Determination of Piperazine Ferulate in Human Plasma by HPLC and Its Pharmacokinetic Study

Aim To establish a sensitive HPLC method for determination of piperazine ferulate and to study its pharmacokinetics in healthy volunteers. Methods Piperazine ferulate was separated on a Shimadzu C_ 18 column with acetic acid (0.1%)-methanol (60 ∶ 40, V/V) as mobile phase after liquid-liquid extraction, and detection was performed at 310 nm. Piperazine ferulate pharmacokinetic parameters after a single oral dose of 200 mg of piperazine ferulate dispersible tablets in 20 healthy male volunteers were calculate...

Inhibitory Effects of Sodium Ferulate on Proliferation of Rabbit Aortic Smooth Muscle Cells Induced by Oxidized LDL

The effects of sodium ferulate(SF), a water-soluble element of Chinese medicine Angelica sinensis diels, on cell-mediated oxidative modification of human low density lipoprotein(LDL) and proliferation of rabbit aortic smooth muscle cells(SMCs) were investigated. Using experimental models of proliferation of cultured rabbit aortic SMCs induced by oxidized LDL(ox-LDL), the extent of oxidation was determined by thiobarbituric acid reactive substances(TBARS) method, MTT colorimetry and 3H-thymidine(3H-TdR) incorporation were used to observe proliferation of SMCs. It showed that SF effectively inhibited cell-mediated oxidation induced by Cu2+ in a concentration-dependent manner. At the final concentration of 40, 80, 120 gmL-1, SF could significantly inhibit 3H-TdR incorporation and cell Proliferation in a dose-dependent manner. The results indicated that SF could, in vitro protect LDL against oxidative modification and inhibit the proliferation of SMC, which might be due to its free radical scavenging capacity.

Biphenyl Ferulate from Glehnia littoralis

From the underground parts of Glehnia littoralis Fr. Schmidt ex Miquel (Umbelliferae), a new compound named glehnilate was obtained. Its structure was determined by analysis of its spectral data.

Rapid analysis of piperazine ferulate tablets by optic-fiber sensing technology and the similarity of ultraviolet spectra

A rapid analysis method of piperazine ferulate tablets by optic-fiber sensing technology with UV-vis absorption spectrum was established. Qualitative and quantitative data were obtained and compared by maximum and minimum wavelength, absorbance and contrast spectra. Similarity method was used to identify authenticity of drugs. The difference of contents measured by this method and UV determination method in China Pharmacopoeia showed no statistical significance (P40.05), while the similarity can be used as a parameter to identify the authenticity of drugs.

The Effects of Ethanolamine Nitrate Ester Ferulate (ENF)on Isolated Working Guinea Pig Heart and Rat AorticRing

The cardiac and vascular effect of ethanolamine nitrate ester ferulate (ENF) wasinvestigated on isolated working guinea pig heart (IWH) and rat aortic ring. The coronary blood flowwas remarkably increased while the cardiac functions of IWH were not significantly altered by ENFranging from 10-8 to 10-4 mol/L. The percentages of vasorelaxation of ENF t 10 μmol/L) and nicoran-dil (NIC, 10 μmol/L) on K+ (80 mmol/L)-induced contraction in aortic rings were 72 ± 8% and17±8%, respectively. The relaxation effects of ENF and NIC on phenylephrine (PE, 5 μmol/L) in-duced contraction were in a dose-dependent manner. When vessel segments were exposed to PE withmethylene blue (MB, 10 μmol/L) or with glibenclamide (GLI, 10 pmol/L), the percentages of relaxa-tion of ENF (10 μmol/L) and NIC ( 1 0 μmol/L) were 4 1 ±11 % and 49±7% or 76± 14% and the 33±9%,respectively. The results suggested that ENF improved coronary circulation and the vasodilation of ENF was mediated bv nitrate-like action.

