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Sample records for additive inhibitory effect

  1. Copper addition prevents the inhibitory effects of interleukin 1-beta on rat pancreatic islets.

    PubMed

    Vinci, C; Caltabiano, V; Santoro, A M; Rabuazzo, A M; Buscema, M; Purrello, R; Rizzarelli, E; Vigneri, R; Purrello, F

    1995-01-01

    Since copper [Cu(II)] is a necessary cofactor for both intra-mitochondrial enzymes involved in energy production and hydroxyl scavenger enzymes, two hypothesised mechanisms for action of interleukin-I beta (IL-1 beta), we studied whether Cu(II) addition could prevent the inhibitory effect of IL-1 beta on insulin release and glucose oxidation in rat pancreatic islets. Islets were incubated with or without 50 U/ml IL-1 beta, in the presence or absence of various concentrations of Cu(II)-GHL (Cu(II) complexed with glycyl-L-histidyl-L-lysine, a tripeptide known to enhance copper uptake into cultured cells). CuSO4 (1-1000 ng/ml) was used as a control for Cu(II) effect when present as an inorganic salt. At the end of the incubation period, insulin secretion was evaluated in the presence of either 2.8 mmol/l (basal insulin secretion) or 16.7 mmol/l glucose (glucose-induced release). In control islets basal insulin secretion was 92.0 +/- 11.4 pg.islet-1 h-1 (mean +/- SEM, n = 7) and glucose-induced release was 2824.0 +/- 249.0 pg.islet-1 h-1. In islets pre-exposed to 50 U/ml IL-1 beta, basal insulin release was not significantly affected but glucose-induced insulin release was greatly reduced (841.2 +/- 76.9, n = 7, p < 0.005). In islets incubated with IL-1 beta and Cu-GHL (0.4 mumol/l, maximal effect) basal secretion was 119.0 +/- 13.1 pg.islet-1 h-1 and glucose-induced release was 2797.2 +/- 242.2, (n = 7, p < 0.01 in respect to islets exposed to IL-1 beta alone).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7744228

  2. Litter Decomposition in a Semiarid Dune Grassland: Neutral Effect of Water Supply and Inhibitory Effect of Nitrogen Addition

    PubMed Central

    Li, Yulin; Ning, Zhiying; Cui, Duo; Mao, Wei; Bi, Jingdong; Zhao, Xueyong

    2016-01-01

    Background The decomposition of plant material in arid ecosystems is considered to be substantially controlled by water and N availability. The responses of litter decomposition to external N and water, however, remain controversial, and the interactive effects of supplementary N and water also have been largely unexamined. Methodology/Principal Findings A 3.5-year field experiment with supplementary nitrogen and water was conducted to assess the effects of N and water addition on mass loss and nitrogen release in leaves and fine roots of three dominant plant species (i.e., Artemisia halondendron, Setaria viridis, and Phragmites australis) with contrasting substrate chemistry (e.g. N concentration, lignin content in this study) in a desertified dune grassland of Inner Mongolia, China. The treatments included N addition, water addition, combination of N and water, and an untreated control. The decomposition rate in both leaves and roots was related to the initial litter N and lignin concentrations of the three species. However, litter quality did not explain the slower mass loss in roots than in leaves in the present study, and thus warrant further research. Nitrogen addition, either alone or in combination with water, significantly inhibited dry mass loss and N release in the leaves and roots of the three species, whereas water input had little effect on the decomposition of leaf litter and fine roots, suggesting that there was no interactive effect of supplementary N and water on litter decomposition in this system. Furthermore, our results clearly indicate that the inhibitory effects of external N on dry mass loss and nitrogen release are relatively strong in high-lignin litter compared with low-lignin litter. Conclusion/Significance These findings suggest that increasing precipitation hardly facilitates ecosystem carbon turnover but atmospheric N deposition can enhance carbon sequestration and nitrogen retention in desertified dune grasslands of northern China

  3. Synthesis and synergistic, additive inhibitory effects of novel spiro derivatives against ringworm infections.

    PubMed

    Sharma, Gajanand; Sharma, Richa; Dandia, Anshu; Bansal, Preeti

    2013-01-01

    An environmentally benign solvent free synthesis of various spiro-1,4-dihydropyridines (1,4-DHPs) incorporating 2-oxindole/piperidines is performed in 5-8 min with reasonable purity in 80-90% yield under microwave irradiation using montmorillonite KSF as an inorganic solid support. The reaction is found to be general with respect to various cyclic carbonyl compounds, e.g. cyclohexanone, substituted indole-2,3-dione, and piperidinone derivatives. In our study, these compounds were also found effective against dermatophytes and other fungal organisms. Our results suggest that novel spiro derivatives can be used for the treatment of dermatophytosis or ringworm infections.

  4. Synthesis and synergistic, additive inhibitory effects of novel spiro derivatives against ringworm infections.

    PubMed

    Sharma, Gajanand; Sharma, Richa; Dandia, Anshu; Bansal, Preeti

    2013-01-01

    An environmentally benign solvent free synthesis of various spiro-1,4-dihydropyridines (1,4-DHPs) incorporating 2-oxindole/piperidines is performed in 5-8 min with reasonable purity in 80-90% yield under microwave irradiation using montmorillonite KSF as an inorganic solid support. The reaction is found to be general with respect to various cyclic carbonyl compounds, e.g. cyclohexanone, substituted indole-2,3-dione, and piperidinone derivatives. In our study, these compounds were also found effective against dermatophytes and other fungal organisms. Our results suggest that novel spiro derivatives can be used for the treatment of dermatophytosis or ringworm infections. PMID:24397035

  5. Inhibitory effect of xanthan gum and synergistic surfactant additives for mild steel corrosion in 1M HCl.

    PubMed

    Mobin, Mohammad; Rizvi, Marziya

    2016-01-20

    Natural polymer xanthan gum (XG) was investigated as eco friendly corrosion inhibitor for mild steel in 1M HCl at 30 °C, 40 °C, 50 °C and 60 °C, respectively. The inhibition studies were performed using gravimetric analysis, potentiodynamic polarization, electrochemical impedance spectroscopy (EIS), quantum chemical calculations, scanning electron microscopy (SEM), and UV-visible spectrophotometry. XG significantly reduces the corrosion rates of mild steel. The inhibition efficiency (IE) of the XG increased with increase in concentration, but decreased with temperature; the maximum IE of 74.24% was obtained at concentration of 1000 ppm at 30 °C. The inhibiting action of XG is synergistically enhanced on addition of very small amount of surfactants sodium dodecyl sulfate (SDS), cetyl pyridinium chloride (CPC) and Triton X-100 (TX). The effect of SDS is more pronounced than other surfactants. Potentiodynamic polarization studies confirm XG as a mixed type inhibitor. Results of weight loss measurements are in good agreement of the results of electrochemical measurements. The UV-visible spectroscopic results indicate the formation of complex between XG and Fe(2+) ions during corrosion reaction. Mechanism of inhibition was also investigated by calculating the thermodynamic and activation parameters like ΔG(0), Ea, ΔH and ΔS. The adsorption of inhibitor on mild steel surface obeys Langmuir adsorption isotherm. SEM micrographs show a clearly different morphology in presence of XG and XG-surfactant additives and confirmed the existence of an adsorbed protective film on the mild steel surface. PMID:26572368

  6. Inhibitory effect of xanthan gum and synergistic surfactant additives for mild steel corrosion in 1M HCl.

    PubMed

    Mobin, Mohammad; Rizvi, Marziya

    2016-01-20

    Natural polymer xanthan gum (XG) was investigated as eco friendly corrosion inhibitor for mild steel in 1M HCl at 30 °C, 40 °C, 50 °C and 60 °C, respectively. The inhibition studies were performed using gravimetric analysis, potentiodynamic polarization, electrochemical impedance spectroscopy (EIS), quantum chemical calculations, scanning electron microscopy (SEM), and UV-visible spectrophotometry. XG significantly reduces the corrosion rates of mild steel. The inhibition efficiency (IE) of the XG increased with increase in concentration, but decreased with temperature; the maximum IE of 74.24% was obtained at concentration of 1000 ppm at 30 °C. The inhibiting action of XG is synergistically enhanced on addition of very small amount of surfactants sodium dodecyl sulfate (SDS), cetyl pyridinium chloride (CPC) and Triton X-100 (TX). The effect of SDS is more pronounced than other surfactants. Potentiodynamic polarization studies confirm XG as a mixed type inhibitor. Results of weight loss measurements are in good agreement of the results of electrochemical measurements. The UV-visible spectroscopic results indicate the formation of complex between XG and Fe(2+) ions during corrosion reaction. Mechanism of inhibition was also investigated by calculating the thermodynamic and activation parameters like ΔG(0), Ea, ΔH and ΔS. The adsorption of inhibitor on mild steel surface obeys Langmuir adsorption isotherm. SEM micrographs show a clearly different morphology in presence of XG and XG-surfactant additives and confirmed the existence of an adsorbed protective film on the mild steel surface.

  7. The combined inhibitory effect of the adenosine A1 and cannabinoid CB1 receptors on cAMP accumulation in the hippocampus is additive and independent of A1 receptor desensitization.

    PubMed

    Serpa, André; Correia, Sara; Ribeiro, Joaquim A; Sebastião, Ana M; Cascalheira, José F

    2015-01-01

    Adenosine A1 and cannabinoid CB1 receptors are highly expressed in hippocampus where they trigger similar transduction pathways. We investigated how the combined acute activation of A1 and CB1 receptors modulates cAMP accumulation in rat hippocampal slices. The CB1 agonist WIN55212-2 (0.3-30 μM) decreased forskolin-stimulated cAMP accumulation with an EC50 of 6.6±2.7 μM and an Emax of 31%±2%, whereas for the A1 agonist, N6-cyclopentyladenosine (CPA, 10-150 nM), an EC50 of 35±19 nM, and an Emax of 29%±5 were obtained. The combined inhibitory effect of WIN55212-2 (30 μM) and CPA (100 nM) on cAMP accumulation was 41%±6% (n=4), which did not differ (P>0.7) from the sum of the individual effects of each agonist (43%±8%) but was different (P<0.05) from the effects of CPA or WIN55212-2 alone. Preincubation with CPA (100 nM) for 95 min caused desensitization of adenosine A1 activity, which did not modify the effect of WIN55212-2 (30 μM) on cAMP accumulation. In conclusion, the combined effect of CB1 and A1 receptors on cAMP formation is additive and CB1 receptor activity is not affected by short-term A1 receptor desensitization.

  8. Inhibitory effect of nuts on iron absorption.

    PubMed

    Macfarlane, B J; Bezwoda, W R; Bothwell, T H; Baynes, R D; Bothwell, J E; MacPhail, A P; Lamparelli, R D; Mayet, F

    1988-02-01

    The effects on iron absorption of nuts, an important source of dietary protein in many developing countries, were measured in 137 Indian women. When the absorption from bread and nut meals (walnuts, almonds, peanuts, and hazelnuts) was compared with that from bread meals, the overall geometric mean absorption from the nut meals (1.8%) was significantly less than from the bread meals alone (6.6%, t = 9.8, p less than 0.0005). In contrast, coconut did not reduce absorption significantly. All the nuts tested contained significant amounts of two known inhibitors of Fe absorption (phytates and polyphenols) but the amounts in coconut were significantly less than in the other nuts. Fifty milligrams ascorbic acid overcame the inhibitory effects of two nuts that were tested (Brazil nuts and peanuts). This is different from that found previously for soy protein, another potent inhibitor of Fe absorption.

  9. Syllable Frequency and Spoken Word Recognition: An Inhibitory Effect.

    PubMed

    González-Alvarez, Julio; Palomar-García, María-Angeles

    2016-08-01

    Research has shown that syllables play a relevant role in lexical access in Spanish, a shallow language with a transparent syllabic structure. Syllable frequency has been shown to have an inhibitory effect on visual word recognition in Spanish. However, no study has examined the syllable frequency effect on spoken word recognition. The present study tested the effect of the frequency of the first syllable on recognition of spoken Spanish words. A sample of 45 young adults (33 women, 12 men; M = 20.4, SD = 2.8; college students) performed an auditory lexical decision on 128 Spanish disyllabic words and 128 disyllabic nonwords. Words were selected so that lexical and first syllable frequency were manipulated in a within-subject 2 × 2 design, and six additional independent variables were controlled: token positional frequency of the second syllable, number of phonemes, position of lexical stress, number of phonological neighbors, number of phonological neighbors that have higher frequencies than the word, and acoustical durations measured in milliseconds. Decision latencies and error rates were submitted to linear mixed models analysis. Results showed a typical facilitatory effect of the lexical frequency and, importantly, an inhibitory effect of the first syllable frequency on reaction times and error rates.

  10. Syllable Frequency and Spoken Word Recognition: An Inhibitory Effect.

    PubMed

    González-Alvarez, Julio; Palomar-García, María-Angeles

    2016-08-01

    Research has shown that syllables play a relevant role in lexical access in Spanish, a shallow language with a transparent syllabic structure. Syllable frequency has been shown to have an inhibitory effect on visual word recognition in Spanish. However, no study has examined the syllable frequency effect on spoken word recognition. The present study tested the effect of the frequency of the first syllable on recognition of spoken Spanish words. A sample of 45 young adults (33 women, 12 men; M = 20.4, SD = 2.8; college students) performed an auditory lexical decision on 128 Spanish disyllabic words and 128 disyllabic nonwords. Words were selected so that lexical and first syllable frequency were manipulated in a within-subject 2 × 2 design, and six additional independent variables were controlled: token positional frequency of the second syllable, number of phonemes, position of lexical stress, number of phonological neighbors, number of phonological neighbors that have higher frequencies than the word, and acoustical durations measured in milliseconds. Decision latencies and error rates were submitted to linear mixed models analysis. Results showed a typical facilitatory effect of the lexical frequency and, importantly, an inhibitory effect of the first syllable frequency on reaction times and error rates. PMID:27287267

  11. Inhibitory effects of antimicrobial agents against Fusarium species.

    PubMed

    Kawakami, Hideaki; Inuzuka, Hiroko; Hori, Nobuhide; Takahashi, Nobumichi; Ishida, Kyoko; Mochizuki, Kiyofumi; Ohkusu, Kiyofumi; Muraosa, Yasunori; Watanabe, Akira; Kamei, Katsuhiko

    2015-08-01

    We investigated the inhibitory effects of antibacterial, biocidal, and antifungal agents against Fusarium spp. Seven Fusarium spp: four F. falciforme (Fusarium solani species complex), one Fusarium spp, one Fusarium spp. (Fusarium incarnatum-equiseti species complex), and one F. napiforme (Gibberella fujikuroi species complex), isolated from eyes with fungal keratitis were used in this study. Their susceptibility to antibacterial agents: flomoxef, imipenem, gatifloxacin, levofloxacin, moxifloxacin, gentamicin, tobramycin, and Tobracin® (contained 3,000 μg/ml of tobramycin and 25 μg/ml of benzalkonium chloride (BAK), a biocidal agent: BAK, and antifungal agents: amphotericin B, pimaricin (natamycin), fluconazole, itraconazole, miconazole, voriconazole, and micafungin, was determined by broth microdilution tests. The half-maximal inhibitory concentration (IC50), 100% inhibitory concentration (IC100), and minimum inhibitory concentration (MIC) against the Fusarium isolates were determined. BAK had the highest activity against the Fusarium spp. except for the antifungal agents. Three fluoroquinolones and two aminoglycosides had inhibitory effects against the Fusarium spp. at relatively high concentrations. Tobracin® had a higher inhibitory effect against Fusarium spp. than tobramycin alone. Amphotericin B had the highest inhibitory effect against the Fusarium spp, although it had different degrees of activity against each isolate. Our findings showed that fluoroquinolones, aminoglycosides, and BAK had some degree of inhibitory effect against the seven Fusarium isolates, although these agents had considerably lower effect than amphotericin B. However, the inhibitory effects of amphotericin B against the Fusarium spp. varied for the different isolates. Further studies for more effective medications against Fusarium, such as different combinations of antibacterial, biocidal, and antifungal agents are needed.

  12. Inhibitory Effect of Glycerin on Vibrio parahaemolyticus and Salmonella

    PubMed Central

    Chun, Doki; Seol, Sung Yong; Tak, Ryunbin; Park, Cheong Kyu

    1972-01-01

    In a study of the effect of glycerin in transport media on Vibrio parahaemolyticus and Salmonella, it was found that a concentration of 30% glycerin was highly inhibitory for V. parahaemolyticus and to a lesser degree for Salmonella. The incorporation of peptone or human feces in media did not reduce the inhibitory effect of glycerin. In media with 15% glycerin, viable counts of V. parahaemolyticus and Salmonella increased after 24 hr of incubation both in the presence and absence of feces. Due to the concurrent increase in the total bacterial count in the media containing feces, no enrichment effect was noted. PMID:4565633

  13. The inhibitory effect of bran on iron absorption in man.

    PubMed

    Simpson, K M; Morris, E R; Cook, J D

    1981-08-01

    The effects of whole wheat bran and its components on the absorption of nonheme dietary iron were measured using a double isotope technique in human volunteers. When 12 g bran was added to a light meal, absorption decreased by 51 to 74%; this inhibitory effect of bran was shown for meals of both high and low iron availability. Inhibition was not explained by monoferric phytate, the major form of iron in bran, because labeled iron from monoferric phytate was absorbed at least as well as the common pool of nonheme dietary iron. Furthermore, removal of phytate from bran by endogenous phytase did not in itself alter the inhibitory effect of the bran on iron absorption. Studies in which dephytinized bran was separated into a soluble, phosphate-rich fraction and an insoluble, high-fiber fraction indicated that the soluble fraction was more inhibitory than the insoluble fraction. PMID:6267927

  14. Anticipated effects of alcohol stimulate craving and impair inhibitory control.

    PubMed

    Christiansen, Paul; Jennings, Emily; Rose, Abigail K

    2016-05-01

    A considerable evidence base has demonstrated that priming doses of alcohol impair inhibitory control and activate motivation to consume alcohol. There is, however, a lack of studies investigating the effect of placebo-alcohol on these processes and their association with alcohol outcome expectancies (AOE). We investigated the effect of placebo-alcohol on craving and inhibitory control, and the extent to which placebo effects correlated with AOE in 32 nondependent drinkers. Participants completed questionnaires assessing typical alcohol use (fortnightly alcohol consumption, AUDIT) and AOE (measured using the Alcohol Outcome Expectancy Scale). On a within-subjects basis participants consumed a placebo-alcohol drink and control drink. Measures of craving were taken pre- and postdrink, and participants completed a go/no-go task following the drink. Craving was increased by the placebo-alcohol and, importantly, placebo-alcohol impaired inhibitory control. Furthermore expectancies of cognitive and behavioral impairment were correlated with go/no-go task performance following a placebo. Increases in craving were associated with a range of elevated outcome expectancies. This suggests that the anticipated effects of alcohol can impair inhibitory control and increase craving; therefore studies using placebo versus alcohol comparisons relative to studies using a pure no-alcohol control are underestimating the real-world effect of alcohol on these processes, which is a combination of pharmacological and anticipated effects of alcohol. Furthermore, individual differences in AOE may influence reactivity to the anticipated effects of alcohol. (PsycINFO Database Record PMID:27031087

  15. Inhibitory and excitatory effects of dopamine on Aplysia neurones

    PubMed Central

    Ascher, P.

    1972-01-01

    1. Electrophoretic application of dopamine (DA) on Aplysia neurones elicits both excitatory and inhibitory effects, which in many cases are observed in the same neurone, and often result in a biphasic response. 2. The DA receptors are localized predominantly on the axons. Desensitization, which occurs after repeated injections or with bath application of DA, is more marked for excitatory responses. 3. Tubocurarine and strychnine block the DA excitatory responses without affecting the inhibitory ones, which can be selectively blocked by ergot derivatives. It is concluded that the excitatory and inhibitory effects are mediated by two distinct receptors. 4. The two DA receptors can be pharmacologically separated from the three ACh receptors described in the same nervous system. 5. In some neurones the dopamine inhibitory responses can be inverted by artificial hyperpolarization of the membrane at the potassium equilibrium potential, EK, indicating that dopamine causes a selective increase in potassium permeability. 6. In other neurones the reversal potential of dopamine inhibitory responses is at a more depolarized level than EK, but can be brought to EK by pharmacological agents known to block the receptors mediating the excitatory effects of DA. 7. In still other neurones, the hyperpolarization induced by DA cannot be inverted in normal conditions, but a reversal can be induced by ouabain or by the substitution of external sodium by lithium. These results are discussed in terms of an hypothesis in which dopamine increases the potassium permeability of a limited region of the axonal membrane. 8. It is concluded that a selective increase in potassium permeability probably accounts for all dopamine inhibitory effects in the neurones studied. PMID:4679683

  16. Inhibitory effect of seven Allium plants upon three Aspergillus species.

    PubMed

    Yin, M C; Tsao, S M

    1999-08-01

    Antifungal activity and minimal fungicidal concentration (MFC) of extracts of garlic, bakeri garlic, Chinese leek, Chinese chive, scallion, onion bulb and shallot bulb against Aspergillus niger, A. flavus and A. fumigatus were examined. These Allium plants possessed antifungal activity, with garlic showing the lowest MFC. With the exception of scallion, the inhibitory effect of Allium plants against three Aspergillus species decreased with increasing incubation and heating temperature (P < 0.05). Acetic acid treatments of the extracts increased the inhibitory effect for all plants against three fungi (P < 0.05), and there was no significant difference in this effect among the three pH (2, 4, 6) treatments (P > 0.05) investigated. Acetic acid, at pH = 4, plus heat treatments of the extracts resulted in a greater inhibitory effect for all Allium plants against the three fungi than heat treatment alone (P < 0.05). Treatments of the extracts with NaCl, at concentrations of 0.2 and 0.4 M, did not affect the inhibitory effect of the plant extracts. The combination of acetic acid plus Allium plants was indicated to be an effective way to inhibit fungal growth. PMID:10477070

  17. The effect of social observation on children's inhibitory control.

    PubMed

    Moriguchi, Yusuke

    2012-10-01

    This study examined the effects of social observation on young children's performance during an inhibitory control task. In Experiment 1, children were randomly assigned to either a neutral, facilitation, or interference condition. In the neutral condition, children were presented with a standard black/white task. In the facilitation and interference conditions, children were asked to observe the task performance of another person, who gave either correct (facilitation) or incorrect (interference) responses, and then complete the task themselves. The results revealed that the performance of children in the interference condition was worse than in the other two conditions, but the difference between the two other conditions was not significant. The results of Experiment 2 show that social observation did not facilitate inhibitory control in children. These results suggest that social observation interferes with but does not facilitate inhibitory control in children. Therefore, social observation may interfere with certain aspects of executive function. PMID:22781163

  18. Chromenylchalcones with inhibitory effects on monoamine oxidase B.

    PubMed

    Jo, Geunhyeong; Ahn, Seunghyun; Kim, Bong-Gyu; Park, Hye Ri; Kim, Young Hwa; Choo, Hyun Ah; Koh, Dongsoo; Chong, Youhoon; Ahn, Joong-Hoon; Lim, Yoongho

    2013-12-15

    Structure-activity relationship (SAR) calculations were used to find monoamine oxidase-B (MAO-B) inhibitors by identifying pharmacophores exhibiting high inhibitory activities. Several such chromenylchalcones were designed and synthesized accordingly. Their inhibitory effects on MAO-B were determined using an HPLC-based method and an MAO-B enzyme assay kit. (E)-3-(6-Methoxy-2H-chromen-3-yl)-1-(2-methoxyphenyl)prop-2-en-1-one exhibited a half-maximal inhibitory concentration of 320 nM. Its molecular-level binding mode with the three-dimensional structure of MAO-B was elucidated using an in silico docking study. The chromenylchalcone scaffold, which is derived from natural products including isoflavonoids and chalcones, had not been previously reported as an MAO-B inhibitor.

  19. The Effect of Social Observation on Children's Inhibitory Control

    ERIC Educational Resources Information Center

    Moriguchi, Yusuke

    2012-01-01

    This study examined the effects of social observation on young children's performance during an inhibitory control task. In Experiment 1, children were randomly assigned to either a neutral, facilitation, or interference condition. In the neutral condition, children were presented with a standard black/white task. In the facilitation and…

  20. Inhibitory effect of metal ions on alkaline mesentericopeptidase.

    PubMed

    Raykova, D; Dorovska-Taran, V; Blagoev, B

    1981-01-01

    The effect of AG+, Cu2+, Cd2+, Co2+ and Ni2+ on the activity of alkaline mesentericopeptidase (EC 3.4.21.-) has been studied. Ag+, Cu2+ and Cd2+ were found to be reversible non-competitive inhibitors of the enzyme. The pH-dependence of Ki for Ag+-inhibition is sigmoidal with a pKa near 6. The Kilim values, calculated for the pH-independent region of the metal-enzyme inhibition, are close to the corresponding dissociation constants of metal-imidazole complexes, thus implying that the inhibitory effect of metal ions on enzyme activity is due to complex formation with the imidazole group of the active site histidine. The method of the two-component inhibition showed that Cu2+ and Ag+ bind to the same ligand of the enzyme molecule. The addition of Cu2+ decreases the rate of deacylation of the hydrolysis of p-nitrophenyl valerate, catalyzed by alkaline mesentericopeptidase in contrast to alpha-chymotrypsin where the acylation step is affected.

  1. Inhibitory effects of tunisian marine algal extracts on digestive lipases.

    PubMed

    Ben Rebah, Faouzi; Smaoui, Sana; Frikha, Fakher; Gargouri, Youssef; Miled, Nabil

    2008-10-01

    The lipase inhibitory activity of ethanol extracts obtained from some marine algae collected on the Tunisian coast was evaluated. Caulerpa prolifera extract markedly reduced both dog gastric (DGL) and human pancreatic lipase (HPL) activities. Generally, the inhibition reached 100% after 40 to 60 min of incubation depending on lipase types and on substrates used. Moreover, the inhibitory effect of C. prolifera extract on lipases appeared to be accelerated by adding bile salts, which likely modified the interface and allowed the inhibitory compound to inactivate the lipase. The separation of C. prolifera extract by thin-layer chromatography (TLC) resulted in eight fractions showing efficient inhibition rate against DGL, compared to the crude extract. In the case of HPL, TLC fractionation reduced the inhibitory rates, suggesting that the effect of algal extract on lipases may be caused by a synergetic action of several compounds within the extract. High-performance liquid chromatograph separation resulted in isolation of a major compound displaying high inhibition capacity of HPL activity. Caulerpa prolifera extract may therefore be useful in developing antiobesity drugs.

  2. Inhibitory Effects of Angelica Polysaccharide on Activation of Mast Cells

    PubMed Central

    Mao, Wei-An; Sun, Yuan-Yuan; Mao, Jing-Yi; Wang, Li; Zhang, Jian; Zhou, Jie; Rahman, Khalid; Ye, Ying

    2016-01-01

    This study was designed to investigate the inhibitory effects of Angelica polysaccharide (AP) on activation of mast cells and its possible molecular mechanism. In our study, we determined the proinflammatory cytokines and allergic mediators in anti-DNP IgE stimulated RBL-2H3 cells and found that AP (50, 100, and 200 μg/mL) significantly decreased the release of histamine, β-hexosaminidase, leukotrienes C4 (LTC4), IL-1, IL-4, TNF-α, IL-6, and human monocyte chemotactic protein-1 (MCP-1/CCL2) (p < 0.05). In addition, Ca2+ entry was inhibited by treatment with AP. AP also downregulated the protein expressions of p-Fyn, p-Akt, p-P38, IL-4, TNF-α, and NF-κB p65 in both Fyn gene upregulated and normal RBL-2H3 cells (p < 0.05). Collectively, our results showed that AP could inhibit the activation of mast cells via suppressing the releases of proinflammatory cytokines allergic mediators, Gab2/PI3-K/Akt and Fyn/Syk pathways. PMID:27200102

  3. Inhibitory effects of ionic liquids on the lactic dehydrogenase activity.

    PubMed

    Dong, Xing; Fan, Yunchang; Zhang, Heng; Zhong, Yingying; Yang, Yang; Miao, Juan; Hua, Shaofeng

    2016-05-01

    Ionic liquids (ILs) were widely used in scientific and industrial application and have been reported to possess potential toxicity to the environment and human health. The effects of six typical N-methylimidazolium-based ILs ([Cnmim]X, n=4, 6, 8; X=Br(-), Cl(-), BF4(-), CF3SO3(-)) on the lactic dehydrogenase (LDH) activity and the molecular interaction mechanism of ILs and the LDH were investigated with the aid of spectroscopic techniques. Experimental results showed that the LDH activity was inhibited in the presence of ILs. For the ILs with the same anion but different cations, their inhibitory ability on the LDH activity increased with increasing the alkyl chain length on the IL cation. Thermodynamic parameters, enthalpy change (ΔH) and entropy change (ΔS) were obtained by analyzing the fluorescence behavior of LDH with the addition of ILs. Both positive ΔH and ΔS suggested that hydrophobicity was the major driven force in the interaction process as expected. PMID:26802246

  4. Galectin-1 Exerts Inhibitory Effects during DENV-1 Infection

    PubMed Central

    Andrade, Camillo del Cistia; Riul, Thalita Bachelli; Alves, Renata Tomé; Muller, Vanessa Danielle Menjon; Russo, Raquel Rinaldi; Stowell, Sean R.; Cummings, Richard D.; Aquino, Victor Hugo; Dias-Baruffi, Marcelo

    2014-01-01

    Dengue virus (DENV) is an enveloped RNA virus that is mosquito-transmitted and can infect a variety of immune and non-immune cells. Response to infection ranges from asymptomatic disease to a severe disorder known as dengue hemorrhagic fever. Despite efforts to control the disease, there are no effective treatments or vaccines. In our search for new antiviral compounds to combat infection by dengue virus type 1 (DENV-1), we investigated the role of galectin-1, a widely-expressed mammalian lectin with functions in cell-pathogen interactions and immunoregulatory properties. We found that DENV-1 infection of cells in vitro exhibited caused decreased expression of Gal-1 in several different human cell lines, suggesting that loss of Gal-1 is associated with virus production. In test of this hypothesis we found that exogenous addition of human recombinant Gal-1 (hrGal-1) inhibits the virus production in the three different cell types. This inhibitory effect was dependent on hrGal-1 dimerization and required its carbohydrate recognition domain. Importantly, the inhibition was specific for hrGal-1, since no effect was observed using recombinant human galectin-3. Interestingly, we found that hrGal-1 directly binds to dengue virus and acts, at least in part, during the early stages of DENV-1 infection, by inhibiting viral adsorption and its internalization to target cells. To test the in vivo role of Gal-1 in DENV infection, Gal-1-deficient-mice were used to demonstrate that the expression of endogenous Galectin-1 contributes to resistance of macrophages to in vitro-infection with DENV-1 and it is also important to physiological susceptibility of mice to in vivo infection with DENV-1. These results provide novel insights into the functions of Gal-1 in resistance to DENV infection and suggest that Gal-1 should be explored as a potential antiviral compound. PMID:25392933

  5. Enzyme inhibitory and radical scavenging effects of some antidiabetic plants of Turkey

    PubMed Central

    Orhan, Nilüfer; Hoçbaç, Sanem; Orhan, Didem Deliorman; Asian, Mustafa; Ergun, Fatma

    2014-01-01

    Objective(s): Ethnopharmacological field surveys demonstrated that many plants, such as Gentiana olivieri, Helichrysum graveolens, Helichrysum plicatum ssp. plicatum, Juniperus oxycedrus ssp. oxycedrus, Juniperus communis var. saxatilis, Viscum album (ssp. album, ssp. austriacum), are used as traditional medicine for diabetes in different regions of Anatolia. The present study was designed to evaluate the in vitro antidiabetic effects of some selected plants, tested in animal models recently. Materials and Methods: α-glucosidase and α-amylase enzyme inhibitory effects of the plant extracts were investigated and Acarbose was used as a reference drug. Additionally, radical scavenging capacities were determined using 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) ABTS radical cation scavenging assay and total phenolic content of the extracts were evaluated using Folin Ciocalteu method. Results: H. graveolens ethanol extract exhibited the highest inhibitory activity (55.7 % ± 2.2) on α-amylase enzyme. Additionally, J. oxycedrus hydro-alcoholic leaf extract had potent α-amylase inhibitory effect, while the hydro-alcoholic extract of J. communis fruit showed the highest α-glucosidase inhibitory activity (IC50: 4.4 μg/ml). Conclusion: Results indicated that, antidiabetic effect of hydro-alcoholic extracts of H. graveolens capitulums, J. communis fruit and J. oxycedrus leaf might arise from inhibition of digestive enzymes. PMID:25140204

  6. Probing inhibitory effects of nanocrystalline cellulose: inhibition versus surface charge

    NASA Astrophysics Data System (ADS)

    Male, Keith B.; Leung, Alfred C. W.; Montes, Johnny; Kamen, Amine; Luong, John H. T.

    2012-02-01

    NCC derived from different biomass sources was probed for its plausible cytotoxicity by electric cell-substrate impedance sensing (ECIS). Two different cell lines, Spodoptera frugiperda Sf9 insect cells and Chinese hamster lung fibroblast V79, were exposed to NCC and their spreading and viability were monitored and quantified by ECIS. Based on the 50%-inhibition concentration (ECIS50), none of the NCC produced was judged to have any significant cytotoxicity on these two cell lines. However, NCC derived from flax exhibited the most pronounced inhibition on Sf9 compared to hemp and cellulose powder. NCCs from flax and hemp pre-treated with pectate lyase were also less inhibitory than NCCs prepared from untreated flax and hemp. Results also suggested a correlation between the inhibitory effect and the carboxylic acid contents on the NCC.

  7. Clinical effects of sulphite additives.

    PubMed

    Vally, H; Misso, N L A; Madan, V

    2009-11-01

    Sulphites are widely used as preservative and antioxidant additives in the food and pharmaceutical industries. Topical, oral or parenteral exposure to sulphites has been reported to induce a range of adverse clinical effects in sensitive individuals, ranging from dermatitis, urticaria, flushing, hypotension, abdominal pain and diarrhoea to life-threatening anaphylactic and asthmatic reactions. Exposure to the sulphites arises mainly from the consumption of foods and drinks that contain these additives; however, exposure may also occur through the use of pharmaceutical products, as well as in occupational settings. While contact sensitivity to sulphite additives in topical medications is increasingly being recognized, skin reactions also occur after ingestion of or parenteral exposure to sulphites. Most studies report a 3-10% prevalence of sulphite sensitivity among asthmatic subjects following ingestion of these additives. However, the severity of these reactions varies, and steroid-dependent asthmatics, those with marked airway hyperresponsiveness, and children with chronic asthma, appear to be at greater risk. In addition to episodic and acute symptoms, sulphites may also contribute to chronic skin and respiratory symptoms. To date, the mechanisms underlying sulphite sensitivity remain unclear, although a number of potential mechanisms have been proposed. Physicians should be aware of the range of clinical manifestations of sulphite sensitivity, as well as the potential sources of exposure. Minor modifications to diet or behaviour lead to excellent clinical outcomes for sulphite-sensitive individuals.

