in oleogels absorbed approximately 33-37% less oil. It was thought that this reduction would help consumers to less total calorie and weight gain from the fried products. There were no negative effects of oleogel usage on the L* value, aroma, crispness/texture, and overall acceptability scores for the onion ring samples fried in the oleogels.
Subject(s)
Onions , Stearates , Glycerol , Organic Chemicals , Polymers , Sunflower Oil/chemistryABSTRACT
This paper addresses sorbitan and sucrose ester in physical transformations of palm mid-fraction (PMF). Both emulsifiers influenced the crystallization properties of PMF, mainly due to emulsifier solubility, which affects its ability to interfere with the kinetics of solution-mediated phase transformations. DSC results corroborate the polymorphism analysis, indicating that the mechanism and rate of phase transformation depend on the chemical structure and amount of each emulsifier. The addition of sorbitan tristearate (STS) and sucrose stearate (S-370) increased the crystallization speed of the PMF and caused changes in the crystallization behavior. STS favored the ß'âß transition, while S-370 stabilized the ß'-form. We can conclude that the presence of emulsifiers dissimilar to the composition of PMF modified its physical structure, either by increasing the liquid fraction or by reducing molecular motion, facilitating or preventing polymorphic transformations.
Subject(s)
Stearates , Sucrose , Crystallization , Hexoses , Palm Oil , Sucrose/analogs & derivativesABSTRACT
Vitamin C (VC)-loaded oleogel (VCOG) with corn oil and monoglyceride stearate was used to replace lipid phase of margarine completely. The oxidative stability of VCOG was evaluated at 60±1°C in a lightproof oven for 18 days and the result showed that VCOG peroxide (> 6 days) and p-anisidine value (> 4 days) was significantly lower than that of bulk oil and VC-free oleogel (p < 0.05). Then, the margarine containing 79.70% VCOG (VCOGM) was in comparison with four commercial butter in sensory and physical characteristic. Results showed that firmness, solid fat content and trans fatty acid of VCOGM were in the lowest values while unsaturated fatty acid and adhesiveness of VCOGM was in the highest values. Furthermore, VCOGM presented the similar springiness, cohesiveness, gumminess, score appearance, texture, taste and overall impression to some/all commercial butters selected in this research (p > 0.05). These results implied that VC-loaded oleogel was an excellent alternative of lipid phase in margarine which confirmed by 55% "definitely buy" and 25% "try once-then decide".
Subject(s)
Ascorbic Acid/chemistry , Corn Oil/chemistry , Fatty Acids, Unsaturated/chemistry , Margarine , Monoglycerides/chemistry , Stearates/chemistry , Butter , Consumer Behavior , Fatty Acids, Unsaturated/analysis , Humans , Organic Chemicals/chemistry , Oxidation-Reduction , Taste , Triglycerides/analysis , Triglycerides/chemistryABSTRACT
The pathological characteristics of Parkinson's disease (PD) include dopaminergic neuron damage, specifically disorders caused by dopamine synthesis, in vivo. Plastrum testudinis extract (PTE) and its bioactive ingredient ethyl stearate (PubChem CID: 8122) were reported to be correlated with tyrosine hydroxylase (TH), which is a biomarker of dopaminergic neurons. This suggests that PTE and its small-molecule active ingredient ethyl stearate have potential for development as a therapeutic drug for PD. In this study, we treated 6-hydroxydopamine (6-OHDA)-induced model rats and PC12 cells with PTE. The mechanism of action of PTE and ethyl stearate was investigated by western blotting, bisulfite sequencing PCR (BSP), real-time PCR, immunofluorescence and siRNA transfection. PTE effectively upregulated the TH expression and downregulated the alpha-synuclein expression in both the substantia nigra and the striatum of the midbrain in a PD model rat. The PC12 cell model showed that both PTE and its active monomer ethyl stearate significantly promoted TH expression and blocked alpha-synuclein, agreeing with the in vivo results. BSP showed that PTE and ethyl stearate increased the methylation level of the Snca intron 1 region. These findings suggest that some of the protective effects of PTE on dopaminergic neurons are mediated by ethyl stearate. The mechanism of ethyl stearate may involve disrupting the abnormal aggregation of DNA (cytosine-5)-methyltransferase 1 (DNMT1) with alpha-synuclein by releasing DNMT1, upregulating Snca intron 1 CpG island methylation, and ultimately, reducing the expression of alpha-synuclein.