Enzymatic Synthesis of Butyl Ferulate by Silica-Immobilized Lipase in a Non-Aqueous Medium

Butyl ferulate was synthesized using a silica-immobilized commercial lipase (Steapsin) in dimethylsulfoxide (DMSO). Lipase-immobilized by surface adsorption onto silica pretreated with 1% glutaraldehyde showed 89% binding of protein. The esterification of butanol (100 mM) and ferulic acid (50 mM) by silica-bound biocatalyst was carried out at 45℃ for 6 h under shaking (120 rpm). The optimization of various reaction conditions like molar concentration of reactants, biocatalyst concentration, reaction time, temperature, addition of molecular sieves, salt ions, and repetitive bio-catalysis in DMSO were studied, consecutively. The bound lipase (15 mg/ml) catalyzed the esterification of ferulic acid and butanol with a yield of 64 mM under optimized reaction conditions. Among the salt ions Cu2+, Zn2+ and Al3+ ions moderately promoted the ester yield (66 mM) while Mg2+, NH4+, Fe2+ and Ca2+ were found to decrease the ester yield. The by-product (H2O) produced in the reaction was scavenged by the molecular sieves (10 mg/ml) added to the reaction mixture, which enhanced the formation of ester up to 74 mM. During the repetitive reactions, the bound lipase produced 32 mM ester after 4th cycle of esterification. On scaling-up the reaction volume to 30 ml, 32.5 mM butyl ferulate was synthesized under optimized conditions.

Effects of sodium ferulate on the ultrarapid delayed rectifier K^+ current in human atrial myocytes

Objective：To study the effects of sodium ferulate on the ultrarapid delayed rectifier K^＋ current（IKur） in human atrial myocytes. Methods：Human atrial myocytes were isolated by enzyme dispersion method. IKur, in human atrial myocytes were recorded by using the whole cell patch clamp. The changes of IKur were compared in the absence and the presence of sodium ferulate. Results：There was no effect of 0.4 g/L sodium ferulate on I-V relation of IKur. However, 0.4 g/L sodium ferulate inhibited IKur to some degrees at each test pulse. The current densities of IKur at ＋60 mV decreased from 4.997 ± 0.35 PA/PF to 3.331 ± 0.26 PA/PF（n = 6, P 〈 0.05）. The inhibitory effect was concentration-dependent. IC50 was（0.41 ±0.03）g/L and the Hill coefficient was 0.95 ± 0.05. Conclusion：Sodium ferulate as a potassium channel blocker can inhibit IKur in human atrial myocytes effectively.

Influence of pretreatment of piperazine ferulate on pharmacokinetic parameters of methotrexate in methotrexate-induced renal injury model rats by HPLC-MS

The present study was designed to investigate the influence of the pretreatment of piperazine ferulate on pharmacokinetic parameters of methotrexate in methotrexate-induced renal injury rats.A simple and efficient high performance liquid chromatography coupled with mass spectrometry(HPLC-MS)method was developed to determine methotrexate in rat plasma.Methotrexate and syringic acid(internal standard)were extracted from rat plasma samples by protein precipitation with acetonitrile.The analysis was performed on a CAPCELL PAK C18column(150 mm×4.6 mm,5μm)with acetonitrile and 5 mmol/l ammonium acetate aqueous(10:90,v/v).The linear range was 5.0×10-2to 100.0μg/ml for methotrexate.Other parameters were all within the acceptance criteria.The validated method was successfully applied the pharmacokinetic study of methotrexate between two methotrexate treated groups(with and without the pretreatment of piperazine ferulate).Compared with the methotrexate treated alone group,the pharmacokinetic parameters in the methotrexate with the pretreatment of piperazine ferulate group showed significantly lower MRT(0-t),MRT(0-∞) and T1/2.Results suggested that methotrexate can be rapidly eliminated,cleared or metabolized in rat blood,which might be related to the pretreatment of piperazine ferulate.The method provided deeper insights into rational clinical use of methotrexate with the pretreatment of piperazine ferulate on cancer patients with renal dysfunction.

