蒲黄总黄酮对Palmitate培养下的C2C12骨骼肌细胞葡萄糖代谢的影响

目的:探讨蒲黄总黄酮(PTF)对骨骼肌细胞葡萄糖代谢的影响。方法:PTF处理棕榈酸(Palmitate)诱导而致胰岛素抵抗(IR)的C2C12骨骼肌细胞,采用XTT法观察药物对细胞活性的影响;通过检测培养液中的葡萄糖含量反映葡萄糖消耗量;3H-葡萄糖摄入法观察细胞对葡萄糖的转运率。结果:0.25mmol/LPalmitate培养16h,造成C2C12骨骼肌细胞葡萄糖消耗量下降34.66%,0.5g/LPTF可使其葡萄糖消耗量显著增加,且呈一定的时间依赖效应,与罗格列酮(ROS)相比,统计学差异显著(P<0.05);0.25mmol/LPalmi-tate培养16h,使C2C12骨骼肌细胞葡萄糖摄取率下降30.43%,造成骨骼肌细胞胰岛素抵抗(IR)模型,0.5g/LPTF可使IR模型葡萄糖转运率增加32.39%,ROS可使其转运率增加45.88%,与模型组相比,差异有统计学意义(P<0.05)。结论:PTF能显著增加C2C12骨骼肌细胞的葡萄糖消耗和摄取,这可能是PTF改善骨骼肌IR的机制之一。

Lipase-Catalyzed Synthesis of Sn-2 Palmitate: A Review

Human milk fat(HMF)is an important source of nutrients and energy for infants.Triacylglycerols(TAGs)account for about 98%of HMF and have a unique molecular structure.HMF is highly enriched in palmitic acid(PA)at the sn-2 position of the glycerol backbone(more than 70%)and in unsaturated fatty acids at the sn-1,3 position.The specific TAG structure in HMF plays a valuable function in infant growth.Sn-2 palmitate(mainly 1,3-dioleoyl-2-palmitoyl-glycerol)is one of the structured TAGs that is commonly supplemented into infant formula in order to enable it to present a similar structure to HMF.In this review,the development of the lipase-catalyzed synthesis of sn-2 palmitate over the last 25 years are summarized,with a focus on reaction schemes in a laboratory setting.Particular attention is also paid to the commercialized sn-1,3 regioselective lipases that are used in structured TAGs synthesis,to general methods of TAG analysis,and to successfully developed sn-2 palmitate products on the market.Prospects for the lipase-catalyzed synthesis of sn-2 palmitate are discussed.

Repression of PKR mediates palmitate-induced apoptosis in HepG2 cells through regulation of Bcl-2

The present study shows that double-stranded RNA-dependent protein kinase （PKR） regulates the protein expres- sion level and phosphorylation of Bcl-2 and plays an anti-apoptotic role in human hepatocellular carcinoma ceils （HepG2）. In various types of cells, saturated free fatty acids （FFAs）, such as palmitate, have been shown to induce cellular apoptosis by several mechanisms. Palmitate down-regulates the activity of PKR and thereby decreases the level of Bcl-2 protein, mediated in part by reduced activation of the NF-KB transcription factor. In addition to the level of Bel-2 protein, the phosphorylation of Bcl-2 at different amino acid residues, such as Ser70 and Ser87, is also important in regulating cellular apoptosis. The decrease in the phosphorylatiou of Bcl-2 at Ser70 upon exposure to palmitate is mediated by inhibition of PKR and possibly by c-Jun N-terminal kinase （JNK）, whereas the phosphory- lation of Bcl-2 at Ser87 is unaffected by palmitate or PKR. In summary, PKR mediates the regulation of the protein level and the phosphorylation status of Bel-2, providing a novel mechanism of palmitate-induced apoptosis in HepG2 cells.

Measurement and Correlation on Viscosity and Apparent Molar Volume of Ternary System for L-ascorbic Acid in Aqueous D-Glucose and Sucrose Solutions

Viscosities and densities at several temperatures from 293.15 K to 313.15K are reported for L-ascorbic acid in aqueous glucose and sucrose solutions at different concentrations. The parameters of density, viscosity coefficient B and partial molar volume are calculated by regression. The experimental results show that densities and viscosities decrease as temperature increases at the same solute and solvent (glucose and sucrose aqueous solution) concentrations, and increase with concentration of glucose and sucrose at the same solute concentration and temperature. B increases with concentration of glucose and sucrose and temperature. L-ascorbic acid is structure-breaker or structure-making for the glucose and sucrose aqueous solutions. Furthermore, the solute-solvent interactions in ternary systems of water-glucose-electrolyte and water-sucrose-electrolyte are discussed.