Subject(s)
Antiparkinson Agents/pharmacology , Antiparkinson Agents/therapeutic use , DNA (Cytosine-5-)-Methyltransferase 1/metabolism , Dopaminergic Neurons/drug effects , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Parkinson Disease, Secondary/drug therapy , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Tissue Extracts/chemistry , alpha-Synuclein/metabolism , Animals , DNA (Cytosine-5-)-Methyltransferase 1/drug effects , Hydroxydopamines , Male , Mesencephalon/drug effects , Mesencephalon/metabolism , PC12 Cells , Parkinson Disease, Secondary/chemically induced , Rats , Rats, Sprague-Dawley , Stearates/pharmacology , Substantia Nigra/drug effects , Substantia Nigra/metabolism , alpha-Synuclein/drug effectsABSTRACT
BACKGROUND: Doxorubicin (DOX) is a leading chemotherapeutic in cancer treatment because of its high potency and broad spectrum. Liposomal doxorubicin (Doxil®) is the first FDA-approved PEG-liposomes of DOX for the treatment of over 600,000 cancer patients, and it can overcome doxorubicin-induced cardiomyopathy and other side effects and prolong life span. The addition of MPEG2000-DSPE could elevate the total cost of cancer treatment. OBJECTIVE: We intended to prepare a novel DOX liposome that was prepared with inexpensive materials egg yolk lecithin and Kolliphor HS15, thus allowing it to be much cheaper for clinical application. METHODS: DOX liposomes were prepared using the combination of thin-film dispersion ultrasonic method and ammonium sulfate gradient method and the factors that influenced formulation quality were optimized. After formulation, particle size, entrapment efficiency, drug loading, stability, and pharmacokinetics were determined. RESULTS: DOX liposomes were near-spherical morphology with the average size of 90 nm and polydispersity index (PDI) of less than 0.30. The drug loading was up to 7.5%, and the entrapment efficiency was over 80%. The pharmacokinetic studies showed that free DOX could be easily removed and the blood concentration of free DOX group was significantly lower than that of DOX liposomes, which indicated that the novel DOX liposome had a certain sustainedrelease effect. CONCLUSION: In summary, DOX liposome is economical and easy-prepared with prolonged circulation time. Lay Summary: Doxorubicin (DOX) is a leading chemotherapeutic in cancer treatment because of its high potency and broad spectrum. Liposomal doxorubicin (Doxil®) is the first FDAapproved PEG-liposomes of DOX to treat over 600.000 cancer patients, overcoming doxorubicin- induced cardiomyopathy and other side effects and prolonging life span. The addition of MPEG2000-DSPE could elevate the total cost of cancer treatment. We intend to prepare a novel DOX liposome prepared with inexpensive materials egg yolk lecithin and Kolliphor HS15, thus allowing it to be much cheaper for clinical use. The novel DOX liposome is economical and easy-prepared with prolonged circulation time.
Subject(s)
Antibiotics, Antineoplastic/pharmacokinetics , Doxorubicin/analogs & derivatives , Lecithins/chemistry , Polyethylene Glycols/chemistry , Stearates/chemistry , Animals , Antibiotics, Antineoplastic/administration & dosage , Antibiotics, Antineoplastic/blood , Antibiotics, Antineoplastic/chemistry , Delayed-Action Preparations , Doxorubicin/administration & dosage , Doxorubicin/blood , Doxorubicin/chemistry , Doxorubicin/pharmacokinetics , Drug Compounding , Drug Liberation , Drug Stability , Injections, Intravenous , Liposomes , Male , Particle Size , Polyethylene Glycols/administration & dosage , Polyethylene Glycols/pharmacokinetics , Rats, Sprague-Dawley , Technology, PharmaceuticalABSTRACT
Structuring of vegetable oils has potential application in food, pharmaceutical and cosmetic products. In this study, structuring effects of stearic acid derivatives on sunflower seed oil were systematically investigated by experimental and molecular simulation methods. Stearic acid (SA), 12-hydroxy stearic acid (HSA) and 2-hydroxyethyl stearate (HES) were able to structure sunflower seed oil, among which the structuring ability of HES was reported for the first time. The oleogel formed with HSA exhibited good mechanical properties (such as hardness, fracturability, adhesiveness, chewiness and storage modulus), which coincided with its highest solid fat content and degree of crystallinity. Oleogels containing SA and HES showed similar mechanical properties. Both the molecular dynamics (MD) simulation and independent gradient model (IGM) confirmed that the HSA dimer possessed the strongest interaction during the self-assembly process while the dimers of HES and SA had similar interactions, which could explain their structuring performance.