Cell Wall Characteristics of a Maize Mutant Selected for Decreased Ferulates

The cross-linked nature of plant cell walls provides structural integrity for continued growth and development, but limits degradation and utilization by ruminants. In grasses a major cross-linking component is ferulic acid that is incorporated into cell walls as an ester linked residue on arabinoxylans. Ferulates can become coupled to each other and to lignin forming a highly cross-linked matrix of carbohydrates and lignin. Seedling ferulate ester mutants (sfe) were produced in maize using the transposon system and evaluated in feeding trials. The work described here was undertaken to characterize changes in the ferulate cross-linked nature as well as other components of the corn cell wall matrix in leaf, sheath and stem tissues. Total ferulates decreased modestly due to the mutation and were more apparent in leaf tissue (16% - 18%) compared to sheath (+5 to?-6% change) and stem (8% - 9% decrease). The most significant changes were in the ether linked ferulates to lignin, both monomer and dehydrodiferulates (14% to 38% decrease). Other characteristics of the cell wall (lignin, neutral sugar composition) also showed modest changes. The change in total ferulates was modest, but led to improved animal performance. These findings suggest that relatively small changes can have a significant impact upon how well plant materials can be broken down and utilized by ruminants such as dairy cows.

Protective effect of sodium ferulate on cardiac hypertrophy in spontaneously hypertensive rats

OBJECTIVE To investigate the inhibitory effect and mechanism of sodium ferulate(SF)on myocardial hypertrophy in spontaneously hypertensive(SHR).METHODS Forty 14-week-old SHR male rats were randomly divided into model group(SHR,receive distilled water)and SF treatment groups(SF 20,40 and 80 mg·kg^-1 per day,respectively).Age-matched male Wistar-Kyoto(WKY)rats gavaged with distilled water served as controls.After 12 weeks of treatment,the effects of SF on cardiac hypertrophy were evaluated using echocardiographic measurement,pathological analysis and the expression of atrial natriuretic peptide(ANP),myosin heavy chainβ(β-MHC)-a gene related to myocardial hypertrophy.In order to explore the mechanism of SF on myocardial hypertrophy,the calcium-sensing receptor(CaSR),calcineurin(CaN),nuclear factor of activated T cell 3(NFAT3),phosphorylation NFAT3(p-NFAT3),zinc finger transcription factor(GATA4),phosphorylation GATA4(p-GATA4),protein kinase Cβ(PKC-β),Raf-1,extracellular regulated protein kinase 1/2(ERK 1/2),phosphorylation ERK1/2(p-ERK 1/2)and mitogen-activated protein kinase phosphatase-1(MKP-1)were detected.RESULTS The myocardial hypertrophy parameters,myocardial cell cross section area,left ventricular wall thickness and expression of ANP and β-MHC,CaSR,CaN,NFAT3,p-GATA4,PKC-β,Raf-1,and p-ERK 1/2 were significantly increased,while the left ventricular cavity was significantly smaller,expression of p-NFAT3 and MKP-1 were significantly decreased,meanwhile,the ultra⁃structure of cardiomyocytes was significantly damaged in 26-week-old SHR rats.Notably,SF significantly ameliorated myocardial hyper⁃trophy in 26-week-old SHR rats;suppressed the overexpression of ANP,β-MHC,CaSR,CaN,NFAT3,p-GATA4,PKC-β,Raf-1,and p-ERK 1/2 and increased the expression of p-NFAT3 and MKP-1.CONCLUSION SF can inhibit cardiac hypertrophy in SHR rats,and the mechanism may be related to the inhibition of CaSR mediated signaling pathway.

Neuroprotective Effects of Sodium Ferulate and Its Antidepressant-Like Effect Measured by Acute and Chronic Experimental Methods in Animal Models of Depression

Antidepressants with novel targets and without side effects are in great demand. Ferulic acid (FA) is a ubiquitous phenolic acid of low toxicity, and sodium ferulate (SF) is its sodium salt. Our previous studies have revealed that FA and SF show significant protective effect on excitotoxicity, we now test its potential neuroprotective and antidepressant-like effects. MTT assay and morphological analysis by fluorescence microscopy were adopted to measure the neuroprotective effects of SF;forced-swimming, tail-suspension, and chronic mild stress (CMS) tests were performed to assess its antidepressant-like activity. The results showed that SF had protection against H2O2-induced oxidative damage and dexamethasone (DXM)-induced neurotoxicity pheochromocytoma (PC12) cells. Acute administration of SF markedly decreased the duration of immobility during forced-swimming in rats and mice and tail-supension tests in mice. However, SF has no any effects on reserpine-induced hypothermia, 5-hydroxytryptophan-induced head-twitch response, and potentiation of noradrenaline toxicity in mice. Chronic administration of SF reversed the effects of CMS on consumption of food and sucrose solution, weight gain, and histopathology of hippocampus by light microscopy, and potently shortened the immobility time during forced-swimming test following CMS in rats. This study provides evidence that SF possesses obviously antidepressant-like activity, and the antidepressant-like effect may result from its neuroprotective effects.