Development of a miniature silicon wafer fuel cell using L-ascorbic acid as fuel

In the current studies a miniature silicon wafer fuel cell(FC) using L-ascorbic acid as fuel was developed. The cell employs L-ascorbic acid and air as reactants and a thin polymer electrolyte as a separator. Inductively coupled plasma(ICP) silicon etching was employed to fabricate high aspect-ratio columns on the silicon substrate to increase the surface area. A thin platinum layer deposited directly on the silicon surface by the sputtering was used as the catalyst layer for L-ascorbic acid electro-oxidation. Cyclic voltammetry shows that the oxidation of L-ascorbic acid on the sputtered platinum layer is irreversible and that the onset potentials for the oxidation of L-ascorbic acid are from 0.27 V to 0.35 V versus an Ag/AgCl reference electrode. It is found that at the room temperature,with 1 mol/L L-ascorbic acid/PBS(phosphate buffered solution) solution pumped to the anode at 1 ml/min flow rate and air spontaneously diffusing to the cathode as the oxidant,the maximum output power density of the cell was 1.95 mW/cm2 at a current density of 10 mA/cm2.

Alteration of chemical behavior of L-ascorbic acid in combination with nickel sulfate at different pH solutions in vitro

Objective:To evaluate the alteration of chemical behavior of L-ascorbic acid(vitamin C) with metal ion(nickel) at different pH solutions in vitro.Methods:Spectra of pure aqueous solution of L-ascorbic acid(E mark) compound and NiSO_4(H_2O)(sigma USA) were evaluated by UV visible spectrophotometer.Spectral analysis of L-ascorbic acid and nickel at various pH(2.0, 7.0,7.4 and 8.6) at room temperature of 29℃ was recorded.In this special analysis,combined solution of L-ascorbic acid and nickel sulfate at different pH was also recorded.Results:The result revealed that λ_(max)(peak wavelength of spectra) of L-ascorbic acid at pH 2.0 was 289.0 run whereas at neutral pH 7.0,λ_(max) was 29S.4 run.In alkaline pH 8.6,λ_(max) was 295.4 nm and at pH 7.4 the λ_(max) of L-ascorbic acid remained the same as 295.4 nm.Nickel solution at acidic pH 2.0 was 394.5 nm,whereas at neutral pH 7.0 and pH 7.4 were the same as 394.5 nm.But at alkaline pH 8.6,λ_(max) value of nickel sulfate became 392.0 nm.The combined solution of L-ascorbic acid and nickel sulfate(6 mg/mL each) at pH 2.0 showed 292.5 nm and 392.5 nm,respectively whereas at pH 7.0,L-ascorbic acid showed 296.5 nm and nickel sulfate showed 391.5 nm.At pH 7.4,L-ascorbic acid showed 297.0 nm and nickel sulfate showed 394.0 nm in the combined solution whereas at pH 8.6(alkaline) L-ascorbic acid and nickel sulfate were showing 297.0 and 393.5 nm,respectively. Conclusions:Results clearly indicate an altered chemical behavior of L-ascorbic acid either alone or in combination with nickel sulfate in vitro at different pH.Perhaps oxidation of L-ascorbic acid to L-dehydro ascorbic acid via the free radical(HSc*) generation from the reaction of H,ASc + Ni(Ⅱ) is the cause of such alteration of λ_(max),value of L-ascorbic acid in the presence of metal nickel.

Reaction kinetics of isopropyl palmitate synthesis

In this study, the kinetics of isopropyl palmitate synthesis including the reaction mechanism was studied based on the two-step noncatalytic method. The liquid-phase diffusion effect on the reaction process was eliminated by adjusting the stirring rate. The results showed that the two-step reaction followed a tetrahedral mechanism and conformed to second-order reaction kinetics. Nucleophilic attack on the carbonyl carbon afforded an intermediate, containing a tetrahedral carbon center. The intermediate ultimately decomposed by elimination of the leaving group, affording isopropyl palmitate. The experimental data were analyzed at different temperatures by the integral method. The kinetic equations of the each step were deduced, and the activation energy and frequency factor were obtained. Experiments were performed to verify the feasibility of kinetic equations, and the result showed that the kinetic equations were reliable. This study could be very signi ficant to both industrial application and determining the continuous production of isopropyl palmitate.