  8. Co-operative inhibitory effects of hydrogen peroxide and iodine against bacterial and yeast species

    PubMed Central

    2013-01-01

    Background Hydrogen peroxide and iodine are powerful antimicrobials widely used as antiseptics and disinfectants. Their antimicrobial properties are known to be enhanced by combining them with other compounds. We studied co-operative inhibitory activities (synergism, additive effects and modes of growth inhibition) of hydrogen peroxide and iodine used concurrently against 3 bacterial and 16 yeast species. Results Synergistic or additive inhibitory effects were shown for hydrogen peroxide and iodine mixtures against all 19 species used in the study. Both biocides were mostly cidal individually and in mixtures against Pseudomonas aeruginosa and Staphylococcus aureus. Both compounds manifested static inhibitory effects individually, but their mixtures were synergistically cidal for Saccharomyces cerevisiae and Escherihia coli. Cells of S. cerevisiae treated with hydrogen peroxide and iodine-hydrogen peroxide mixture produced increased numbers of respiratory deficient mutants indicating genotoxic effects. Conclusion Iodine and hydrogen peroxide used concurrently interact synergistically or additively against a range of prokaryotic and eukaryotic microorganisms. The study provides an insight as to how these traditional antimicrobials could be used more effectively for disinfection and antisepsis. In addition, a simple approach is proposed for scoring genotoxicity of different biocides by using the budding yeast system. PMID:23856115

  9. Inhibitory effects of butyrate on biological hydrogen production with mixed anaerobic cultures.

    PubMed

    Zheng, Xian-Jun; Yu, Han-Qing

    2005-01-01

    In this study batch experiments were conducted to investigate the inhibitory effects of butyrate addition on hydrogen production from glucose by using anaerobic mixed cultures. Experimental results showed that addition of butyrate at 4.18 and 6.27 g/l only slightly inhibited hydrogen production, and addition of butyrate at 8.36-12.54 g/l imposed a moderate inhibitory effect on hydrogen production. At addition of 25.08 g/l, butyrate had a strong inhibitory influence on substrate degradation and hydrogen production. The distribution of the volatile fatty acids produced from the acidogeneisis of glucose was significantly influenced by the addition of butyrate. The inhibition of butyrate addition on hydrogen production was described well by a non-competitive and non-linear inhibition model, with the maximum hydrogen production rate of 59.3 ml/g-SS/h, critical added butyrate concentration of 25.08 g/l, and inhibition degree of 0.323, respectively. The C(I,50) values (the butyrate concentration at which bioactivity is reduced by 50%) for hydrogen production rate and yield were estimated as 19.39 and 20.78 g/l of added butyrate, respectively.

  10. Self-DNA inhibitory effects: Underlying mechanisms and ecological implications

    PubMed Central

    Cartenì, Fabrizio; Bonanomi, Giuliano; Giannino, Francesco; Incerti, Guido; Vincenot, Christian Ernest; Chiusano, Maria Luisa; Mazzoleni, Stefano

    2016-01-01

    ABSTRACT DNA is usually known as the molecule that carries the instructions necessary for cell functioning and genetic inheritance. A recent discovery reported a new functional role for extracellular DNA. After fragmentation, either by natural or artificial decomposition, small DNA molecules (between ∼50 and ∼2000 bp) exert a species specific inhibitory effect on individuals of the same species. Evidence shows that such effect occurs for a wide range of organisms, suggesting a general biological process. In this paper we explore the possible molecular mechanisms behind those findings and discuss the ecological implications, specifically those related to plant species coexistence. PMID:26950417

  11. Inhibitory effects of some plant essential oils against Arcobacter butzleri and potential for rosemary oil as a natural food preservative.

    PubMed

    Irkin, Reyhan; Abay, Secil; Aydin, Fuat

    2011-03-01

    We investigated the inhibitory activity of commercially marketed essential oils of mint, rosemary, orange, sage, cinnamon, bay, clove, and cumin against Arcobacter butzleri and Arcobacter skirrowii and the effects of the essential oil of rosemary against A. butzleri in a cooked minced beef system. Using the disc diffusion method to determine the inhibitory activities of these plant essential oils against strains of Arcobacter, we found that those of rosemary, bay, cinnamon, and clove had strong inhibitory activity against these organisms, whereas the essential oils of cumin, mint, and sage failed to show inhibitory activity against most of the Arcobacter strains tested. The 0.5% (vol/wt) essential oil of rosemary was completely inhibitory against A. butzleri in the cooked minced beef system at 4°C. These essential oils may be further investigated as a natural solution to the food industry by creating an additional barrier (hurdle technology) to inhibit the growth of Arcobacter strains.

  12. The Mozart Effect: Additional Data.

    PubMed

    Hughes, John R.

    2002-04-01

    After the review of the Mozart effect was published in this journal (Hughes JR. Epilepsy Behav 2001;2:369-417), additional data from the music of Haydn and Liszt have been analyzed that may account for the decrease in seizure activity originally reported during Mozart music. Even with these added data Mozart music continued to score significantly higher than the selections from the other six composers in one of the important characteristics of this music, namely, the repetition of the melody. However Haydn's values were second highest among Mozart, J. S. Bach, Wagner, Beethoven, Chopin, and Liszt.

  13. Neighborhood effects in visual word recognition: facilitatory or inhibitory?

    PubMed

    Snodgrass, J G; Mintzer, M

    1993-03-01

    In five experiments, in which subjects were to identify a target word as it was gradually clarified, we manipulated the target's frequency of occurrence in the language and its neighborhood size--the number of words that can be constructed from a target word by changing one letter, while preserving letter position. In Experiments 1-4, visual identification performance to screen-fragmented words was measured. In Experiments 1 and 2, we used the ascending method of limits, whereas Experiments 3 and 4 presented a fixed-level fragment. In Experiment 1, there was no relation between overall accuracy and neighborhood size for words between three and six letters in length. However, more errors of commission (guesses) were made for high-neighborhood words and more errors of omission (blanks) were made for low-neighborhood words. Letter errors within guesses occurred at serial positions having many neighbors, and these positions were also likely to contain consonants rather than vowels. In Experiment 2, a small facilitatory effect of neighborhood size on both high- and low-frequency words was found. In contrast, in Experiments 3 and 4, using the same set of words, inhibitory effects of neighborhood size, but only for low-frequency words, were found. Experiment 5, using a speeded identification task, showed results parallel to those of Experiments 3 and 4. We suggest that whether neighborhood effects are facilitatory or inhibitory depends on whether feedback allows subjects to disconfirm initial hypotheses that the target is a high-frequency neighbor.

  14. Acute effect of vigorous aerobic exercise on the inhibitory control in adolescents

    PubMed Central

    Browne, Rodrigo Alberto Vieira; Costa, Eduardo Caldas; Sales, Marcelo Magalhães; Fonteles, André Igor; de Moraes, José Fernando Vila Nova; Barros, Jônatas de França

    2016-01-01

    Abstract Objective: To assess the acute effect of vigorous aerobic exercise on the inhibitory control in adolescents. Methods: Controlled, randomized study with crossover design. Twenty pubertal individuals underwent two 30-minute sessions: (1) aerobic exercise session performed between 65% and 75% of heart rate reserve, divided into 5 min of warm-up, 20 min at the target intensity and 5 min of cool down; and (2) control session watching a cartoon. Before and after the sessions, the computerized Stroop test-Testinpacs™ was applied to evaluate the inhibitory control. Reaction time (ms) and errors (n) were recorded. Results: The control session reaction time showed no significant difference. On the other hand, the reaction time of the exercise session decreased after the intervention (p<0.001). The number of errors made at the exercise session were lower than in the control session (p=0.011). Additionally, there was a positive association between reaction time (Δ) of the exercise session and age (r 2=0.404, p=0.003). Conclusions: Vigorous aerobic exercise seems to promote acute improvement in the inhibitory control in adolescents. The effect of exercise on the inhibitory control performance was associated with age, showing that it was reduced at older age ranges. PMID:26564328

  15. The inhibitory effect of selenium nanoparticles on protein glycation in vitro

    NASA Astrophysics Data System (ADS)

    Yu, Shaoxuan; Zhang, Wentao; Liu, Wei; Zhu, Wenxin; Guo, Ruochen; Wang, Yashan; Zhang, Daohong; Wang, Jianlong

    2015-04-01

    Selenium nanoparticles (Se NPs) possess well-known excellent biological activities and low toxicity, and have been employed for numerous applications except as inhibitors to protein glycation. Herein, the present study is carried out to investigate the inhibitory effect of Se NPs on protein glycation in a bovine serum albumin (BSA)/glucose system. By measuring the amount of glucose covalently bound onto BSA, the formation of fructosamine and fluorescent products, it is found that Se NPs can hinder the development of protein glycation in a dose-dependent but time-independent manner under the selected reaction conditions (55 °C, 40 h). And after comparing the increase of inhibitory rate in different stages, it is observed that Se NPs show the greatest inhibitory effect in the early stage, then in the advanced stage, but no effect in the intermediate stage. Fourier transform infrared spectroscopy characterization of Se NPs collected after glycation and determination of ·OH influence and glyoxal formation show that the mechanism for the inhibitory efficacy of Se NPs is related to their strong competitive activity against available amino groups in proteins, their great scavenging activity on reactive oxygen species and their inhibitory effect on α-dicarbonyl compounds’ formation. In addition, it is proved that Se NPs protect proteins from structural modifications in the system and they do not exhibit significant cytotoxicity towards BV-2 and BRL-3A cells at low concentrations (10 and 50 μg mL-1). Consequently, Se NPs may be suitable for further in vivo studies as novel anti-glycation agents.

  16. The inhibitory spillover effect: Controlling the bladder makes better liars *

    PubMed Central

    Fenn, Elise; Blandón-Gitlin, Iris; Coons, Jennifer; Pineda, Catherine; Echon, Reinalyn

    2015-01-01

    The Inhibitory-Spillover-Effect (ISE) on a deception task was investigated. The ISE occurs when performance in one self-control task facilitates performance in another (simultaneously conducted) self-control task. Deceiving requires increased access to inhibitory control. We hypothesized that inducing liars to control urination urgency (physical inhibition) would facilitate control during deceptive interviews (cognitive inhibition). Participants drank small (low-control) or large (high-control) amounts of water. Next, they lied or told the truth to an interviewer. Third-party observers assessed the presence of behavioral cues and made true/lie judgments. In the high-control, but not the low-control condition, liars displayed significantly fewer behavioral cues to deception, more behavioral cues signaling truth, and provided longer and more complex accounts than truth-tellers. Accuracy detecting liars in the high-control condition was significantly impaired; observers revealed bias toward perceiving liars as truth-tellers. The ISE can operate in complex behaviors. Acts of deception can be facilitated by covert manipulations of self-control. PMID:26366466

  17. Addition of interleukin 1 (IL1) and IL17 soluble receptors to a tumour necrosis factor α soluble receptor more effectively reduces the production of IL6 and macrophage inhibitory protein-3α and increases that of collagen in an in vitro model of rheumatoid synoviocyte activation

    PubMed Central

    Chevrel, G; Garnero, P; Miossec, P

    2002-01-01

    Methods: A simplified model was set up to evaluate the effect of tumour necrosis factor α (TNFα) soluble receptors (sTNFR) used alone and in combination with soluble interleukin 1 receptor (sIL1R) and sIL17R on the production of markers of inflammation (IL6), of migration of dendritic cells (macrophage inhibitory protein-3α (MIP-3α)), and of matrix synthesis (C-propeptide of type 1 collagen (P1CP)). Synoviocytes were stimulated with supernatants of activated peripheral blood mononuclear cells (PBMC) from patients with rheumatoid arthritis (RA). Soluble receptors (sR) were preincubated at 1 γg/ml alone or in combination with the supernatants before addition to RA synoviocytes. IL6, MIP-3α, and P1CP production was measured by enzyme linked immunosorbent assay (ELISA) in 48 hour synoviocyte supernatants. Results: IL6 production decreased by 16% with sTNFR alone compared with no sTNFR (p<0.001) and by 41% with the combination of the three sR (p<0.001). MIP-3α production decreased by 77% with sTNFR alone compared with no sTNFR (p<0.001) and by 98% with the combination of the three sR (p<0.001). In the presence of sTNFR alone, P1CP production increased by 25% compared with no sR (p<0.01). The combination of the three sR increased P1CP production by 48% (p<0.01). Conclusion: The effect of sTNFR on IL6, MIP-3α, and P1CP production by RA synoviocytes stimulated by activated PBMC supernatants was further enhanced when combined with sIL1R and sIL17R. PMID:12117682

  18. Inhibitory effect of hemin on the mutagenic activities of carcinogens.

    PubMed

    Arimoto, S; Negishi, T; Hayatsu, H

    1980-11-01

    An inhibitory effect of hemin on mutagenicities of a range of carcinogens was found by adding hemin to the preincubation mixture of the Ames' test. Strong inhibitions were observed for benzo[alpha]pyrene, 3-methylcholanthrene, 7,10-dimethylbenz[alpha]anthracene, chrysene, 2-acetylaminofluorene, 2-nitrofluorene and aflatoxin B1. Generally, 50% inhibition was caused by an amount of hemin 1--2 equivalents to the mutagen. Excess of hemin caused complete inhibitions. Hemin did not affect the mutagenicities of 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide, 4-nitroquinoline-1-oxide, nitromin, N-methyl-N-nitrosourea, N-methyl-N'-nitro-N-nitrosoguanidine, N-nitrosodi-n-butyl-amine, quinoxaline-1,4-dioxide and carbadox. Biliverdin, bilirubin and chlorophyllin were also effective as inhibitors for the mutagenicity of benzo[alpha]pyrene. PMID:7226136

  19. A subliminal inhibitory mechanism for the negative compatibility effect: a continuous versus threshold mechanism.

    PubMed

    Liu, Peng; Chen, Xuhai; Dai, Dongyang; Wang, Yongchun; Wang, Yonghui

    2014-07-01

    The current study investigated the mechanism underlying subliminal inhibition using the negative compatibility effect (NCE) paradigm. We hypothesized that a decrease in prime activation affects the subsequent inhibitory process, delaying onset of inhibition and reducing its strength. Two experiments tested this hypothesis using arrow stimuli as primes and targets. Two different irrelevant masks (i.e., a mask sharing no prime features) were presented in succession in each trial to not only ensure that primes were processed subliminally, but also avoid feature updating between primes and masks. Prime/target compatibility and prime background density were manipulated in Experiment 1. Results showed that under subliminal inhibitory condition, the NCE disappears when the density increases (i.e., pixel density in the prime's background of 25 %) in Experiment 1. However, when we fixed the prime's background at the density of 25 % and manipulated prime/target compatibility as well as inter-stimuli-interval (ISI) between mask and target in Experiment 2, behavioral results showed marginally significant NCEs in the 150-ms ISI condition. Electrophysiological evidence showed the lateralized readiness potential for compatible trials was significantly more positive than that for incompatible trials during the two consecutive time windows (i.e., 400-450 and 450-500 ms) in the 150-ms ISI condition. In addition, the NCE size was significant smaller in Experiment 2 than in Experiment 1. All of the results support predictions of the continuous subliminal inhibitory mechanism hypothesis which posits that decreases in prime activation strength lead to delay in inhibitory onset and decline in inhibitory strength. PMID:24715101

  20. Effect of cigarette smoke on human serum trypsin inhibitory capacity and antitrypsin concentration

    SciTech Connect

    Chowdhury, P.; Bone, R.C.; Louria, D.B.; Rayford, P.L.

    1982-07-01

    Investigation of the effect of cigarette smoke on the serum trypsin inhibitory capacity (TIC) and antitrypsin content in 89 smokers compared with 37 nonsmokers revealed that cigarette smoking is associated with a significantly lower level of TIC. No alteration in serum antitrypsin content was found because of cigarette smoking. Further analysis of the data indicated a correlation between the magnitude of smoking and the reduction in serum TIC. The reduction of TIC in cigarette smokers is consistent with the recent findings of decreased alpha 1-antitrypsin activity in rat lung and the reduced elastase inhibitory capacity per mg of alpha 1-antitrypsin found in the serum of smokers. The decrease in TIC in the serum of smokers, in addition to the reported decrease in elastolytic activity, may be useful in explaining the pathogenesis of emphysema frequently found in smokers.

  1. Inhibitory effects of magnolol and honokiol on human calcitonin aggregation

    PubMed Central

    Guo, Caiao; Ma, Liang; Zhao, Yudan; Peng, Anlin; Cheng, Biao; Zhou, Qiaoqiao; Zheng, Ling; Huang, Kun

    2015-01-01

    Amyloid formation is associated with multiple amyloidosis diseases. Human calcitonin (hCT) is a typical amyloidogenic peptide, its aggregation is associated with medullary carcinoma of the thyroid (MTC), and also limits its clinical application. Magnolia officinalis is a traditional Chinese herbal medicine; its two major polyphenol components, magnolol (Mag) and honokiol (Hon), have displayed multiple functions. Polyphenols like flavonoids and their derivatives have been extensively studied as amyloid inhibitors. However, the anti-amyloidogenic property of a biphenyl backbone containing polyphenols such as Mag and Hon has not been reported. In this study, these two compounds were tested for their effects on hCT aggregation. We found that Mag and Hon both inhibited the amyloid formation of hCT, whereas Mag showed a stronger inhibitory effect; moreover, they both dose-dependently disassembled preformed hCT aggregates. Further immuno-dot blot and dynamic light scattering studies suggested Mag and Hon suppressed the aggregation of hCT both at the oligomerization and the fibrillation stages, while MTT-based and dye-leakage assays demonstrated that Mag and Hon effectively reduced cytotoxicity caused by hCT aggregates. Furthermore, isothermal titration calorimetry indicated Mag and Hon both interact with hCT. Together, our study suggested a potential anti-amyloidogenic property of these two compounds and their structure related derivatives. PMID:26324190

  2. Controlled versus automatic processes: which is dominant to safety? The moderating effect of inhibitory control.

    PubMed

    Xu, Yaoshan; Li, Yongjuan; Ding, Weidong; Lu, Fan

    2014-01-01

    This study explores the precursors of employees' safety behaviors based on a dual-process model, which suggests that human behaviors are determined by both controlled and automatic cognitive processes. Employees' responses to a self-reported survey on safety attitudes capture their controlled cognitive process, while the automatic association concerning safety measured by an Implicit Association Test (IAT) reflects employees' automatic cognitive processes about safety. In addition, this study investigates the moderating effects of inhibition on the relationship between self-reported safety attitude and safety behavior, and that between automatic associations towards safety and safety behavior. The results suggest significant main effects of self-reported safety attitude and automatic association on safety behaviors. Further, the interaction between self-reported safety attitude and inhibition and that between automatic association and inhibition each predict unique variances in safety behavior. Specifically, the safety behaviors of employees with lower level of inhibitory control are influenced more by automatic association, whereas those of employees with higher level of inhibitory control are guided more by self-reported safety attitudes. These results suggest that safety behavior is the joint outcome of both controlled and automatic cognitive processes, and the relative importance of these cognitive processes depends on employees' individual differences in inhibitory control. The implications of these findings for theoretical and practical issues are discussed at the end.

  3. Inhibitory effect of quercetin on periodontal pathogens in vitro.

    PubMed

    Geoghegan, F; Wong, R W K; Rabie, A B M

    2010-06-01

    Actinobacillus actinomycetemcomitans (Aa) and Porphyromonas gingivalis (Pg) are bacteria strongly associated with early onset, progressive and refractory periodontal disease and associated alveolar bone loss. Quercetin is a flavonoid found in many foods including apples, onions and tea. The aim of this study was to evaluate the effect of quercetin on in vitro growth of periodontal pathogens Aa and Pg. For comparison, quercetin's effect on several oral microbes was also evaluated. Different concentrations of quercetin solution were added to calibrated suspensions of Aa and Pg. All suspensions were incubated for 1, 3, 6, and 24 h in an anaerobic chamber at 37 degrees C. At each time point, selected dilutions from each culture broth were plated on blood agar plates. Colonies appearing on blood agar plates were visually counted on 3 days for Aa and 5 days for Pg. Minimum inhibitory concentrations of both periodontal pathogens were also determined. Both periodontal bacteria showed a significant decrease (p < 0.05) in viable counts after 1 h. No colony forming units of Pg could be observed after 24 h. The results suggest that quercetin possesses significant antimicrobial properties on periodontal pathogens in vitro. PMID:19957242

  4. Inhibitory effects of fruit juices on cytochrome P450 2C9 activity in vitro.

    PubMed

    Hidaka, Muneaki; Nagata, Masashi; Kawano, Yohei; Sekiya, Hiroshi; Kai, Hirofumi; Yamasaki, Keishi; Okumura, Manabu; Arimori, Kazuhiko

    2008-02-01

    There is limited information on the effect of fruits on human cytochrome P450 (CYP) 2C9 activity. The objective of this study was to determine the effect of fruit juice on CYP2C9-mediated drug metabolism. Nine citrus fruits and eight tropical fruits were chosen. We investigated effects of the fruits on diclofenac 4'-hydroxylation and tolbutamide hydroxylation by human liver microsomes. Among the fruits, pineapple juice showed potent inhibition of CYP2C9 activity. The addition of 25 microl (5.0% v/v) of pineapple juice resulted in almost complete inhibition. Next we examined the inhibitory effect of bromelain, a cysteine protease in pineapple. Bromelain also strongly inhibited CYP2C9 activity. In addition, E-64, a cysteine protease inhibitor, almost entirely blocked inhibition by pineapple juice and bromelain. Thus we found that pineapple juice was a potent inhibitor of CYP2C9, and that the inhibitory effect might be due to the bromelain contained in pineapple.

  5. Inhibitory effects of armepavine against hepatic fibrosis in rats

    PubMed Central

    Weng, Ting-Chun; Shen, Chien-Chang; Chiu, Yung-Tsung; Lin, Yun-Lian; Kuo, Cheng-Deng; Huang, Yi-Tsau

    2009-01-01

    Activation of hepatic stellate cells (HSCs) plays a crucial role in liver fibrogenesis. armepavine (Arm, C19H23O3N), an active compound from Nelumbo nucifera, has been shown to exert immunosuppressive effects on T lymphocytes and on lupus nephritic mice. The aim of this study was to investigate whether Arm could exert anti-hepatic fibrogenic effects in vitro and in vivo. A cell line of rat HSCs (HSC-T6) was stimulated with tumor necrosis factor-α (TNF-α) or lipopolysaccharide (LPS) to evaluate the inhibitory effects of Arm. An in vivo therapeutic study was conducted in bile duct-ligated (BDL) rats. BDL rats were given Arm (3 or 10 mg/kg) by gavage twice daily for 3 weeks starting from the onset of BDL. Liver sections were taken for fibrosis scoring, immuno-fluorescence staining and quantitative real-time mRNA measurements. In vitro, Arm (1-10 μM) concentration-dependently attenuated TNF-α- and LPS-stimulated α-SMA protein expression and AP-1 activation by HSC-T6 cells without adverse cytotoxicity. Arm also suppressed TNF-α-induced collagen collagen deposition, NFκB activation and MAPK (p38, ERK1/2, and JNK) phosphorylations. In vivo, Arm treatment significantly reduced plasma AST and ALT levels, hepatic α-SMA expression and collagen contents, and fibrosis scores of BDL rats as compared with vehicle treatment. Moreover, Arm attenuated the mRNA expression levels of col 1α2, TGF-β1, TIMP-1, ICAM-1, iNOS, and IL-6 genes, but up-regulated metallothionein genes. Our study results showed that Arm exerted both in vitro and in vivo antifibrotic effects in rats, possibly through anti-NF-κB activation pathways. PMID:19723340

  6. Kinetics of inhibitory effect of isoferulic acid on mushroom tyrosinase.

    PubMed

    Gong, Shengzhao; Yin, Meijuan; Yun, Zhimian

    2013-01-01

    A study on the kinetics of inhibitory effect of isoferulic acid on the monophenolase and diphenolase activity of mushroom tyrosinase was carried out using enzymological kinetic analysis method in a Na2HPO4-NaH2PO4 buffer solution (pH = 6.8) at 30°C. It was found that isoferulic acid efficiently inhibits both monophenolase and diphenolase activities of mushroom tyrosinase under experimental conditions. Concentrations of isoferulic acid leading to 50% rate inhibition (IC50) on monophenolase and diphenolase activity were calculated to be 0.13 mmol/L and 0.39 mmol/L, respectively, which are much lower than that of arbutin (IC50 = 5.3 mmol/L for diphenolase activity). The presence of isoferulic acid also prolongs the lag period in the oxidation process of l-tyrosine via tyrosinase-a 4.3-min lagging was observed with the presence of 0.20 mmol/L isoferulic acid-compared to a 1.1-min lagging in the absence of isoferulic acid. The Lineweaver-Burk plot demonstrates a competitive behavior of isoferulic acid in the tyrosinase oxidation of l-3,4-dihydroxyphenylalanine, with maximum reaction rate (vm) and inhibition constant (KI) at 64.5 µM/min and 0.11 mmol/L, respectively.

  7. Melanogenesis-inhibitory activity and cancer chemopreventive effect of glucosylcucurbic acid from shea (Vitellaria paradoxa) kernels.

    PubMed

    Zhang, Jie; Kurita, Masahiro; Ebina, Kodai; Ukiya, Motohiko; Tokuda, Harukuni; Yasukawa, Ken; Masters, Eliot T; Shimizu, Naoto; Akihisa, Momoko; Feng, Feng; Akihisa, Toshihiro

    2015-04-01

    Two jasmonate derivatives, glucosylcucurbic acid (1) and methyl glucosylcucurbate (2), were isolated from the MeOH extract of defatted shea (Vitellaria paradoxa; Sapotaceae) kernels. These and their deglucosylated derivatives, cucurbic acid (3) and methyl cucurbate (4), were evaluated for their melanogenesis-inhibitory and cancer chemopreventive potencies. Compounds 1, 3, and 4 exhibited potent melanogenesis-inhibitory activities in α-melanocyte-stimulating hormone (α-MSH)-stimulated B16 melanoma cells. Western-blot analysis revealed that compounds 1 and 3 reduced the protein levels of MITF (=microphthalmia-associated transcription factor), tyrosinase, TRP-1 (=tyrosine-related protein 1), and TRP-2 mostly in a concentration-dependent manner. In addition, compound 1 exhibited inhibitory effects against Epstein-Barr virus early antigen (EBV-EA) activation induced with 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells, against TPA-induced inflammation in mice, and against skin tumor promotion in an in vivo two-stage mouse skin carcinogenesis test based on 7,12-dimethylbenz[a]anthracene (DMBA) as initiator, and with TPA as promoter. PMID:25879500

  8. Effects of Response Preparation on Developmental Improvements in Inhibitory Control

    PubMed Central

    Ordaz, Sarah; Stephanie, Davis; Luna, Beatriz

    2010-01-01

    Studies in adults indicate that response preparation is crucial to inhibitory control, but it remains unclear whether preparation contributes to improvements in inhibitory control over the course of childhood and adolescence. In order to assess the role of response preparation in developmental improvements in inhibitory control, we parametrically manipulated the duration of the instruction period in an antisaccade (AS) task given to participants ages 8 to 31 years. Regressions showing a protracted development of AS performance were consistent with existing research, and two novel findings emerged. First, all participants showed improved performance with increased preparation time, indicating that response preparation is crucial to inhibitory control at all stages of development. Preparatory processes did not deteriorate at even the longest preparatory period, indicating that the youngest participants were able to sustain preparation at even the longest interval. Second, developmental trajectories did not differ for different preparatory period lengths, highlighting that the processes supporting response preparation continue to mature in tandem with improvements in AS performance. Our findings suggest that developmental improvements are not simply due to an inhibitory system that is faster to engage but may also reflect qualitative changes in the processes engaged during the preparatory period. PMID:20347061

  9. [Inhibitory effect of human saliva on HIV-1 infectivity].

    PubMed

    Etsuko, K; Wei, S

    2001-08-01

    Human saliva is known to decrease human immunodeficiency virus type 1 (HIV-1) infectivity in vitro. The purpose of this study was to confirm these findings and to explore the mechanism of action of saliva. Whole saliva from seronegative donors was incubated with HIV-1IIIB chronically infected MOLT 4 cells (MOLT 4/HIV-1IIIB cells) or cell-free HIV-1IIIB or KMT strains. We monitored viral infectivity by using MAGI/CCR5 cells. Whole saliva with Na levels less than 20 mEq/l rapidly damaged MOLT 4/HIV-1IIIB cells, thereby HIV infection to MAGI/CCR5 cells by MOLT 4/HIV-1IIIB cells was nearly abolished. On the contrary, in the cace of whole saliva with Na levels more than 23 mEq/l which damaged few cells, cell-to-cell transmission of HIV-1IIIB was prevented by more than 50%. The infectivity of cell-free HIV-1IIIB to MAGI/CCR5 cells was abolished after incubating and filtering the HIV with whole saliva. Depletion of secretory leukocyte protease inhibitor (SLPI) from whole saliva resulted in a 11-28% decrease in the anti HIV-1KMT activity of saliva. Preincubation of host cells with whole saliva led to an enhancement of the HIV infection rather than inhibition. Whole saliva had no effect on the expression level of the cellular receptors (CD4, CXCR4 and CCR5). These results suggest that the inhibitory effect of whole saliva on HIV-1 infectivity is directly linked to the virus itself rather than on the host cell. Moreover, the physical entrapment of cell-free HIV-1 by whole saliva seems to have major salivaly defence mechanisms against HIV-1 infection through the oral cavity. PMID:16578966

  10. Inhibitory effects of kale ingestion on metabolism by cytochrome P450 enzymes in rats.

    PubMed

    Yamasaki, Izumi; Yamada, Masayoshi; Uotsu, Nobuo; Teramoto, Sachiyuki; Takayanagi, Risa; Yamada, Yasuhiko

    2012-01-01

    Kale (Brassica oleracea L. var acephala DC) is a leafy green vegetable belonging to the cabbage family (Brassicaceae) that contains a large amount of health-promoting phytochemicals. There are any reports about the effects of kale ingestion on the chemoprevention function and mechanism, but the interactions between kale and drugs have not been researched. We investigated the effects of kale intake on cytochrome P450 (CYP) metabolism by using cocktail probe drugs, including midazolam (for CYP3A4), caffeine (for CYP1A2), dextromethorphan (for CYP2D6), tolbutamide (for CYP2C9), omeprazole (for CYP2C19), and chlorzoxazone (for CYP2E1). Cocktail drugs were administered into rats treated with kale and cabbage (2000 mg/kg) for a week. The results showed that kale intake induced a significant increase in plasma levels and the AUC of midazolam, caffeine, and dextromethorphan. In addition, the plasma concentration and AUC of omeprazole tended to increase. Additionally, no almost differences in the mRNA expression levels of CYP enzymes in the liver were observed. In conclusion, kale ingestion was considered to have an inhibitory effect on the activities of CYP3A4, 1A2, 2D6, and 2C19 for a reason competitive inhibition than inhibitory changes in the mRNA expressions.

  11. Pattern separability and the effect of the number of connections in a random neural net with inhibitory connections.

    PubMed

    Torioka, T

    1978-11-10

    It has been claimed that pattern separation in cerebellar cortex plays an important role in controlling movements and balance for vertebrates. A number of the neural models for cerebellar cortex have been proposed and their pattern separability has been analyzed. These results, however, only explain a part of pattern separability in random neural nets. The present paper is intended to study an extended theory of pattern separability in a new model with inhibitory connections. In addition to this, the effect of the number of connections on pattern separability is cleared up. It is also shown that the signal from the inhibitory connections has crucial importance for pattern separability.

  12. Evaluation of antioxidant activity and inhibitory effect on nitric oxide production of some common vegetables.

    PubMed

    Bor, Jung-Yi; Chen, Hui-Yin; Yen, Gow-Chin

    2006-03-01

    The objectives of this study were to study the antioxidant activities and nitric oxide (NO) scavenging effects of vegetables in vitro systems and to study the inhibitory effects of vegetables on the NO production and NO-induced DNA damage in RAW 264.7 macrophage. The results indicated that water extracts from Indian lotus, Jew's ear, shiitake, eggplant, and winter mushroom showed stronger antioxidant activity and free-radical-scavenging ability than that of other vegetable extracts. The scavenging effects of vegetable extracts on NO derived from sodium nitroprusside (SNP) were in decreasing order of water spinach > Indian lotus > eggplant and garland chrysanthemum. In the macrophage model system, the water extracts from fresh daylily flower, sponge gourd, pea sprout, and eggplant exhibited over 80% inhibition on NO generation stimulated by lipopolysaccharide. The extract from fresh daylily flower that expressed the strongest inhibition on NO production was attributed to the ability to reduce the inducible nitric oxide synthase (iNOS) induction. However, the extracts from pea sprout and eggplant suppressed the NO production by scavenging on NO and inactivating toward iNOS enzyme. In addition, the water extracts from fresh daylily flower, sponge gourd, pea sprout, and eggplant also showed over 40% inhibitory effect on DNA damage induced by SNP in RAW 264.7 macrophage. The data also indicated that eggplant and pea sprout extracts contained higher total phenolic compounds, anthocyanins, and ascorbic acids and appeared to be responsible for their antioxidant activities and scavenging effects on NO derived from SNP. PMID:16506819

  13. Inhibitory effect of alpha-fetoprotein on the binding of myasthenia gravis antibody to acetylcholine receptor.

    PubMed Central

    Brenner, T; Beyth, Y; Abramsky, O

    1980-01-01

    The binding of myasthenia gravis antibody acetylcholine receptor (AcChoR) as measured in vitro by Radioimmunoassay with 125I-labeled alpha-bungarotoxin (alpha-BuTx), can be blocked by amniotic fluid, maternal serum, and umbilical cord serum. This inhibitory effect is due to alpha-fetoprotein present in high concentrations in amniotic fluid and serum, as shown by: (i) selective removal of several components from amniotic fluid and serum; (ii) selective addition of different components present in amniotic fluid and serum, including alpha-fetoprotein, to be radioimmunoassay; (iii) correlation between the inhibitory effect of both amniotic fluid and serum and between the amounts of alpha-fetoprotein they contain; (iv) blocking of the alpha-fetoprotein in vitro suggests a similar effect in vivo in pregnant women with myasthenia gravis. This effect may explain in part the variability in the development of neonatal myasthenia gravis in the babies, due to transplacental transfer of maternal anti-AcChoR antibody, only after delivery and only in the minority of the cases. It also may explain the appearnace of remissions in females with myasthenia gravis during the second and third trimesters of pregnancy. Similar phenomena observed during pregnancy in other autoimmune and immunopathogenic diseases also might be attributed to activity of alpha-fetoprotein. PMID:6158053

  14. Mechanism of growth inhibitory effect of cape aloe extract in ehrlich ascites tumor cells.

    PubMed

    Kametani, Saeda; Oikawa, Tomoko; Kojima-Yuasa, Akiko; Kennedy, David Opare; Norikura, Toshio; Honzawa, Mayumi; Matsui-Yuasa, Isao

    2007-12-01

    Cape aloe (Aloe ferox Miller) has been a herb well known for its cathartic properties and has also been used popularly as a health drink (juice, tea and tonic) in the United States and in Europe. Cape aloe extract also has been reported to possess several pharmacological effects, such as anti-inflammatory, anti-bacterial, anti-fungal and protective effect against liver injury. However, the investigations on an anti-tumor activity in cape aloe extract are very few and subsequent mechanisms have not been well elucidated. In this study, we examined the effect of the selective growth inhibitory activity of cape aloe extract and found that the cape aloe extract, especially the dichloromethane (CH(2)Cl(2)) extract, caused a dose-dependent growth inhibitory effect in Ehrlich ascites tumor cells (EATC), but not in mouse embryo fibroblast (NIH3T3) cells, which was used as a normal cell model. Furthermore, the CH(2)Cl(2) extract caused an accumulation of cells in the G1 phase and a decrease of cells in the S and G2/M phase of the cell cycle and inhibited DNA synthesis in a dose-dependent manner. In addition, other results suggest that cell cycle arrest and inhibition of proliferation in EATC by the CH(2)Cl(2 )extract are associated with decreased retinoblastoma protein (Rb) phosphorylation.