Comparison of the effects of perinatal and neonatal administration of sodium ferulate on repair following excitotoxic neuronal damages induced by maternal oral administration of monosodium glutamate at a late stage of pregnancy

Objective: Our previous studies have revealed that ferulic acid (FA) and sodium ferulate (SF) show significant protective effect on excitotoxicity, the present study was conducted to compare its potential favorable effects of maternal,newborn,and both maternal and newborn intraperitoneal (ip) injection of SF on repair following excitotoxic neuronal damages induced by monosodium glutamate (MSG). Methods: The maternal mice were assigned randomly into seven groups (n = 10 animals in each group): control, 3SF, 20SF, 23SF, MSG, MSG + 3SF, MSG + 20SF, MSG + 23SF groups. The mice at 17 days of pregnancy were treated with or without MSG (2.0 g/kg body weight, ig, once) or/and SF (40 mg/kg body weight, ip), and their offerings treated with or without SF. And then their filial behaviors and hippocampal histopathology were studied. Results: The results showed that maternal, newborn, and both maternal and newborn administration of SF facilitated their filial brain repair, and attenuated the behavioral disorders and histopathological damages of their filial mice in MSG + 3SF, MSG + 20SF, and MSG + 23SF groups in varying degrees. However, the best effects were detected in the filial mice in MSG + 23SF group. Conclusion: Both maternal and newborn administration of SF is conducive to the filial neuronal repair following excitotoxic damages induced by glutamate.

Neurogenesis-enhancing effect of sodium ferulate and its role in repair following stress-induced neuronal damage

Ferulic acid (FA) is a ubiquitous phenolic acid of low toxicity, and sodium ferulate (SF) is its sodium salt. Our previous studies have revealed that FA shows neuroprotective effect and significant antidepressant- like effect. The aim of this study was to investigate its potential neurogenesis-enhancing effect and its role in repair following stress-induced neuronal damage. MTT assay was performed to measure the effect of SF on the growth of rat pheochromocytoma (PC12) cells;morphological and immunocytochemical meth- ods were used for assessing its differentiation-induc- ing action. Chronic mild stress (CMS) tests were per- formed to establish rat model of depression. The histopathology of animal brains was studied to ana- lyze CMS-induced morphological changes and the effect of SF on the repair of CMS-induced brain in- jury. The expressions of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) and the proliferation of neural stem cell/neural progenitor cells were assessed in the hippocampi of chronic mild stress (CMS)-induced depression-like model rats by immunohistochemistry and bromodeoxyuridine (BrdU)- incorporation assays, respectively. Our in vitro tests showed that SF promoted the proliferation of PC12 cells in the concentration range of 5 - 320 μM, and induced PC12 cells to differentiate to more mature cells with the morphological characteristics and mo- lecular marker of neuronal-like cells. In vivo tests showed that SF up-regulated the expressions of NGF and BDNF, and induced the proliferation of neural stem cell/neural progenitor cells in the hippocampi of CMS-induced depression-like model rats. This study provides evidences that SF shows neurogenesis-en- hancing effect, and its antidepressant-like effect of SF may be related directly and closely to its above-men- tioned effect.

Effect of sodium ferulate on activation of postsynaptic density-95 after transient facol cerebral ischemia

It was confirmed that sodium ferulate (SF) could significantly improve neurologic function deficit, reduce cerebral infarct volume at 24 h after reperfusion, and weakened postsynaptic density-95 (PSD-95) activation in ische-mic area reacting to ischemia after transient middle cerebral artery occlusion ( MCAO) by Western immunoblot analy-

Protective effects of sodium ferulate in vascular endothelial function during cardiopulmonary bypass

Objective Cardiopulmonary bypass (CPB) and its related ischemia reperfusion injury may cause endothelial cell injury. To study the protective effects of sodium ferulate in vascular endothelial function during CPB by testing the changes of vascular endothelial cell(CEC) ,nitric oxide(NO) and endothelin-1 (ET-1) in children with congenital heart disease. Methods Sixty patients