HPLC Quantification of Dexamethasone Palmitate in Bronchoalveolar Lavage Fluid of Rat after Lung Delivery with Large Porous Particles

A high-performance liquid chromatography (HPLC) method has been developed and validated for the determination of dexamethasone palmitate (DXP) in bronchoalveolar fluid lavage samples (BALF). DXP in rat BALFs containing the internal standard (IS), testosterone decanoate (TD), was extracted using a mixture of chloroform and methanol (9:1, v/v). Extracts were then centrifuged, dried and dissolved in acetonitrile. A chromatographic separation based on an isocratic elution was done using acetonitrile and water (85:15, v/v) as a mobile phase at a flow rate of 1.2 mL/min. The graph of the developed method was linear within the tested calibration range of 0.5 - 40 μg/mL. The overall extraction recovery of DXP from BALF samples was 84.3% ± 1.6%. The accuracy (relative error) and precision (coefficient of variation) values were within the pre-defined limits of ≤15% at all concentrations. This methodology has been applied to determine levels of DXP in BALF samples collected from rats treated with DXP large porous particles. The measured concentrations were successfully evaluated using a non-compartment pharmacokinetic model. Since the developed method requires only a microvolume (100 μL) of BALF sample for analysis, it is therefore particularly suitable for the evaluation of drug biodistribution in lung.

Microencapsulation by Spray Drying of Vitamin A Palmitate from Oil to Powder and Its Application in Topical Delivery System

Vitamin A palmitate (VAP) contains retinol and palmitic acid which is easily absorbed by body and widely used in skin care products. But, it is a hydrophobic and oxidation sensitive molecule which undergoes rapid degradation especially in an aqueous environment. The purpose of this study was to prepare microcapsules of VAP using combination maltodextrin and modified starches. Emulsion of VAP was prepared using cremophore RH 40 with Tween 80 in a homogenizer and formed emulsion was spray-dried. The spray process was optimized using a central composite design for two variables to obtain microcapsules with desirable characteristics. Microcapsules containing 30% of VAP were produced using different concentration of wall materials. The prepared microcapsules were evaluated for their physical, morphological, in-vitro drug release and SEM study. The results showed that obtained microcapsules are nearly spherical in shape with a particle size ranged from 1 to 12 μm. The drug content and encapsulation efficiency (53% - 63%) of different batches were found within acceptable range. These stabilized drug loaded microcapsules were incorporated into silicone cream based formulation for convenient topical application and evaluated for its physicochemical parameters. The drug release study showed 80.18% to 83.43% of drug release from VAP microcapsules while topical formulations prepared by VAP microcapsules showed 67.09% to 71.45% drug release at the end of 24 hrs. The formulations were kept for 3 months stability study as per ICH guidelines and found to be stable.

Effects of methyl palmitate and lutein on LPS-induced acute lung injury in rats

AIM: To investigate the effects of methyl palmitate and lutein on lipopolysaccharide(LPS)-induced acute lung injury(ALI) in rats and explore the possible mechanisms. METHODS: Male Sprague-Dawley rats were divided into 4 groups:(1) control;(2) LPS;(3) Methyl palmitate; and(4) Lutein groups. Methyl palmitate(300 mg/kg, ip) was administered 3 times per week on alternating days while lutein(100 mg/kg, oral) was given once daily. After 1 wk of vehicle/methyl palmitate/lutein treatment, ALI was induced by a single dose of LPS(7.5 mg/kg, iv). After 24 h of LPS injection, animals were sacrificed then biochemical parameters and histopathology were assessed. RESULTS: Treatment with methyl palmitate attenuated ALI, as it significantly decreased the lung wet/dry weight(W/D) ratio, the accumulation of the inflammatory cells in the bronchoalveolar lavage fluid(BALF) andhistopathological damage. However, methyl palmitate failed to decrease lactate dehydrogenase(LDH) activity in BALF. On the other hand, lutein treatment produced significant anti-inflammatory effects as revealed by significant decrease in accumulation of inflammatory cells in lung, LDH level in BALF and histopathological damage. Methyl palmitate and lutein significantly increased superoxide dismutase(SOD) and reduced glutathione(GSH) activities with significant decrease in the lung malondialdehyde(MDA) content. Importantly, methyl palmitate and lutein decreased the level of the inflammatory cytokine tumor necrosis factor-α(TNF-α) in the lung. Lutein also reduced LPS-mediated overproduction of pulmonary nitrite/nitrate(NO-2/NO-3), which was not affected by methyl palmitate pretreatment. CONCLUSION: These results demonstrate the potent protective effects of both methyl palmitate and lutein against LPS-induced ALI in rats. These effects can be attributed to potent antioxidant activities of these agents, which suppress inflammatory cell infiltration and regulated cytokine effects.