Subject(s)
Stearates/chemistry , Stearic Acids/chemistry , Sunflower Oil/chemistry , Food Storage , Hardness , Models, Molecular , Molecular Dynamics Simulation , Organic Chemicals/chemistry , TemperatureABSTRACT
Therapeutic advances for osteosarcoma have stagnated over the past several decades, leading to an unmet clinical need for patients. The purpose of this study was to develop a novel therapy for osteosarcoma by reformulating and validating niclosamide, an established anthelminthic agent, as a niclosamide stearate prodrug therapeutic (NSPT). We sought to improve the low and inefficient clinical bioavailability of oral dosing, especially for the relatively hydrophobic classes of anticancer drugs. Nanoparticles were fabricated by rapid solvent shifting and verified using dynamic light scattering and UV-vis spectrophotometry. NSPT efficacy was then studied in vitro for cell viability, cell proliferation, and intracellular signaling by Western blot analysis; ex vivo pulmonary metastatic assay model; and in vivo pharmacokinetic and lung mouse metastatic model of osteosarcoma. NSPT formulation stabilizes niclosamide stearate against hydrolysis and delays enzymolysis; increases circulation in vivo with t 1/2 approximately 5 hours; reduces cell viability and cell proliferation in human and canine osteosarcoma cells in vitro at 0.2-2 µmol/L IC50; inhibits recognized growth pathways and induces apoptosis at 20 µmol/L; eliminates metastatic lesions in the ex vivo lung metastatic model; and when injected intravenously at 50 mg/kg weekly, it prevents metastatic spread in the lungs in a mouse model of osteosarcoma over 30 days. In conclusion, niclosamide was optimized for preclinical drug delivery as a unique prodrug nanoparticle injected intravenously at 50 mg/kg (1.9 mmol/L). This increased bioavailability of niclosamide in the blood stream prevented metastatic disease in the mouse. This chemotherapeutic strategy is now ready for canine trials, and if successful, will be targeted for human trials in patients with osteosarcoma.
Subject(s)
Antineoplastic Agents/pharmacology , Bone Neoplasms/drug therapy , Niclosamide/pharmacology , Osteosarcoma/drug therapy , Prodrugs/pharmacology , Stearates/pharmacology , Animals , Antinematodal Agents/chemistry , Antinematodal Agents/pharmacokinetics , Antinematodal Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacokinetics , Apoptosis , Bone Neoplasms/metabolism , Bone Neoplasms/pathology , Cell Proliferation , Dogs , Drug Evaluation, Preclinical , Drug Repositioning , Humans , Mice , Mice, Inbred C57BL , Niclosamide/chemistry , Niclosamide/pharmacokinetics , Osteosarcoma/metabolism , Osteosarcoma/pathology , Prodrugs/chemistry , Prodrugs/pharmacokinetics , Stearates/chemistry , Stearates/pharmacokinetics , Tissue Distribution , Tumor Cells, Cultured , Xenograft Model Antitumor AssaysABSTRACT
The objective of this study was to investigate the effects of diets supplemented with sodium stearoyl-2-lactylate (SSL), polyglycerol fatty acid ester (PGFE), and combined emulsifiers (0.02% SSL and 0.08% PGFE) on growth performance, nutrient digestibility, and plasma lipid profiles in weaned piglets and to further evaluate the possible effects of feeding exogenous emulsifiers on digestive enzyme activities and liver bile acid (BA) metabolism. Twenty-eight barrows (age at 35 d, Duroc × Landrace × Yorkshire) with an initial BW of 10.13 ± 0.16 kg were randomly assigned to 4 dietary treatment groups (7 pigs/treatment). Dietary treatment groups included the following: 1) basal diet (Control, CTR); 2) basal diet with 0.1% SSL (SSL); 3) basal diet with 0.1% PGFE (PGFE); and 4) basal diet with 0.08% PGFE+0.02% SSL (PG-SL). SSL diet increased ADG and ADFI of piglets during day 0 to 17 (P < 0.05) compared with the CTR treatment. Piglets fed emulsifier diets experienced a significant improvement in the digestibility of nutrients (DM, CP, ether extract, energy, calcium, and phosphorus) during the first 17 d (P < 0.05). The level of low-density lipoprotein cholesterol (LDL-C) was lower in the PGFE and PG-SL treatment groups than in the CTR treatment group (P < 0.05). Feeding emulsifier diets increased the lipase activity of the pancreas when compared with the CTR diet (P < 0.05). Moreover, the emulsifier diets significantly increased the mRNA expression of FXR (P < 0.05) and decreased the mRNA expression of CYP27A1 (P < 0.05) in the liver. In conclusion, the addition of emulsifiers improved nutrient digestibility and increased the mRNA expression of FXR BA receptors while inhibiting the mRNA expression of BA biosynthesis by CYP27A1 in weanling piglets.