Effect of sodium ferulate in combined with atorvastatin on the renal interstitial fibrosis and inflammatory cytokines in patients with diabetic nephropathy

Objective:To explore the effect of sodium ferulate in combined with atorvastatin on the renal interstitial fibrosis and inflammatory cytokines in patients with diabetic nephropathy (DN). Methods: A total of 111 patients with DN who were admitted in our hospital from January, 2016 to April, 2017 were included in the study and randomized into the observation group and the control 1 and 2 group with 37 cases in each group. The patients in the control group were given routine blood sugar reducing, blood pressure reducing, and high quality low protein diet. On the above basis, the patients in the control 2 group were orally administrated with atorvastatin before sleep (20 mg). On the basis of treatments in the control 1 group, the patients in the observation group were given sodium ferulate (0.3 g) + 0.9% NaCl (250 mL), ivdrip, 1 time/d, and administrated with atorvastatin before sleep (20 mg). The fasting peripheral venous blood before and after treatment in the three groups was collected. The glycse oxidase (GOD) method was used to detect FPG. ELISA was used to detect SCr, TGF-β, AngⅡ, CTGF, hs-CRP, TNF-α, and IL-6. RIA was used to detect BUN and 24hUAER. The strengthened chemiluminescence immunoassay was used to detect CⅣ and PCⅢ. MAP was recorded. Results: FPG, MAP, BUN, 24hUAER, and SCr after treatment in the control 2 group were significantly lower than those in the control 1 group. FPG, MAP, BUN, 24hUAER, and SCr after treatment in the observation group were significantly lower than those in the control 2 group. AngⅡ, TGF-β, CTGF, PCⅢ, and CⅣ after treatment in the control 2 group were significantly lower than those in the control 1 group. AngⅡ, TGF-β, CTGF, PCⅢ, and CⅣ after treatment in the observation group were significantly lower than those in the control 2 group. TNF-α, IL-6, and hs-CRP after treatments in the control 2 group were significantly lower than those in the control 1 group. TNF-α, IL-6, and hs-CRP after treatment in the observation group were significantly lower than those in the control 2 group.Conclusions:The sodium ferulate in combined with atorvastatin can effectively improve the renal function in patients with DN, alleviate the systemic inflammatory reaction, and delay the renal interstitial fibrosis speed.

Clinical value of sodium ferulate + Shenmai injection in the adjuvant treatment of acute myocardial infarction

Objective: To explore the clinical value of sodium ferulate + Shenmai injection in the adjuvant treatment of acute myocardial infarction (AMI). Methods: A total of 119 patients with AMI who were treated in our hospital between December 2014 and December 2017 were reviewed and divided into the control group (n=60) who received conventional western medicine +Shenmai injection therapy and the sodium ferulate group (n=59) who received conventional western medicine + sodium ferulate + Shenmai injection therapy. The differences in serum levels of myocardial injury markers, inflammatory mediators and ventricular remodeling-related indexes were compared between the two groups before treatment and after 2 weeks of treatment. Results: Before treatment, serum levels of myocardial injury markers, inflammatory mediators and ventricular remodeling-related indexes were not significantly different between the two groups. After 2 weeks of treatment, serum myocardial injury markers GMP-140, cTnT, MYO, NT-proBNP and H-FABP levels of sodium ferulate group were lower than those of control group;serum inflammatory mediators MCP-1, IL-18 and hs-CRP levels were lower than those of control group;serum ventricular remodeling-related indexes GDF-15, MMP-10 and CgA levels were lower than those of control group whereas IGF-1 level was higher than that of control group. Conclusion: Western medicine combined with sodium ferulate+ Shenmai injection therapy can effectively protect the myocardial function and inhibit the systemic inflammatory response and ventricular remodeling in patients with AMI.