  15. Inhibitory effects of arabitol on caries-associated microbiologic parameters of oral Streptococci and Lactobacilli.

    PubMed

    Loman, Abdullah Al; Ju, Lu-Kwang

    2015-12-01

    The aim of this study was to compare arabitol with its better studied isomer xylitol for their inhibitory effects on cell growth and acid production of oral bacteria. Streptococcus mutans, Streptococcus salivarius and Streptococcus sobrinus were used as representatives of oral streptococci and Lactobacillus acidophilus and Lactobacillus fermentum were used for oral lactobacilli. Growth was followed by measuring the absorbance at 660nm, acid production by pH change. Sensitivity of these oral bacteria to arabitol and xylitol was first compared at 1% (65mM) additive concentration with glucose as sugar substrate. For all bacteria tested, the inhibitory effects of the two polyols were comparable; both were significantly stronger on streptococci (with 20-60% inhibition) than on lactobacilli (with 5-10% inhibition). Effects of arabitol and xylitol were also compared for S. mutans and S. salivarius in media with 1% of different sugar substrates: glucose (55mM), fructose (55mM), galactose (55mM) and sucrose (30mM). Inhibition occurred for all sugars: stronger on glucose and galactose (60-65%) than on fructose and sucrose (40-45%). Inhibition dependency on the arabitol/xylitol concentration from 0.01% (0.65mM) to 2% (130mM) was further determined for S. mutans and S. salivarius. Regardless of the concentration, sugar substrate and bacterial species tested, arabitol showed very similar inhibition effects to its isomer xylitol.

  16. Primacy in causal strength judgments: the effect of initial evidence for generative versus inhibitory relationships.

    PubMed

    Dennis, M J; Ahn, W K

    2001-01-01

    The order in which people receive information has a substantial effect on subsequent judgment and inference. Our focus is on the order of covariation evidence in causal learning. The first experiment shows that the initial presentation of evidence suggesting a generative causal relationship (the joint presence or joint absence of cause and effect) leads to higher judged causal strength than does the initial presentation of evidence suggesting an inhibitory relationship (the presence of cause or effect in the absence of the other). Additional studies show that this primacy effect is unlikely to be due to fatigue or to an insufficient number of learning trials. These results are not readily explained by current contingency-based or associative theories of causal induction.

  17. Inhibitory effect of artocarpanone from Artocarpus heterophyllus on melanin biosynthesis.

    PubMed

    Arung, Enos Tangke; Shimizu, Kuniyoshi; Kondo, Ryuichiro

    2006-09-01

    In our previous efforts to find new tyrosinase inhibitory materials, we investigated 44 Indonesian medicinal plants belonging to 24 families. Among those plants, the extract of Artocarpus heterophyllus was one of the strongest inhibitors of tyrosinase activity. By activity-guided fractionation of A. heterophyllus wood extract, we isolated artocarpanone, which inhibited both mushroom tyrosinase activity and melanin production in B16 melanoma cells. This compound is a strong candidate as a remedy for hyperpigmentation in human skin.

  18. The effects of prenatal cocaine exposure and gender on inhibitory control and attention.

    PubMed

    Carmody, Dennis P; Bennett, David S; Lewis, Michael

    2011-01-01

    Children exposed prenatally to cocaine show deficits in emotion regulation and inhibitory control. While controlling for the measures of medical complication in the perinatal period, environmental risk, and prenatal polydrug exposure (alcohol, tobacco, and marijuana), we examined the effects of prenatal cocaine exposure and gender on attention and inhibitory control in 203 children at ages 6, 9, and 11. Cocaine exposure affected the performance of males, but not females. Heavily exposed males showed deficits in the attention and the inhibition tasks. In addition, a significantly greater proportion of heavily exposed males (21%) than unexposed males (7%) or heavily exposed females (7%) failed to complete the task (p<0.01). Even without those poorest performing subjects, the overall accuracy for heavily exposed males (81%) was significantly reduced (p<0.05) compared to lightly exposed males (87%) and unexposed males (89%). The findings highlight the importance of considering gender specificity in cocaine exposure effects. Processes by which cocaine effects may be specific to males are discussed.

  19. Isolation and tyrosinase inhibitory effects of polyphenols from the leaves of persimmon, Diospyros kaki.

    PubMed

    Xue, You-Lin; Miyakawa, Takuya; Hayashi, Yasuna; Okamoto, Kyoko; Hu, Fangyu; Mitani, Nobuhito; Furihata, Kazuo; Sawano, Yoriko; Tanokura, Masaru

    2011-06-01

    The main polyphenols were isolated from the leaves of six selected persimmon cultivars. Seven compounds were obtained by reverse-phase HPLC, and their structures were elucidated by multiple NMR measurements. These compounds are hyperoside, isoquercitrin, trifolin, astragalin, chrysontemin, quercetin-3-O-(2''-O-galloyl-β-D-glucopyranoside) (QOG), and kaempferol-3-O-(2''-O-galloyl-β-D-glucopyranoside) (KOG). Their inhibitory activity was tested against tyrosinase for the oxidation of L-DOPA, and only chrysontemin showed inhibitory activity. To investigate the differences of their inhibitory effects, the tyrosinase inhibitory activities of their aglycons, cyanidin, quercetin, and kaempferol, were also tested. As a result, it was confirmed that the most influential moiety for tyrosinase inhibition was the 3',4'-dihydroxy groups of the catechol moiety. Moreover, the tyrosinase inhibitory activity of chrysontemin, which was identified in persimmon leaves for the first time, is supported by a simulated model of chrysontemin docking into mushroom tyrosinase.

  20. Inhibitory effect of ciprofloxacin on β-glucuronidase-mediated deconjugation of mycophenolic acid glucuronide.

    PubMed

    Kodawara, Takaaki; Masuda, Satohiro; Yano, Yoshitaka; Matsubara, Kazuo; Nakamura, Toshiaki; Masada, Mikio

    2014-07-01

    The interaction between mycophenolate (MPA) and quinolone antibiotics such as ciprofloxacin is considered to reduce the enterohepatic recycling of MPA, which is biotransformed in the intestine from MPA glucuronide (MPAG) conjugate excreted via the biliary system; however, the molecular mechanism underlying this biotransformation of MPA is still unclear. In this study, an in vitro system was established to evaluate β-glucuronidase-mediated deconjugation and to examine the influence of ciprofloxacin on the enzymatic deconjugation of MPAG and MPA resynthesis. Resynthesis of MPA via deconjugation of MPAG increased in a time-dependent manner from 5 to 60 min in the presence of β-glucuronidase. Ciprofloxacin and phenolphthalein-β-d-glucuronide (PhePG), a typical β-glucuronidase substrate, significantly decreased the production of MPA from MPAG in the β-glucuronidase-mediated deconjugation system. In addition, enoxacin significantly inhibited the production of MPA from MPAG, while levofloxacin and ofloxacin had no inhibitory effect on MPA synthesis. Pharmacokinetic analysis revealed that ciprofloxacin showed a dose-dependent inhibitory effect on MPA production from MPAG via β-glucuronidase with a half-maximal inhibitory concentration (IC50 ) value of 30.4 µm. While PhePG inhibited the β-glucuronidase-mediated production of MPA from MPAG in a competitive manner, ciprofloxacin inhibited MPA synthesis via noncompetitive inhibition. These findings suggest that the reduction in the serum MPA concentration during the co-administration of ciprofloxacin is at least in part due to the decreased enterohepatic circulation of MPA because of noncompetitive inhibition of deconjugation of MPAG by intestinal β-glucuronidase.

  1. Inhibitory effects of SKF96365 on the activities of K+ channels in mouse small intestinal smooth muscle cells

    PubMed Central

    TANAHASHI, Yasuyuki; WANG, Ban; MURAKAMI, Yuri; UNNO, Toshihiro; MATSUYAMA, Hayato; NAGANO, Hiroshi; KOMORI, Seiichi

    2015-01-01

    In order to investigate the effects of SKF96365 (SKF), which is a non-selective cationic channel blocker, on K+ channel currents, we recorded currents through ATP sensitive K+ (IKATP), voltage-gated K+ (IKv) and Ca2+ activated K+ channels (IBK) in the absence and presence of SKF in single small intestinal myocytes of mice with patch-clamp techniques. SKF (10 µM) reversibly abolished IKATP that was induced by cromakalim (10 µM), which is a selective ATP sensitive K+ channel opener. These inhibitory effects were induced in a concentration-dependent and voltage-independent manner. The 50% inhibitory concentration (IC50) was 0.85 µM, which was obviously lower than that reported for the muscarinic cationic current. In addition, SKF (1 µM ≈ the IC50 value in IKATP suppression) reversibly inhibited the IKv that was induced by repetitive depolarizing pulses from −80 to 20 mV. However, the extent of the inhibitory effects was only ~30%. In contrast, SKF (1 µM) had no significant effects on spontaneous transient IBK and caffeine-induced IBK. These results indicated that SKF inhibited ATP sensitive K+ channels and voltage-gated K+ channels, with the ATP sensitive K+ channels being more sensitive than the voltage-gated K+ channels. These inhibitory effects on K+ channels should be considered when SKF is used as a cationic channel blocker. PMID:26498720

  2. Spectroscopic studies on the inhibitory effects of ionic liquids on lipase activity

    NASA Astrophysics Data System (ADS)

    Fan, Yunchang; Dong, Xing; Li, Xiaojing; Zhong, Yingying; Kong, Jichuan; Hua, Shaofeng; Miao, Juan; Li, Yan

    2016-04-01

    The effects of ionic liquids (ILs) on the lipase activity were studied by UV-Vis spectroscopy and the IL-lipase interaction mechanism at the molecular level was investigated by fluorescence technique. Experimental results indicated that the lipase activity was inhibited by ILs and the degree of inhibition highly depended on the chemical structures of ILs. The inhibitory ability of the Cl-- and Br--based ILs increased with increasing the alkyl chain length in the IL cation. Thermodynamic parameters, enthalpy change (ΔH) and entropy change (ΔS) were obtained by analyzing the fluorescence behavior of lipase with the addition of ILs. Both ΔH and ΔS were positive suggesting hydrophobicity was the major driven force for the Cl-- and Br--based ILs. For the BF4--, CF3SO3--, ClO4-- and N(CN)2--based ILs, hydrogen bonding was the main driven force. For a more comprehensive understanding of the effects of ILs on lipase activity, the roles of hydrophobicity and hydrogen bonding must be considered simultaneously. A regression-based equation was developed to describe the relationship of the inhibitory ability of ILs and their hydrophobicity and hydrogen bonding ability.

  3. Spectroscopic studies on the inhibitory effects of ionic liquids on lipase activity.

    PubMed

    Fan, Yunchang; Dong, Xing; Li, Xiaojing; Zhong, Yingying; Kong, Jichuan; Hua, Shaofeng; Miao, Juan; Li, Yan

    2016-04-15

    The effects of ionic liquids (ILs) on the lipase activity were studied by UV-Vis spectroscopy and the IL-lipase interaction mechanism at the molecular level was investigated by fluorescence technique. Experimental results indicated that the lipase activity was inhibited by ILs and the degree of inhibition highly depended on the chemical structures of ILs. The inhibitory ability of the Cl(-)- and Br(-)-based ILs increased with increasing the alkyl chain length in the IL cation. Thermodynamic parameters, enthalpy change (ΔH) and entropy change (ΔS) were obtained by analyzing the fluorescence behavior of lipase with the addition of ILs. Both ΔH and ΔS were positive suggesting hydrophobicity was the major driven force for the Cl(-)- and Br(-)-based ILs. For the BF4(-)-, CF3SO3(-)-, ClO4(-)- and N(CN)2(-)-based ILs, hydrogen bonding was the main driven force. For a more comprehensive understanding of the effects of ILs on lipase activity, the roles of hydrophobicity and hydrogen bonding must be considered simultaneously. A regression-based equation was developed to describe the relationship of the inhibitory ability of ILs and their hydrophobicity and hydrogen bonding ability. PMID:26836454

  4. Inhibitory Effects of Some Carbohydrates on Nano-Globular Aggregation of both Normal and Glycated Albumin

    PubMed Central

    Moosavi-Movahedi, Ali Akbar; Sattarahmady, Naghmeh; Sharifi, Esmaeil; Heli, Hossein

    2016-01-01

    Background: Protein aggregation is one of the important, common and troubling problems in biotechnology, pharmaceutical industries and amyloid-re-lated disorders. Methods: In the present study, the inhibitory effects of some carbohydrates (alginate, β-cyclodextrin and trehalose) on the formation of nano-globular aggregates from normal (HSA) and glycated (GHSA) human serum albumin were studied; when the formation of aggregates was induced by the simultaneous heating and addition of dithiotheritol. For the investigations, the biophysical methods of UV-vis spectrophotometry, circular dichroism spectroscopy, transmission electron microscopy and tensiometry were employed. Results: The effect of inhibitory mechanism of these inhibitors on the aggregation of HSA and GHSA was expressed and compared together. Conclusion: The results showed that the nucleus formation step of the aggregation process of HSA and GHSA was different in the presence of alginate (compared to β-cyclodextrin and trehalose). The inhibition efficiencies of the carbohydrates on the aggregate formation of HSA and GHSA were different, arising from the differences in the hydrophobicities of HSA and GHSA, and also, the differences between HSA- and GHSA-carbohydrate interactions. PMID:27563425

  5. Mechanisms underlying the inhibitory effect of the feed contaminant deoxynivalenol on glucose absorption in broiler chickens.

    PubMed

    Awad, W A; Ghareeb, K; Zentek, J

    2014-10-01

    Deoxynivalenol (DON), a major contaminant of cereals and grains, is of public health concern worldwide and has been shown to reduce the electrogenic transport of glucose. However, the full effects of Fusarium mycotoxins on nutrient absorption are still not clear. The aim of this study was to investigate whether decreased nutrient absorption was due to specific effects on transporter trafficking in the intestine and whether inhibition of phosphoinositol-3-kinase (PI-3-kinase) affected the electrogenic jejunal transport of glucose. Jejunal mucosa of 6-week-old broiler chickens were mounted in Ussing chambers and treated with DON, wortmannin (a specific inhibitor of PI-3-kinase), DON + wortmannin, phlorizin and cytochalasin B. DON was found to decrease the short-circuit current (Isc) after glucose addition. A similar decline in Isc after glucose addition was observed following pre-application of wortmannin, or phlorizin (Na(+)/glucose co-transporter, SGLT1 inhibitor). The results indicate that DON decreased glucose absorption in the absence of wortmannin or phlorizin but had no additional effect on glucose absorption in their presence. Glucose transport was not affected by cytochalasin B (facilitative glucose transporter, GLUT2 inhibitor). The study provides evidence that the suppressive effect of DON on the electrogenic transport of glucose may be due to an inhibitory activity of the PI3 kinase pathway and intestinal SGLT1. Furthermore, the effect of cytochalasin B on glucose transport in chicken tissues differs from that in mammals. PMID:25011710

  6. Mechanisms underlying the inhibitory effect of the feed contaminant deoxynivalenol on glucose absorption in broiler chickens.

    PubMed

    Awad, W A; Ghareeb, K; Zentek, J

    2014-10-01

    Deoxynivalenol (DON), a major contaminant of cereals and grains, is of public health concern worldwide and has been shown to reduce the electrogenic transport of glucose. However, the full effects of Fusarium mycotoxins on nutrient absorption are still not clear. The aim of this study was to investigate whether decreased nutrient absorption was due to specific effects on transporter trafficking in the intestine and whether inhibition of phosphoinositol-3-kinase (PI-3-kinase) affected the electrogenic jejunal transport of glucose. Jejunal mucosa of 6-week-old broiler chickens were mounted in Ussing chambers and treated with DON, wortmannin (a specific inhibitor of PI-3-kinase), DON + wortmannin, phlorizin and cytochalasin B. DON was found to decrease the short-circuit current (Isc) after glucose addition. A similar decline in Isc after glucose addition was observed following pre-application of wortmannin, or phlorizin (Na(+)/glucose co-transporter, SGLT1 inhibitor). The results indicate that DON decreased glucose absorption in the absence of wortmannin or phlorizin but had no additional effect on glucose absorption in their presence. Glucose transport was not affected by cytochalasin B (facilitative glucose transporter, GLUT2 inhibitor). The study provides evidence that the suppressive effect of DON on the electrogenic transport of glucose may be due to an inhibitory activity of the PI3 kinase pathway and intestinal SGLT1. Furthermore, the effect of cytochalasin B on glucose transport in chicken tissues differs from that in mammals.

  7. Cholinestrase inhibitory effects of geranylated flavonoids from Paulownia tomentosa fruits.

    PubMed

    Cho, Jung Keun; Ryu, Young Bae; Curtis-Long, Marcus J; Ryu, Hyung Won; Yuk, Heung Joo; Kim, Dae Wook; Kim, Hye Jin; Lee, Woo Song; Park, Ki Hun

    2012-04-15

    Alzheimer's disease is rapidly becoming one of the most prevalent human diseases. Inhibition of human acetylcholinestrase (hAChE) and butyrylcholinestrase (BChE) has been linked to amelioration of Alzheimer's symptoms and research into inhibitors is of critical importance. Purification of the methanol extract of Paulownia tomentosa fruits yielded potent hAChE and BChE inhibitory flavonoids (1-9). A comparative activity screen indicated that a geranyl group at C6 is crucial for both hAChE and BChE. For example, diplacone (8) showed 250-fold higher efficacy than its parent eriodictyol (12). IC(50)s of diplacone (8) were 7.2 μM for hAChE and 1.4 μM for BChE. Similar trends were also observed for 4'-O-methyldiplacone (4) (vs its parent, hesperetin 10) and mimulone (7) (vs its parent, naringenin 11). Representative inhibitors (1-8) showed mixed inhibition kinetics as well as time-dependent, reversible inhibition toward hAChE. The binding affinities of these compounds to hAChE were investigated by monitoring quenching of inherent enzyme fluorescence. The affinity constants (K(SA)) increased in proportion to inhibitory potencies. PMID:22445674

  8. Inhibitory effects of hydroxylated cinnamoyl esters on lipid absorption and accumulation.

    PubMed

    Imai, Masahiko; Kumaoka, Takaya; Hosaka, Makiko; Sato, Yui; Li, Chuan; Sudoh, Masashi; Tamada, Yoshiko; Yokoe, Hiromasa; Saito, Setsu; Tsubuki, Masayoshi; Takahashi, Noriko

    2015-07-01

    Obesity is a risk factor associated with several lifestyle-related diseases, for example, diabetes, high blood pressure, hyperlipidemia and cancer. Caffeic acid 2-phenylethyl ester (CAPE, 1), a naturally-occurring compound found in various plants and propolis, which exhibits anti-inflammatory, immunomodulatory and cytotoxic activities and inhibits 3T3-L1 differentiation to adipocytes. As part of our efforts to moderate lifestyle-related diseases, we synthesized analogs of 1 and studied their effects on pancreatic lipase activities, lipid absorption, and 3T3-L1 differentiation. We found that catechols 1-4 show inhibitory activities against pancreatic lipase in a dose-dependent manner in vitro. Compounds 1-3 proved to be more potent inhibitors of pancreatic lipase than 5, 6, 8, and 9, which have one hydroxyl group, respectively. Compound 7 has three aromatic hydroxyl groups and restrains greater lipase inhibitory activity than the other compounds. In addition, 7 and 3 significantly suppress a rise in blood triglyceride (TG) levels in mice given corn oil orally. Furthermore, 2 and 3 are more potent at preventing 3T3-L1 differentiation (lipid accumulation) than 1, while 7 is more potent than 3, 8, and 9 in these assays. Compounds 2, 3, and 7 inhibit lipid absorption and accumulation, with new compound 7 being the most potent. These results indicate that 7 may have potential benefits as a health agent with anti-obesity properties. PMID:25910587

  9. Inhibitory Effect of Camptothecin against Rice Bacterial Brown Stripe Pathogen Acidovorax avenae subsp. avenae RS-2.

    PubMed

    Dong, Qiaolin; Luo, Ju; Qiu, Wen; Cai, Li; Anjum, Syed Ishtiaq; Li, Bin; Hou, Mingsheng; Xie, Guanlin; Sun, Guochang

    2016-01-01

    Camptothecin (CPT) has anticancer, antiviral, and antifungal properties. However, there is a dearth of information about antibacterial activity of CPT. Therefore, in this study, we investigated the inhibitory effect of CPT on Acidovorax avenae subsp. avenae strain RS-2, the pathogen of rice bacterial brown stripe, by measuring cell growth, DNA damage, cell membrane integrity, the expression of secretion systems, and topoisomerase-related genes, as well as the secretion of effector protein Hcp. Results indicated that CPT solutions at 0.05, 0.25, and 0.50 mg/mL inhibited the growth of strain RS-2 in vitro, while the inhibitory efficiency increased with an increase in CPT concentration, pH, and incubation time. Furthermore, CPT treatment affected bacterial growth and replication by causing membrane damage, which was evidenced by transmission electron microscopic observation and live/dead cell staining. In addition, quantitative real-time PCR analysis indicated that CPT treatment caused differential expression of eight secretion system-related genes and one topoisomerase-related gene, while the up-regulated expression of hcp could be justified by the increased secretion of Hcp based on the ELISA test. Overall, this study indicated that CPT has the potential to control the bacterial brown stripe pathogen of rice. PMID:27472315

  10. Inhibitory Effect of Arctigenin from Fructus Arctii Extract on Melanin Synthesis via Repression of Tyrosinase Expression.

    PubMed

    Park, Hwayong; Song, Kwang Hoon; Jung, Pil Mun; Kim, Ji-Eun; Ro, Hyunju; Kim, Mi Yoon; Ma, Jin Yeul

    2013-01-01

    To identify the active compound arctigenin in Fructus Arctii (dried seed of medicinal plant Arctium lappa) and to elucidate the inhibitory mechanism in melanogenesis, we analyzed melanin content and tyrosinase activity on B16BL6 murine melanoma and melan-A cell cultures. Water extracts of Fructus Arctii were shown to inhibit tyrosinase activity in vitro and melanin content in α -melanocyte stimulating hormone-stimulated cells to similar levels as the well-known kojic acid and arbutin, respectively. The active compound arctigenin of Fructus Arctii displayed little or no cytotoxicity at all concentrations examined and decreased the relative melanin content and tyrosinase activity in a dose-dependent manner. Melanogenic inhibitory activity was also identified in vivo with zebrafish embryo. To determine the mechanism of inhibition, the effects of arctigenin on tyrosinase gene expression and tyrosinase promoter activity were examined. Also in addition, in the signaling cascade, arctigenin dose dependently decreased the cAMP level and promoted the phosphorylation of extracellular signal-regulated kinase. This result suggests that arctigenin downregulates cAMP and the tyrosinase enzyme through its gene promoter and subsequently upregulates extracellular signal-regulated kinase activity by increasing phosphorylation in the melanogenesis signaling pathway, which leads to a lower melanin content.

  11. Effects of multiple inhibitory components on anaerobic treatment processes in municipal solid waste incineration leachate.

    PubMed

    Lei, Yuqing; Dang, Yan; Lan, Zhangheng; Sun, Dezhi

    2016-06-01

    This study served to investigate the comparative and combined effects of calcium, ammonia nitrogen, and aquatic humic substances (AHS) on specific methanogenic activity (SMA) in municipal solid waste leachate at mesophilic conditions. Using orthogonal experiments, anaerobic granular sludge was cultured with different concentrations combinations of the three added components for 13 days. The combination of 6000 mg/L calcium, 400 mg/L ammonia nitrogen, and 4000 mg/L AHS was the most inhibitory combination on the SMA of granular sludge, with a calculated 4.49 mL (standard temperature and atmospheric pressure) (STP) CH4/(gVSS·d) of SMA. The SMA with the addition of the inhibitory components was much lower than the control group's (1000 mg/L calcium, 200 mg/L ammonia nitrogen and 2000 mg/L AHS) with a calculated 12.97 mL (STP) CH4/(gVSS·d) of SMA. Calcium was the major inhibitor among the three components followed by AHS. High concentrations of calcium significantly inhibited the utilization of propionate and butyrate in the substrate and further affected the methanogenic process.

  12. Inhibitory Effect of Arctigenin from Fructus Arctii Extract on Melanin Synthesis via Repression of Tyrosinase Expression.

    PubMed

    Park, Hwayong; Song, Kwang Hoon; Jung, Pil Mun; Kim, Ji-Eun; Ro, Hyunju; Kim, Mi Yoon; Ma, Jin Yeul

    2013-01-01

    To identify the active compound arctigenin in Fructus Arctii (dried seed of medicinal plant Arctium lappa) and to elucidate the inhibitory mechanism in melanogenesis, we analyzed melanin content and tyrosinase activity on B16BL6 murine melanoma and melan-A cell cultures. Water extracts of Fructus Arctii were shown to inhibit tyrosinase activity in vitro and melanin content in α -melanocyte stimulating hormone-stimulated cells to similar levels as the well-known kojic acid and arbutin, respectively. The active compound arctigenin of Fructus Arctii displayed little or no cytotoxicity at all concentrations examined and decreased the relative melanin content and tyrosinase activity in a dose-dependent manner. Melanogenic inhibitory activity was also identified in vivo with zebrafish embryo. To determine the mechanism of inhibition, the effects of arctigenin on tyrosinase gene expression and tyrosinase promoter activity were examined. Also in addition, in the signaling cascade, arctigenin dose dependently decreased the cAMP level and promoted the phosphorylation of extracellular signal-regulated kinase. This result suggests that arctigenin downregulates cAMP and the tyrosinase enzyme through its gene promoter and subsequently upregulates extracellular signal-regulated kinase activity by increasing phosphorylation in the melanogenesis signaling pathway, which leads to a lower melanin content. PMID:23781272

  13. Inhibitory effect of Lactobacillus salivarius on Streptococcus mutans biofilm formation.

    PubMed

    Wu, C-C; Lin, C-T; Wu, C-Y; Peng, W-S; Lee, M-J; Tsai, Y-C

    2015-02-01

    Dental caries arises from an imbalance of metabolic activities in dental biofilms developed primarily by Streptococcus mutans. This study was conducted to isolate potential oral probiotics with antagonistic activities against S. mutans biofilm formation from Lactobacillus salivarius, frequently found in human saliva. We analysed 64 L. salivarius strains and found that two, K35 and K43, significantly inhibited S. mutans biofilm formation with inhibitory activities more pronounced than those of Lactobacillus rhamnosus GG (LGG), a prototypical probiotic that shows anti-caries activity. Scanning electron microscopy showed that co-culture of S. mutans with K35 or K43 resulted in significantly reduced amounts of attached bacteria and network-like structures, typically comprising exopolysaccharides. Spot assay for S. mutans indicated that K35 and K43 strains possessed a stronger bactericidal activity against S. mutans than LGG. Moreover, quantitative real-time polymerase chain reaction showed that the expression of genes encoding glucosyltransferases, gtfB, gtfC, and gtfD was reduced when S. mutans were co-cultured with K35 or K43. However, LGG activated the expression of gtfB and gtfC, but did not influence the expression of gtfD in the co-culture. A transwell-based biofilm assay indicated that these lactobacilli inhibited S. mutans biofilm formation in a contact-independent manner. In conclusion, we identified two L. salivarius strains with inhibitory activities on the growth and expression of S. mutans virulence genes to reduce its biofilm formation. This is not a general characteristic of the species, so presents a potential strategy for in vivo alteration of plaque biofilm and caries. PMID:24961744

  14. Inhibitory effects of pretreatment with radon on acute alcohol-induced hepatopathy in mice.

    PubMed

    Toyota, Teruaki; Kataoka, Takahiro; Nishiyama, Yuichi; Taguchi, Takehito; Yamaoka, Kiyonori

    2012-01-01

    We previously reported that radon inhalation activates antioxidative functions in the liver and inhibits carbon tetrachloride-induced hepatopathy in mice. In addition, it has been reported that reactive oxygen species contribute to alcohol-induced hepatopathy. In this study, we examined the inhibitory effects of radon inhalation on acute alcohol-induced hepatopathy in mice. C57BL/6J mice were subjected to intraperitoneal injection of 50% alcohol (5 g/kg bodyweight) after inhaling approximately 4000 Bq/m(3) radon for 24 h. Alcohol administration significantly increased the activities of glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT) in serum, and the levels of triglyceride and lipid peroxide in the liver, suggesting acute alcohol-induced hepatopathy. Radon inhalation activated antioxidative functions in the liver. Furthermore, pretreatment with radon inhibited the depression of hepatic functions and antioxidative functions. These findings suggested that radon inhalation activated antioxidative functions in the liver and inhibited acute alcohol-induced hepatopathy in mice.

  15. A cyclohexanecarboxamide derivative with inhibitory effects on Schistosoma mansoni cercarial serine protease and penetration of mice skin by the parasite.

    PubMed

    Bahgat, Mahmoud; Aboul-Enein, Mohamed N; El Azzouny, Aida A; Maghraby, Amany; Ruppel, Andreas; Soliman, Wael M

    2009-01-01

    A cyclohexanecarboxamide derivative, N-phenyl-N-[1-(piperidine-1-carbonyl)cyclohexyl] benzamide (MNRC-5), was evaluated for its inhibitory effects on Schistosoma mansoni cercarial serine protease activity and cercarial penetration. MNRC-5 exerted an inhibitory effect on S. mansoni cercarial serine protease at serial concentrations of the specific chromogenic substrate Boc-Val-Leu-Gly-Arg-PNA for such enzyme family and the inhibitory coefficient (Ki) value was deduced. Moreover, topical treatment of mice tails with the most potent inhibitory concentration of MNRC-5 formulated in jojoba oil successfully blocked cercarial penetration as demonstrated by a significant reduction (75%; p < 0.05) in the recovered S. mansoni worms from treated mice in comparison to control ones whose tails were painted with jojoba oil base containing no MNRC-5. In addition, the IgM and IgG reactivities to crude S. mansoni cercarial, worm and egg antigens were generally lower in sera from treated infected mice than untreated infected mice. In conclusion, we report on a new serine protease inhibitor capable for blocking penetration of host skin by S. mansoni cercariae as measured by lowering worm burden and decrease in the levels of both IgM and IgG towards different bilharzial antigens upon topical treatment.

  16. Inhibitory effect of 5- and 6-ring PAHs on pyrene mineralization by a mixed enrichment culture

    SciTech Connect

    Molina, M.; Agraujo, R.

    1995-12-31

    This research investigates the mineralization of pyrene in mixtures of PAHs to identify potential synergistic or antagonistic interactions that affect the degradation of individual compounds. Mineralization of {sup 14}C pyrene (25 RM) by a mixed enrichment culture was studied in systems containing mixtures of 5- and 6-ring PAHs in minimal salts medium (MSM). In the absence of the High Molecular Weight (HMW)-PAHs, the culture mineralized 62% of the added pyrene. Addition of an equal mixture of benzo(a)pyrene, dibenzanthracene, and benzo(g,h,i)peryiene (25 {micro}M total concentration) reduced pyrene mineralization to 25% after a 9-day lag phase. An increase on the molar concentration of the HMW-PAH mixture to 75 and 125 {micro}M decreased pyrene mineralization to 9.2 and 1%, respectively. Results from treatments containing individual (25 {micro}M each), or pairs of the HMW-compounds demonstrated that none of the three individual compounds caused a significant reduction in the extent of pyrene mineralization. However, the combination of benzo(a)pyrene and benzanthracene significantly inhibited pyrene activity. In addition, the presence of both benzo(a)pyrene and benzo(g,h,i)peryiene reduced mineralization by almost 23%. Determination of bacterial density by epifluorescence microscopy showed that mineralization of pyrene coincides with growth of the bacterial culture; presence of the 5- and 6-ring PAHs delayed growth with a concurrent inhibition of mineralization. When growth resumes, the inhibitory effect is reduced. A decrease of pyrene inhibition was also noted when MSM was replaced with sediment extract, or when sediment (1 {micro}g/ml) was added to the medium. These results suggest a synergistic inhibitory effect by combinations of specific HMW-PAHs rather than inhibition by individual compounds of the mixture on both the growth of the bacterial culture and the extent of pyrene mineralization.