Subject(s)
Animal Feed/analysis , Dietary Supplements/analysis , Fatty Acids/administration & dosage , Stearates/administration & dosage , Swine/physiology , Animals , Bile Acids and Salts/metabolism , Diet/veterinary , Digestion , Emulsifying Agents/administration & dosage , Female , Male , Nutrients , Random Allocation , Swine/growth & development , WeaningABSTRACT
Sodium stearoyl lactylate (SSL) was used as a gelling agent to structure oleogels at concentrations of 7%, 9%, 11%, and 13% (w/w) with sunflower oils in this study, respectively. The physical characteristics of oleogels, such as solid fat content (SFC), oil bonding capability (OBC) and firmness, were influenced by SSL crystals. Therefore, the microstructure and interaction of oleogels was further investigated by polarizing light microscopy (PLM), X-ray diffraction (XRD), rheology, differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR). It was found that the higher concentration of oleogelator resulted in a denser crystalline network, which provided stronger mechanical strength and enhanced the ability to retain the oil phase. Space-spanning networks were attributed to surface interactions among crystals of SSL, such as van der Waals interactions and electrostatic repulsion. Crystal network in the SSL oleogels imitated the typical functionality of crystalline network structures formed by triacylglycerol.
Subject(s)
Bread/analysis , Stearates/chemistry , Calorimetry, Differential Scanning , Crystallization , Organic Chemicals/analysis , Organic Chemicals/chemistry , Rheology , Spectroscopy, Fourier Transform Infrared , Sunflower Oil/chemistry , X-Ray DiffractionABSTRACT
This study used a rice bran oil solid fat fraction (RBOSF) to produce cocoa butter alternatives via interesterification reaction catalyzed by immobilized lipase (Lipozyme® RM IM) in hexane. Effects of reaction time (6, 12, and 18 h), temperature (55, 60, and 65°C), mole ratios of 3 substrates [RBOSF:palm olein:C18:0 donors (1:1:2, 1:2:3, and 1:2:6)] were determined. The substrate system was dissolved in 3 mL of hexane and 10% of lipase was added. Two sources of C18:0 donors, stearic acid (SAd) and ethyl stearate (ESd) were used. Pancreatic lipase - catalyzed sn-2 positional analysis was also performed on both substrates and structured lipids (interesterification products). Structured lipids (SL) were analyzed by gas - liquid chromatography (G40.35LC) for fatty acid composition. Major fatty acids of RBOSF were C18:1, oleic acid (OA, 41.15±0.01%), C18:2, linoleic acid (LA, 30.05±0.01%) and C16:0, palmitic acid (PA, 22.64±0.01%), respectively. A commercial raw cocoa butter (CB) contained C18:0, stearic acid (SA, 33.13±0.04%), OA (32.52±0.03%), and PA (28.90±0.01%), respectively. Fatty acids at sn-2 position of RBOSF were OA (46.52±0.63%) and LA (42.98±1.1%), while major fatty acid at sn-2 position of CB was OA (85.24±1.22%). The RBOSF had low SA (2.40±0.01%) compared to CB (33.13±0.04%). The content of OA (46.52±0.63%) at sn-2 position in RBOSF was half of that found in CB (85.24±1.22%). Optimal reaction was 1:2:6 mole ratio of the substrate (RBOSF:PO:SAd), at 65°C for 12 h. Fatty acid compositions of the SL were 31.72±0.99% SA, 30.91±0.53% LA, 23.18±0.32% OA, and 13.26±0.34% PA, respectively. Fatty acids at sn-2 position of the SL were 53.72±4.21% OA, 25.11±3.69% LA, 14.18±1.58% PA, and 6.99±0.02% SA, respectively. DSC curves showed the melting point of CB at 20.94°C, while those of the SL were 14.15 and 40.35°C, respectively. The melting completion temperature (Tmc) of CB was 25.5°C while that of SL was 43.9°C, respectively.