Research progress on the application of ferulic acid in cosmetics

Ferulic acid is a phenolic compound widely exists in plants.Currently ferulic acid on the market is mainly extracted from plants,but it can also be obtained via biosynthesis or chemical synthesis.The biosynthesis method has a great potential for future production of ferulic acid.Ferulic acid is frequently used as a whitening ingredient in cosmetics,since it reduces melanin production by competitively inhibiting tyrosinase activity.It also has strong antioxidant activity,including elimination of free radicals,inhibition of ROS production,and regulation of various signaling pathways and the activity of antioxidant enzymes.The anti-UV activity of ferulic acid makes it applicable in sunscreen cosmetics.It can absorb UV rays and inhibit UVB-induced matrix metalloproteinase MMP-2 and MMP-9 activities to attenuate the damage caused by UV radiation.Ferulic acid is also reported to display protective effects on human keratinocytes and human skin fibroblasts.In addition,it is found to have effective anti-aging effect,mainly through inhibiting the degradation of hyaluronic acid by reducing the activities of collagenase and hyaluronidase,and inducing the biosynthesis of pre-collagen and hyaluronic acid.Ferulic acid shows potential for the treatment of atopic dermatitis,psoriasis and other inflammatory diseases of the skin.Its anti-inflammatory effect results from the inhibition of multiple inflammatory factors and signaling pathways.Ferulic acid displays broad-spectrum antibacterial effect,by damaging the cell membranes of bacteria and fungi which leads to membrane leakage and cell death.Furthermore,ferulic acid can also promote skin healing and regeneration.However,the instability of ferulic acid limits its applications in cosmetics.

Effect of sodium ferulate in combined with Huangqi injection on the coagulation and immunological function in patients with primary nephrotic syndrome

Objective:To explore the effect of sodium ferulate in combined with Huangqi injection on the coagulation and immunological function in patients with primary nephrotic syndrome (PNS).Methods: A total of 137 patients with PNS were included in the study and randomized into the observation group (n=69) and the control group (n=68). The patients in the treatment group were given routine treatment, anticoagulation, lipid regulation, and other symptomatic treatments. On this basis, the patients in the observation group were given sodium ferulate in combined with Huangqi injection. The coagulation, immunological function, and hemorrheology indicators before and after treatment in the two groups were compared.Results:Alb content after treatment in the two groups was significantly elevated when compared with before treatment (P<0.05), while ET, 24 h UPQ, Scr, and BUN levels were significantly reduced when compared with before treatment (P<0.05);moreover, the improvement degree of the above indicators in the observation group was significantly greater than that in the control group (P<0.05). PT and APTT after treatment in the two groups were significantly prolonged when compared with before treatment (P<0.05), while FIB, D-D content, whole blood high shear viscosity, low shear viscosity, blood viscosity, and ARBC were significantly reduced when compared with before treatment (P<0.05);moreover, the improvement degree of the above indicators in the observation group was significantly greater than that in the control group (P<0.05). CD3+, CD4+, and CD8+ after treatment in the two groups were significantly elevated when compared with before treatment (P<0.05). CD3+ and CD4+ after treatment in the observation group were significantly higher than those in the control group (P<0.05). CD4+/CD8+, IgG, and IgA after treatment in the observation group were significantly higher than those in the control group (P<0.05).Conclusions:Sodium ferulate in combined with Huangqi injection in the treatment of PNS can improve the coagulation function and hemorheology, alleviate the blood coagulation, enhance the immunological function, and recover the renal function.

High Efficient Synthesis of Enzymatic 2-Ethylhexyl Ferulate at Solvent-Free and Reduced Pressure Evaporation System

The use of immobilized lipase from Candida antarctica (Novozymò 435) to catalyze ferulic acid of esterification was investigated in this study. The synthesis product was analyzed using HPLC. The results revealed that the major product was 2-ethylhexyl ferulate. Response surface methodology and 3-level-3-factor central composite rotatable design were adopted to evaluate the effects of synthesis variables, including reaction temperature (60℃- 80℃), enzyme amount (500 - 1500 PLU) and reaction time (8 - 24 h) on the percentage molar conversion of 2-ethylhexyl ferulate. The results showed that reaction temperature and reaction time were the most important parameters on percentage molar conversion. Based on ridge max analysis, the optimum conditions for synthesis were: reaction time 23 h, reaction temperature 71℃?and enzyme amount 1422 PLU. The molar conversion of actual experimental values was 98% under optimal conditions.