  17. Cholecystokinin receptor-1 mediates the inhibitory effects of exogenous cholecystokinin octapeptide on cellular morphine dependence

    PubMed Central

    2012-01-01

    Background Cholecystokinin octapeptide (CCK-8), the most potent endogenous anti-opioid peptide, has been shown to regulate the processes of morphine dependence. In our previous study, we found that exogenous CCK-8 attenuated naloxone induced withdrawal symptoms. To investigate the precise effect of exogenous CCK-8 and the role of cholecystokinin (CCK) 1 and/or 2 receptors in morphine dependence, a SH-SY5Y cell model was employed, in which the μ-opioid receptor, CCK1/2 receptors, and endogenous CCK are co-expressed. Results Forty-eight hours after treating SH-SY5Y cells with morphine (10 μM), naloxone (10 μM) induced a cAMP overshoot, indicating that cellular morphine dependence had been induced. The CCK receptor and endogenous CCK were up-regulated after chronic morphine exposure. The CCK2 receptor antagonist (LY-288,513) at 1–10 μM inhibited the naloxone-precipitated cAMP overshoot, but the CCK1 receptor antagonist (L-364,718) did not. Interestingly, CCK-8 (0.1-1 μM), a strong CCK receptor agonist, dose-dependently inhibited the naloxone-precipitated cAMP overshoot in SH-SY5Y cells when co-pretreated with morphine. The L-364,718 significantly blocked the inhibitory effect of exogenous CCK-8 on the cAMP overshoot at 1–10 μM, while the LY-288,513 did not. Therefore, the CCK2 receptor appears to be necessary for low concentrations of endogenous CCK to potentiate morphine dependence in SH-SY5Y cells. An additional inhibitory effect of CCK-8 at higher concentrations appears to involve the CCK1 receptor. Conclusions This study reveals the difference between exogenous CCK-8 and endogenous CCK effects on the development of morphine dependence, and provides the first evidence for the participation of the CCK1 receptor in the inhibitory effects of exogenous CCK-8 on morphine dependence. PMID:22682150

  18. Inhibitory effects of zingerone, a pungent component of Zingiber officinale Roscoe, on colonic motility in rats.

    PubMed

    Iwami, Momoe; Shiina, Takahiko; Hirayama, Haruko; Shima, Takeshi; Takewaki, Tadashi; Shimizu, Yasutake

    2011-01-01

    Ginger (rhizome of Zingiber officinale Roscoe) is an herbal medicine for the treatment of gastrointestinal disorders including constipation and diarrhea. Zingerone is a likely active constituent responsible for the antidiarrheal activity of ginger. The current study was designed to characterize pharmacological actions of zingerone on colonic motility. To evaluate pharmacological effects of zingerone on colonic motility, we used isolated colonic segments from rats, in which mechanical responses were recorded in the longitudinal direction. In addition, we evaluated the effects on colonic motility in vivo by measuring intraluminal pressure changes and expelled fluid volume from the colon in anesthetized rats. Zingerone was applied to the lumen of the colon to allow the drug to access from the mucosal side. Zingerone inhibited spontaneous contractile movements in the isolated colonic segments in a dose-dependent manner. The inhibitory effects of zingerone on colonic movements were not affected by pretreatment with capsazepine, a typical antagonist of transient receptor potential vanilloid 1. In addition, tetrodotoxin, a blocker of voltage-dependent sodium channels on neurons, did not affect the suppression of colonic movements by zingerone, suggesting that zingerone acts on the smooth muscles directly. Zingerone also attenuated colonic motility in vivo without affecting blood pressure and heart rate. The effects were reversible and reproducible. Our findings suggest that zingerone can inhibit colonic motility via direct action on smooth muscles. Zingerone might exert beneficial therapeutic effects on hypermotility-induced diarrhea by abrogating excessive gastrointestinal motility. PMID:20799069

  19. Inhibitory effects of xylitol on gastric emptying and food intake

    SciTech Connect

    Shafer, R.B.; Levine, A.S.; Marlette, J.M.; Morley, J.E.

    1985-05-01

    The authors have previously shown, using a 99m-Tc scrambled egg meal, that pentose sugars (i.e. xylose and arabinose) markedly prolong gastric emptying. Others have reported that slowing of gastric emptying may decrease appetite and thus decrease food intake. In the present study, the authors utilized the effects of xylitol (an FDA-approved pentose sugar) on gastric emptying to study the correlation between gastric emptying and food intake. Initially, gastric emptying was measured in human volunteers utilizing a standardized 99m-Tc-scrambled egg meal washed with 50 cc tap water. Results demonstrated a significant reduction in food intake (892 +- 65 kcal with water vs 654 +- 26 kcal following the ingestion of 25 gm xylitol (p<0.05). We conclude that the effect of pentose sugars in prolonging gastric emptying directly influences food intake and contributes to early satiety. The data suggest a role of xylitol as an essentially non-caloric food additive potentially important in diet control.

  20. Inhibitory effects of spices and herbs on iron availability.

    PubMed

    Tuntipopipat, Siriporn; Zeder, Christophe; Siriprapa, Pudsadee; Charoenkiatkul, Somsri

    2009-01-01

    Spices and herbs are extensively used in indigenous diets in tropical regions where prevalence of iron deficiency is still high. They are rich in polyphenolic compounds that are expected to inhibit iron absorption by forming iron complexes in the intestine, making dietary iron less available for absorption. The effects of six spices and herbs (chili pepper, garlic, 'Pak kyheng' (Thai leafy vegetable), shallot, tamarind, turmeric) and one mixture of spices (curry paste) on iron availability were determined by measuring the percentage dialyzable iron after addition of spices and herbs to a rice meal after simulated digestion. All tested spices and herbs contained from 0.5 to 33 mg polyphenol per meal and were potent inhibitors of iron availability (20-90%), reducing iron availability in a dose-dependent manner--with the exception of tamarind, which at 11 mg polyphenol per meal enhanced iron availability. Our findings demonstrate that culinary spices and herbs can play an important role in iron nutrition. PMID:18651292

  1. Additive effects on lubricant fuel economy

    SciTech Connect

    Kennedy, S.; Moore, L.D.

    1987-01-01

    Bench and engine tests were used to determine the effects of typical lubricating oil components on the fuel economy performance of energy conserving oils. The bench studies identified negative fuel economy effects of zinc dialkyldithiophosphates and positive effects of overbased sulfonates. The Sequence VI dynamometer test quantified viscometric influences on fuel economy; results indicated that SAE 5W-30 oils are not always more fuel efficient than 10W-30 analogs, and that viscosity index improver type has a large impact on fuel economy. These effects were integrated with additive effects on other formulation criteria to design an overall system.

  2. Inhibitory self-control moderates the effect of changed implicit food evaluations on snack food consumption.

    PubMed

    Haynes, Ashleigh; Kemps, Eva; Moffitt, Robyn

    2015-07-01

    The current study used a modified implicit association test (IAT) to change implicit evaluations of unhealthy snack food and tested its effects on subsequent consumption. Furthermore, we investigated whether these effects were moderated by inhibitory self-control. A sample of 148 women (17-25 years) motivated to manage weight through healthy eating completed an IAT intervention, and pre- and post-intervention IATs assessing implicit evaluations of unhealthy food. The intervention IAT trained participants to pair unhealthy food stimuli with either positive or negative stimuli. A task disguised as a taste-test was used to assess consumption of unhealthy snack foods. Inhibitory self-control was measured using a self-report scale. As predicted, the implicit evaluation of unhealthy food became more negative from pre- to post-training among participants in the food negative pairing condition; however, there was no corresponding change in the food positive pairing condition. The effect of the training on snack consumption was moderated by inhibitory self-control with only participants low in inhibitory self-control having lower snack intake following the food negative training. This finding is consistent with dual-process models of behaviour which predict that self-control capacity renders impulses less influential on behaviour. Furthermore, it suggests that an intervention that retrains implicit food evaluations could be effective at reducing unhealthy eating, particularly among those with low inhibitory self-control. PMID:25765247

  3. Inhibitory effect of intensity and interstimulus interval of conditioning stimuli on somatosensory evoked magnetic fields.

    PubMed

    Onishi, Hideaki; Sugawara, Kazuhiro; Yamashiro, Koya; Sato, Daisuke; Kirimoto, Hikari; Tamaki, Hiroyuki; Shirozu, Hiroshi; Kameyama, Shigeki

    2016-08-01

    Magnetoencephalography (MEG) recordings were performed to investigate the inhibitory effects of conditioning stimuli with various types of interstimulus intervals (ISIs) or intensities on somatosensory evoked magnetic fields (SEFs) using a 306-ch whole-head MEG system. Twenty-three healthy volunteers participated in this study. Electrical stimuli were applied to the right median nerve at the wrist. Six pulse trains with ISIs of 500 ms were presented in Experiment 1. A paired-pulse paradigm with three kinds of conditioning stimulus (CON) intensities, 500 ms before the test stimulus (TS), was applied in Experiment 2. Finally, three CONs 500 or 1000 ms before TS were presented in Experiment 3. Three main SEF deflections (N20m, P35m, and P60m) were observed, and the source activities of P35m and P60m significantly decreased after the 2nd pulse of a six pulse trains. These source activities also significantly decreased with increasing intensity of CON. In addition, these attenuations of source activities were affected by CON-CON or CON-TS intervals. These results indicated that the source activities were modulated by the intensity and ISIs of CONs. Furthermore, P35m after the stimulation were very sensitive to CONs; however, the attenuation of P60m after the stimulation lasted for a longer period than that of P35m. Our findings suggest that the conditioning stimulation had inhibitory effects on subsequent evoked cortical responses for more than 500 ms. Our results also provide important clues about the nature of short-latency somatosensory responses in human studies. PMID:27319980

  4. Effect of additives on protein aggregation.

    PubMed

    Hamada, Hiroyuki; Arakawa, Tsutomu; Shiraki, Kentaro

    2009-06-01

    This paper overviews solution additives that affect protein stability and aggregation during refolding, heating, and freezing processes. Solution additives are mainly grouped into two classes, i.e., protein denaturants and stabilizers. The former includes guanidine, urea, strong ionic detergents, and certain chaotropic salts; the latter includes certain amino acids, sugars, polyhydric alcohols, osmolytes, and kosmotropic salts. However, there are solution additives that are not unambiguously placed into these two classes, including arginine, certain divalent cation salts (e.g., MgCl(2)) and certain polyhydric alcohols (e.g., ethylene glycol). Certain non-ionic or non-detergent surfactants, ionic liquids, amino acid derivatives, polyamines, and certain amphiphilic polymers may belong to this class. They have marginal effects on protein structure and stability, but are able to disrupt protein interactions. Information on additives that do not catalyze chemical reactions nor affect protein functions helps us to design protein solutions for increased stability or reduced aggregation. PMID:19519415

  5. Inhibitory effect of coated mannan against the adhesion of Candida biofilms to denture base resin.

    PubMed

    Sato, Maki; Ohshima, Tomoko; Maeda, Nobuko; Ohkubo, Chikahiro

    2013-01-01

    The adherence of Candida on dentures is related to diseases such as denture stomatitis and aspiration pneumonia. Mannan is a major component of the Candida cell surface, and contributes to the cell adherence. A previous report indicated that the adherence of C. albicans to culture dishes was inhibited by the coating them with mannan. The purpose of this study was to examine the adhesion inhibitory effect of mannan coating on acrylic denture surfaces against C. albicans and C. glabrata. The amount of Candida attached on the acrylic surfaces coated with mannan was calibrated by culture methods. Mannan showed significant inhibitory effects on Candida adhesion in both the yeast and hyphal form in a concentration-dependent manner, and the durability of the inhibitory effect continued for three days. These results suggest that mannan coating on the denture base acrylic can prevent Candida adhesion on the denture.

  6. Cantaloupe melon peroxidase: characterization and effects of additives on activity.

    PubMed

    Lamikanra, O; Watson, M A

    2000-06-01

    Peroxidase in cantaloupe melon (Cucumis melo L. var. reticulatus Naud.), a fruit commonly fresh cut processed, was characterized to determine reaction pathway, optimal conditions for activity and effect of some additives on enzymatic action. Mn2+, CaCl2, NaNO2 and kinetin had partial inhibitory effects on enzyme activity. Activity was effectively inhibited by compounds capable of chelating peroxidase heme iron such as diethyldithiocarbamate and tiron, but unaffected by EDTA. Free radical scavenger, superoxide dismutase, also had no effect on reaction velocity. Enzymatic action was consistent with that of ascorbate peroxidase based on the relatively higher affinity for ascorbate over guaiacol. Optimum activity temperature was 50-55 degrees C. The enzyme was stable at temperatures below 40 degrees C and at 50 degrees C for up to 10 min. Over 90% of total activity was lost at 80 degrees C within 5 min. Broad pH optima, 5.5-7.5 at 50 degrees C and 6-7 at 30 degrees C, were obtained. Peroxidase activity in cantaloupe was higher than those in strawberry (Fragaria ananassa Duch.) and lettuce (Lactuca sativa L.), suggesting a relatively high oxidative stress in fresh cut cantaloupe. The potential use of ascorbate as an additive in fresh cut cantaloupe melon was demonstrated by its ability to preserve color in minimally processed fruits for 25 days at 4 degrees C, possibly as a result of an enhanced antioxidative action of the ascorbate-peroxidase complex and trace metal ion cofactors.

  7. Inhibitory effects of whisky congeners on melanogenesis in mouse B16 melanoma cells.

    PubMed

    Ohguchi, Kenji; Koike, Minako; Suwa, Yoshihide; Koshimizu, Seiichi; Mizutani, Yuki; Nozawa, Yoshinori; Akao, Yukihiro

    2008-04-01

    We examined the effect of whisky congeners, substances other than ethanol in whisky, on melanogenesis in mouse B16 melanoma cells. Treatment with whisky congeners significantly blocked melanogenesis. Our results indicate that the inhibitory effects of whisky congeners on melanogenesis is due to direct inhibition of tyrosinase activity and to suppression of tyrosinase protein levels.

  8. Growth kinetic model that describes the inhibitory and lytic effects of phenol on Candida tropicalis yeast.

    PubMed

    Ruiz-Ordaz, N; Hernández-Manzano, E; Ruiz-Lagúnez, J C; Cristiani-Urbina, E; Galíndez-Mayer, J

    1998-01-01

    The object of this work was to carry out a kinetic study on the Candida tropicalis cell lysis and to obtain a kinetic model that would describe the inhibitory and lytic effects of phenol on the yeast growth. From the experiments, a model for the growth kinetic behavior of the yeast was evolved. The proposed model describes satisfactorily the inhibitory and lytic effects of phenol on yeast cultures. From the kinetic model constants, it was found that C. tropicalis showed high affinity and tolerance toward phenol. The overall growth yields decreased when the initial phenol concentration increased, and it may be due to an increased maintenance coefficient and to cell lysis.

  9. INHIBITORY EFFECT OF TETRAMETHYLPYRAZINE ON HEPATOCELLULAR CARCINOMA: POSSIBLE ROLE OF APOPTOSIS AND CELL CYCLE ARREST.

    PubMed

    Cao, J; Miao, Q; Zhang, J; Miao, S; Bi, L; Zhang, S; Yang, Q; Zhou, X; Zhang, M; Xie, Y; Wang, S

    2015-01-01

    Hepatocellular carcinoma (HCC) is the fifth most common cancer. An important approach to control HCC is chemoprevention. This study aims at investigating the antitumor effect of Tetramethylpyrazine (TMP). Rats were injected with N-Nitrosodiethylamine (DEN) to establish HCC. Tumor development was observed. Liver function was evaluated. Apoptosis and cell cycle arrest-related makers and signaling cascades were determined by Western blot, RT-PCR and flow cytometric analysis. The administration of TMP could significantly inhibit tumor development in DEN-induced HCC rats, shown by reduced incidence of tumor, decreased number of tumor nodules and reduced maximal size of tumor. DEN-induced increase of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase and alkaline phosphatase activities were significantly inhibited by TMP. TMP exhibited inhibitory effect on HCC through induction of apoptosis and cell cycle arrest in rats. TMP induced apoptosis through increasing Bax, decreasing Bcl-2, increasing the release of cytochrome c, and activating caspase, which consisted of the mitochondrial apoptotic pathway. TMP induced G2/M cell cycle arrest through down-regulation of cyclin B1/cdc2. In addition, inhibition of Akt and ERK signaling and the antioxidant activities of TMP may also contribute to its antitumor effect. These data provide new insight into the mechanisms underlying the antitumor effect of TMP. PMID:26122217

  10. Inhibitory effect of the herbal antidepressant St. John's wort (Hypericum perforatum) on rat gastric motility.

    PubMed

    Capasso, Raffaele; Borrelli, Francesca; Aviello, Gabriella; Capasso, Francesco; Izzo, Angelo A

    2008-02-01

    St. John's wort (Hypericum perforatum) is a highly popular and effective herbal antidepressant that clinically interacts with a number of conventional drugs. Because alterations in gastric emptying can cause pharmacokinetic interactions, in the present study we evaluated the effect of a standardized extract prepared from the flowering tops of Hypericum perforatum (SJW extract) on rat gastric motility. Orally administered SJW extract delayed gastric emptying in vivo. In vitro studies showed that SJW extract was significantly more active in inhibiting acetylcholine (or prostaglandin E2)-induced contractions than electrical field stimulation (EFS)-induced contractions. The effect of SJW extract on EFS-induced contractions was unaffected by drugs that inhibit intrinsic inhibitory nerves or by tachykinin antagonists, but it was reduced by the 5-hydroxytryptamine antagonist methysergide. The inhibitory effect of SJW extract on acetylcholine-induced contractions was reduced by the sarcoplasmic reticulum Ca2+-ATPase inhibitor cyclopiazonic acid, but not by the L-type Ca2+ channel blocker nifedipine or by methysergide. Among the chemical constituents of SJW extract tested, hyperforin and, to a lesser extent, the flavonoids kaempferol and quercitrin, inhibited acetylcholine-induced contractions. It is concluded that SJW has a direct inhibitory effect on smooth muscle and could also possibly modulate gastric neurotransmission. If extended to humans, the inhibitory effect of SJW extract on gastric emptying in vivo could contribute, at least in part, to the clinical pharmacokinetic interactions between conventional medicines and this herbal antidepressant. PMID:18172613

  11. Diffused and Sustained Inhibitory Effects of Intestinal Electrical Stimulation on Intestinal Motility Mediated via Sympathetic Pathway

    PubMed Central

    Zhao, Xiaotuan; Yin, Jieyun; Wang, Lijie; Chen, J D Z

    2013-01-01

    Objective The aims was to investigate the energy-dose response effect of IES on small bowel motility, to compare the effect of forward and backward IES; to explore the possibility of using intermittent IES and mechanism of IES on intestinal motility. Material and Methods Five dogs implanted with a duodenal cannula and one pair of intestinal serosal electrodes were studied in 5 sessions: 1) energy-dose response study; 2) forward IES; 3) backward IES; 4) intermittent IES vs. continuous IES; 5) administration of guanethidine. The contractile activity and tonic pressure of the small intestine were recorded. The duration of sustained effect after turning off IES was manually calculated. Results 1) IES with long pulses energy-dose dependently inhibited contractile activity and tonic pressure of the small intestine (p < 0.001). 2) The duration of sustained inhibitory effect of IES on the small intestine depended on the energy of IES delivered (p < 0.001). 3) The potency of the inhibitory effect was the same between forward and backward IES. 4) The efficacy of intermittent IES was the same as continuous IES in inhibiting motility of the small intestine. 5) Guanethidine blocked the inhibitory effect of IES on intestinal motility. Conclusions IES with long pulses inhibits small intestinal motility; the effect is energy-dose dependent, diffused and sustained. Intermittent IES has the same efficacy as the continuous IES in inhibiting small intestinal motility. Forward and backward IES have similar inhibitory effects on small bowel motility. This IES-induced inhibitory effect is mediated via the sympathetic pathway. PMID:23924055

  12. Potent Inhibitory Effect of Chinese Dietary Spices on Fatty Acid Synthase.

    PubMed

    Jiang, Bing; Liang, Yan; Sun, Xuebing; Liu, Xiaoxin; Tian, Weixi; Ma, Xiaofeng

    2015-09-01

    Dietary spices have been adopted in cooking since ancient times to enhance flavor and also as food preservatives and disease remedies. In China, the use of spices and other aromatic plants as food flavoring is an integral part of dietary behavior, but relatively little is known about their functions. Fatty acid synthase (FAS) has been recognized as a remedy target, and its inhibitors might be applied in disease treatment. The present work was designed to assess the inhibitory activities on FAS of spices extracts in Chinese menu. The in vitro inhibitory activities on FAS of 22 extracts of spices were assessed by spectrophotometrically monitoring oxidation of NADPH at 340 nm. Results showed that 20 spices extracts (90.9 %) exhibited inhibitory activities on FAS, with half inhibition concentration (IC(50)) values ranging from 1.72 to 810.7 μg/ml. Among them, seven spices showed strong inhibitory effect with IC(50) values lower than 10 μg/ml. These findings suggest that a large proportion of the dietary spices studied possess promising inhibitory activities on FAS, and subsequently might be applied in the treatment of obesity and obesity-related human diseases.

  13. Inhibitory effects of fermented extract of Ophiopogon japonicas on thrombin-induced vascular smooth muscle cells.

    PubMed

    Song, Jun-Hui; Jeong, Gi Hee; Park, Sung Lyea; Won, Se Yeon; Paek, Nam Soo; Lee, Bog-Hieu; Moon, Sung-Kwon

    2016-01-01

    Ophiopogon japonicus is known to have various pharmacological effects. The present study investigated the effects of an extract of fermented Ophiopogon japonicas (FEOJ) on thrombin‑treated vascular smooth muscle cells (VSMCs). FEOJ treatment inhibited the proliferation of VSMCs treated with thrombin as indicated by an MTT assay. These inhibitory effects were associated with decreased phosphorylation of AKT, reduced expression of cyclin D1 and increased expression of p27KIP1 in thrombin‑induced VSMCs. In addition, FEOJ treatment suppressed the thrombin‑stimulated migration of VSMCs as demonstrated by a wound‑healing migration assay. Furthermore, zymographic analyses demonstrated that treatment of FEOJ with VSMCs suppressed the thrombin‑induced expression of matrix metalloproteinase (MMP)‑2, which was attributed to the reduction of nuclear factor (NF)‑κB binding activity. Collectively, these results demonstrated that FEOJ induced p27KIP1 expression, reduced cyclin D1 expression and AKT phosphorylation, and inhibited MMP‑2 expression mediated by downregulation of NF‑κB binding activity in thrombin‑treated VSMCs, which led to growth inhibition and repression of migration. These results supported the use of FEOJ for the prevention of vascular diseases and provided novel insight into the underlying mechanism of action.

  14. Medium effects on minimum inhibitory concentrations of nylon-3 polymers against E. coli.

    PubMed

    Choi, Heejun; Chakraborty, Saswata; Liu, Runhui; Gellman, Samuel H; Weisshaar, James C

    2014-01-01

    Minimum inhibitory concentrations (MICs) against E. coli were measured for three nylon-3 polymers using Luria-Bertani broth (LB), brain-heart infusion broth (BHI), and a chemically defined complete medium (EZRDM). The polymers differ in the ratio of hydrophobic to cationic subunits. The cationic homopolymer is inert against E. coli in BHI and LB, but becomes highly potent in EZRDM. A mixed hydrophobic/cationic polymer with a hydrophobic t-butylbenzoyl group at its N-terminus is effective in BHI, but becomes more effective in EZRDM. Supplementation of EZRDM with the tryptic digest of casein (often found in LB) recapitulates the LB and BHI behavior. Additional evidence suggests that polyanionic peptides present in LB and BHI may form electrostatic complexes with cationic polymers, decreasing activity by diminishing binding to the anionic lipopolysaccharide layer of E. coli. In contrast, two natural antimicrobial peptides show no medium effects. Thus, the use of a chemically defined medium helps to reveal factors that influence antimicrobial potency of cationic polymers and functional differences between these polymers and evolved antimicrobial peptides.

  15. Inhibitory effects of extracellular self-DNA: a general biological process?

    PubMed

    Mazzoleni, Stefano; Cartenì, Fabrizio; Bonanomi, Giuliano; Senatore, Mauro; Termolino, Pasquale; Giannino, Francesco; Incerti, Guido; Rietkerk, Max; Lanzotti, Virginia; Chiusano, Maria Luisa

    2015-04-01

    Self-inhibition of growth has been observed in different organisms, but an underlying common mechanism has not been proposed so far. Recently, extracellular DNA (exDNA) has been reported as species-specific growth inhibitor in plants and proposed as an explanation of negative plant-soil feedback. In this work the effect of exDNA was tested on different species to assess the occurrence of such inhibition in organisms other than plants. Bioassays were performed on six species of different taxonomic groups, including bacteria, fungi, algae, plants, protozoa and insects. Treatments consisted in the addition to the growth substrate of conspecific and heterologous DNA at different concentration levels. Results showed that treatments with conspecific DNA always produced a concentration dependent growth inhibition, which instead was not observed in the case of heterologous DNA. Reported evidence suggests the generality of the observed phenomenon which opens new perspectives in the context of self-inhibition processes. Moreover, the existence of a general species-specific biological effect of exDNA raises interesting questions on its possible involvement in self-recognition mechanisms. Further investigation at molecular level will be required to unravel the specific functioning of the observed inhibitory effects. PMID:25628124

  16. Investigation of selective inhibitory effects of glycyrol on human CYP 1A1 and 2C9.

    PubMed

    Kim, Sun Joo; Kim, Su Jin; Hong, Miri; Choi, Hyun Gyu; Kim, Jeong Ah; Lee, Sangkyu

    2016-10-01

    1. Glycyrol is a coumarin derivative isolated from the roots of Glycyrrhiza uralensis called Gamcho in Korea and commonly used as a sweetener in oriental medicine. Glycyrol shows several biological activities, including anti-oxidative, anti-inflammatory, antibacterial, anti-angiogenic, and anti-allergenic properties. Although there have been studies on the biological effects of glycyrol, the inhibitory effects of glycyrol on cytochrome P450 (CYP) activities have not been investigated. 2. We investigated the inhibitory effects of glycyrol on the activities of CYP isoforms using a cocktail of probe substrates in pooled human liver microsome (HLM) and human recombinant cDNA-expressed CYPs. Glycyrol strongly inhibited CYP1A-mediated phenacetin O-deethylation and CYP2C9-mediated diclofenac 4'-hydroxylation in HLMs, which were the result of competitive inhibition as revealed by a Dixon plot. In addition, glycyrol showed selective inhibition of CYP1A1- and CYP1A2-catalyzed phenacetin O-deethylase activity with a half-maximal inhibitory concentration of (IC50) 1.3 and 16.1 μM in human recombinant cDNA-expressed CYP1A1 and CYP1A2, respectively. 3. Glycyrol decreased CYP2C9-catalyzed diclofenac 4'-hydroxylation activity with IC50 values of 0.67 μM in human recombinant cDNA-expressed CYP2C9. This is the first investigation of competitive inhibitory effects on CYP1A1 and CYP2C9 in HLMs. PMID:26750984

  17. Investigation of selective inhibitory effects of glycyrol on human CYP 1A1 and 2C9.

    PubMed

    Kim, Sun Joo; Kim, Su Jin; Hong, Miri; Choi, Hyun Gyu; Kim, Jeong Ah; Lee, Sangkyu

    2016-10-01

    1. Glycyrol is a coumarin derivative isolated from the roots of Glycyrrhiza uralensis called Gamcho in Korea and commonly used as a sweetener in oriental medicine. Glycyrol shows several biological activities, including anti-oxidative, anti-inflammatory, antibacterial, anti-angiogenic, and anti-allergenic properties. Although there have been studies on the biological effects of glycyrol, the inhibitory effects of glycyrol on cytochrome P450 (CYP) activities have not been investigated. 2. We investigated the inhibitory effects of glycyrol on the activities of CYP isoforms using a cocktail of probe substrates in pooled human liver microsome (HLM) and human recombinant cDNA-expressed CYPs. Glycyrol strongly inhibited CYP1A-mediated phenacetin O-deethylation and CYP2C9-mediated diclofenac 4'-hydroxylation in HLMs, which were the result of competitive inhibition as revealed by a Dixon plot. In addition, glycyrol showed selective inhibition of CYP1A1- and CYP1A2-catalyzed phenacetin O-deethylase activity with a half-maximal inhibitory concentration of (IC50) 1.3 and 16.1 μM in human recombinant cDNA-expressed CYP1A1 and CYP1A2, respectively. 3. Glycyrol decreased CYP2C9-catalyzed diclofenac 4'-hydroxylation activity with IC50 values of 0.67 μM in human recombinant cDNA-expressed CYP2C9. This is the first investigation of competitive inhibitory effects on CYP1A1 and CYP2C9 in HLMs.

  18. INHIBITORY EFFECTS OF PERCHLOROETHYLENE ON HUMAN NEURONAL NICOTINIC ACETYLCHOLINE RECEPTORS.

    EPA Science Inventory

    Perchloroethylene (PERC) is a volatile organic solvent with a variety of industrial uses. PERC exposure has been shown to cause adverse neurological effects including deficits in vision and memory in exposed individuals. Despite knowledge of these effects, the mechanisms by whi...

  19. Inhibitory Aromatase Effects of Flavonoids from Ginkgo Biloba Extracts on Estrogen Biosynthesis.

    PubMed

    Park, Yong Joo; Choo, Wun Hak; Kim, Ha Ryong; Chung, Kyu Hyuck; Oh, Seung Min

    2015-01-01

    Ginkgo biloba extract (GBE) is a popular phytomedicine and has been used for disorders of the central nervous system, cardiovascular, renal, respiratory, and circulatory diseases. Although GBE is a complex mixture of over 300 compounds, its major components are 24% flavonoids and 6% terpene lactones. In this study, we tested the inhibitory effects of the three major flavonoids (kaempferol, quercetin, and isorhamnetin) from GBE, independently and as mixtures, on aromatase activity using JEG-3 cells (human placental cells) and recombinant proteins (human placental microsome). In both systems, kaempferol showed the strongest inhibitory effects among the three flavonoids; the flavanoid mixtures exerted increased inhibitory effects. The results of exon I.1-driven luciferase reporter gene assays supported the increased inhibitory effects of flavonoid mixtures, accompanied by suppression of estrogen biosynthesis. In the RT-PCR analysis, decreased patterns of aromatase promoter I.1 mRNA expressions were observed, which were similar to the aromatase inhibition patterns of flavonoids and their mixtures. The present study demonstrated that three flavonoids synergistically inhibit estrogen biosynthesis through aromatase inhibition, decrease CYP19 mRNA, and induce transcriptional suppression. Our results support the usefulness of flavonoids in adjuvant therapy for breast cancer by reducing estrogen levels with reduced adverse effects due to estrogen depletion. PMID:26434836

  20. Effect of reactive site loop elongation on the inhibitory activity of C1-inhibitor.

    PubMed

    Bos, Ineke G A; Lubbers, Yvonne T P; Eldering, Eric; Abrahams, Jan Pieter; Hack, C Erik

    2004-06-01

    The serine protease inhibitor C1-Inhibitor (C1-Inh) inhibits several complement- and contact-system proteases, which play an important role in inflammation. C1-Inh has a short reactive site loop (RSL) compared to other serpins. RSL length determines the inhibitory activity of serpins. We investigated the effect of RSL elongation on inhibitory activity of C1-Inh by insertion of one or two alanine residues in the RSL. One of five mutants had an increased association rate with kallikrein, but was nevertheless a poor inhibitor because of a simultaneous high stoichiometry of inhibition (>10). The association rate of the other variants was lower than that of wild-type C1-Inh. These data suggest that the relatively weak inhibitory activity of C1-Inh is not the result of its short RSL. The short RSL of C1-Inh has, surprisingly, the optimal length for inhibition.

  1. Sesquiterpenes from the rhizomes of Alpinia japonica and their inhibitory effects on nitric oxide production.

    PubMed

    Li, Qiang-Ming; Luo, Jian-Guang; Wang, Xiao-Bing; Yang, Ming-Hua; Kong, Ling-Yi

    2013-04-01

    A novel norsesquiterpene (1), three new bisabolenes sesquiterpenes (2-4), along with 7 known compounds (5-11), were isolated from the rhizomes of Alpinia japonica. The structures of the new compounds were elucidated by analysis of spectroscopic data. The absolute configuration of C-1 in 3 was deduced via the circular dichroism data of the in situ formed [Rh2(OCOCF3)4] complexes. Inhibitory effects of the isolates on nitric oxide production in lipopolysaccaride-activated RAW264.7 macrophages were evaluated. Compound 6 showed significant inhibitory activity with IC50 value of 5.3 μΜ, and compounds 1, 3, 5 and 7-10 exhibited moderate inhibitory activities with IC50 values between 24.5 and 46.3 μM.

  2. Inhibitory effect of lipoic acid on firefly luciferase bioluminescence.

    PubMed

    Niwa, Kazuki; Ohmiya, Yoshihiro

    2004-10-15

    Lipoic acid was found to inhibit the firefly luciferin-luciferase reaction. The inhibition is competitive and is the strongest known (Ki = 0.026 +/- 0.013 microM) compared with other reported inhibitors. Considering the structure-activity correlations, the mechanism of inhibition may originate from the sulfur atom and carboxyl moiety of lipoic acid giving it structural specificity. Subsequent addition of lipoic acid and nitric oxide accelerated the inhibition in vitro, suggesting that lipoic acid may have a functional role in regulating firefly bioluminescence.

  3. Inhibitory Effects of Ferrihydrite on a Thermophilic Methanogenic Community

    PubMed Central

    Yamada, Chihaya; Kato, Souichiro; Ueno, Yoshiyuki; Ishii, Masaharu; Igarashi, Yasuo

    2014-01-01

    The addition of ferrihydrite to methanogenic microbial communities obtained from a thermophilic anaerobic digester suppressed methanogenesis in a dose-dependent manner. The amount of reducing equivalents consumed by the reduction of iron was significantly smaller than that expected from the decrease in the production of CH4, which suggested that competition between iron-reducing microorganisms and methanogens was not the most significant cause for the suppression of methanogenesis. Microbial community analyses revealed that the presence of ferrihydrite markedly affected the bacterial composition, but not the archaeal composition. These results indicate that the presence of ferrihydrite directly and indirectly suppresses thermophilic methanogenesis. PMID:24859310

  4. No Evidence for True Training and Transfer Effects after Inhibitory Control Training in Young Healthy Adults

    ERIC Educational Resources Information Center

    Enge, Sören; Behnke, Alexander; Fleischhauer, Monika; Küttler, Lena; Kliegel, Matthias; Strobel, Alexander

    2014-01-01

    Recent studies reported that training of working memory may improve performance in the trained function and beyond. Other executive functions, however, have been rarely or not yet systematically examined. The aim of this study was to test the effectiveness of inhibitory control (IC) training to produce true training-related function improvements…

  5. Imagined Positive Emotions and Inhibitory Control: The Differentiated Effect of Pride versus Happiness

    ERIC Educational Resources Information Center

    Katzir, Maayan; Eyal, Tal; Meiran, Nachshon; Kessler, Yoav

    2010-01-01

    "Inhibitory control" is a cognitive mechanism that contributes to successful self-control (i.e., adherence to a long-term goal in the face of an interfering short-term goal). This research explored the effect of imagined positive emotional events on inhibition. The authors proposed that the influence of imagined emotions on inhibition depends on…

  6. Telomerase inhibitory effects of medicinal mushrooms and lichens, and their anticancer activity.

    PubMed

    Xu, Baojun; Li, Chantian; Sung, Changkeun

    2014-01-01

    Telomerase has been widely accepted as a cancer marker and a promising therapeutic target for novel anticancer drugs. The aim of this study was to investigate the in vitro telomerase inhibitory effects of mushrooms and their anticancer properties. The inhibitory effects of mushrooms and lichens against telomerase activity of HL-60 cells were systematically assessed using polymerase chain reaction based on assay of telomeric repeat amplification protocol. Telomerase inhibitory samples were further tested for antiproliferation effects against the gastric cell line SNU-1 using the MTT method. Ethyl acetate extract of Pleurotus ostreatus, ethyl acetate and water extracts of Lasiosphaera fenzlii, hexane extract of Strobilomyces floccopus, water extract of Sarcodon aspratus, and hexane, ethyl acetate, and water extracts from Umbilicaria esculenta showed strong positive telomerase inhibitory activity. Hexane extract of S. floccopus and water extracts from the edible lichen U. esculenta exhibited strong anticancer effects against SNU-1 cells through antiproliferation assay. The water extract of U. esculenta has a great potential to be developed into an anticancer agent that targets telomerase.