Subject(s)
Lipase/chemistry , Rice Bran Oil/chemistry , Catalysis , Esterification , Hexanes/chemistry , Linoleic Acid/analysis , Lipids/chemistry , Oleic Acid/analysis , Palmitic Acid/analysis , Stearates/chemistry , Stearic Acids/chemistry , Temperature , Time Factors , Transition TemperatureABSTRACT
In this study, 19 octadecanoid derivatives-four pairs of enantiomers (1â»8), two racemic/scalemic mixtures (9â»10), and nine biosynthetically related analogues-were obtained from the ethanolic extract of a Chinese medicinal plant, Plantago depressa Willd. Their structures were elucidated on the basis of detailed spectroscopic analyses, with the absolute configurations of the new compounds assigned by time-dependent density functional theory (TD-DFT)-based electronic circular dichroism (ECD) calculations. Six of them (1, 3â»6, and 9) were reported for the first time, while 2, 7, and 8 have been previously described as derivatives and are currently obtained as natural products. Our bioassays have established that selective compounds show in vitro anti-inflammatory activity by inhibiting lipopolysaccharide-induced nitric oxide (NO) production in mouse macrophage RAW 264.7 cells.
Subject(s)
Anti-Inflammatory Agents , Macrophages/metabolism , Nitric Oxide/metabolism , Plantago/chemistry , Stearates , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Anti-Inflammatory Agents/pharmacology , Lipopolysaccharides/toxicity , Macrophages/pathology , Mice , RAW 264.7 Cells , Stearates/chemistry , Stearates/isolation & purification , Stearates/pharmacologyABSTRACT
In this study, we compared the impact of administration of size-calibrated lipid emulsions prepared with either synthetic or natural emulsifiers on the post-absorptive plasma triacylglycerol responses in rats. We did this using four types of size-calibrated (10 µm diameter) and metastable (3 days) emulsions with 20% of an oleic acid-rich sunflower oil and 1% of either synthetic emulsifiers (Tween 80 or sodium 2-stearoyl-lactylate) or two proteins (ß-lactoglobulin or sodium caseinate). An oral fat tolerance test was performed in fasted rats by oral administration of each of these formulations in continuous or emulsified forms. Kinetic parameters (AUC0-inf., AUC0-6h, Cmax, Tmax, and T1/2) for the description of the plasma triacylglycerol responses were calculated. AUC0-6h and AUC0-inf. calculated for the protein groups were significantly lower than those of the control and the synthetic groups. These lower values were associated with significant decreases in the Cmax, exacerbated by the emulsion form and with marked decreases in the Tmax as compared to the control group. T1/2 values were differentially affected by the lipid administration forms and by the nature of the emulsifiers. As compared with the control group, T1/2 was largely increased in the sodium stearoyl-2-lactylate group, but on the contrary, largely lowered in the casein group. We concluded that the use of proteins as natural emulsifiers in lipid emulsions decreased the magnitude of post-prandial triacylglycerolemia for the same amount of ingested lipids, when the emulsion size is controlled for. Proteins could be a promising alternative to the widespread use of synthetic emulsifiers in the food industry.