Synthesis, Crystal Structure and Antioxidant Activity of 5,6-O-(4-bromophenyl)-L-ascorbic Acid

The title compound 5,6-O-（4-bromophenyl）-L-ascorbic acid （C13H11BrO6, Mr = 343.13） has been synthesized and its structure was characterized by IR, 1H NMR and single-crystal X-ray diffraction. The product is a mixture of two diastereomer compounds （a （7S） and b （7R））. The crystal of a （7S） belongs to orthorhombic system, space group P212121 with a = 6.5362（10）, b = 7.8226（11）, c = 25.294（4） ？, V = 1293.3（3） ？3, Z = 4, Dc = 1.762 g/cm3, μ（MoKα） = 3.202 mm-1, F（000） = 688, R = 0.0235 and wR （I 〉 2σ（I）） = 0.0566. The hydrogen bonding interactions link the molecules to form a three-dimensional system. In addition, 5,6-O-（4-bromophenyl）-L-ascorbic acid （BPAA） exhibits strong free-radical scavenging activities in vitro against 2,2-diphenyl-1-picrylhy- drazyl and superoxide anion. BPAA should be investigated further as a worthy antioxidant.

Synthesis of L-Ascorbic Acid Lactone Derivatives

A small focused library which comprised of L-AA lactone derivatives was built with a facile method.This reported method was optimized by modifying the acidity of the solvent.As a result,12 L-AA lactones were synthesized.Among these lactones,lactones 8–12 were new compounds.The cytotoxicity of these synthetic compounds were investigated.

Supplementation of L-ascorbic acid improves the in vitro development of buffalo(Bubalus bubalis)embryos and alters the expression of apoptosis-related genes

Objective:To study the effect of L-ascorbic acid supplementation on the in vitro development of buffalo embryos and evaluate the relative mRNA abundance of some pro-apoptotic,anti-apoptotic,and embryonic development-related genes.Methods:In experiment 1,we evaluated the effect of the addition of 0(control),50,and 100μM L-ascorbic acid to the in vitro maturation medium on the developmental competence in terms of blastocyst rate and relative mRNA abundance of some pro-apoptotic(BAX,BID),anti-apoptotic(BCL-XL,MCL1),and embryonic development(GDF9,BMP15)related genes.Based on the results,we chose 50μM as the suitable dose of L-ascorbic acid for the subsequent experiments.We further evaluated the blastocyst rates following the addition of 50μM L-ascorbic acid to the in vitro culture medium(experiment 2),and in vitro maturation and in vitro culture media(experiment 3).In all three experiments,the maturation and culture media devoid of L-ascorbic acid served as the control group.Results:The blastocyst rate after adding 50μM L-ascorbic acid to the in vitro maturation medium was significantly higher than the control group(P<0.05),whereas 100μM L-ascorbic acid exhibited a negative effect on the blastocyst rate.The blastocyst rates for embryos cultured in 50μM L-ascorbic acid in the in vitro culture medium alone and both in vitro maturation and in vitro culture media were significantly higher than their corresponding control groups(P<0.05).The relative mRNA abundance of BAX significantly decreased in blastocysts produced after the addition of 50μM L-ascorbic acid as compared with the control group(P<0.05),whereas,for MCL1,it significantly decreased in blastocysts produced after the addition of 100μM L-ascorbic acid(P<0.05).Conclusions:The supplementation of 50μM L-ascorbic acid to in vitro maturation and in vitro culture media supports in vitro embryonic development in buffaloes by improving developmental competence and altering the expression of apoptosis-related genes.