  7. INHIBITORY EFFECTS OF VOLATILE ORGANIC COMPOUNDS ON NEURONAL NICOTINIC ACETYLCHOLINE RECEPTORS.

    EPA Science Inventory

    INHIBITORY EFFECTS OF VOLATILE ORGANIC COMPOUNDS ON NEURONAL NICOTINIC ACETYLCHOLINE RECEPTORS.
    A.S. Bale*; P.J. Bushnell; C.A. Meacham; T.J. Shafer
    Neurotoxicology Division, NHEERL, ORD, US Environmental Protection Agency, Research Triangle Park, NC, USA
    Toluene (TOL...

  8. Investigations of the inhibitory effects of tocopherol (vitamin E) on free radical deterioration of cellular membranes

    NASA Technical Reports Server (NTRS)

    Richardson, D.

    1975-01-01

    The inhibitory effects are investigated of d,1-alpha-tocopherol and d,1-alpha-tocopheryl acetate on the free radical deterioration of cellular membranes. The level of toxicity of d,1-alpha-tocopherol and d,1-alpha-tocopheryl acetate in mice is determined.

  9. Melanogenesis inhibitory, anti-inflammatory, and chemopreventive effects of limonoids from the seeds of Azadirachta indicia A. Juss. (neem).

    PubMed

    Akihisa, Toshihiro; Noto, Taisuke; Takahashi, Akitomo; Fujita, Yukiko; Banno, Norihiro; Tokuda, Harukuni; Koike, Kazuo; Suzuki, Takashi; Yasukawa, Ken; Kimura, Yumiko

    2009-01-01

    Thirty-one nortriterpenoids, including 28 limonoids (1-28) and 3 degraded limonoids (29-31), and one diterpenoid (32), were isolated from the seed extract of Azadirachta indica (neem). Among these, six were new compounds and their structures were established to be 15-hydroxyazadiradione (3), 7-benzoyl-17-hydroxynimbocinol (5), 23-deoxyazadironolide (12), limocin E (13), 23-epilimocin E (14), and 7alpha-acetoxy-3-oxoisocopala-1,13-dien-15-oic acid (32). Upon evaluation of compounds 1-32 on the melanogenesis in the B16 melanoma cells, five compounds, 20, 26, 27, 29, and 31, exhibited marked inhibitory effect (74-91% reduction of melanin content at 25 microg/mL) with no or almost no toxicity to the cells. Seven compounds, 1, 6, 9, 10, 18, 20, and 26, on evaluation for their inhibitory effect against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation (1 microg/ear) in mice, exhibited, except for compound 26, marked anti-inflammatory activity (ID(50) values 0.09-0.26 mg/ear). In addition, all of the 32 compounds exhibited moderate or potent inhibitory effects (IC(50) values of 230-501 mol ratio/32 pmol TPA) against the Epstein-Barr virus early antigen (EBV-EA) activation induced by TPA. Furthermore, on evaluation of azadirachtin B (21) for its anti-tumor-initiating activity on the two-stage carcinogenesis of mouse skin tumor induced by peroxynitrite (ONOO-; PN) as an initiator and TPA as a promoter, this exhibited marked inhibitory activity. PMID:19844073

  10. Inhibitory effects of caffeine on hippocampal neurogenesis and function.

    PubMed

    Han, Myoung-Eun; Park, Kyu-Hyun; Baek, Sun-Yong; Kim, Bong-Seon; Kim, Jae-Bong; Kim, Hak-Jin; Oh, Sae-Ock

    2007-05-18

    Caffeine is one of the most extensively consumed psychostimulants in the world. However, compared to short-term effects of caffeine, the long-term effects of caffeine consumption on learning and memory are poorly characterized. The present study found that long-term consumption of low dose caffeine (0.3 g/L) slowed hippocampus-dependent learning and impaired long-term memory. Caffeine consumption for 4 weeks also significantly reduced hippocampal neurogenesis compared to controls. From these results, we concluded that long-term consumption of caffeine could inhibit hippocampus-dependent learning and memory partially through inhibition of hippocampal neurogenesis.

  11. Oxymetazoline: potential mechanisms of inhibitory effects on aqueous humor dynamics.

    PubMed

    Chu, T C; Ogidigben, M J; Potter, D E

    1996-10-01

    Oxymetazoline, an alpha 2 agonist, was active in lowering intraocular pressure in normal and sympathetically denervated rabbit eyes. Ocular hypotension was accompanied by decreased aqueous humor inflow. Topical pretreatment with rauwolscine, an alpha 2 antagonist, reduced the oxymetazoline-induced hypotensive effect more in contralateral than in ipsilateral eyes indicating the possible involvement of central alpha 2 adrenoceptors. Efaroxan, a relatively selective imidazoline antagonist, and diclofenac, a cyclooxygenase inhibitor, failed to inhibit the oxymetazoline-induced ocular hypotensive response. Oxymetazoline induced mydriasis in treated eyes at all doses. In in vitro studies, oxymetazoline inhibited isoproterenol-stimulated cAMP production in rabbit iris-ciliary bodies and cultured rabbit nonpigmented ciliary epithelial cells. The inhibition of cAMP accumulation induced by oxymetazoline was antagonized by rauwolscine or by BRL-44408, a relatively selective alpha 2A-adrenoceptor antagonist. These data indicate that oxymetazoline lowered intraocular pressure by activating alpha 2A receptors (ciliary epithelium) and that the ocular hypotensive effect was not totally dependent on intact sympathetic nerves. Results suggest that mechanisms involving centrally mediated effects of oxymetazoline are probable and this possibility is currently under investigation.

  12. Inhibitory Effects of Antimicrobial Peptides on Lipopolysaccharide-Induced Inflammation

    PubMed Central

    Sun, Yue; Shang, Dejing

    2015-01-01

    Antimicrobial peptides (AMPs) are usually small molecule peptides, which display broad-spectrum antimicrobial activity, high efficiency, and stability. For the multiple-antibiotic-resistant strains, AMPs play a significant role in the development of novel antibiotics because of their broad-spectrum antimicrobial activities and specific antimicrobial mechanism. Besides broad-spectrum antibacterial activity, AMPs also have anti-inflammatory activity. The neutralization of lipopolysaccharides (LPS) plays a key role in anti-inflammatory action of AMPs. On the one hand, AMPs can readily penetrate the cell wall barrier by neutralizing LPS to remove Gram-negative bacteria that can lead to infection. On the contrary, AMPs can also inhibit the production of biological inflammatory cytokines to reduce the inflammatory response through neutralizing circulating LPS. In addition, AMPs also modulate the host immune system by chemotaxis of leukocytes, to promote immune cell proliferation, epithelialization, and angiogenesis and thus play a protective role. This review summarizes some recent researches about anti-inflammatory AMPs, with a focus on the interaction of AMPs and LPS on the past decade. PMID:26612970

  13. Inhibitory effect of modified 5'-capped short RNA fragments on influenza virus RNA polymerase gene expression.

    PubMed

    Tado, M; Abe, T; Hatta, T; Ishikawa, M; Nakada, S; Yokota, T; Takaku, H

    2001-11-01

    We have shown previously that the 5'-capped short phosphodiester RNA fragments, Cap decoy, (Gm 12 nt) are potent inhibitors of influenza virus RNA polymerase gene expression. Here we investigate the modified capped RNA derivative containing phosphorothioate oligonucleotides (Cap decoy) as a potential influenza virus RNA polymerase inhibitor. The modified 5'-capped short phosphorothioate RNA fragments (Gms 12-15 nt) with the 5'-capped structure (m7GpppGm) were synthesized by T7 RNA polymerase. The 5'-capped short RNA fragments (Gms 12-15 nt) were encapsulated in liposome particulates and tested for their inhibitory effects on influenza virus RNA polymerase gene expression in the clone 76 cells. The 12-15 nt long Gms RNA fragments showed highly inhibitory effects. By contrast, the inhibitory effects of the 13 nt long short RNA fragments (Gm 13 nt) were considerably less in comparison with the 5'-capped short phosphorothioate RNA fragments (Gms 12-15 nt). In particular, the various Gms RNA chain lengths showed no significant differences in the inhibition of influenza virus RNA polymerase gene expression. Furthermore, the capped RNA with a phosphorothioate backbone was resistant to nuclease activity. These phosphorothioate RNA fragments exhibited higher inhibitory activity than the 5'-capped short RNA fragments (Gm 12 nt). These decoys may prove to be useful in anti-influenza virus therapeutics. PMID:12018680

  14. Inhibitory effect of several fluoroquinolones on hepatic microsomal cytochrome P-450 1A activities in dogs.

    PubMed

    Regmi, N L; Abd El-Aty, A M; Kuroha, M; Nakamura, M; Shimoda, M

    2005-12-01

    We examined inhibitory effects of ofloxacin (OFX), orbifloxacin (OBFX), ciprofloxacin (CFX), enrofloxacin (EFX) and norfloxacin (NFX) on cytochrome P-450 1A (CYP1A) activities using hepatic microsomes from four beagle dogs. Ethoxyresorufin O-de-ethylation was referred as CYP1A activities. All the fluoroquinolones inhibited the reaction in a noncompetitive manner. The determined inhibitory constants were the followings; 10.1 +/- 3.8 mM for OFX, 6.43 +/- 2.01 mM for OBFX, 0.726 +/- 0.134 mM for CFX, 4.06 +/- 1.19 mM for EFX and 4.75 +/- 1.63 mM for NFX respectively. As these values are >100-fold of plasma concentrations after a clinical single dose of the fluoroquinolones, it is suggested that the inhibitory effect on CYP1A activities is not so high to elicit drug-drug interaction with CYP1A substrates, when these fluoroquinolones are co-administered. Mechanism based inhibition was also examined in this study. Of the five fluoroquinolones examined, OFX, OBFX and CFX had this inhibition manner. As this inhibition is irreversible, inhibitory effects of the three fluoroquinolones may accumulate, when they are repeatedly administered. Therefore, OFX, OBFX and CFX may result in substantial drug-drug interaction with a CYP1A substrate even in clinical states. As EFX is metabolized to CFX in the body, it may also have the same possibility.

  15. Addition agents effects on hydrocarbon fuels burning

    NASA Astrophysics Data System (ADS)

    Larionov, V. M.; Mitrofanov, G. A.; Sakhovskii, A. V.

    2016-01-01

    Literature review on addition agents effects on hydrocarbon fuels burning has been conducted. The impact results in flame pattern and burning velocity change, energy efficiency increase, environmentally harmful NOx and CO emission reduction and damping of self-oscillations in flow. An assumption about water molecules dissociation phenomenon existing in a number of practical applications and being neglected in most explanations for physical- chemical processes taking place in case of injection of water/steam into combustion zone has been noted. The hypothesis about necessity of water dissociation account has been proposed. It can be useful for low temperature combustion process control and NOx emission reduction.

  16. Inhibitory effects of beryllium chloride on rat liver microsomal enzymes.

    PubMed

    Teixeira, C F; Yasaka, W J; Silva, L F; Oshiro, T T; Oga, S

    1990-04-30

    A single i.v. dose (0.1 mmol Be2+/kg) of beryllium chloride prolonged the duration of pentobarbital-induced sleep and zoxazolamine-induced paralysis, in rats. The effects are correlated with changes of the pharmacokinetic parameters and with the in vitro inhibition of both aliphatic and aromatic hydroxylation of pentobarbital and zoxazolamine. In vitro N-demethylation of meperidine and aminopyrine was partially inhibited while O-demethylation of quinidine was unaffected by liver microsomes of rats pretreated with beryllium salt. The findings give clues that beryllium chloride inhibits some forms of cytochrome P-450, especially those responsible for hydroxylation of substrates, like pentobarbital and zoxazolamine.

  17. Inhibitory effects of ethanol on phosphatidylinositol breakdown in pancreatic acini

    SciTech Connect

    Towner, S.J.; Peppin, J.F.; Tsukamoto, H.

    1986-03-01

    Recently the physiological relationship between the phospholipid effect and secretagogue-induced cellular function has begun to be understood. In this study, the authors investigated acute and chronic effects of ethanol on phosphatidylinositol (PI) synthesis and breakdown in pancreatic acini. Five pairs of male Wistar rats were intragastrically infused for 30 days with high fat diet (25% total calories) plus ethanol or isocaloric dextrose. After intoxication, isolated in HEPES media, followed by 30 min incubation with CCK-8 (0, 100, 300 or 600 pM) and ethanol (0 or 100 mM). Acinar lipids were extracted and counted for labeled PI. Incorporation of /sup 3/H-inositol into alcoholic acinar PI was reduced to 38.2% of that in controls. A percent maximal PI break down by CCK-8 was similar in the two groups (13-24% of basal). However, the magnitude of PI breakdown was markedly lower in alcoholic acini (482 vs 1081 dpm) due to the decreased PI synthesis rate. The presence of 100 mM ethanol in the media further inhibited the breakdown by 50% in this group. These results strongly indicate that chronic ethanol intoxication inhibits PI synthesis and breakdown in pancreatic acini, and that this inhibition can be potentiated by acute ethanol administration.

  18. The inhibitory effect of propofol on bovine lactoperoxidase.

    PubMed

    Sişecioğlu, Melda; Cankaya, Murat; Gülçin, Ilhami; Ozdemir, Hasan

    2009-01-01

    Propofol (2,6-diisopropylphenol) is a hypnotic intravenous agent with in vivo antioxidant properties. This study was undertaken to examine the in vitro effect of propofol on lactoperoxidase (LPO; E.C. 1.11.1.7) obtained from bovine milk. Lactoperoxidase was purified with three purification steps: Amberlite CG-50 resin, CM-Sephadex C-50 ion-exchange chromatography and Sephadex G-100 gel filtration chromatography, respectively. Lactoperoxidase was purified with a yield of 21.6%, a specific activity of 34 EU/mg proteins and 14.7-fold purification. One enzyme unit is defined as the oxidation of 1 micromol ABTS per min under the assay condition (25( degrees )C, pH: 6.0). To determine enzyme purity, sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) was performed and single band was observed. The effect of propofol on lactoperoxidase were determined using 2,2'-azino-bis (3-ethylbenzthiazoline-6 sulfonic acid) diammonium salt (ABTS) as a chromogenic substrate. The IC(50) value of propofol was found as 15.97 microM. Also, K(i) constant for propofol was 3.72 microM and propofol was found as competitive inhibitor.

  19. Inhibitory effects of Hedyotis diffusa Willd. on colorectal cancer stem cells

    PubMed Central

    SUN, GUODONG; WEI, LIHUI; FENG, JIANYU; LIN, JIUMAO; PENG, JUN

    2016-01-01

    Cancer stem cells (CSCs) are proposed to be closely correlated with the development and progression of tumors, as well as with chemo- and radioresistance. Targeting CSCs may therefore be a promising potential strategy for the treatment of cancer. Currently, natural products have received great interest due to their therapeutic efficacy and reduced adverse effects compared with modern chemotherapeutics. As a significant component of a number of traditional Chinese medicine formulas, the medicinal herb Hedyotis diffusa Willd. (HDW) has long been utilized in China to clinically treat a variety of malignancies, including colorectal cancer (CRC). Previously, the authors of the present study reported that HDW suppressed CRC growth through multiple mechanisms, including promoting apoptosis, and inhibiting cell proliferation and tumor angiogenesis. To additionally investigate its mode of action, the present study isolated a stem-like side population (SP) from colorectal cancer HT-29 cells to investigate the effect of ethanol extract of HDW on CSCs. It was observed that HDW was able to markedly downregulate the expression of CSC marker leucine-rich repeat-containing G-protein coupled receptor 5 and also significantly decrease the proportion of SP in HT-29 cells, in a dose-dependent manner. Furthermore, HDW treatment significantly and dose-dependently inhibited the viability and sphere formation, and induced cell morphological changes of isolated HT-29 SP cells. In addition, HDW greatly suppressed the messenger RNA expression of several critical genes that mediate CSC features, including ATP-binding cassette, sub-family B, member 1, β-catenin, c-Myc, proliferating cell nuclear antigen and survivin. In conclusion, the present study indicates that HDW may exert inhibitory effects on cancer stem cells. PMID:27313710

  20. Inhibitory effect of chondroitin sulfate oligosaccharides on bovine testicular hyaluronidase.

    PubMed

    Kakizaki, Ikuko; Koizumi, Hideyo; Chen, Fengchao; Endo, Masahiko

    2015-05-01

    Hyaluronan and chondroitin sulfates are prominent components of the extracellular matrices of animal tissues; however, their functions in relation to their oligosaccharide structures have not yet been fully elucidated. The oligosaccharides of hyaluronan and chondroitin sulfate were prepared and used to investigate their effects on the hydrolysis and transglycosylation reactions of bovine testicular hyaluronidase when hyaluronan was used as a substrate. Hydrolysis and transglycosylation activities were assessed in independent reaction systems by analyzing the products by HPLC. The hydrolysis and transglycosylation reactions of bovine testicular hyaluronidase were dose-dependently inhibited by chondroitin sulfate oligosaccharides, but not by hyaluronan or chondroitin oligosaccharides. A kinetic analysis of the hydrolysis reaction using hyaluronan octasaccharide revealed that the inhibition mode by chondroitin sulfate oligosaccharides was competitive.

  1. Inhibitory effects of cefotaxime on the activity of mushroom tyrosinase.

    PubMed

    Hu, Yong-Hua; Zhuang, Jiang-Xing; Yu, Feng; Cui, Yi; Yu, Wen-Wen; Yan, Chong-Ling; Chen, Qing-Xi

    2016-04-01

    Tyrosinase (EC 1.14.18.1) catalyzes both the hydroxylation of tyrosine into o-diphenols and the oxidation of o-diphenols into o-quinones that form brown or black pigments. In the present paper, cefotaxime, a cephalosporin antibacterial drug, was tested as an inhibitor of tyrosinase. The results show that cefotaxime inhibits both the monophenolase and diphenolase activities of tyrosinase. For the monophenolase activity, cefotaxime increased the lag time and decreased the steady-state activity with an IC50 of 3.2 mM. For the diphenolase activity, the inhibition by cefotaxime is reversible and mix-I type with an IC50 of 0.14 mM. The inhibition constants (K(I) and K(IS)) were determined to be 0.14 and 0.36 mM, respectively. The molecular mechanism of inhibition of tyrosinase by cefotaxime was determined by fluorescence quenching and molecular docking. The results demonstrated that cefotaxime was a static quencher of tyrosinase and that cefotaxime could dock favorably in the active site of tyrosinase. This research may offer a lead for designing and synthesizing novel and effective tyrosinase inhibitors in the future.

  2. Inhibitory effect of chlorogenic acid on digestion of potato starch.

    PubMed

    Karim, Zida; Holmes, Melvin; Orfila, Caroline

    2017-02-15

    The effect of the chlorogenic acid isomer 5-O-caffeoylquinic acid (5-CQA) on digestion of potato starch by porcine pancreatic alpha amylase (PPAA) was investigated using isolated starch and cooked potato tuber as substrates. In vitro digestion was performed on five varieties of potato with varying phenolic content. Co- and pre-incubation of PPAA with 5-CQA significantly reduced PPAA activity in a dose dependent manner with an IC50 value of about 2mgmL(-1). Lineweaver-Burk plots indicated that 5-CQA exerts a mixed type inhibition as km increased and Vmax decreased. The total polyphenol content (TPC) of peeled tuber tissue ranged from 320.59 to 528.94mg 100g(-1)dry weight (DW) in raw tubers and 282.03-543.96mg 100g(-1)DW in cooked tubers. With the exception of Désirée, TPC and 5-CQA levels decreased after cooking. Principle component analysis indicated that digestibility is affected by multiple factors including phenolic, dry matter and starch content. PMID:27664664

  3. Inhibitory effect of cucurbitacin B on imiquimod-induced skin inflammation

    SciTech Connect

    Li, Zheng Jun; Shin, Jung-Min; Choi, Dae-Kyoung; Lim, Seul Ki; Yoon, Tae-Jin; Lee, Young Ho; Sohn, Kyung-Cheol; Im, Myung; Lee, Young; Seo, Young-Joon; Kim, Chang Deok; Lee, Jeung-Hoon

    2015-04-17

    Psoriasis is a common skin disease, of which pathogenesis involves the increase of inflammatory reaction in epidermal cells. In an attempt to find therapeutics for psoriasis, we found that cucurbitacin B has an inhibitory potential on imiquimod-induced inflammation of keratinocytes. Cucurbitacin B significantly inhibited imiquimod-induced expression of crucial psoriatic cytokines, such as IL-8 and CCL20, via down-regulation of NF-κB and STAT3 signaling pathway in human keratinocytes. In addition, keratinocyte proliferation was markedly inhibited by cucurbitacin B. The potential beneficial effect of cucurbitacin B on psoriasis was further validated in imiquimod-induced psoriasiform dermatitis of experimental animal. Topical application of cucurbitacin B resulted in significant reduction of epidermal hyperplasia and inflammatory cytokines production, and ameliorated the psoriatic symptom. Taken together, these results suggest that cucurbitacin B may be a potential candidate for the treatment of psoriasis. - Highlights: • Cucurbitacin B has a potential for inhibiting the growth of keratinocytes. • Cucurbitacin B inhibits imiquimod-induced inflammatory reaction in keratinocytes. • Cucurbitacin B inhibits imiquimod-induced psoriasiform dermatitis in experimental animal.

  4. Inhibitory effects of hyssop (Hyssopus officinalis) extracts on intestinal alpha-glucosidase activity and postprandial hyperglycemia.

    PubMed

    Miyazaki, Hiroyuki; Matsuura, Hideyuki; Yanagiya, Chikako; Mizutani, Junya; Tsuji, Masayoshi; Ishihara, Chiaki

    2003-10-01

    It has been known that Hyssopus officinalis (hyssop) is a herb that grows in the wild and is a source of natural antioxidants. We previously reported that a-glucosidase inhibitors, (2S, 3S)1-O-beta-D-6'-O-cinnamoylglucopyranosyl-3-(3", 5"-dimethoxy-4"-hydroxyphenyl)-1,2,3-propanetriol and (2S, 3S)1-O-beta-D-glucopranosyl-3-(3", 5"-dimethoxy-4"-hydroxyphenyl)-1,2,3-propanetriol, from the dry leaves of hyssop, were isolated. This study examined the alpha-glucosidase inhibitory effects of hyssop extracts on intestinal carbohydrate absorption in rat everted gut sac and carbohydrate-loaded hyperglycemia in mice. In the everted gut sac experiment, 10 mM sucrose- and 5 mM maltose-treated increases in glucose concentration in the serosal compartment were inhibited in the presence of 0.5 and 1.0 mg/ mL hyssop extracts, although a 10 mM glucose-induced increase in serosal glucose was not inhibited by the extracts. Additionally, hyperglycemia in sucrose- and maltose-loaded mice was significantly suppressed at an early stage, within 30 to 60 min by oral pre-administration of 300 and 100 mg/kg hyssop extracts, respectively. These findings suggest that hyssop extracts inhibited the digestion of complex carbohydrates, but not that of absorbable monosaccharide, and might be a useful supplemental food for hyperglycemia.

  5. Inhibitory effect and enzymatic analysis of E-cinnamaldehyde against sclerotinia carrot rot.

    PubMed

    Ojaghian, Mohammad Reza; Wang, Qi; Li, Xiaolin; Sun, Xiaoting; Xie, Guan-Lin; Zhang, Jingze; Hai-Wei, Fan; Wang, Li

    2016-02-01

    This study was conducted to determine the inhibitory effect of E-cinnamaldehyde (EC) against causal agent of storage carrot rot, Sclerotinia sclerotiorum, under in vivo and in vitro conditions. Based on the results, EC was able to completely inhibit mycelial growth of three isolates (P>0.05) in both volatile and contact phases after 6days at the concentrations 200μl and 1μl/ml, respectively. In addition, EC at concentrations 1 and 10μl/ml completely inhibited carpogenic germination of three isolates. The results of in vivo trials showed that EC at the concentration of 10μl/ml was able to control the disease caused by isolates 1 and 3. However the disease caused by isolate 2 was inhibited with the concentration of 20μl/ml. In enzyme analyses, the activity of polyphenoloxidase and peroxidase did not change in the inoculated carrots after application of EC. Furthermore, the level of phenylalanine ammonia lyase decreased. These results indicated that EC does not have any potential to be considered as resistance inducers against sclerotinia carrot rot. PMID:26821652

  6. Inhibitory effects of hyssop (Hyssopus officinalis) extracts on intestinal alpha-glucosidase activity and postprandial hyperglycemia.

    PubMed

    Miyazaki, Hiroyuki; Matsuura, Hideyuki; Yanagiya, Chikako; Mizutani, Junya; Tsuji, Masayoshi; Ishihara, Chiaki

    2003-10-01

    It has been known that Hyssopus officinalis (hyssop) is a herb that grows in the wild and is a source of natural antioxidants. We previously reported that a-glucosidase inhibitors, (2S, 3S)1-O-beta-D-6'-O-cinnamoylglucopyranosyl-3-(3", 5"-dimethoxy-4"-hydroxyphenyl)-1,2,3-propanetriol and (2S, 3S)1-O-beta-D-glucopranosyl-3-(3", 5"-dimethoxy-4"-hydroxyphenyl)-1,2,3-propanetriol, from the dry leaves of hyssop, were isolated. This study examined the alpha-glucosidase inhibitory effects of hyssop extracts on intestinal carbohydrate absorption in rat everted gut sac and carbohydrate-loaded hyperglycemia in mice. In the everted gut sac experiment, 10 mM sucrose- and 5 mM maltose-treated increases in glucose concentration in the serosal compartment were inhibited in the presence of 0.5 and 1.0 mg/ mL hyssop extracts, although a 10 mM glucose-induced increase in serosal glucose was not inhibited by the extracts. Additionally, hyperglycemia in sucrose- and maltose-loaded mice was significantly suppressed at an early stage, within 30 to 60 min by oral pre-administration of 300 and 100 mg/kg hyssop extracts, respectively. These findings suggest that hyssop extracts inhibited the digestion of complex carbohydrates, but not that of absorbable monosaccharide, and might be a useful supplemental food for hyperglycemia. PMID:14703310

  7. Inhibitory effects of stress on postprandial gastric myoelectrical activity and vagal tone in healthy subjects.

    PubMed

    Yin, J; Levanon, D; Chen, J D Z

    2004-12-01

    The aim was to investigate gastric myoelectrical activity (GMA) and vagal activity in response to stress. The study was performed in 10 healthy subjects in three sessions (control, relaxation and stress). The control session was composed of 30-min recordings before and 30-min recordings after a test meal. The protocol of two other sessions was similar except that the fasting recording was extended to 60 min and the subjects were continuously watching a horror movie (stress) or guided meditation tape (relaxation) after the 30-min baseline. GMA was recorded using electrogastrography and heart rate variability (HRV) was derived from the electrocardiogram. Meal resulted in a postprandial increase in the dominant frequency (2.91 cpm vs 3.17 cpm, P < 0.007), dominant power (30.0 dB vs 32.5 dB, P < 0.05), and percentage of normal slow waves (79.8%vs 87.4%, P = 0.09). Similar responses were found in the relaxation session. Stress inhibited all these normal postprandial response and reduced the regularity of gastric slow waves (82.0%vs 66.0%, P < 0.01). In addition, spectral analysis of the HRV demonstrated an inhibition of postprandial vagal activity and an increase of postprandial sympathetic activity with stress. Stress has an inhibitory effect on postprandial GMA and this may involve both vagal and sympathetic pathway.

  8. High gravity and high cell density mitigate some of the fermentation inhibitory effects of softwood hydrolysates

    PubMed Central

    2013-01-01

    After steam pretreatment of lignocellulosic substrates the fermentation of the biomass derived sugars to ethanol is typically problematic because of both the generally low sugar concentrations that can be supplied and the presence of naturally occurring and process derived inhibitors. As the majority of the inhibitory materials are usually associated with the hemicellulose rich, water soluble component, this fraction was supplemented with glucose to simulate high solids, un-detoxified substrate to see if a high gravity/high cell consistency approach might better cope with inhibition. Several yeast strains were assessed, with the Tembec T1, T2 and Lallemand LYCC 6469 strains showing the greatest ethanol productivity and yield. The addition of supplemental glucose enabled the faster and quantitatively higher removal of hydroxymethylfurfural (HMF). High cell density could provide effective fermentation at high sugar concentrations while enhancing inhibitor reduction. A 77% ethanol yield could be achieved using strain LYCC 6469 after 48 h at high cell density. It was apparent that a high cell density approach improved ethanol production by all of the evaluated yeast strains. PMID:23410516

  9. Inhibitory Effects of Glycyrrhetinic Acid on DNA Polymerase and Inflammatory Activities

    PubMed Central

    Ishida, Tsukasa; Mizushina, Yoshiyuki; Yagi, Saori; Irino, Yasuhiro; Nishiumi, Shin; Miki, Ikuya; Kondo, Yasuyuki; Mizuno, Shigeto; Yoshida, Hiromi; Azuma, Takeshi; Yoshida, Masaru

    2012-01-01

    We investigated the inhibitory effect of three glycyrrhizin derivatives, such as Glycyrrhizin (compound 1), dipotassium glycyrrhizate (compound 2) and glycyrrhetinic acid (compound 3), on the activity of mammalian pols. Among these derivatives, compound 3 was the strongest inhibitor of mammalian pols α, β, κ, and λ, which belong to the B, A, Y, and X families of pols, respectively, whereas compounds 1 and 2 showed moderate inhibition. Among the these derivatives tested, compound 3 displayed strongest suppression of the production of tumor necrosis factor-α (TNF-α) induced by lipopolysaccharide (LPS) in a cell-culture system using mouse macrophages RAW264.7 and peritoneal macrophages derived from mice. Moreover, compound 3 was found to inhibit the action of nuclear factor-κB (NF-κB) in engineered human embryonic kidney (HEK) 293 cells. In addition, compound 3 caused greater reduction of 12-O-tetradecanoylphorbol-13-acetate-(TPA-) induced acute inflammation in mouse ear than compounds 1 and 2. In conclusion, this study has identified compound 3, which is the aglycone of compounds 1 and 2, as a promising anti-inflammatory candidate based on mammalian pol inhibition. PMID:21785649

  10. Inhibitory effect of aroma on the bitterness of branched-chain amino acid solutions.

    PubMed

    Mukai, Junji; Tokuyama, Emi; Ishizaka, Toshihiko; Okada, Sachie; Uchida, Takahiro

    2007-11-01

    Nutritional products for patients with liver failure available on the Japanese market contain many branched-chain amino acids (BCAAs) such as L-leucine, L-isoleucine, and L-valine, which not only have a bitter taste but also strong, unpleasant odours, leading to low palatability. The palatability of these nutritional products can be significantly improved by the addition of flavoured powders containing various kinds of tastants (sucrose, citric acid, etc.) and odourants (fruit, coffee aromas, etc.). The specific effects of the aroma of flavoured powders have not yet been clearly evaluated. In the present article, the inhibitory effect of aroma on the bitterness of BCAA solutions was examined. The bitterness intensity of a BCAA solution at the same concentration as Aminoleban EN was defined as 3.5 (measured by a previously described gustatory sensation method). The bitterness threshold of a BCAA standard solution without added aroma was estimated to be 1.87, while those of BCAA solutions containing green-tea, coffee, apple, vanilla, or strawberry aromas were 2.02, 1.98, 2.35, 2.40 and 2.87, respectively, when evaluated by the probit method. This shows that the addition of an aroma can elevate the bitterness threshold in human volunteers. The green-tea and coffee aromas predominantly evoked bitterness, while the vanilla aroma predominantly evoked sweetness. Apple and strawberry aromas evoked both sweetness and sourness, with the apple aroma having stronger sourness and the strawberry aroma stronger sweetness. Thus, a 'sweet' aroma suppresses the bitterness of BCAA, with coexisting sourness also participating in the bitterness inhibition.

  11. Effect of salts addition on hydrogen production by C. acetobutylicum.

    PubMed

    Alshiyab, H; Kalil, M S; Hamid, A A; Wan Yusoff, W M

    2008-09-15

    The objective of this study is to investigate the effect of salts addition to fermentation medium on hydrogen production, under anaerobic batch culture system. In this study, batch experiments were conducted to investigate the inhibitory effect of both NaCl and sodium acetate on hydrogen production. The optimum pH and temperature for hydrogen production were at initial pH of 7.0 and 30 degrees C. Enhanced production of hydrogen, using glucose as substrate was achieved. In the absence of Sodium Chloride and Sodium Acetate enhanced hydrogen yield (Y(P/S)) from 350 mL g(-1) glucose utilized to 391 mL g(-1) glucose utilized with maximum hydrogen productivity of 77.5 ml/L/h. Results also show that sodium chloride and sodium acetate in the medium adversely affect growth. Hydrogen yield per biomass (Y(P/X)) of 254 ml/L/g, biomass per substrate utilized (Y(X/S)) of 0.268 and (Y(H2/S) of 0.0349. The results suggested that Sodium at any concentration resulted to inhibit the bacterial productivity of hydrogen.

  12. Possible neurologic effects of aspartame, a widely used food additive.

    PubMed

    Maher, T J; Wurtman, R J

    1987-11-01

    The artificial sweetener aspartame (L-aspartyl-L-phenylalanyl-methyl ester), is consumed, primarily in beverages, by a very large number of Americans, causing significant elevations in plasma and, probably, brain phenylalanine levels. Anecdotal reports suggest that some people suffer neurologic or behavioral reactions in association with aspartame consumption. Since phenylalanine can be neurotoxic and can affect the synthesis of inhibitory monoamine neurotransmitters, the phenylalanine in aspartame could conceiveably mediate neurologic effects. If mice are given aspartame in doses that elevate plasma phenylalanine levels more than those of tyrosine (which probably occurs after any aspartame dose in humans), the frequency of seizures following the administration of an epileptogenic drug, pentylenetetrazole, is enhanced. This effect is simulated by equimolar phenylalanine and blocked by concurrent administration of valine, which blocks phenylalanine's entry into the brain. Aspartame also potentiates the induction of seizures by inhaled fluorothyl or by electroconvulsive shock. Perhaps regulations concerning the sale of food additives should be modified to require the reporting of adverse reactions and the continuing conduct of mandated safety research.