Subject(s)
Dietary Fats, Unsaturated/administration & dosage , Dietary Proteins/chemistry , Emulsifying Agents/chemistry , Food Additives/chemistry , Hypertriglyceridemia/prevention & control , Oleic Acid/administration & dosage , Sunflower Oil/administration & dosage , Animals , Area Under Curve , Caseins/adverse effects , Caseins/chemistry , Dietary Fats, Unsaturated/adverse effects , Dietary Fats, Unsaturated/metabolism , Dietary Proteins/adverse effects , Digestion , Emulsifying Agents/adverse effects , Emulsions , Food Additives/adverse effects , Half-Life , Hypertriglyceridemia/blood , Hypertriglyceridemia/etiology , Intestinal Absorption , Lactoglobulins/adverse effects , Lactoglobulins/chemistry , Male , Oleic Acid/adverse effects , Oleic Acid/chemistry , Oleic Acid/metabolism , Particle Size , Polysorbates/adverse effects , Polysorbates/chemistry , Postprandial Period , Rats, Wistar , Stearates/adverse effects , Stearates/chemistry , Sunflower Oil/adverse effects , Sunflower Oil/chemistry , Sunflower Oil/metabolism , Triglycerides/bloodABSTRACT
Pentalinon andrieuxii Muell Arg is a Mexican-Central American plant anciently used by local people to treat cutaneous leishmaniasis. We evaluated a hexane extract of the root we called PAE for its chemical content and for its immunochemical and in vitro activity against Leishmania donovani and healing of experimental Kala-azar. Chemical analysis using gas chromatography coupled to mass spectrometry (GC-MS) identified hexadecanoic acid, hexadecanoic acid ethyl ester, 9, 12-octadecadienoic acid ethyl ester, octadecanoic acid ethyl ester, 9-octadecenoic acid ethyl ester and diethyl phthalate as the main compounds present in PAE. We also demonstrated PAE kills promastigotes and amastigotes in vitro and significantly reduces parasite loads in liver and spleen of infected Balb/c mice. PAE induces expression of NFkB/AP-1 transcription factors and production of IL-2 and IFN-γ by spleen cells of PAE treated but not in the untreated control mice. Furthermore, there were not IL-6, IL-10 nor TNF production in macrophages treated in vitro with PAE. We developed an affordable extract of P. andrieuxii effective to treat experimental Kala-azar in Balb/c mice.
Subject(s)
Apocynaceae/chemistry , Leishmania donovani/drug effects , Leishmaniasis, Visceral/drug therapy , Plant Extracts/therapeutic use , Animals , Fatty Acids, Unsaturated/analysis , Gas Chromatography-Mass Spectrometry , Interferon-gamma/biosynthesis , Interleukin-2/biosynthesis , Leishmaniasis, Cutaneous/drug therapy , Liver/parasitology , Macrophages/immunology , Mice , Mice, Inbred BALB C , NF-kappa B/biosynthesis , Oleic Acid/analysis , Oleic Acids , Parasite Load , Phthalic Acids/analysis , Spleen/parasitology , Stearates/analysis , Transcription Factor AP-1/biosynthesisABSTRACT
Coenzyme Q10 (CoQ10) is an antioxidant substance indicated as a dietary supplement which has been proposed as adjuvant in the treatment of cardiovascular disorders and cancer for its protective and immunostimulating activities. The aim of this work was the production by high-pressure homogenization, characterization and stability investigation of three different CoQ10 nanosuspensions designed to be administered to the lungs by nebulization. Three surfactants, i.e. lecithin, PEG32 stearate and vitamin-E TPGS, were selected to stabilize CoQ10 formulations. Preparations were identified as nanosuspensions (particle size in the range 35-60nm): the smallest particles were obtained with vitamin-E TPGS and denoted a core-shell structure. The CoQ10 delivered from a commercial air-jet nebulizer was in all the cases around 30% of the loaded dose. The nanosuspension containing PEG32 stearate presented the highest respirable fraction (70.6%) and smallest MMAD (3.02µm). Stability tests showed that the most stable formulation, after 90days, was the one containing vitamin-E TPGS, followed by the CoQ10-lecithin formulation. Interestingly, those formulations were demonstrated to be suitable also for nebulizers using other mechanisms of aerosol production such as ultrasound and vibrating mesh nebulizers. Studies focused on in vitro cellular toxicity of the formulations and their single components using A549 human lung cells showed no obvious cytotoxicity for the formulations containing lecithin and PEG 32 stearate. Vitamin-E TPGS alone was shown to be able to damage the plasma membrane, nevertheless, cell damage was decreased when vitamin-E TPGS was present in the formulation with CoQ10.