Paliperidone palmitate-induced facial angioedema:A case report

BACKGROUND Paliperidone palmitate is a once-monthly injectable,atypical antipsychotic.To our knowledge,there has been only one report of paliperidone palmitate-induced angioedema presenting with acute laryngeal edema with subsequent respiratory arrest.Here,we present a case report of paliperidone palmitate-induced angioedema with a relatively mild clinical presentation compared with the previously reported case,and the patient's condition was not complicated by lifethreatening anaphylaxis.CASE SUMMARY A 79-year-old female,who had a major neurocognitive disorder due to Alzheimer's disease with behavioral disturbances.Paliperidone palmitate was offlabel used to control her aggression,irritability,and psychosis.After induction doses(150 mg and 100 mg intramuscularly,given 1 wk apart),she developed intermittent swelling of the face,eyelids,and lips on day 17 after the initial dose,and the edema was explicitly seen on day 20.The diagnosis was paliperidone palmitate-induced angioedema.The monthly injection dose was discontinued on day 33 after the initial dose.The angioedema was subsequently alleviated,and it had completely resolved by day 40 after the initial dose.CONCLUSION Paliperidone palmitate-induced angioedema is a rare condition and can present with a mild,intermittent facial edema,which may be overlooked in clinical practice.

Dihydroartemisinin ameliorates palmitate-induced apoptosis in cardiomyocytes via regulation on miR-133b/Sirt1 axis

Excessive fat ectopically deposited in the non-adipose tissues is considered as one of the leading causes of myopathy.The aim of this study was to investigate the role of Dihydroartemisinin(DHA)in palmitate(PAL)-incubated H9c2 cells(lipotoxicity-induced cell injury model).Cell viability of PAL-treated cells was determined by MTT assay,and apoptotic regulators were examined by qRT-PCR and western blot analysis,in the absence or in the presence of DHA,respectively.Expression levels of miR-133b and Sirt1 were also evaluated by qRT-PCR and western blotting examination.PAL decreased the viability of H9c2 cells and enhanced the expression of apoptotic genes.DHA reversed the effect of PAL on cell viability and lowed the level of Caspase3 and Bax.It also lowered the expression of miR-133b,while enhanced the expression of Bcl-2.Sirt1 was revealed as target of miR-133b through transcriptional regulation and the process was affected by DHA.DHA partially protected against the PAL-induced lipotoxicity by influencing the expression of miR-133b that hindered the activity of Sirt1.DHA may be used as a potential treatment in clinical management for lipotoxicity induced heart complications.

Development and Application of a Validated HPLC Method for the Determination of Clindamycin Palmitate Hydrochloride in Marketed Drug Products: An Optimization of the Current USP Methodology for Assay

A simple efficient isocratic reversed-phase HPLC method was developed and validated for the determination of clindamycin palmitate hydrochloride (CPH) and its commercially available oral solution products. Separation was achieved on a Phenomenex Zorbax (Luna) cyano column (150 × 4.6 mm, 5 μm) with a Phenomenex cyano guard cartridge (4 × 3.0 mm) on Agilent 1050 series HPLC system. CPH and its resolution standard lincomycin were eluted isocratically at a flow rate of 1 mL/min with a simplified mobile phase (potassium phosphate buffer (5 mM, pH 3.0)—acetonitrile—tetrahydrofuran (20:75:5, v/v/v)) and detected at 210 nm. The column was maintained at 25?C. The method was validated according to USP category I requirements. Robustness and forced degradation studies were also conducted. CPH marketed drug products were obtained from a drug distributor and assayed for potency using the validated method. Validation acceptance criteria were met in all cases. The analytical range for CPH was 15 - 500 μg/mL and the linearity was r2 > 0.999 over three days. The method was determined to be specific and robust. Both accuracy (92.0% - 103.8%) and precision (0.67% - 1.52%) were established across the analytical range for low, intermediate and high QC concentrations. Method applicability was demonstrated by analyzing two marketed products of CPH, in which results showed potency >98%. The method was determined to be an enhancement over the current USP methodology for assay as a result of increased efficiency, reduced organic solvents and the elimination of matrix modifiers. This method was successfully applied for the quality assessment of: 1) currently marketed drug products and 2) will in future assess the product quality of novel dosage forms of CPH for pediatric use.