  13. Inhibitory effect of cyproheptadine on ACTH secretion in patients with Addison's disease.

    PubMed

    Loli, P; Frascatani, F; Gelli, D; Maggioni, M; Muratori, F; Ronzoni, M

    1983-01-01

    In 14 patients with Addison's disease plasma levels of ACTH were studied after administration of a single oral dose (16 mg) of cyproheptadine. The drug administration was followed by an inhibition of ACTH release. These results support the view that cyproheptadine may exert an inhibitory effect on ACTH secretion in subjects whose corticosteroid feedback mechanism is normal. We hypothesize that the effect of cyproheptadine might be related to its anti-serotonin or anti-histaminergic action.

  14. Incentive effect on inhibitory control in adolescents with early-life stress: an antisaccade study

    PubMed Central

    Mueller, Sven C.; Hardin, Michael G.; Korelitz, Katherine; Daniele, Teresa; Bemis, Jessica; Dozier, Mary; Peloso, Elizabeth; Maheu, Francoise; Pine, Daniel S.; Ernst, Monique

    2012-01-01

    Objective Early-life stress (ES) such as adoption, change of caregiver, or experience of emotional neglect [0]may influence the way in which affected individuals respond to emotional stimuli of positive or negative valence. These modified responses may stem from a direct alteration of how emotional stimuli are coded, and/or the cognitive function implicated in emotion modulation, such as self-regulation or inhibition. These ES effects have been probed on tasks either targeting reward and inhibitory function. Findings revealed deficits in both reward processing and inhibitory control in ES youths. However, no work has yet examined whether incentives can improve automatic response or inhibitory control in ES youths. Method To determine whether incentives would only improve self-regulated voluntary actions or generalize to automated motoric responses, participants were tested on a mixed eye movement task that included reflex-like prosaccades and voluntary controlled antisaccade eye movements. Seventeen adopted children (10 females, mean age 11.3 years) with a documented history of neglect and 29 typical healthy youths (16 females, mean age 11.9 years) performed the mixed prosaccade/antisaccade task during monetary incentive conditions or during no-incentive conditions. Results Across both saccade types, ES adolescents responded more slowly than controls. As expected, control participants committed fewer errors on antisaccades during the monetary incentive condition relative to the no-incentive condition. By contrast, ES youths failed to show this incentive-related improvement on inhibitory control. No significant incentive effects were found with prepotent prosaccades trials in either group. Finally, co-morbid psychopathology did not modulate the findings. Conclusions These data suggest that youths with experience of early stress exhibit deficient modulation of inhibitory control by reward processes, in tandem with a reward-independent deficit in preparation for both

  15. Impairment of inhibitory control processing related to acute psychotomimetic effects of cannabis.

    PubMed

    Bhattacharyya, Sagnik; Atakan, Z; Martin-Santos, R; Crippa, J A; Kambeitz, J; Malhi, S; Giampietro, V; Williams, S; Brammer, M; Rubia, K; Collier, D A; McGuire, P K

    2015-01-01

    Cannabis use can induce acute psychotic symptoms and increase the risk of schizophrenia. Impairments in inhibitory control and processing are known to occur both under the influence of cannabis and in schizophrenia. Whether cannabis-induced impairment in inhibitory processing is related to the acute induction of psychotic symptoms under its influence is unclear. We investigated the effects of acute oral administration of 10mg of delta-9-tetrahydrocannabinol (delta-9-THC), the main psychoactive ingredient of cannabis, on inhibitory control and regional brain activation during inhibitory processing in humans and examined whether these effects are related to the induction of psychotic symptoms under its influence using a repeated-measures, placebo-controlled, double-blind, within-subject design. We studied thirty-six healthy, English-speaking, right-handed men with minimal previous exposure to cannabis and other illicit drugs twice using functional magnetic resonance imaging (fMRI) while they performed a response inhibition (Go/No-Go) task. Relative to placebo, delta-9-THC caused transient psychotic symptoms, anxiety, intoxication and sedation, inhibition errors and impaired inhibition efficiency. Severity of psychotic symptoms was directly correlated with inhibition error frequency and inversely with inhibition efficiency under the influence of delta-9-THC. Delta-9-THC attenuated left inferior frontal activation which was inversely correlated with the frequency of inhibition errors and severity of psychotic symptoms and positively with inhibition efficiency under its influence. These results provide experimental evidence that impairments in cognitive processes involved in the inhibitory control of thoughts and actions and inferior frontal function under the influence of cannabis may have a role in the emergence of transient psychotic symptoms under its influence.

  16. Impairment of inhibitory control processing related to acute psychotomimetic effects of cannabis.

    PubMed

    Bhattacharyya, Sagnik; Atakan, Z; Martin-Santos, R; Crippa, J A; Kambeitz, J; Malhi, S; Giampietro, V; Williams, S; Brammer, M; Rubia, K; Collier, D A; McGuire, P K

    2015-01-01

    Cannabis use can induce acute psychotic symptoms and increase the risk of schizophrenia. Impairments in inhibitory control and processing are known to occur both under the influence of cannabis and in schizophrenia. Whether cannabis-induced impairment in inhibitory processing is related to the acute induction of psychotic symptoms under its influence is unclear. We investigated the effects of acute oral administration of 10mg of delta-9-tetrahydrocannabinol (delta-9-THC), the main psychoactive ingredient of cannabis, on inhibitory control and regional brain activation during inhibitory processing in humans and examined whether these effects are related to the induction of psychotic symptoms under its influence using a repeated-measures, placebo-controlled, double-blind, within-subject design. We studied thirty-six healthy, English-speaking, right-handed men with minimal previous exposure to cannabis and other illicit drugs twice using functional magnetic resonance imaging (fMRI) while they performed a response inhibition (Go/No-Go) task. Relative to placebo, delta-9-THC caused transient psychotic symptoms, anxiety, intoxication and sedation, inhibition errors and impaired inhibition efficiency. Severity of psychotic symptoms was directly correlated with inhibition error frequency and inversely with inhibition efficiency under the influence of delta-9-THC. Delta-9-THC attenuated left inferior frontal activation which was inversely correlated with the frequency of inhibition errors and severity of psychotic symptoms and positively with inhibition efficiency under its influence. These results provide experimental evidence that impairments in cognitive processes involved in the inhibitory control of thoughts and actions and inferior frontal function under the influence of cannabis may have a role in the emergence of transient psychotic symptoms under its influence. PMID:25532865

  17. Additives

    NASA Technical Reports Server (NTRS)

    Smalheer, C. V.

    1973-01-01

    The chemistry of lubricant additives is discussed to show what the additives are chemically and what functions they perform in the lubrication of various kinds of equipment. Current theories regarding the mode of action of lubricant additives are presented. The additive groups discussed include the following: (1) detergents and dispersants, (2) corrosion inhibitors, (3) antioxidants, (4) viscosity index improvers, (5) pour point depressants, and (6) antifouling agents.

  18. Inhibitory Effect of Alpha-Mangostin on Adhesion of Candida albicans to Denture Acrylic

    PubMed Central

    Kaomongkolgit, Ruchadaporn; Jamdee, Kusuma

    2015-01-01

    Objective: Candida-associated denture stomatitis is a very common disease affecting denture wearers. It is characterized by the presence of yeast biofilm on the denture, primarily associated with C. albicans. The investigation of agents that can reduce C. albicans adhesion may represent a significant advancement in the prevention and treatment of this disease. This study aims to investigate the effect of alpha-mangostin on the in vitro adhesion of C. albicans to denture acrylic and germ tube formation by C. albicans and to compare its activity with clotrimazole which is a topical antifungal agent commonly used for the treatment of Candida-associated denture stomatitis. Materials and Methodology: Alpha-mangostin was extracted by thin layer chromatography. The effect of alpha-mangostin on adhesion of C. albicans to denture acrylic was determined by using a colorimetric tetrazolium assay and germ tube formation by C. albicans was determined by using the counting chamber. Results: A significant reduction of C. albicans adhesion to denture acrylic was evident after exposure to 2,000 µg/ml of alpha-mangostin for only 15 min. In addition, the 2,000 µg/ml of the alpha-mangostin-treated C. albicans had a reduced ability for germ tube formation. These inhibitory effects of alpha-mangostin were as effective as clotrimazole. Conclusion: Alpha-mangostin has antifungal property against C. albicans by inhibiting the adhesion to denture acrylic and germ tube formation in vitro. These results suggest the potential application of alpha-mangostin as a topical medication or a natural oral hygiene product for treatment of Candida-associated denture stomatitis. PMID:26962371

  19. Specific inhibitory effects of the NO donor MAHMA/NONOate on human platelets.

    PubMed

    Kobsar, Anna; Simonis, Sandra; Klinker, Erdwine; Koessler, Angela; Kuhn, Sabine; Boeck, Markus; Koessler, Juergen

    2014-07-15

    Nitric oxide (NO) is a physiological inhibitor of platelet function and has vaso-dilating effects. Therefore, synthesized NO releasing agents are used e.g. in cardiovascular medicine. The aim of this study was to characterise specific effects of the short living agent MAHMA/NONOate, a NO donor of the diazeniumdiolate class, on human platelets. Whole blood was obtained from healthy volunteers. In washed human platelets, the MAHMA/NONOate induced phosphorylation of the vasodilator-stimulated phosphoprotein (VASP) and cyclic nucleotide production were studied by Western Blot and by enzyme immunoassay kits. Agonist induced aggregation was measured in platelet rich plasma. Paired Student׳s t-test was used for statistical analysis. MAHMA/NONOate significantly stimulated platelet VASP phosphorylation in a concentration dependent manner and increased intracellular cGMP, but not cAMP levels, transiently. ODQ, a specific inhibitor of the soluble guanylyl cyclase, completely prevented VASP phosphorylation induced by low MAHMA/NONOate concentrations (5nM-15nM). The effects of higher concentrations (30-200nM) were only partially inhibited by ODQ. MAHMA/NONOate reduced platelet aggregation induced by low doses of agonists (2µM ADP, 0.5µg/mL collagen, 5µM TRAP-6) in a concentration dependent manner. MAHMA/NONOate leads to a rapid and transient activation of platelet inhibitory systems, accompanied by decreased platelet aggregation induced by low dose agonists. At low MAHMA/NONOate concentrations, the effects are cGMP dependent and at higher concentrations additionally cGMP independent. The substance could be of interest for clinical situations requiring transient and subtotal inhibition of platelet function. PMID:24780647

  20. Essential Oils from Ugandan Aromatic Medicinal Plants: Chemical Composition and Growth Inhibitory Effects on Oral Pathogens.

    PubMed

    Ocheng, Francis; Bwanga, Freddie; Joloba, Moses; Softrata, Abier; Azeem, Muhammad; Pütsep, Katrin; Borg-Karlson, Anna-Karin; Obua, Celestino; Gustafsson, Anders

    2015-01-01

    The study assessed the growth inhibitory effects of essential oils extracted from ten Ugandan medicinal plants (Bidens pilosa, Helichrysum odoratissimum, Vernonia amygdalina, Hoslundia opposita, Ocimum gratissimum, Cymbopogon citratus, Cymbopogon nardus, Teclea nobilis, Zanthoxylum chalybeum, and Lantana trifolia) used traditionally in the management of oral diseases against oral pathogens. Chemical compositions of the oils were explored by GC-MS. Inhibitory effects of the oils were assessed on periodontopathic Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans and cariogenic Streptococcus mutans and Lactobacillus acidophilus using broth dilution methods at concentrations of 1%, 0.1%, and 0.01%. The most sensitive organism was A. actinomycetemcomitans. Its growth was markedly inhibited by six of the oils at all the concentrations tested. Essential oil from C. nardus exhibited the highest activity with complete growth inhibition of A. actinomycetemcomitans and P. gingivalis at all the three concentrations tested, the major constituents in the oil being mainly oxygenated sesquiterpenes. Most of the oils exhibited limited effects on L. acidophilus. We conclude that essential oils from the studied plants show marked growth inhibitory effects on periodontopathic A. actinomycetemcomitans and P. gingivalis, moderate effects on cariogenic S. mutans, and the least effect on L. acidophilus. The present study constitutes a basis for further investigations and development of certain oils into alternative antiplaque agents. PMID:26170872

  1. Inhibitory Effect of Long-Chain Fatty Acids on Biogas Production and the Protective Effect of Membrane Bioreactor

    PubMed Central

    Dasa, Kris Triwulan; Westman, Supansa Y.; Cahyanto, Muhammad Nur; Niklasson, Claes

    2016-01-01

    Anaerobic digestion of lipid-containing wastes for biogas production is often hampered by the inhibitory effect of long-chain fatty acids (LCFAs). In this study, the inhibitory effects of LCFAs (palmitic, stearic, and oleic acid) on biogas production as well as the protective effect of a membrane bioreactor (MBR) against LCFAs were examined in thermophilic batch digesters. The results showed that palmitic and oleic acid with concentrations of 3.0 and 4.5 g/L resulted in >50% inhibition on the biogas production, while stearic acid had an even stronger inhibitory effect. The encased cells in the MBR system were able to perform better in the presence of LCFAs. This system exhibited a significantly lower percentage of inhibition than the free cell system, not reaching over 50% at any LCFA concentration tested. PMID:27699172

  2. Inhibitory Effect of Long-Chain Fatty Acids on Biogas Production and the Protective Effect of Membrane Bioreactor

    PubMed Central

    Dasa, Kris Triwulan; Westman, Supansa Y.; Cahyanto, Muhammad Nur; Niklasson, Claes

    2016-01-01

    Anaerobic digestion of lipid-containing wastes for biogas production is often hampered by the inhibitory effect of long-chain fatty acids (LCFAs). In this study, the inhibitory effects of LCFAs (palmitic, stearic, and oleic acid) on biogas production as well as the protective effect of a membrane bioreactor (MBR) against LCFAs were examined in thermophilic batch digesters. The results showed that palmitic and oleic acid with concentrations of 3.0 and 4.5 g/L resulted in >50% inhibition on the biogas production, while stearic acid had an even stronger inhibitory effect. The encased cells in the MBR system were able to perform better in the presence of LCFAs. This system exhibited a significantly lower percentage of inhibition than the free cell system, not reaching over 50% at any LCFA concentration tested.

  3. Inhibitory effect of Salicornia europaea on the marine alga Skeletonema costatum.

    PubMed

    Jiang, Dan; Huang, Lingfeng; Lin, Yongqing; Nie, Lingling; Lv, Sulian; Kuang, Tingyun; Li, Yinxin

    2012-06-01

    Exploiting the negative biochemical interference between plants and algal species has been suggested as a method to control harmful algal blooms. In this work, we investigated the inhibitory effect of the salt marsh halophyte Salicornia europaea against the marine alga Skeletonema costatum. S. europaea suppressed the growth of S. costatum in a nutrient-sufficient co-culture system, indicating that the inhibition of algal growth was because of the phytotoxic effect of S. europaea, rather than nutrient competition. We tested aqueous and organic extracts from S. europaea roots against S. costatum. The organic extracts inhibited growth and affected the cell size and chlorophyll a content of S. costatum in a dose-dependent manner. Among the three tested organic extracts, the methanol extract had the greatest effects on S. costatum, followed by butanol extract, and then the chloroform extract. Two flavonoids, rutin and quercetin-3-β-D-glucoside, were identified in the methanol extract by high performance liquid chromatography. The concentration of rutin was much higher than that of quercetin-3-β-D-glucoside. In an algal bioassay, rutin inhibited the growth of S. costatum and the inhibitory effect increased with increasing rutin concentration and with decreasing initial algal density. Therefore, we concluded that S. europaea negatively affects the growth of S. costatum, and that rutin, a metabolite of S. europaea, may play a role in this inhibitory effect. PMID:22744186

  4. Inhibitory effects of Ruta graveolens L. extract on guinea pig liver aldehyde oxidase.

    PubMed

    Pirouzpanah, Saieed; Saieed, Pirouzpanah; Rashidi, Mohammad Reza; Reza, Rashidi Mohammad; Delazar, Abbas; Abbas, Delazar; Razavieh, Seyyed-Vali; Seyyedvali, Razavieh; Hamidi, Aliasghar; Aliasghar, Hamidi

    2006-01-01

    Ruta graveolens L. is a flavonoid-containing medicinal plant with various biological properties. In the present study, the effects of R. graveolens extract on aldehyde oxidase, a molybdenum hydroxylase, are investigated. Aldehyde oxidase was partially purified from liver homogenates of mature male guinea pigs by heat treatment and ammonium sulphate precipitation. The total extract was obtained by macerating the aerial parts of R. graveolens in MeOH 70% and the effect of this extract on the enzyme activity was assayed using phenanthridine, vanillin and benzaldehyde as substrates. Quercetin and its glycoside form, rutin were isolated, purified and identified from the extract and their inhibitory effects on the enzyme were investigated. R. graveolens extract exhibited a high inhibition on aldehyde oxidase activity (89-96%) at 100 microg/ml which was comparable with 10 microM of menadione, a specific potent inhibitor of aldehyde oxidase. The IC50 values for the inhibitory effect of extract against the oxidation of benzaldehyde, vanillin and phenanthridine were 10.4, 10.1, 43.2 microg/ml, respectively. Both quercetin and rutin at 10 microM caused 70-96% and 27-52% inhibition on the enzyme activity, respectively. Quercetin was more potent inhibitor than rutin, but both flavonols exerted their inhibitory effects mostly in a linear mixed-type.

  5. Effect of Jatropha curcas Peptide Fractions on the Angiotensin I-Converting Enzyme Inhibitory Activity

    PubMed Central

    Segura-Campos, Maira R.; Peralta-González, Fanny; Castellanos-Ruelas, Arturo; Chel-Guerrero, Luis A.; Betancur-Ancona, David A.

    2013-01-01

    Hypertension is one of the most common worldwide diseases in humans. Angiotensin I-converting enzyme (ACE) plays an important role in regulating blood pressure and hypertension. An evaluation was done on the effect of Alcalase hydrolysis of defatted Jatropha curcas kernel meal on ACE inhibitory activity in the resulting hydrolysate and its purified fractions. Alcalase exhibited broad specificity and produced a protein hydrolysate with a 21.35% degree of hydrolysis and 34.87% ACE inhibition. Ultrafiltration of the hydrolysate produced peptide fractions with increased biological activity (24.46–61.41%). Hydrophobic residues contributed substantially to the peptides' inhibitory potency. The 5–10 and <1 kDa fractions were selected for further fractionation by gel filtration chromatography. ACE inhibitory activity (%) ranged from 22.66 to 45.96% with the 5–10 kDa ultrafiltered fraction and from 36.91 to 55.83% with the <1 kDa ultrafiltered fraction. The highest ACE inhibitory activity was observed in F2 (IC50 = 6.7 μg/mL) from the 5–10 kDa fraction and F1 (IC50 = 4.78 μg/mL) from the <1 kDa fraction. ACE inhibitory fractions from Jatropha kernel have potential applications in alternative hypertension therapies, adding a new application for the Jatropha plant protein fraction and improving the financial viability and sustainability of a Jatropha-based biodiesel industry. PMID:24224169

  6. Paradoxical inhibitory effect of cromakalim on sup 86 Rb outflow from pancreatic islet cells

    SciTech Connect

    Lebrun, P.; Antoine, M.H.; Devreux, V.; Hermann, M.; Herchuelz, A. )

    1990-12-01

    Cromakalim appears to be the most potent pharmacologic agent belonging to the new class of smooth muscle relaxants: the K+ channel openers. The present study aimed at characterizing the effects of cromakalim on 86Rb outflow, 45Ca outflow and insulin release from prelabeled and perifused rat pancreatic islets. Cromakalim provoked a concentration-dependent reduction in 86Rb outflow. This inhibitory effect was attenuated in islets exposed throughout to glibenclamide or to a Ca+(+)-free medium. In islets exposed to glucose and extracellular Ca++, cromakalim induced a dose-dependent reduction in 45Ca outflow. The drug also inhibited the increase in 45Ca outflow mediated by K+ depolarization. Lastly, cromakalim elicited a concentration-dependent inhibition of insulin release from islets perifused in the presence of glucose and extracellular Ca++. The present data suggest that the paradoxical inhibitory effect of cromakalim on 86Rb outflow probably reflects the capacity of the drug to reduce the activity of the ATP-sensitive K+ channels and to indirectly inhibit the Ca+(+)-activated K+ channels. Furthermore, the cromakalim-induced changes in 45Ca outflow are compatible with an inhibitory effect of the drug on the voltage-dependent Ca++ channels.

  7. Effects of lipids on thermophilic anaerobic digestion and reduction of lipid inhibition upon addition of bentonite.

    PubMed

    Angelidaki, I; Petersen, S P; Ahring, B K

    1990-07-01

    The effect of bentonite-bound oil on thermophilic anaerobic digestion of cattle manure was investigated. In digestor experiments, addition of oil was found to be inhibitory during start-up and the inhibitory effect was less pronounced when the oil was added in the form of bentonite-bound oil compared to when the oil was added alone. After adaptation of the digestors, very rapid degradation of oil was observed and more than 80% of the oil was degraded within a few hours after daily feeding. In batch experiments, glyceride trioleate was found to be inhibitory to thermophilic anaerobic digestion when the concentrations were higher than 2.0 g/l. However, addition of bentonite (a clay mineral) at concentrations of 0.15% and 0.45% was found to partly overcome this inhibition. Addition of calcium chloride in concentration of 3 mM (0.033% w/v) showed a similar positive effect on the utilization of oil, but the effect was lower than with bentonite. PMID:1366749

  8. Anaerobic biodegradability and inhibitory effects of some anionic and cationic surfactants.

    PubMed

    Pérez-Armendáriz, Beatriz; Moreno, Yésica Mayett; Monroy-Hermosillo, Oscar; Guyot, Jean Pierre; González, Rosa O

    2010-09-01

    The anaerobic biodegradability and inhibitory effects on the methane production of three different surfactants, two anionic: sodium lauryl sulfate (SLS) and sodium dodecylbenzene sulfonate (SDBS), and a cationic surfactant: trialkyl-methylammonium chloride (TMAC), were evaluated with two different anaerobic sludges, granular and flocculent. Five different concentrations of the surfactants, 5, 50, 100, 250 and 500 mg/L, were tested. SLS was biodegraded at concentrations of 5, 50 and 100 mg/L with flocculent sludge and at 100 and 250 mg/L with granular sludge. However an inhibitory effect on methane production was observed in both sludges at 500 mg/L. The results indicate that SDBS was not biodegradable under anoxic conditions. TMAC was slightly degraded 50 and 100 mg/L with the flocculent sludge, and from 100 to 500 mg/L with the granular sludge.

  9. Inhibitory effect of vanillin on cellulase activity in hydrolysis of cellulosic biomass.

    PubMed

    Li, Yun; Qi, Benkun; Wan, Yinhua

    2014-09-01

    Pretreatment of lignocellulosic material produces a wide variety of inhibitory compounds, which strongly inhibit the following enzymatic hydrolysis of cellulosic biomass. Vanillin is a kind of phenolics derived from degradation of lignin. The effect of vanillin on cellulase activity for the hydrolysis of cellulose was investigated in detail. The results clearly showed that vanillin can reversibly and non-competitively inhibit the cellulase activity at appropriate concentrations and the value of IC50 was estimated to be 30 g/L. The inhibition kinetics of cellulase by vanillin was studied using HCH-1 model and inhibition constants were determined. Moreover, investigation of three compounds with similar structure of vanillin on cellulase activity demonstrated that aldehyde group and phenolic hydroxyl groups of vanillin had inhibitory effect on cellulase. These results provide valuable and detailed information for understanding the inhibition of lignin derived phenolics on cellulase.

  10. Evaluation of the effect of Thai breadfruit's heartwood extract on melanogenesis-inhibitory and antioxidation activities.

    PubMed

    Donsing, Piyaporn; Limpeanchob, Nanteetip; Viyoch, Jarupa

    2008-01-01

    The aim of this study was to clarify the melanogenesis-inhibitory and antioxidant activity of Thai breadfruit's heartwood extract for application as a skin-lightening agent. The heartwood of breadfruit (Artocarpus incisus ) grown in Phitsanulok Province, Thailand, was extracted by using diethyl ether or methanol. The amount of artocarpin, a major component of A. incisus extract, was determined by using the HPLC method. The artocarpin content found in ether extract was 45.19 +/- 0.45% w/w, whereas that in methanol extract was 19.61 +/- 0.05% w/w. The ether extract was then evaluated for tyrosinase-inhibitory, melanogenesis-inhibitory, and antioxidant activities. The tyrosinase-inhibitory activity was tested in vitro by monitoring the inhibition of the extract against the formation of DOPAchrome by tyrosinase enzyme. The results showed that the tyrosinase-inhibitory activity of the extract was in a dose-dependent manner. The obtained IC50 value was 10.26 +/- 3.04 microg/ml, while kojic acid, a well-known tyrosinase inhibitor, provided an IC50 of 7.89 +/- 0.18 microg/ml. Melanocyte B16F1 melanoma cells (ATCC No. CRL-6323) were then used for determination of the melanogenesis-inhibitory activity of the extract, comparing it to hydroquinone, kojic acid, and purified artocarpin. The amount of melanin produced by the cells was monitored by measuring an absorbence at 490 nm. The obtained results indicated that A. incisus extract at a concentration of 2 to 25 microg/ml was able to decrease the melanin production of the melanocyte B16F1 cells. The obtained micrograph also confirmed that the extract did not change the cell morphology but reduced the melanin content by inhibiting melanin synthesis, whereas the purified artocarpin at a concentration of 4.5 microg/ml caused changes in cell morphology. Additionally, the extract exhibited antioxidant activity in a dose-dependent manner at an EC50 of 169.53 +/- 9.73 microg/ml, according to DPPH assay. The obtained results indicated

  11. Inhibitory effects of propofol on excitatory synaptic transmission in supraoptic nucleus neurons in vitro.

    PubMed

    Zhang, Huan-Huan; Zheng, Chao; Wang, Bang-An; Wang, Meng-Ya

    2015-12-25

    The present study was designed to investigate the inhibitory effects of intravenous general anesthetic propofol (0.1-3.0 mmol/L) on excitatory synaptic transmission in supraoptic nucleus (SON) neurons of rats, and to explore the underlying mechanisms by using intracellular recording technique and hypothalamic slice preparation. It was observed that stimulation of the dorsolateral region of SON could elicit the postsynaptic potentials (PSPs) in SON neurons. Of the 8 tested SON neurons, the PSPs of 7 (88%, 7/8) neurons were decreased by propofol in a concentration-dependent manner, in terms of the PSPs' amplitude (P < 0.01), area under curve, duration, half-width and 10%-90% decay time (P < 0.05). The PSPs were completely and reversibly abolished by 1.0 mmol/L propofol at 2 out of 7 tested cells. The depolarization responses induced by pressure ejection of exogenous glutamate were reversibly and concentration-dependently decreased by bath application of propofol. The PSPs and glutamate-induced responses recorded simultaneously were reversibly and concentration-dependently decreased by propofol, but 0.3 mmol/L propofol only abolished PSPs. The excitatory postsynaptic potentials (EPSPs) of 7 cells increased in the condition of picrotoxin (30 µmol/L, a GABA(A) receptor antagonist) pretreatment. On this basis, the inhibitory effects of propofol on EPSPs were decreased. These data indicate that the presynaptic and postsynaptic mechanisms may be both involved in the inhibitory effects of propofol on excitatory synaptic transmission in SON neurons. The inhibitory effects of propofol on excitatory synaptic transmission of SON neurons may be related to the activation of GABA(A) receptors, but at a high concentration, propofol may also act directly on glutamate receptors.

  12. Guaiane-type sesquiterpenes from Curcuma wenyujin and their inhibitory effects on nitric oxide production.

    PubMed

    Lou, Yan; Zhao, Feng; He, Hao; Peng, Kai-Feng; Zhou, Xiao-Hua; Chen, Li-Xia; Qiu, Feng

    2009-08-01

    Four new guaiane-type sesquiterpenes (1S,4S,5S,10R)-zedoarondiol, zedoalactones D, E, and F (1-4), along with 10 known ones (5-14), were isolated from Curcuma wenyujin Y.H. Chen et C. Ling. The structures of these new compounds were elucidated by spectroscopic methods. The inhibitory effects of compounds 1-14 on nitric oxide production in lipopolysaccharide-activated macrophages were evaluated. PMID:20183317

  13. Inhibitory effect of antioxidant-rich marinades on the formation of heterocyclic aromatic amines in pan-fried beef.

    PubMed

    Viegas, Olga; Amaro, L Filipe; Ferreira, Isabel M P L V O; Pinho, Olívia

    2012-06-20

    The inhibitory effect of antioxidant-rich marinades containing beer and white wine (with/without alcohol) alone or mixed with herbs commonly used as meat flavoring (garlic, ginger, thyme, rosemary, and red chili pepper) on the formation of heterocyclic aromatic amines (HAs) in pan-fried beef was studied. Radical-scavenging activity was evaluated by DPPH assay, before the addition of meat to the marinade (T0) and after 4 h of meat marinating (T4). At T0, wine with herbs possessed the highest scavenging activity (73.5%), followed by wine (72.5%), dealcoholized wine with herbs (53.4%), beer and herbs (41.7%), dealcoholized wine (39.6%), and beer (25.9%). At T4, a decrease in the radical-scavenging activity of all marinades was observed, although with a similar radical-scavenging profile. All of the six marinades under the study reduced the total amount of HAs, keeping meat with good overall sensory quality. Beer marinades were more efficient than white wine marinades, and the addition of herbs provided a superior inhibitory effect, reducing around 90% of HAs. No correlation was observed between radical-scavenging activity of marinades and total or individual HAs formation. Herbs explained around 30% of inhibition of PhIP formation, whereas alcohol increased PhIP formation.

  14. Inhibitory effect of antioxidant-rich marinades on the formation of heterocyclic aromatic amines in pan-fried beef.

    PubMed

    Viegas, Olga; Amaro, L Filipe; Ferreira, Isabel M P L V O; Pinho, Olívia

    2012-06-20

    The inhibitory effect of antioxidant-rich marinades containing beer and white wine (with/without alcohol) alone or mixed with herbs commonly used as meat flavoring (garlic, ginger, thyme, rosemary, and red chili pepper) on the formation of heterocyclic aromatic amines (HAs) in pan-fried beef was studied. Radical-scavenging activity was evaluated by DPPH assay, before the addition of meat to the marinade (T0) and after 4 h of meat marinating (T4). At T0, wine with herbs possessed the highest scavenging activity (73.5%), followed by wine (72.5%), dealcoholized wine with herbs (53.4%), beer and herbs (41.7%), dealcoholized wine (39.6%), and beer (25.9%). At T4, a decrease in the radical-scavenging activity of all marinades was observed, although with a similar radical-scavenging profile. All of the six marinades under the study reduced the total amount of HAs, keeping meat with good overall sensory quality. Beer marinades were more efficient than white wine marinades, and the addition of herbs provided a superior inhibitory effect, reducing around 90% of HAs. No correlation was observed between radical-scavenging activity of marinades and total or individual HAs formation. Herbs explained around 30% of inhibition of PhIP formation, whereas alcohol increased PhIP formation. PMID:22642699

  15. Uptake of dexamethasone incorporated into liposomes by macrophages and foam cells and its inhibitory effect on cellular cholesterol ester accumulation.

    PubMed

    Chono, Sumio; Morimoto, Kazuhiro

    2006-09-01

    To confirm the efficacy of dexamethasone incorporated into liposomes in the treatment of atherosclerosis, the uptake of dexamethasone-liposomes by macrophages and foam cells and its inhibitory effect on cellular cholesterol ester accumulation in these cells were investigated in-vitro. Dexamethasone-liposomes were prepared with egg yolk phosphatidylcholine, cholesterol and dicetylphosphate in a lipid molar ratio of 7/2/1 by the hydration method. This was adjusted to three different particle sizes to clarify the influence of particle size on the uptake by the macrophages and foam cells, and the inhibitory effect on cellular cholesterol ester accumulation. The distribution of particle sizes of dexamethasone-liposomes were 518.7+/-49.5 nm (L500), 202.2+/-23.1 nm (L200), and 68.6+/-6.5 nm (L70), respectively. For each size, dexamethasone concentration and dexamethasone/lipid molar ratio in dexamethasone-liposome suspension were 1 mg dexamethasone mL-1 and 0.134 mol dexamethasone mol-1 total lipids, respectively. The zeta potential was approximately -70 mV for all sizes. Dexamethasone-liposomes or free dexamethasone were added to the macrophages in the presence of oxidized low density lipoprotein (oxLDL) and foam cells, and then incubated at 37 degrees C. The uptake amount of dexamethasone by the macrophages and foam cells after a 24-h incubation was L500>L200>free dexamethasone>L70. The macrophages in the presence of oxLDL and foam cells were incubated with dexamethasone-liposomes or free dexamethasone for 24 h at 37 degrees C to evaluate the inhibitory effect on the cellular cholesterol ester accumulation. The cellular cholesterol ester level in the macrophages treated with oxLDL was significantly increased compared with that in macrophages without additives. L500, L200 and free dexamethasone significantly inhibited this cholesterol ester accumulation. L500, L200 and free dexamethasone also significantly reduced cellular cholesterol ester accumulation in foam cells. In

  16. Acute neuropharmacological effects of atomoxetine on inhibitory control in ADHD children: a fNIRS study.

    PubMed

    Nagashima, Masako; Monden, Yukifumi; Dan, Ippeita; Dan, Haruka; Tsuzuki, Daisuke; Mizutani, Tsutomu; Kyutoku, Yasushi; Gunji, Yuji; Hirano, Daisuke; Taniguchi, Takamichi; Shimoizumi, Hideo; Momoi, Mariko Y; Watanabe, Eiju; Yamagata, Takanori

    2014-01-01

    The object of the current study is to explore the neural substrate for effects of atomoxetine (ATX) on inhibitory control in school-aged children with attention deficit hyperactivity disorder (ADHD) using functional near-infrared spectroscopy (fNIRS). We monitored the oxy-hemoglobin signal changes of sixteen ADHD children (6-14 years old) performing a go/no-go task before and 1.5 h after ATX or placebo administration, in a randomized, double-blind, placebo-controlled, crossover design. Sixteen age- and gender-matched normal controls without ATX administration were also monitored. In the control subjects, the go/no-go task recruited the right inferior and middle prefrontal gyri (IFG/MFG), and this activation was absent in pre-medicated ADHD children. The reduction of right IFG/MFG activation was acutely normalized after ATX administration but not placebo administration in ADHD children. These results are reminiscent of the neuropharmacological effects of methylphenidate to up-regulate reduced right IFG/MFG function in ADHD children during inhibitory tasks. As with methylphenidate, activation in the IFG/MFG could serve as an objective neuro-functional biomarker to indicate the effects of ATX on inhibitory control in ADHD children. This promising technique will enhance early clinical diagnosis and treatment of ADHD in children, especially in those with a hyperactivity/impulsivity phenotype.