Subject(s)
Antioxidants/chemistry , Drug Delivery Systems/methods , Nanoparticles/chemistry , Nebulizers and Vaporizers , Ubiquinone/analogs & derivatives , A549 Cells , Aerosols/chemistry , Antioxidants/pharmacology , Biological Transport , Calibration , Cell Survival , Chemistry, Pharmaceutical/methods , Drug Liberation , Drug Stability , Humans , Lecithins/chemistry , Lung , Particle Size , Stearates/chemistry , Surface Properties , Ubiquinone/chemistry , Ubiquinone/pharmacology , Viscosity , Vitamin E/chemistryABSTRACT
Energy is a major cost component in diets for poultry. We hypothesized that the supplementation of emulsifier blends in broiler diets may contribute to the efficient utilization of energy and in increasing fat digestibility, thereby improving performance. To test our hypothesis, an experiment was conducted to evaluate the effect of a blend of emulsifiers on growth performance, nutrient digestibility, serum lipid profiles, and meat quality of broilers. A total of 768 1-d-old Ross 308 male broiler chicks with an average initial body weight of 45.55 ± 0.34 g were used in a 35 days feeding trial. Broilers were sorted into 4 treatments, 12 replications per treatment, and 16 birds per pen. Dietary treatments consisted of corn-soybean meal based basal diet and the basal diet supplemented with 0.05%, 0.075%, and 0.10% emulsifier. As a result of this study, the inclusion of 0.05%, 0.075%, and 0.10% emulsifier blends (sodium stearoyl-2-lactylate (SSL) and Tween 20) in the basal diet linearly increased (P = 0.0001) body weight gain (BWG) and improved feed conversion ratio (FCR) (linear effect P = 0.0001) on d 7 to 21, d 21 to 35 as well as overall. Broilers fed with different levels of emulsifier blends also showed a linear increment (P < 0.05) in dry matter (DM) and fat digestibility. A trend of linear reduction (P = 0.051) in low density lipoprotein (LDL) in the serum of broilers fed emulsifier blend was observed. The lightness value of breast muscle color linearly increased (P = 0.001), the redness and yellowness values tended to increase (P = 0.072 and P = 0.094 respectively), and the water holding capacity (WHC) showed trends in reduction (P = 0.078) with an increase in the level of emulsifier blends. With regards to relative organ weight, spleen weight was linearly (P = 0.001) reduced with the increase in the supplemental levels of emulsifier blends. A positive correlation between emulsifier content in the diet and BWG, DM and fat digestibility, and breast muscle color indices, were also observed. In conclusion, emulsifier blend supplementation positively influenced growth performance and nutrient digestibility in broiler chickens.
Subject(s)
Chickens/growth & development , Emulsifying Agents/metabolism , Lipids/blood , Meat/analysis , Polysorbates/metabolism , Stearates/metabolism , Animal Feed/analysis , Animals , Chickens/blood , Chickens/physiology , Diet/veterinary , Dietary Supplements/analysis , Dose-Response Relationship, Drug , Emulsifying Agents/administration & dosage , Male , Polysorbates/administration & dosage , Random Allocation , Stearates/administration & dosageABSTRACT
Saussurea lappa (SL) has been reported for its antioxidant and anti-ageing properties. Due to this reason it can be incorporated in a stable phytoformulations for cosmetic use. The objective of the study was to evaluate the anti-aging potential of cosmetic o/w emulsion containing the botanical extract of SL. An emulsion (o/w) was prepared using TEGO® Care 450 (Polyglceryl-3-Methyl Glucose Distearate) emulsifier and final emulsion was loaded with 4 % extract of SL in aqueous phase. This emulsion evaluated for its antioxidant and anti-ageing properties on healthy human subjects using a non-invasive technique called surface evaluation of living skin (SELS). The formulation containing SL extract showed significant (p<0.05) changes in Skin roughness (SEr) as -3.13%, -6.26%, -9.39%; Skin Scaliness (SEsc) as - 4.19%, -8.39%, -12.58%; Skin wrinkles (SEw) as -0.5%, -1.08%, -1.63%; and Skin smoothness (SEsm) as 3.28%, 6.57%, 9.85%, respectively, after 30, 60 and 90 days of continous use. Topical application of the cosmetic cream containing SL extract exerts have a significant anti-aging effects, perhaps due to the presence of Kaempferol, gallic acid, Caffeic acid and other essential phenolics.