Process Improvement on the Lipase-Catalyzed Synthesis of Oleyl Palmitate, a Wax Ester via Response Surface Methodology （RSM）

High performance enzymatic synthesis of oleyl palmitate, a wax ester was carried out by lipase-catalyzed esterification of palmitic acid and oleyl alcohol. Response surface methodology （RSM） based on 5-level, 3-variable of centre composite rotatable design （CCRD） was used to evaluate the interactive effects of synthesis, of temperature （40-60 ℃）; amount of enzyme （0.1-0.4 g） and substrate molar ratio of oleyl alcohol to palmitic acid （1：1-4：1） on the percentage yield of wax ester. All reactions were fixed at 1 hour of reaction time. The optimum condition obtained from RSM for the reactions were temperature of 57.9 ℃, enzyme amount of 0.26 g and molar ratio of substrates of 2.92. The actual experimental yield was 91.2% under the optimum condition, which compared well with the maximum predicted value of 92.0%. Comparison of predicted and experimental values reveal good correspondence between them, implying that empirical models derived from RSM can be used to adequately describe the relationship between the factors and response in the synthesis of oleyl palmitate.

Conductive Polyacrylonitrile Fiber Prepared by Copper Plating with L-Ascorbic Acid as Reducing Agent

Conductive polyacrylonitrile fibers were prepared by electroless copper plating under weak alkaline conditions,with L-ascorbic acid as reducing agent.The influences of CuSO_(4)·5H_(2)O,L-ascorbic acid,2,2′-bipyridine and K_(4)Fe(CN)_(6) concentration on the conductivity and mass gain percentage of the fibers were studied.The morphological structure of the fibers was characterized by scanning electron microscopy(SEM),and the mechanical properties of the fibers were analyzed through the mechanical property test.The results showed that the optimal reaction conditions were as follows:26 g/L CuSO_(4)·5H_(2)O,26 g/L L-ascorbic acid,12 mg/L 2,2′-bipyridine,7 mg/L K 4Fe(CN)6,and 38℃.The volume resistivity of the conductive PAN fibers prepared by the process was only 3.84×10^(-3)Ω·cm.

Microencapsulation of L-Ascorbic Acid by Spray Drying Using Sodium Alginate as Wall Material

L-ascorbic acid is a water soluble vitamin (vitamin C) widely used as an additive in foods and cosmetics. It has high instability against certain environmental factors;the main cause of its deterioration is oxidation. Microencapsulation is an effective protection technique of L-ascorbic acid from its degradation reactions. This work is focused on the encapsulation of L-ascorbic acid by spray drying technique using sodium alginate as wall material. The microcapsules morphology was observed by scanning electron microscopy (SEM) and the encapsulation efficiency was determined by spectrophotometric analysis. Results showed that encapsulation efficiency was of 93.48% and after 30 days was of 92.55%;differences were not significant, so that the stability of L-ascorbic acid was not affected. Encapsulation yields obtained were low, at around 30%, but the microcapsules morphology obtained is spherical.

Nerve growth factor protects against palmitic acid- induced injury in retinal ganglion cells

Accumulating evidence supports an important role for nerve growth factor （NGF） in diabetic retinopathy. We hypothesized that NGF has a protective effect on rat retinal ganglion RGC-5 cells injured by palmitic acid （PA）, a metabolic factor implicated in the development of dia- betes and its complications. Our results show that PA exposure caused apoptosis of RGC-5 cells, while NGF protected against PA insult in a concentration-dependent manner. Additionally, NGF significantly attenuated the levels of reactive oxygen species （ROS） and malondialde- hyde （MDA） in RGC-5 cells. Pathway inhibitor tests showed that the protective effect of NGF was completely reversed by LY294002 （PI3K inhibitor）, Akt VIII inhibitor, and PD98059 （ERK1/2 inhibitor）. Western blot analysis revealed that NGF induced the phosphorylation of Akt/FoxO1 and ERK1/2 and reversed the PA-evoked reduction in the levels of these proteins. These results indicate that NGF protects RGC-5 cells against PA-induced injury through anti-oxidation and inhibition of apoptosis by modulation of the PI3K/Akt and ERK1/2 signaling pathways.