  17. Inhibitory effects of H2-receptor antagonists on cytochrome P450 in male ICR mice.

    PubMed

    Kim, D H; Kim, E J; Han, S S; Roh, J K; Jeong, T C; Park, J H

    1995-08-01

    1. The present study was undertaken to examine the effects of H2-receptor antagonists including newly developed mifentidine derivatives, IY-80843 and IY-80845, on cytochrome P450(P450) in vitro and in vivo. 2. Initially, 3-methylcholanthrene-, phenobarbital-, ethanol- and dexamethasone-induced liver microsomes were prepared from male ICR mice to study in vitro effects of above chemicals on ethoxyresorufin O-deethylase(EROD), pentoxyresorufin O-dealkylase(PROD), p-nitrophenol hydroxylase and erythromycin N-demethylase(ERDM) activities, respectively. It was found that histamine, cimetidine and famotidine were not inhibitory to four enzyme activities. Meanwhile, mifentidine slightly inhibited EROD and PROD activities and its derivatives IY-80843 and IY-80845 strongly inhibited PROD, EROD and ERDM activities. 3. Prolongation of hexobarbital-induced sleeping time was determined in male ICR mice to confirm in vitro inhibitory effects of mifentidine and its derivatives in vivo. It was observed that cimetidine, mifentidine, IY-80843 and IY-80845 caused dose-dependent increases in the sleeping time, indicating the inhibition of P450 responsible for hexobarbital metabolism. 4. It was concluded that mifentidine and its derivatives are P450 inhibitors and that our newly synthesized IY-80843 is most inhibitory. 5. The present results indicate that mifentidine and its derivatives not only antagonise the H2-receptor but also inhibit P450 enzymes. PMID:7576828

  18. Inhibitory effect of putranjivain A on allergic inflammation through suppression of mast cell activation

    SciTech Connect

    Kim, Hui-Hun; Park, Seung-Bin; Lee, Soyoung; Kwon, Taeg Kyu; Shin, Tae-Yong; Park, Pil-Hoon; Lee, Seung-Ho; Kim, Sang-Hyun

    2014-02-01

    A great number of people are suffering from allergic inflammatory disease such as asthma, atopic dermatitis, and sinusitis. Therefore discovery of drugs for the treatment of these diseases is an important subject in human health. Putranjivain A (PJA), member of ellagitannin, is known to possess beneficial effects including anti-cancer and anti-viral activities. The aim of the present study was to elucidate whether PJA modulates the allergic inflammatory reaction and to study its possible mechanisms of action using mast cell-based in vitro and in vivo models. The study was performed in anaphylaxis mouse model and cultured mast cells. PJA inhibited the expression of pro-inflammatory cytokines in immunoglobulin E-stimulated mast cells. PJA reduced this expression by inhibiting nuclear factor (NF)-κB and nuclear factor of activated T cell. The oral administration of PJA reduced systemic and cutaneous anaphylaxis, the release of serum histamine, and the expression of the histamine H{sub 1} receptor. In addition, PJA attenuated the activation of mast cells. PJA inhibited the release of histamine from various types of mast cells by the suppression of intracellular calcium. The inhibitory activity of PJA on the allergic reaction was similar to that of disodium cromoglycate, a known anti-allergic drug. These results suggest that PJA can facilitate the prevention or treatment of allergic inflammatory diseases mediated by mast cells. - Highlights: • PJA reduced the degranulation of mast cells. • PJA inhibited the production of inflammatory cytokines. • The effect of PJA on allergic reaction was comparable to the DSCG. • PJA might be a candidate for the treatment of allergic inflammatory diseases.

  19. Inhibitory effect of three C-glycosylflavonoids from Cymbopogon citratus (Lemongrass) on human low density lipoprotein oxidation.

    PubMed

    Orrego, Roxana; Leiva, Elba; Cheel, José

    2009-09-30

    This study assessed the inhibitory effect of three C-glycosylflavonoids from Cymbopogon citratus leaves--isoorientin (1), swertiajaponin (2) and isoorientin 2"-Orhamnoside (3)--on human LDL oxidation. Isolated LDL was incubated with compounds 1-3 and the kinetics of lipid peroxidation were assessed by conjugated diene and malondialdehyde-thiobarbituric acid reactive substances (MDA-TBARS) formation after addition of copper ions. Significant differences (p < 0.05) between the lag time phase of the control and the lag time phase in the presence of the compounds 1 (0.25 microM) and 2 (0.50 microM) were observed. After five hours of incubation all three compounds showed a significant inhibitory effect on MDA-TBARS formation with respect to the control. After six hours of incubation only compound 1 kept a remarkable antioxidant effect. This study demonstrates that isoorientin (1) is an effective inhibitor of in vitro LDL oxidation. As oxidative damage to LDL is a key event in the formation of atherosclerotic lesions, the use of this natural antioxidant may be beneficial to prevent or attenuate atherosclerosis.

  20. Effects of repetition on the facilitatory and inhibitory components of orienting in visual space.

    PubMed

    Maylor, E A; Hockey, R

    1987-01-01

    Three experiments are reported which investigate the possibility of habituation of externally-controlled covert orienting with repetition. A brief event in the visual field (for example, a luminance change) can speed the detection response to a target if it occurs in the same location within approx. 100 msec and can bias temporal order judgments in the absence of eye movements. This early facilitatory component is seen as the result of an externally-controlled covert orienting response, that is, the realignment of attention, but not the eyes, with the location of the initial event. However, after approx. 300 msec, the response to a target appearing in the same location is slower than to one appearing elsewhere (the inhibitory component). Experiment 1 employed a cue-target procedure, the subject's task being to ignore each non-informative cue but to respond as quickly as possible to the onset of each target. Three conditions were investigated which differed according to the number of consecutive cues presented in the same location [1, 5, 30]. Facilitatory and inhibitory components were present in all three, indicating that under these conditions, externally-controlled covert orienting does not habituate with repetition and occurs to non-random as well as random sequences of cues. In addition, there was evidence that the inhibitory component is larger for a response to a target appearing in the same location as the cue and the previous target than in the same location as the cue only. In order to investigate this further, a continuous target-target procedure was used in experiments 2 and 3 (simple and choice reaction time, with 3 and 1 response-stimulus intervals respectively), which demonstrated that inhibition does not build up over successive repetitions of targets appearing in the same location, but actually decreases. The results are discussed in relation to the possible functions of the facilitatory and inhibitory components in maintaining selectivity in visual

  1. Inhibitory effect of brazilein on tyrosinase and melanin synthesis: Kinetics and in silico approach.

    PubMed

    Hridya, Hemachandran; Amrita, Anantharaman; Sankari, Mohan; George Priya Doss, C; Gopalakrishnan, Mohan; Gopalakrishnan, Chandrasekaran; Siva, Ramamoorthy

    2015-11-01

    In our present study, the inhibitory effect of brazilein from Caesalpinia sappan on tyrosinase activity was investigated through multi-spectroscopic and molecular docking techniques. The result has shown that brazilein reversibly inhibited tyrosinase in a mixed type manner. The interaction of brazilein with the amino acid residues of tyrosinase has been validated through fluorescence quenching studies. Copper interaction studies suggested that brazilein could bind with copper ions of the enzyme. Circular dichroism analysis confirmed that brazilein induced secondary structural changes in tyrosinase. Docking studies further authenticate that brazilein forms hydrophobic and hydrogen bonding with the active site residues of tyrosinase. Moreover, in vitro studies confirmed that the inhibitory mechanism of cellular tyrosinase and melanin synthesis by brazilein in B16F0 melanoma cells. These results suggested that brazilein act as a potential tyrosinase inhibitor and it would contribute as a of novel tyrosinase inhibitor in food, cosmetic and pharmaceutical industry.

  2. Inhibitory effect of mimosine on polyphenoloxidase from cephalothoraxes of Pacific white shrimp (Litopenaeus vannamei).

    PubMed

    Nirmal, Nilesh Prakash; Benjakul, Soottawat

    2011-09-28

    The inhibitory effect of mimosine on polyphenoloxidase (PPO) from the cephalothorax of Pacific white shrimp (Litopenaeus vannamei) was studied. Mimosine showed inhibitory activity toward PPO from white shrimp with an apparent molecular weight of 210 kDa as evidenced by the decrease in the activity staining band, as compared to the control. An inhibition kinetic study revealed that mimosine exhibited the mixed type reversible inhibition on PPO from white shrimp with a Ki value of 3.7 mM. Mimosine showed copper (Cu2+) reduction and chelating capacity in a dose dependent manner. Mimosine could react with the intermediate browning product, thereby rendering lower red-brown color formation. Therefore, mimosine could inhibit PPO by different modes of inhibition and could be used to prevent melanosis formation in Pacific white shrimp. PMID:21863871

  3. Inhibitory effect of brazilein on tyrosinase and melanin synthesis: Kinetics and in silico approach.

    PubMed

    Hridya, Hemachandran; Amrita, Anantharaman; Sankari, Mohan; George Priya Doss, C; Gopalakrishnan, Mohan; Gopalakrishnan, Chandrasekaran; Siva, Ramamoorthy

    2015-11-01

    In our present study, the inhibitory effect of brazilein from Caesalpinia sappan on tyrosinase activity was investigated through multi-spectroscopic and molecular docking techniques. The result has shown that brazilein reversibly inhibited tyrosinase in a mixed type manner. The interaction of brazilein with the amino acid residues of tyrosinase has been validated through fluorescence quenching studies. Copper interaction studies suggested that brazilein could bind with copper ions of the enzyme. Circular dichroism analysis confirmed that brazilein induced secondary structural changes in tyrosinase. Docking studies further authenticate that brazilein forms hydrophobic and hydrogen bonding with the active site residues of tyrosinase. Moreover, in vitro studies confirmed that the inhibitory mechanism of cellular tyrosinase and melanin synthesis by brazilein in B16F0 melanoma cells. These results suggested that brazilein act as a potential tyrosinase inhibitor and it would contribute as a of novel tyrosinase inhibitor in food, cosmetic and pharmaceutical industry. PMID:26254246

  4. Mechanism of growth inhibitory effect of Blumea balsamifera extract in hepatocellular carcinoma.

    PubMed

    Norikura, Toshio; Kojima-Yuasa, Akiko; Shimizu, Miki; Huang, Xuedan; Xu, Shenghui; Kametani, Saeda; Rho, Sook-Nyung; Kennedy, David Opare; Matsui-Yuasa, Isao

    2008-05-01

    Blumea balsamifera is known to improve physiological disorders such as rheumatism and hypertension, but its anticancer activity has not been well elucidated. In this study, we found that Blumea balsamifera MeOH extract (BME) induced growth-inhibitory activity in rat and human hepatocellular carcinoma cells without cytotoxicity in rat hepatocytes which were used as a normal cell model. BME induced cell cycle arrest at the G1 phase via decreases in the expression of cyclin-E and phosphorylation of retinoblastoma protein. Furthermore, BME reduced the level of a proliferation-inducing ligand, that stimulates tumor cell growth. These findings suggest that BME has possible therapeutic potential in hepatoma cancer patients and that depletion of cellular APRIL is an important mechanism in the growth-inhibitory effect of BME. PMID:18460811

  5. Sex Differences in COMT Polymorphism Effects on Prefrontal Inhibitory Control in Adolescence

    PubMed Central

    White, Thomas P; Loth, Eva; Rubia, Katya; Krabbendam, Lydia; Whelan, Robert; Banaschewski, Tobias; Barker, Gareth J; Bokde, Arun LW; Büchel, Christian; Conrod, Patricia; Fauth-Bühler, Mira; Flor, Herta; Frouin, Vincent; Gallinat, Jürgen; Garavan, Hugh; Gowland, Penny; Heinz, Andreas; Ittermann, Bernd; Lawrence, Claire; Mann, Karl; Paillère, Marie-Laure; Nees, Frauke; Paus, Tomas; Pausova, Zdenka; Rietschel, Marcella; Robbins, Trevor; Smolka, Michael N; Shergill, Sukhwinder S; Schumann, Gunter

    2014-01-01

    Catecholamine-0-methyl-transferase (COMT) gene variation effects on prefrontal blood oxygenation-level-dependent (BOLD) activation are robust; however, despite observations that COMT is estrogenically catabolized, sex differences in its prefrontal repercussions remain unclear. Here, in a large sample of healthy adolescents stratified by sex and Val158Met genotype (n=1133), we examine BOLD responses during performance of the stop-signal task in right-hemispheric prefrontal regions fundamental to inhibitory control. A significant sex-by-genotype interaction was observed in pre-SMA during successful-inhibition trials and in both pre-SMA and inferior frontal cortex during failed-inhibition trials with Val homozygotes displaying elevated activation compared with other genotypes in males but not in females. BOLD activation in the same regions significantly mediated the relationship between COMT genotype and inhibitory proficiency as indexed by stop-signal reaction time in males alone. These sexually dimorphic effects of COMT on inhibitory brain activation have important implications for our understanding of the contrasting patterns of prefrontally governed psychopathology observed in males and females. PMID:24820538

  6. Synthesis and carbonic anhydrase inhibitory effects of novel sulfamides derived from 1-aminoindanes and anilines.

    PubMed

    Akbaba, Yusuf; Bastem, Enes; Topal, Fevzi; Gülçin, Ilhami; Maraş, Ahmet; Göksu, Süleyman

    2014-12-01

    Three 1-aminoindanes, four anilines and BnOH or t-BuOH were reacted with chlorosulfonyl isocyanate to give sulfamoyl carbamates. Pd-C catalysed hydrogenolysis reactions of carbamates or deprotection of the Boc group of the carbamates with CF3 CO2 H afforded seven novel sulfamides. Human carbonic anhydrase (hCA) isoenzymes I and II (hCA I and hCA II) were purified from fresh human blood erythrocytes with one-step affinity chromatography on Sepharose 4B-tyrosine-sulfanilamide. The inhibitory properties of the novel sulfamides on both isoenzymes were determined using the esterase activity with 4-nitrophenyl acetate (NPA) as substrate. The tested novel sulfamides derived from 1-aminoindanes and anilines effectively inhibited hCA I and II competitively in the nanomolar range. Among these compounds, the novel sulfamide derivative 17 showed the most potent inhibitory effect against hCA I (Ki : 153.88 nM), while sulfamide derivative 26 showed the highest inhibitory potential against hCA II (Ki : 117.80 nM). PMID:25223956

  7. Inhibitory effect of flavonoid derivatives on Epstein-Barr virus activation and two-stage carcinogenesis of skin tumors.

    PubMed

    Iwase, Y; Takemura, Y; Ju-ichi, M; Mukainaka, T; Ichiishi, E; Ito, C; Furukawa, H; Yano, M; Tokuda, H; Nishino, H

    2001-11-28

    To search for possible anti-tumor promoters, ten flavonoid derivatives (1-10) synthesized from morin and quercetin were examined for their inhibitory effects on the Epstein-Barr virus early antigen (EBV-EA) activation by a short-term in vitro assay. Of these compounds, pentaallyl ethers (9, 10) showed significant inhibitory effects on EBV-EA activation induced by the tumor promoter, 12-O-tetradecanoylphorbol 13-acetate. Further, quercetin pentaallyl ether (10) exhibited remarkable inhibitory effects on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test.

  8. Anxiolytic-like effect of chlorpheniramine in inhibitory avoidance in goldfish submitted to telencephalic ablation.

    PubMed

    Faganello, Flávia Roberta; Mattioli, Rosana

    2007-01-30

    The aim of the present study was to verify the consequences of telencephalic ablation on the learning of inhibitory avoidance and anxiety in goldfish. The animals were submitted to telencephalic ablation or sham operations five days prior to the experimental procedure. The inhibitory avoidance procedure was performed in 3 days using a rectangular aquarium divided into two compartments (black and white) with a central door. On the first day, the animals were habituated for 10 min. On the second and third days, they were injected with saline (SAL), 16 mg/kg Chlorpheniramine (CPA), 40% Propylene glycol (PPG) or 1 mg/kg Diazepam (DZP) twenty minutes before training. Then the animals were placed in the white compartment, the central door was opened and the time spent for crossing between compartments was recorded. After the fish crossed the line between the compartments a 45-g weight was dropped. This procedure was performed three times in a row. The groups submitted or not to telencephalic ablation and treated with SAL presented a difference between training sessions; however, the groups treated with CPA, PPG or DZP did not show any differences between them. These results suggest that the treatment with CPA, PPG or DZP impaired the acquisition of inhibitory avoidance conditioning in animals regardless of telecenphalic ablation. In conclusion, telencephalic ablation does not disrupt the animals' capacity to learn the inhibitory avoidance task, and based on the fact that CPA showed similar effects to those of DZP on the animals submitted or not to telencephalic ablation, we suggest that the CPA presents an anxiolytic-like effect mediated by the diencephalon in goldfish.

  9. Inhibitory effects of K/sup +/ channel-blocking agents on T lymphocyte proliferation and lymphokine production are nonspecific

    SciTech Connect

    Schell, S.R.; Nelson, D.J.; Fozzard, H.A.; Fitch, F.W.

    1987-11-15

    The effect of K/sup +/ channel-blocking agents, tetraethylammonium (TEA) and 4-aminopyridine (4AP), on the responses of cloned murine helper and cytolytic T lymphocytes stimulated with mitogen, anti-T cell receptor monoclonal antibody, or interleukin 2 was examined. The addition of TEA and 4AP reduced (/sup 3/H)thymidine incorporation and lymphokine production to levels observed in unstimulated cells. However, thymidine incorporation by the tumor cell lines P-815 and SP2/0, which replicate autonomously, also was inhibited by these drugs. Treatment of cloned murine helper T lymphocyte, L2, with TEA appeared to inhibit uptake of (/sup 3/H)thymidine and (/sup 3/H) phenylalanine after stimulation with interleukin 2. These results suggest that the inhibitory effects of the K/sup +/ channel-blocking agents TEA and 4AP may not be specific for the sequence of events that are initiated by activation of T lymphocytes through the antigen receptor. Instead, the observed inhibitory effects by these agents may result from inhibition of transport of thymidine, amino acids, and other essential metabolites across the cell membrane.

  10. Inhibitory effect of Paeonia lactiflora Pallas extract (PE) on poly (I:C)-induced immune response of epidermal keratinocytes.

    PubMed

    Choi, Mi-Ra; Choi, Dae-Kyoung; Sohn, Kyung-Cheol; Lim, Seul Ki; Kim, Dong-Il; Lee, Young Ho; Im, Myung; Lee, Young; Seo, Young-Joon; Kim, Chang Deok; Lee, Jeung-Hoon

    2015-01-01

    Epidermal keratinocytes provide protective role against external stimuli by barrier formation. In addition, kertinocytes exerts their role as the defense cells via activation of innate immunity. Disturbance of keratinocyte functions is related with skin disorders. Psoriasis is a common skin disease related with inflammatory reaction in epidermal cells. We attempted to find therapeutics for psoriasis, and found that Paeonia lactiflora Pallas extract (PE) has an inhibitory potential on poly (I:C)-induced inflammation of keratinocytes. PE significantly inhibited poly (I:C)-induced expression of crucial psoriatic cytokines, such as IL-6, IL-8, CCL20 and TNF-α, via down-regulation of NF-κB signaling pathway in human keratinocytes. In addition, PE significantly inhibited poly (I:C)-induced inflammasome activation, in terms of IL-1β and caspase-1 secretion. Finally, PE markedly inhibited poly (I:C)-increased NLRP3, an important component of inflammasome. These results indicate that PE has an inhibitory effect on poly (I:C)-induced inflammatory reaction of keratinocytes, suggesting that PE can be developed for the treatment of psoriasis.

  11. Inhibitory effect of Paeonia lactiflora Pallas extract (PE) on poly (I:C)-induced immune response of epidermal keratinocytes

    PubMed Central

    Choi, Mi-Ra; Choi, Dae-Kyoung; Sohn, Kyung-Cheol; Lim, Seul Ki; Kim, Dong-Il; Lee, Young Ho; Im, Myung; Lee, Young; Seo, Young-Joon; Kim, Chang Deok; Lee, Jeung-Hoon

    2015-01-01

    Epidermal keratinocytes provide protective role against external stimuli by barrier formation. In addition, kertinocytes exerts their role as the defense cells via activation of innate immunity. Disturbance of keratinocyte functions is related with skin disorders. Psoriasis is a common skin disease related with inflammatory reaction in epidermal cells. We attempted to find therapeutics for psoriasis, and found that Paeonia lactiflora Pallas extract (PE) has an inhibitory potential on poly (I:C)-induced inflammation of keratinocytes. PE significantly inhibited poly (I:C)-induced expression of crucial psoriatic cytokines, such as IL-6, IL-8, CCL20 and TNF-α, via down-regulation of NF-κB signaling pathway in human keratinocytes. In addition, PE significantly inhibited poly (I:C)-induced inflammasome activation, in terms of IL-1β and caspase-1 secretion. Finally, PE markedly inhibited poly (I:C)-increased NLRP3, an important component of inflammasome. These results indicate that PE has an inhibitory effect on poly (I:C)-induced inflammatory reaction of keratinocytes, suggesting that PE can be developed for the treatment of psoriasis. PMID:26191223

  12. Inhibitory effect of Paeonia lactiflora Pallas extract (PE) on poly (I:C)-induced immune response of epidermal keratinocytes.

    PubMed

    Choi, Mi-Ra; Choi, Dae-Kyoung; Sohn, Kyung-Cheol; Lim, Seul Ki; Kim, Dong-Il; Lee, Young Ho; Im, Myung; Lee, Young; Seo, Young-Joon; Kim, Chang Deok; Lee, Jeung-Hoon

    2015-01-01

    Epidermal keratinocytes provide protective role against external stimuli by barrier formation. In addition, kertinocytes exerts their role as the defense cells via activation of innate immunity. Disturbance of keratinocyte functions is related with skin disorders. Psoriasis is a common skin disease related with inflammatory reaction in epidermal cells. We attempted to find therapeutics for psoriasis, and found that Paeonia lactiflora Pallas extract (PE) has an inhibitory potential on poly (I:C)-induced inflammation of keratinocytes. PE significantly inhibited poly (I:C)-induced expression of crucial psoriatic cytokines, such as IL-6, IL-8, CCL20 and TNF-α, via down-regulation of NF-κB signaling pathway in human keratinocytes. In addition, PE significantly inhibited poly (I:C)-induced inflammasome activation, in terms of IL-1β and caspase-1 secretion. Finally, PE markedly inhibited poly (I:C)-increased NLRP3, an important component of inflammasome. These results indicate that PE has an inhibitory effect on poly (I:C)-induced inflammatory reaction of keratinocytes, suggesting that PE can be developed for the treatment of psoriasis. PMID:26191223

  13. Inhibitory Effect of Bridged Nucleosides on Thermus aquaticus DNA Polymerase and Insight into the Binding Interactions

    PubMed Central

    Kim, Sung-Kun; Castro, Aaron; Kim, Edward S.; Dinkel, Austin P.; Liu, Xiaoyun; Castro, Miguel

    2016-01-01

    Modified nucleosides have the potential to inhibit DNA polymerases for the treatment of viral infections and cancer. With the hope of developing potent drug candidates by the modification of the 2’,4’-position of the ribose with the inclusion of a bridge, efforts were focused on the inhibition of Taq DNA polymerase using quantitative real time PCR, and the results revealed the significant inhibitory effects of 2’,4’-bridged thymidine nucleoside on the polymerase. Study on the mode of inhibition revealed the competitive mechanism with which the 2’,4’-bridged thymidine operates. With a Ki value of 9.7 ± 1.1 μM, the 2’,4’-bridged thymidine proved to be a very promising inhibitor. Additionally, docking analysis showed that all the nucleosides including 2’,4’-bridged thymidine were able to dock in the active site, indicating that the substrate analogs reflect a structural complementarity to the enzyme active site. The analysis also provided evidence that Asp610 was a key binding site for 2’,4’-bridged thymidine. Molecular dynamics (MD) simulations were performed to further understand the conformational variations of the binding. The root-mean-square deviation (RMSD) values for the peptide backbone of the enzyme and the nitrogenous base of the inhibitor stabilized within 0.8 and 0.2 ns, respectively. Furthermore, the MD analysis indicates substantial conformational change in the ligand (inhibitor) as the nitrogenous base rotated anticlockwise with respect to the sugar moiety, complemented by the formation of several new hydrogen bonds where Arg587 served as a pivot axis for binding formation. In conclusion, the active site inhibition of Taq DNA polymerase by 2’,4’-bridged thymidine suggests the potential of bridged nucleosides as drug candidates. PMID:26820310

  14. Inhibitory Effects of Lipophilic Acids and Related Compounds on Bacteria and Mammalian Cells

    PubMed Central

    Sheu, C. W.; Salomon, D.; Simmons, J. L.; Sreevalsan, T.; Freese, E.

    1975-01-01

    The inhibitory effect of lipophilic acids, antimicrobial food additives, and analgesics-antipyretics was examined at concentrations from 0.1 to 100 mM in bacteria (Bacillus subtilis and Escherichia coli) and mammalian cells (HeLa, human fibroblasts, and mouse neuroblastoma cells). Most compounds inhibit the growth of HeLa cells about as efficiently as that of B. subtilis. However, butyrate and propionate, as well as acetaminophen, antipyrene, phenacetin, and salicylamide, inhibit HeLa at millimolar concentrations whereas, at least 10 times higher concentrations are needed to inhibit B. subtilis. The concentrations needed to inhibit growth by 50% decrease with increasing octanol-water partition coefficients of the compound. Growth of E. coli is inhibited similar to that of B. subtilis by all compounds except butylbenzoate, decanoate, and linoleate which cannot penetrate the lipopolysaccharide layer. All growth inhibitors inhibit amino acid uptake into bacteria and their vesicles, and oxygen consumption in bacteria. In HeLa cells or human fibroblasts, neither amino acid uptake nor adenine 5′-triphosphate synthesis are inhibited by fatty acids at concentrations that completely inhibit growth. Short chain fatty acids (propionate, butyrate, and pentanoate) induce in HeLa the formation of cell processes. In neuroblastoma cells, grown in the presence of 10% fetal calf serum, butyrate also induces such processes which slowly continue to grow in length for at least 7 days; these processes differ in speed of formation, width, and cycloheximide susceptibility from the thin processes produced by serum deprivation alone. Images PMID:1137388

  15. Inhibitory effects of Colocasia esculenta (L.) Schott constituents on aldose reductase.

    PubMed

    Li, Hong Mei; Hwang, Seung Hwan; Kang, Beom Goo; Hong, Jae Seung; Lim, Soon Sung

    2014-01-01

    The goal of this study was to determine the rat lens aldose reductase-inhibitory effects of 95% ethanol extracts from the leaves of C. esculenta and, its organic solvent soluble fractions, including the dichloromethane (CH2Cl2), ethyl acetate (EtOAc), n-butanol (BuOH) and water (H2O) layers, using dl-glyceraldehyde as a substrate. Ten compounds, namely tryptophan (1), orientin (2), isoorientin (3), vitexin (4), isovitexin (5), luteolin-7-O-glucoside (6), luteolin-7-O-rutinoside (7), rosmarinic acid (8), 1-O-feruloyl-d-glucoside (9) and 1-O-caffeoyl-d-glucoside (10) were isolated from the EtOAc and BuOH fractions of C. esculenta. The structures of compounds 1-10 were elucidated by spectroscopic methods and comparison with previous reports. All the isolates were subjected to an in vitro bioassay to evaluate their inhibitory activity against rat lens aldose reductase. Among tested compounds, compounds 2 and 3 significantly inhibited rat lens aldose reductase, with IC50 values of 1.65 and 1.92 μM, respectively. Notably, the inhibitory activity of orientin was 3.9 times greater than that of the positive control, quercetin (4.12 μM). However, the isolated compounds showed only moderate ABTS+ [2,29-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid)] activity. These results suggest that flavonoid derivatives from Colocasia esculenta (L.) Schott represent potential compounds for the prevention and/or treatment of diabetic complications.

  16. Inhibitory effects of chickpea and Tribulus terrestris on lipase, α-amylase and α-glucosidase.

    PubMed

    Ercan, Pınar; El, Sedef Nehir

    2016-08-15

    The total saponin content and its in vitro bioaccessibilities in Tribulus terrestris and chickpea were determined by a static in vitro digestion method (COST FA1005 Action INFOGEST). Also, in vitro inhibitory effects of the chosen food samples on lipid and starch digestive enzymes were determined by evaluating the lipase, α-amylase and α-glucosidase activities. The tested T. terrestris and chickpea showed inhibitory activity against α-glucosidase (IC50 6967 ± 343 and 2885 ± 85.4 μg/ml, respectively) and α-amylase (IC50 343 ± 26.2 and 167 ± 6.12 μg/ml, respectively). The inhibitory activities of T. terrestris and chickpea against lipase were 15.3 ± 2.03 and 9.74 ± 1.09 μg/ml, respectively. The present study provides the first evidence that these food samples (T. terrestris, chickpea) are potent inhibitors of key enzymes in digestion of carbohydrates and lipids in vitro. PMID:27006227

  17. Inhibitory effects of Colocasia esculenta (L.) Schott constituents on aldose reductase.

    PubMed

    Li, Hong Mei; Hwang, Seung Hwan; Kang, Beom Goo; Hong, Jae Seung; Lim, Soon Sung

    2014-01-01

    The goal of this study was to determine the rat lens aldose reductase-inhibitory effects of 95% ethanol extracts from the leaves of C. esculenta and, its organic solvent soluble fractions, including the dichloromethane (CH2Cl2), ethyl acetate (EtOAc), n-butanol (BuOH) and water (H2O) layers, using dl-glyceraldehyde as a substrate. Ten compounds, namely tryptophan (1), orientin (2), isoorientin (3), vitexin (4), isovitexin (5), luteolin-7-O-glucoside (6), luteolin-7-O-rutinoside (7), rosmarinic acid (8), 1-O-feruloyl-d-glucoside (9) and 1-O-caffeoyl-d-glucoside (10) were isolated from the EtOAc and BuOH fractions of C. esculenta. The structures of compounds 1-10 were elucidated by spectroscopic methods and comparison with previous reports. All the isolates were subjected to an in vitro bioassay to evaluate their inhibitory activity against rat lens aldose reductase. Among tested compounds, compounds 2 and 3 significantly inhibited rat lens aldose reductase, with IC50 values of 1.65 and 1.92 μM, respectively. Notably, the inhibitory activity of orientin was 3.9 times greater than that of the positive control, quercetin (4.12 μM). However, the isolated compounds showed only moderate ABTS+ [2,29-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid)] activity. These results suggest that flavonoid derivatives from Colocasia esculenta (L.) Schott represent potential compounds for the prevention and/or treatment of diabetic complications. PMID:25255750

  18. Evaluation of traditional Indian antidiabetic medicinal plants for human pancreatic amylase inhibitory effect in vitro.

    PubMed

    Ponnusamy, Sudha; Ravindran, Remya; Zinjarde, Smita; Bhargava, Shobha; Ravi Kumar, Ameeta

    2011-01-01

    Pancreatic α-amylase inhibitors offer an effective strategy to lower the levels of post prandial hyperglycemia via control of starch breakdown. Eleven Ayurvedic Indian medicinal plants with known hypoglycemic properties were subjected to sequential solvent extraction and tested for α-amylase inhibition, in order to assess and evaluate their inhibitory potential on pancreatic α-amylase. Analysis of 91 extracts, showed that 10 exhibited strong Human Pancreatic Amylase (HPA) inhibitory potential. Of these, 6 extracts showed concentration dependent inhibition with IC(50) values, namely, cold and hot water extracts from Ficus bengalensis bark (4.4 and 125 μgmL(-1)), Syzygium cumini seeds (42.1 and 4.1 μgmL(-1)), isopropanol extracts of Cinnamomum verum leaves (1.0 μgmL(-1)) and Curcuma longa rhizome (0.16 μgmL(-1)). The other 4 extracts exhibited concentration independent inhibition, namely, methanol extract of Bixa orellana leaves (49 μgmL(-1)), isopropanol extract from Murraya koenigii leaves (127 μgmL(-1)), acetone extracts from C. longa rhizome (7.4 μgmL(-1)) and Tribulus terrestris seeds (511 μgmL(-1)). Thus, the probable mechanism of action of the above fractions is due to their inhibitory action on HPA, thereby reducing the rate of starch hydrolysis leading to lowered glucose levels. Phytochemical analysis revealed the presence of alkaloids, proteins, tannins, cardiac glycosides, flavonoids, saponins and steroids as probable inhibitory compounds.

  19. Inhibitory effect of oolong tea polyphenols on glycosyltransferases of mutans Streptococci.

    PubMed Central

    Nakahara, K; Kawabata, S; Ono, H; Ogura, K; Tanaka, T; Ooshima, T; Hamada, S

    1993-01-01

    Oolong tea extract (OTE) was found to inhibit the water-insoluble glucan-synthesizing enzyme, glucosyltransferase I (GTase-I), of Streptococcus sobrinus 6715. The GTase-inhibitory substance in the OTE was purified successive adsorption chromatography on Diaion HP-21 and HP-20 columns; this was followed by further purification by Sephadex LH-20 column chromatography. A major fraction that inhibited GTase activity (fraction OTF10) was obtained, and the chemical analysis of OTF10 indicated that it was a novel polymeric polyphenol compound that had a molecular weight of approximately 2,000 and differed from other tea polyphenols. Catechins and all other low-molecular-weight polyphenols except theaflavin derived from balck tea did not show significant GTase-inhibitory activities. It was found that OTE amd PTF10 markedly inhibit GTase-I and yeast alpha-glucosidase, but not salivary alpha-amylase. Various GTases purified from S. sobrinus and Streptococcus mutans were examined for inhibition by OTE and OTF10. It was determined that S. sobrinus GTase-I and S. mutans cell-free GTase synthesizing water-soluble glucan were most susceptible to the inhibitory action of OTF10, while S. sobrinus GTase-Sa and S. mutans cell-associated GTase were moderately inhibited; no inhibition of S. sobrinus GTase-Sb was observed. Inhibition of a specific GTase or specific GTases of mutants streptococci resulted in decreased adherence of the growing cells of these organisms. The inhibitory effect of OTF10 on cellular adherence was significantly stronger than that of OTE. PMID:8489234

  20. Evaluation of traditional Indian antidiabetic medicinal plants for human pancreatic amylase inhibitory effect in vitro.