Subject(s)
Emulsifying Agents/administration & dosage , Phytochemicals/administration & dosage , Plant Extracts/administration & dosage , Saussurea/chemistry , Skin Aging/drug effects , Skin Cream/administration & dosage , Skin/drug effects , Stearates/administration & dosage , Administration, Cutaneous , Adult , Emulsifying Agents/adverse effects , Emulsions , Humans , Male , Pakistan , Phytochemicals/adverse effects , Plant Extracts/adverse effects , Plant Extracts/isolation & purification , Plant Roots/chemistry , Single-Blind Method , Skin/pathology , Skin Cream/adverse effects , Stearates/adverse effects , Time Factors , Treatment Outcome , Young AdultABSTRACT
A new amphiphilic antioxidant (tannyl stearate) derived from reaction of tannic acid with stearic acid was synthesized in order to improve tannic acid solubility in lipid materials. This reaction gives many products having different degree of esterification (tannyl mono, di, tri, tetra, penta, hexa, hepta stearate) which were separated using silica gel column chromatography and tentative identification was carried out using thin layer chromatography (TLC). The intrinsic viscosities (η) were used to differentiate between the different molecular weight of the produced esters1). Tannyl penta stearate is assumed to be the most suitable amphiphilic antioxidant derivative, where those derivatives with less degree of esterification would be less soluble in fat, and those of higher degree of esterification would exhaust more hydroxyl group that cause decreases of antioxidant activity. The structure of tannyl penta stearate was approved depending on its chemical analysis and spectral data (IR, H1 NMR,). The emulsification power of tannyl penta stearate was then determined according to method described by El-Sukkary et al.2), in order to prove its amphiphilic property. Then tannyl penta stearate was tested for its antioxidant and radical scavenging activities in three different manners, those are, lipid oxidation in sunflower oil using Rancimat, (DPPH) free radical scavenging and total antioxidant activity. {Pure tannic acid (T), butylhydroxyanisol (BHA) and butylhydroxytoluene (BHT) were used as reference antioxidant radical saving compounds}. Then tannyl penta stearate was added to sunflower oil, frying process was carried out and all physicochemical parameters of the oil were considered, and compared to other reference antioxidant in order to study the effect of this new antioxidant toward oil stability. Acute oral toxicity of the tannyl penta stearate was carried out using albino mice of 21-25 g body weight to determine its safety according to the method described by Goodman et al.3). Also liver and kidney functions of those mice were checked. Thus it could be concluded that the addition of tannyl penta stearate to frying oils offers a good protection against oxidation. The effectiveness of tannyl penta stearate as lipid antioxidant has been attributed mainly to its stability at high temperature. And according to acute lethal toxicity test tannyl penta stearate was found to be a safe compound that can be used as food additive.
Subject(s)
Antioxidants/chemical synthesis , Emulsifying Agents/chemical synthesis , Stearates/chemical synthesis , Tannins/chemical synthesis , Animals , Antioxidants/pharmacology , Antioxidants/toxicity , Biphenyl Compounds/chemistry , Butylated Hydroxyanisole/chemistry , Butylated Hydroxytoluene/chemistry , Emulsifying Agents/pharmacology , Emulsifying Agents/toxicity , Fatty Acids/chemistry , Free Radical Scavengers/chemical synthesis , Free Radical Scavengers/pharmacology , Free Radical Scavengers/toxicity , Kidney Function Tests , Liver Function Tests , Mice , Picrates/chemistry , Rats , Solubility , Stearates/pharmacology , Stearates/toxicity , Stearic Acids/chemistry , Sunflower Oil/chemistry , Tannins/chemistry , Tannins/pharmacology , Tannins/toxicity , ViscosityABSTRACT
Lipid nanocapsules (LNCs) are biomimetic nanocarriers used for the encapsulation of a broad variety of active ingredients. Similar to surface active compounds, LNCs contain both hydrophilic and hydrophobic parts in their structure. Moreover, the components of LNCs, macrogol 15 hydroxystearate (MHS) and lecithin, are known for their surface active properties. Therefore, the aim of this paper was to investigate the capability of the LNCs to decrease surface tension using two techniques: drop tensiometry and the Wilhelmy plate method. LNCs with diameters ranging from 30 to 100 nm were successfully obtained using a phase inversion technique. The LNCs' properties, such as size and zeta potential, depend on the composition. LNCs exhibit a lower limiting surface tension compared to MHS (34.8-35.0 mN/m and 37.7-38.8 mN/m, respectively), as confirmed by both drop tensiometry and the Wilhelmy plate method. LNCs have exhibited a saturated interfacial concentration (SIC) that was 10-fold higher than the critical micellar concentration (CMC) of MHS or the SIC of binary and ternary mixtures of LNC ingredients. The SIC of the LNC formulations depended on the mass mixing ratio of the MHS/triglycerides but not on the presence of lecithin. The CMC/SIC values measured by the Wilhelmy plate method were higher than those obtained using drop tensiometry because of the longer duration of the tensiometry measurement. In conclusion, the surfactant-like properties of the LNCs offer new possibilities for medical and pharmaceutical applications.