    PubMed

    Ponnusamy, Sudha; Ravindran, Remya; Zinjarde, Smita; Bhargava, Shobha; Ravi Kumar, Ameeta

    2011-01-01

    Pancreatic α-amylase inhibitors offer an effective strategy to lower the levels of post prandial hyperglycemia via control of starch breakdown. Eleven Ayurvedic Indian medicinal plants with known hypoglycemic properties were subjected to sequential solvent extraction and tested for α-amylase inhibition, in order to assess and evaluate their inhibitory potential on pancreatic α-amylase. Analysis of 91 extracts, showed that 10 exhibited strong Human Pancreatic Amylase (HPA) inhibitory potential. Of these, 6 extracts showed concentration dependent inhibition with IC(50) values, namely, cold and hot water extracts from Ficus bengalensis bark (4.4 and 125 μgmL(-1)), Syzygium cumini seeds (42.1 and 4.1 μgmL(-1)), isopropanol extracts of Cinnamomum verum leaves (1.0 μgmL(-1)) and Curcuma longa rhizome (0.16 μgmL(-1)). The other 4 extracts exhibited concentration independent inhibition, namely, methanol extract of Bixa orellana leaves (49 μgmL(-1)), isopropanol extract from Murraya koenigii leaves (127 μgmL(-1)), acetone extracts from C. longa rhizome (7.4 μgmL(-1)) and Tribulus terrestris seeds (511 μgmL(-1)). Thus, the probable mechanism of action of the above fractions is due to their inhibitory action on HPA, thereby reducing the rate of starch hydrolysis leading to lowered glucose levels. Phytochemical analysis revealed the presence of alkaloids, proteins, tannins, cardiac glycosides, flavonoids, saponins and steroids as probable inhibitory compounds. PMID:20953430

  1. Acute Effects of Alcohol on Inhibitory Control and Simulated Driving in DUI Offenders

    PubMed Central

    Van Dyke, Nicholas; Fillmore, Mark T.

    2014-01-01

    Introduction The public health costs associated with alcohol-related traffic accidents have prompted considerable research aimed at identifying characteristics of individuals who drive under the influence (DUI) in order to improve treatment and prevention strategies. Survey studies consistently show that DUI offenders self-report higher levels of impulsivity compared to their nonoffending counterparts. However, little is known about how individuals with a DUI history respond under alcohol. Inhibitory control is a behavioral component of impulsivity thought to underlie risky drinking and driving behaviors. Method The present study examined the degree to which DUI drivers display deficits of inhibitory control in response to alcohol and the degree to which alcohol impaired their simulated driving performance. It was hypothesized that DUI offenders would display an increased sensitivity to the acute impairing effects of alcohol on simulated driving performance. Young adult drivers with a history of DUI and a demographically-comparable group of drivers with no history of DUI (controls) were tested following a 0.65 g/kg dose of alcohol and a placebo. Inhibitory control was measured using a cued go/no-go task. Drivers then completed a driving simulation task that yielded multiple indicators of driving performance, such as within-lane deviation, steering rate, centerline crossings and road edge excursions, and drive speed. Results Results showed that although DUI offenders self-reported greater levels of impulsivity than did controls, no group differences were observed in the degree to which alcohol impaired inhibitory control and driving performance. The findings point to the need to identify other aspects of behavioral dysfunction underlying the self-reported impulsivity among DUI offenders, and to better understand the specific driving situations that might pose greater risk to DUI offenders. PMID:24913486

  2. Inhibitory effects of Korean medicinal plants and camelliatannin H from Camellia japonica on human immunodeficiency virus type 1 protease.

    PubMed

    Park, Jong Cheol; Hur, Jong Moon; Park, Ju Gwon; Hatano, Tsutomu; Yoshida, Takashi; Miyashiro, Hirotsugu; Min, Byung Sun; Hattori, Masao

    2002-08-01

    To identify substances with anti-human immunodeficiency virus (HIV) activity in traditional medicines, 101 extracts of Korean medicinal plants were screened for their inhibitory effects on HIV type 1 protease (PR). The enzyme activity was determined by HPLC. Of the extracts tested, strong inhibitory effects were observed in the acetone extracts of the pericarp and leaves of Camellia japonica, the water extract of the leaves of Sageretia theezans and the methanol extract of the aerial part of Sophora flavescens. Camelliatannin H from the pericarp of C. japonica, showed a potent inhibitory activity on HIV-1 PR with IC(50) of 0.9 microM. PMID:12203260

  3. Inhibitory effect of delphinidin from Solanum melongena on human fibrosarcoma HT-1080 invasiveness in vitro.

    PubMed

    Nagase, H; Sasaki, K; Kito, H; Haga, A; Sato, T

    1998-04-01

    We investigated the inhibitory effect of eggplant (Solanum melongena var. marunasu) extract on human fibrosarcoma HT-1080 cell invasion of reconstituted basement membrane [Matrigel (MG)]. We found that the effective component of the plant extract was delphinidin, a flavonoid pigment contained in the peel. The extract and delphinidin did not affect tumor cell adhesion to MG or haptotactic migration to MG. HT-1080 secretes matrix metalloproteinase(MMP)-2 and MMP-9, which degrade extracellular matrix as part of the invasive process. Delphinidin slightly inhibited the activity of MMPs, which may have been responsible, in part, for the inhibition of tumor cell invasiveness. PMID:9581517

  4. The tumor-inhibitory effectiveness of a novel anti-Trop2 Fab conjugate in pancreatic cancer

    PubMed Central

    Mao, Yuan; Wang, Xiaoying; Zheng, Feng; Wang, Changjun; Tang, Qi; Tang, Xiaojun; Xu, Ning; Zhang, Huiling; Zhang, Dawei; Xiong, Lin; Liang, Jie; Zhu, Jin

    2016-01-01

    Human trophoblastic cell surface antigen 2 (Trop2) has been reported to act oncogenically. In this study, one-step quantitative real-time polymerase chain reaction (qPCR) test and immunohistochemistry (IHC) analysis with were employed to evaluate the relationship between Trop2 expression and the clinicopathological features of patients with PC. Then a novel anti-Trop2 Fab antibody was conjugated with Doxorubicin (DOX) to form Trop2Fab-DOX, an antibody-drug conjugate. This Trop2Fab-DOX conjugate was characterized by cell ELISA and immunofluorescence assay. MTT and wound healing analyses were used to evaluate the inhibitory effect of Trop2Fab-DOX on PC cell growth in vitro, while xenograft nude mice model was established to examine the tumor-inhibitory effects of PC in vivo. High Trop2 expression was observed in PC tissues and Trop2 expression was associated with several malignant attributes of PC patients, including overall survival. Trop2Fab-DOX can bind to the Trop2-expressing PC cells and provide an improved releasing type of DOX. In addition, Trop2Fab-DOX inhibited the proliferation and suppressed the migration of PC cells in a dose-dependent manner in vitro, while inhibited the growth of PC xenografts in vivo. Trop2 is a specific marker for PC, and a novel Trop2Fab-DOX ADC has a potent antitumor activity PMID:27050150

  5. Exposure of activated sludge to nanosilver and silver ion: Inhibitory effects and binding to the fractions of extracellular polymeric substances.

    PubMed

    Geyik, Ayse Gul; Çeçen, Ferhan

    2016-07-01

    The main aim of the study was to determine the inhibitory effects of Ag(+) and AgNP (commercial and synthesized) on activated sludge by using respirometry. Along with this aim, also the changes taking place in extracellular polymeric substances (EPS) were studied. Additionally, the binding of Ag(+) or AgNP to the different fractions in EPS was assessed using voltammetry. Synthesized AgNP led to an obvious inhibition whereas commercial AgNP had no effect on activated sludge. For Ag(+) and AgNP, IC50 values were found between 2.3-3.0mg/L and 3.2-11.1mg/L, respectively. Thus, AgNP was less inhibitory than silver ion, since the release of free silver from AgNP was very small. The protein and carbohydrate content of EPS generally increased when Ag(+) was added. Both tightly- and loosely bound fractions in EPS could bind Ag(+) and AgNP. Silver binding capacity of EPS was seen to depend on the molecular weight of proteins.

  6. The tumor-inhibitory effectiveness of a novel anti-Trop2 Fab conjugate in pancreatic cancer.

    PubMed

    Mao, Yuan; Wang, Xiaoying; Zheng, Feng; Wang, Changjun; Tang, Qi; Tang, Xiaojun; Xu, Ning; Zhang, Huiling; Zhang, Dawei; Xiong, Lin; Liang, Jie; Zhu, Jin

    2016-04-26

    Human trophoblastic cell surface antigen 2 (Trop2) has been reported to act oncogenically. In this study, one-step quantitative real-time polymerase chain reaction (qPCR) test and immunohistochemistry (IHC) analysis with were employed to evaluate the relationship between Trop2 expression and the clinicopathological features of patients with PC. Then a novel anti-Trop2 Fab antibody was conjugated with Doxorubicin (DOX) to form Trop2Fab-DOX, an antibody-drug conjugate. This Trop2Fab-DOX conjugate was characterized by cell ELISA and immunofluorescence assay. MTT and wound healing analyses were used to evaluate the inhibitory effect of Trop2Fab-DOX on PC cell growth in vitro, while xenograft nude mice model was established to examine the tumor-inhibitory effects of PC in vivo. High Trop2 expression was observed in PC tissues and Trop2 expression was associated with several malignant attributes of PC patients, including overall survival. Trop2Fab-DOX can bind to the Trop2-expressing PC cells and provide an improved releasing type of DOX. In addition, Trop2Fab-DOX inhibited the proliferation and suppressed the migration of PC cells in a dose-dependent manner in vitro, while inhibited the growth of PC xenografts in vivo. Trop2 is a specific marker for PC, and a novel Trop2Fab-DOX ADC has a potent antitumor activity.

  7. The signaling of amitriptyline-induced inhibitory effect on electrical field stimulation response in colon smooth muscle.

    PubMed

    Zaw, Tin Sandar; Khin, Phyu Phyu; Sohn, Uy Dong

    2016-09-01

    Amitriptyline, a well-known antidepressant, exerts inhibitory effect on electrically stimulated rat colon smooth muscle contraction. In this study, we investigated the signaling pathway of amitriptyline-induced inhibitory effect. Changes in isometric force of colon muscle were recorded on polygraph, and data were analyzed by measuring the inhibitory extent induced by amitriptyline. Firstly, muscles were contracted by stimulation with electric field stimulation (EFS), and then, amitriptyline was added cumulatively to determine its influence effect on EFS. Amitriptyline significantly inhibited EFS-induced contraction dose dependently. Then, the mechanism of inhibitory effect of amitriptyline was evaluated by pretreating with various antagonists such as L-NAME, methylene blue, atropine, 5-HT receptors blockers, guanethidine, prazosin, guanabenz, isoprenaline, Y27632 (Rho-kinase inhibitor), ML9 (myosin light chain kinase (MLCK) inhibitor), U73122 (PLC inhibitor), and chelerythrine (PKC inhibitor). Then, Ca(2+) channel blocker (nifedipine) and K(+)channel blockers, tetraethylammonium (TEA), 4-aminopyridine (4-AP), and glybenclamide, were used to determine the involvement of ion channels. L-NAME, guanabenz, 5HT4 receptor blocker, ML9, and Y27632 enhanced the effect of amitriptyline. Meanwhile, methylene blue, atropine, guanethidine, prazosin, methylsergide, ondansetron, U73122, and chelerythrine blocked its effect. It was also shown that nifedipine enhanced but TEA and glybenclamide blocked amitriptyline-induced inhibitory effect on EFS. Our results indicated that amitriptyline may exert inhibitory effect in response to EFS by inhibiting muscarinic receptors and then PLC-mediated PKC pathway leading to opening of ATP-sensitive potassium channel.

  8. The signaling of amitriptyline-induced inhibitory effect on electrical field stimulation response in colon smooth muscle.

    PubMed

    Zaw, Tin Sandar; Khin, Phyu Phyu; Sohn, Uy Dong

    2016-09-01

    Amitriptyline, a well-known antidepressant, exerts inhibitory effect on electrically stimulated rat colon smooth muscle contraction. In this study, we investigated the signaling pathway of amitriptyline-induced inhibitory effect. Changes in isometric force of colon muscle were recorded on polygraph, and data were analyzed by measuring the inhibitory extent induced by amitriptyline. Firstly, muscles were contracted by stimulation with electric field stimulation (EFS), and then, amitriptyline was added cumulatively to determine its influence effect on EFS. Amitriptyline significantly inhibited EFS-induced contraction dose dependently. Then, the mechanism of inhibitory effect of amitriptyline was evaluated by pretreating with various antagonists such as L-NAME, methylene blue, atropine, 5-HT receptors blockers, guanethidine, prazosin, guanabenz, isoprenaline, Y27632 (Rho-kinase inhibitor), ML9 (myosin light chain kinase (MLCK) inhibitor), U73122 (PLC inhibitor), and chelerythrine (PKC inhibitor). Then, Ca(2+) channel blocker (nifedipine) and K(+)channel blockers, tetraethylammonium (TEA), 4-aminopyridine (4-AP), and glybenclamide, were used to determine the involvement of ion channels. L-NAME, guanabenz, 5HT4 receptor blocker, ML9, and Y27632 enhanced the effect of amitriptyline. Meanwhile, methylene blue, atropine, guanethidine, prazosin, methylsergide, ondansetron, U73122, and chelerythrine blocked its effect. It was also shown that nifedipine enhanced but TEA and glybenclamide blocked amitriptyline-induced inhibitory effect on EFS. Our results indicated that amitriptyline may exert inhibitory effect in response to EFS by inhibiting muscarinic receptors and then PLC-mediated PKC pathway leading to opening of ATP-sensitive potassium channel. PMID:27234925

  9. Olmesartan is an angiotensin II receptor blocker with an inhibitory effect on angiotensin-converting enzyme.

    PubMed

    Agata, Jun; Ura, Nobuyuki; Yoshida, Hideaki; Shinshi, Yasuyuki; Sasaki, Haruki; Hyakkoku, Masaya; Taniguchi, Shinya; Shimamoto, Kazuaki

    2006-11-01

    this anti-remodeling effect and the increase in nitrite/nitrate. These findings suggest that olmesartan may exhibit an ACE inhibitory action in addition to an Ang II receptor blocking action, prevent an increase in Ang II level, and protect cardiovascular remodeling through an increase in cardiac nitric oxide production and endogenous Ang-(1-7) via over-expression of ACE2. PMID:17345786

  10. inhibitory effects of citral, cinnamaldehyde, and tea polyphenols on mixed biofilm formation by foodborne Staphylococcus aureus and Salmonella enteritidis.

    PubMed

    Zhang, Hongmei; Zhou, Wenyuan; Zhang, Wenyan; Yang, Anlin; Liu, Yanlan; Jiang, Yan; Huang, Shaosong; Su, Jianyu

    2014-06-01

    Biofilms are significant hazards in the food industry. In this study, we investigated the effects of food additive such as citral, cinnamaldehyde, and tea polyphenols on mixed biofilm formation by foodborne Staphylococcus aureus and Salmonella serotype Enteritidis. The adhesion rates of mixed strains in sub-MIC of additives were determined by a microtiter plate assay and bacterial communication signal autoinducer 2 (AI-2) production via a bioluminescence reporter Vibrio harveyi BB170. The structure of mixed biofilm was analyzed using scanning electron microscopy. The effect of the disinfectants hydrogen peroxide, sodium hypochlorite, and peracetic acid was tested on the mixed biofilm. Our results demonstrated that citral, cinnamaldehyde, and tea polyphenols were able to significantly inhibit mixed biofilm formation, while citral could reduce the synthesis of AI-2. Conversely, we observed a significant increase in AI-2 mediated by cinnamaldehyde. Tea polyphenols at lower concentrations induced AI-2 synthesis; however, AI-2 synthesis was significantly inhibited at higher concentrations (300 m g/ml). Food additives inhibited the adhesion of mixed bacteria on stainless steel chips and increased the sensitivity of the mixed biofilm to disinfectants. In conclusion, citral, cinnamaldehyde, and tea polyphenols had strong inhibitory effects on mixed biofilm formation and also enhanced the effect of disinfectant on mixed biofilm formation. This study provides a scientific basis for the application of natural food additives to control biofilm formation of foodborne bacteria. PMID:24853514

  11. Mechanisms involved in the inhibitory effect of chronic alcohol exposure on pancreatic acinar thiamin uptake.

    PubMed

    Srinivasan, Padmanabhan; Subramanian, Veedamali S; Said, Hamid M

    2014-04-01

    Pancreatic acinar cells (PAC) obtain thiamin from the circulation via a carrier-mediated process that involves thiamin transporters 1 and 2 (THTR-1 and THTR-2; products of SLC19A2 and SLC19A3, respectively). Chronic alcohol exposure of PAC inhibits thiamin uptake, and, on the basis of in vitro studies, this inhibition appears to be transcriptionally mediated. The aim of this study was to confirm the involvement of a transcriptional mechanism in mediating the chronic alcohol effect in in vivo settings and to delineate the molecular mechanisms involved. Using transgenic mice carrying full-length SLC19A2 and SLC19A3 promoters, we found that chronic alcohol feeding led to a significant reduction in the activity of SLC19A2 and SLC19A3 promoters (as well as in thiamin uptake and expression of THTR-1 and -2). Similar findings were seen in 266-6 cells chronically exposed to alcohol in vitro. In the latter studies, the alcohol inhibitory effect was found to be mediated via the minimal SLC19A2 and SLC19A3 promoters and involved the cis-regulatory elements stimulating protein 1 (SP1)/gut-enriched Kruppel-like factor and SP1-GG-box and SP1/GC, respectively. Chronic alcohol exposure of PAC also led to a significant reduction in the expression of the SP1 transcription factor, which upon correction (via expression) led to the prevention of alcohol inhibitory effects on not only the activity of SLC19A2 and SLC19A3 promoters but also on the expression of THTR-1 and -2 mRNA and thiamin uptake. These results demonstrate that the inhibitory effect of chronic alcohol exposure on physiological/molecular parameters of thiamin uptake by PAC is mediated via specific cis-regulatory elements in SLC19A2 and SLC19A3 minimal promoters.

  12. Inhibitory Effect of Epigallocatechin Gallate on the Virulence of Clostridium difficile PCR Ribotype 027.

    PubMed

    Yun, Bohyun; Oh, Seunghan; Song, Minyu; Hong, Young-Shick; Park, Sungsu; Park, Dong-June; Griffiths, Mansel W; Oh, Sejong

    2015-12-01

    Clostridium difficile infection (CDI) is the most prevalent cause of health-care-associated infections. CDI-related health-care costs and deaths are both increasing annually on a global scale. C. difficile have been reported in food products in Canada, Europe, and the United States; however, the systematic transmission of C. difficile between humans and animals is yet to be understood. Because of the limitations of current therapeutic options, there is a need for the development of new patient treatments. Epigallocatechin gallate (EGCG) is a major catechin compound found in green tea extracts and exhibits antioxidant and antimicrobial activities. This study was conducted to investigate the inhibitory effects of EGCG on the expression of virulence genes in C. difficile and in C. difficile-associated diseases by inhibition of quorum sensing. The protein expression of autoinducer-2 (AI-2) was evaluated by AI-2 activity. EGCG at various concentrations had an inhibitory effect on AI-2 production, especially at 10 μg/mL. EGCG also significantly repressed the transcription of virulence genes, including luxS and tcdA, and prolonged the survival of Caenorhabditis elegans infected with C. difficile. Furthermore, treatment with EGCG effectively protected C. difficile-infected mice from C. difficile-induced death. Histological analysis of the colon and cecum of these mice revealed that EGCG protected tissues of the lower intestinal tract from damage. EGCG exerted growth-inhibitory and bactericidal activities on C. difficile in C. difficile-infected mice. Our results suggest that EGCG has significant antipathogenic effects on C. difficile and can be used to prevent or treat C. difficile-associated diseases or C. difficile infections.

  13. Inhibitory Effect of Epigallocatechin Gallate on the Virulence of Clostridium difficile PCR Ribotype 027.

    PubMed

    Yun, Bohyun; Oh, Seunghan; Song, Minyu; Hong, Young-Shick; Park, Sungsu; Park, Dong-June; Griffiths, Mansel W; Oh, Sejong

    2015-12-01

    Clostridium difficile infection (CDI) is the most prevalent cause of health-care-associated infections. CDI-related health-care costs and deaths are both increasing annually on a global scale. C. difficile have been reported in food products in Canada, Europe, and the United States; however, the systematic transmission of C. difficile between humans and animals is yet to be understood. Because of the limitations of current therapeutic options, there is a need for the development of new patient treatments. Epigallocatechin gallate (EGCG) is a major catechin compound found in green tea extracts and exhibits antioxidant and antimicrobial activities. This study was conducted to investigate the inhibitory effects of EGCG on the expression of virulence genes in C. difficile and in C. difficile-associated diseases by inhibition of quorum sensing. The protein expression of autoinducer-2 (AI-2) was evaluated by AI-2 activity. EGCG at various concentrations had an inhibitory effect on AI-2 production, especially at 10 μg/mL. EGCG also significantly repressed the transcription of virulence genes, including luxS and tcdA, and prolonged the survival of Caenorhabditis elegans infected with C. difficile. Furthermore, treatment with EGCG effectively protected C. difficile-infected mice from C. difficile-induced death. Histological analysis of the colon and cecum of these mice revealed that EGCG protected tissues of the lower intestinal tract from damage. EGCG exerted growth-inhibitory and bactericidal activities on C. difficile in C. difficile-infected mice. Our results suggest that EGCG has significant antipathogenic effects on C. difficile and can be used to prevent or treat C. difficile-associated diseases or C. difficile infections. PMID:26556797

  14. Inhibitory avoidance learning in zebrafish (Danio rerio): effects of shock intensity and unraveling differences in task performance.

    PubMed

    Manuel, Remy; Gorissen, Marnix; Roca, Carme Piza; Zethof, Jan; van de Vis, Hans; Flik, Gert; van den Bos, Ruud

    2014-08-01

    The zebrafish (Danio rerio) is increasingly used as a model in neurobehavioral and neuroendocrine studies. The inhibitory avoidance paradigm has been proposed as tool to study mechanisms underlying learning and memory in zebrafish. In this paradigm subjects receive a shock after entering the black compartment of a black-white box. On the next day, latency to enter the black compartment is assessed; higher latencies are indicative of increased avoidance learning. Here, we aimed to understand the effects of different shock intensities (0, 1, 3, and 9 V) and to unravel variation in inhibitory avoidance learning in an in-house reared Tuebingen Long-Fin zebrafish (D. rerio) strain. While median latencies had increased in the 1, 3, and 9 V groups, no increase in median latency was found in the 0 V group. In addition, higher shock intensities resulted in a higher number of avoiders (latency ≥180 s) over nonavoiders (latency <60 s). Both changes are indicative of increased avoidance learning. We assessed whole-body cortisol content and the expression levels of genes relevant to stress, anxiety, fear, and learning 2 h after testing. Shock intensity was associated with whole-body cortisol content and the expression of glucocorticoid receptor alpha [nr3c1(alpha)], cocaine- and amphetamine-regulated transcript (cart4), and mineralocorticoid receptor (nr3c2), while avoidance behavior was associated with whole-body cortisol content only. The inhibitory avoidance paradigm in combination with measuring whole-body cortisol content and gene expression is suitable to unravel (genetic) mechanisms of fear avoidance learning. Our data further show differences in brain-behavior relationships underlying fear avoidance learning and memory in zebrafish. These findings serve as starting point for further unraveling differences in brain-behavior relationships underlying (fear avoidance) learning and memory in zebrafish.

  15. Inhibitory Avoidance Learning in Zebrafish (Danio Rerio): Effects of Shock Intensity and Unraveling Differences in Task Performance

    PubMed Central

    Gorissen, Marnix; Piza Roca, Carme; Zethof, Jan; van de Vis, Hans; Flik, Gert; van den Bos, Ruud

    2014-01-01

    Abstract The zebrafish (Danio rerio) is increasingly used as a model in neurobehavioral and neuroendocrine studies. The inhibitory avoidance paradigm has been proposed as tool to study mechanisms underlying learning and memory in zebrafish. In this paradigm subjects receive a shock after entering the black compartment of a black-white box. On the next day, latency to enter the black compartment is assessed; higher latencies are indicative of increased avoidance learning. Here, we aimed to understand the effects of different shock intensities (0, 1, 3, and 9 V) and to unravel variation in inhibitory avoidance learning in an in-house reared Tuebingen Long-Fin zebrafish (D. rerio) strain. While median latencies had increased in the 1, 3, and 9 V groups, no increase in median latency was found in the 0 V group. In addition, higher shock intensities resulted in a higher number of avoiders (latency ≥180 s) over nonavoiders (latency <60 s). Both changes are indicative of increased avoidance learning. We assessed whole-body cortisol content and the expression levels of genes relevant to stress, anxiety, fear, and learning 2 h after testing. Shock intensity was associated with whole-body cortisol content and the expression of glucocorticoid receptor alpha [nr3c1(alpha)], cocaine- and amphetamine-regulated transcript (cart4), and mineralocorticoid receptor (nr3c2), while avoidance behavior was associated with whole-body cortisol content only. The inhibitory avoidance paradigm in combination with measuring whole-body cortisol content and gene expression is suitable to unravel (genetic) mechanisms of fear avoidance learning. Our data further show differences in brain-behavior relationships underlying fear avoidance learning and memory in zebrafish. These findings serve as starting point for further unraveling differences in brain-behavior relationships underlying (fear avoidance) learning and memory in zebrafish. PMID:25004302

  16. Inhibitory effect of the recombinant Phoneutria nigriventer Tx1 toxin on voltage-gated sodium channels.

    PubMed

    Silva, Anita O; Peigneur, Steve; Diniz, Marcelo R V; Tytgat, Jan; Beirão, Paulo S L

    2012-12-01

    Phoneutria nigriventer toxin Tx1 (PnTx1, also referred to in the literature as Tx1) exerts inhibitory effect on neuronal (Na(V)1.2) sodium channels in a way dependent on the holding potential, and competes with μ-conotoxins but not with tetrodotoxin for their binding sites. In the present study we investigated the electrophysiological properties of the recombinant toxin (rPnTx1), which has the complete amino acid sequence of the natural toxin with 3 additional residues: AM on the N-terminal and G on the C-terminal. At the concentration of 1.5 μM, the recombinant toxin inhibits Na(+) currents of dorsal root ganglia neurons (38.4 ± 6.1% inhibition at -80 mV holding potential) and tetrodotoxin-resistant Na(+) currents (26.2 ± 4.9% at the same holding potential). At -50 mV holding potential the inhibition of the total current reached 71.3 ± 2.3% with 1.5 μM rPnTx1. The selectivity of rPnTx1 was investigated on ten different isoforms of voltage-gated sodium channels expressed in Xenopus oocytes. The order of potency for rPnTx1 was: rNa(V)1.2 > rNa(V)1.7 ≈ rNa(V)1.4 ≥ rNa(V)1.3 > mNa(V)1.6 ≥ hNa(V)1.8. No effect was seen on hNa(V)1.5 and on the arthropods isoforms (DmNa(V)1, BGNa(V)1.1a and VdNa(V)1). The IC(50) for Na(V)1.2 was 33.7 ± 2.9 nM with a maximum inhibition of 83.3 ± 1.9%. The toxin did not alter the voltage-dependence of channel gating and was effective on Na(V)1.2 channels devoid of inactivation. It was ineffective on neuronal calcium channels. We conclude that rPnTx1 has a promising selectivity, and that it may be a valuable model to achieve pharmacological activities of interest for the treatment of channelopathies and neuropathic pain. PMID:22968173

  17. Differential inhibitory effects of methylmalonic acid on respiratory chain complex activities in rat tissues.

    PubMed

    Pettenuzzo, Leticia F; Ferreira, Gustavo da C; Schmidt, Anna Laura; Dutra-Filho, Carlos S; Wyse, Angela T S; Wajner, Moacir

    2006-02-01

    Methylmalonic acidemia is an inherited metabolic disorder biochemically characterized by tissue accumulation of methylmalonic acid (MMA) and clinically by progressive neurological deterioration and kidney failure, whose pathophysiology is so far poorly established. Previous studies have shown that MMA inhibits complex II of the respiratory chain in rat cerebral cortex, although no inhibition of complexes I-V was found in bovine heart. Therefore, in the present study we investigated the in vitro effect of 2.5mM MMA on the activity of complexes I-III, II, II-III and IV in striatum, hippocampus, heart, liver and kidney homogenates from young rats. We observed that MMA caused a significant inhibition of complex II activity in striatum and hippocampus (15-20%) at low concentrations of succinate in the medium, but not in the peripheral tissues. We also verified that the inhibitory property of MMA only occurred after exposing brain homogenates for at least 10 min with the acid, suggesting that this inhibition was mediated by indirect mechanisms. Simultaneous preincubation with the nitric oxide synthase inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME) and catalase (CAT) plus superoxide dismutase (SOD) did not prevent MMA-induced inhibition of complex II, suggesting that common reactive oxygen (superoxide, hydrogen peroxide and hydroxyl radical) and nitric (nitric oxide) species were not involved in this effect. In addition, complex II-III (20-35%) was also inhibited by MMA in all tissues tested, and complex I-III only in the kidney (53%) and liver (38%). In contrast, complex IV activity was not changed by MMA in all tissues studied. These results indicate that MMA differentially affects the activity of the respiratory chain pending on the tissues studied, being striatum and hippocampus more vulnerable to its effect. In case our in vitro data are confirmed in vivo in tissues from methylmalonic acidemic patients, it is feasible that that the present findings may be

  18. Photosensitizing and Inhibitory Effects of Ozonated Dissolved Organic Matter on Triplet-Induced Contaminant Transformation.

    PubMed

    Wenk, Jannis; Aeschbacher, Michael; Sander, Michael; von Gunten, Urs; Canonica, Silvio

    2015-07-21

    Dissolved organic matter (DOM) is both a promoter and an inhibitor of triplet-induced organic contaminant oxidation. This dual role was systematically investigated through photochemical experiments with three types of DOM of terrestrial and aquatic origins that were preoxidized to varying extents by ozonation. The inhibitory effect of DOM was assessed by determining the 4-carboxybenzophenone photosensitized transformation rate constants of two sulfonamide antibiotics (sulfamethoxazole and sulfadiazine) in the presence of untreated or preoxidized DOM. The inhibitory effect decreased with the increasing extent of DOM preoxidation, and it was correlated to the loss of phenolic antioxidant moieties, as quantified electrochemically, and to the loss of DOM ultraviolet absorbance. The triplet photosensitizing ability of preoxidized DOM was determined using the conversion of the probe compound 2,4,6-trimethylphenol (TMP), which is unaffected by DOM inhibition effects. The DOM photosensitized transformation rate constants of TMP decreased with increasing DOM preoxidation and were correlated to the concomitant loss of chromophores (i.e., photosensitizing moieties). The combined effects of DOM preoxidation on the inhibiting and photosensitizing properties were assessed by phototransformation experiments of the sulfonamides in DOM-containing solutions. At low extents of DOM preoxidation, the sulfonamide phototransformation rate constants remained either unchanged or slightly increased, indicating that the removal of antioxidant moieties had larger effects than the loss of photosensitizing moieties. At higher extents of DOM preoxidation, transformation rates declined, mainly reflecting the destruction of photosensitizing moieties. PMID:26091366

  19. Cox-2 inhibitory effects of naturally occurring and modified fatty acids.

    PubMed

    Ringbom, T; Huss, U; Stenholm, A; Flock, S; Skattebøl, L; Perera, P; Bohlin, L

    2001-06-01

    In the search for new cyclooxygenase-2 (COX-2) selective inhibitors, the inhibitory effects of naturally occurring fatty acids and some of their structural derivatives on COX-2-catalyzed prostaglandin biosynthesis were investigated. Among these fatty acids, linoleic acid (LA), alpha-linolenic acid (alpha-LNA), myristic acid, and palmitic acid were isolated from a CH(2)Cl(2) extract of the plant Plantago major by bioassay-guided fractionation. Inhibitory effects of other natural, structurally related fatty acids were also investigated: stearic acid, oleic acid, pentadecanoic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Further, the inhibitory effects of these compounds on COX-2- and COX-1-catalyzed prostaglandin biosynthesis was compared with the inhibition of some synthesized analogues of EPA and DHA with ether or thioether functions. The most potent COX-2-catalyzed prostaglandin biosynthesis inhibitor was all-(Z)-5-thia-8,11,14,17-eicosatetraenoic acid (2), followed by EPA, DHA, alpha-LNA, LA, (7E,11Z,14Z,17Z)-5-thiaeicosa-7,11,14,17-tetraenoic acid, all-(Z)-3-thia-6,9,12,15-octadecatetraenoic acid, and (5E,9Z,12Z,15Z,18Z)-3-oxaheneicosa-5,9,12,15,18-pentaenoic acid, with IC(50) values ranging from 3.9 to180 microM. The modified compound 2 and alpha-LNA were most selective toward COX-2, with COX-2/COX-1 ratios of 0.2 and 0.1, respectively. This study shows that several of the natural fatty acids as well as all of the semisynthetic thioether-containing fatty acids inhibited COX-2-catalyzed prostaglandin biosynthesis, where alpha-LNA and compound 2 showed selectivity toward COX-2. PMID:11421736

  20. [Inhibitory effect of methyl esters of arginine-containing oligopeptides on thrombin and trypsin].

    PubMed

    Poiarkova, S A; Kibirev, V K; Serebrianyĭ, S B

    1987-01-01

    Stereoisomeric oligopeptides were studied for their inhibitory effect on the hydrolysis of benzoyl-L-arginine methyl ester catalyzed by thrombin and trypsin, as well as on the thrombin-fibrinogen reaction. Comparison of the peptide structures, their conformational flexibility and inhibitory effects on thrombin and trypsin shows the availability of the essential differences in organization and functioning of the subsites S3, S2 and S'1 of these enzymes. In contrast to trypsin, thrombin is shown to be characterized by more pronounced secondary stereospecificity. This manifests in the more vigorous dropping of the catalytic constants of thrombin-catalyzed esterolysis than those of trypsin-catalyzed hydrolysis of the substrates, containing D-amino acids at the subsite P2. It is revealed that the peptide Tos-D-Val-D-Ala-D-Agr-D-Phe-OCH3 is the most powerful inhibitor among studied compounds. It is noteworthy that its antithrombin effect is almost an order of magnitude higher than its antitrypsin effect.

  1. Increasing Pain Sensation Eliminates the Inhibitory Effect of Depression on Evoked Pain in Rats

    PubMed Central

    Wang, Ning; Li, Sheng-Guang; Lin, Xiao-Xiao; Su, Yuan-Lin; Qi, Wei-Jing; Wang, Jin-Yan; Luo, Fei

    2016-01-01

    Although previous studies have suggested that depression may be associated with inhibition of evoked pain but facilitation of spontaneous pain, the mechanisms underlying these relationships are unclear. The present study investigated whether the difference between evoked and spontaneous pain on sensory (descending inhibition) and affective (avoidance motivation) components contributes to the divergent effects of depression on them. Depressive-like behavior was produced in male Wistar rats by unpredictable chronic mild stress (UCMS). Tone-laser conditioning and formalin-induced conditioned place avoidance (F-CPA) were used to explore avoidance motivation in evoked and spontaneous pain, respectively. Behavioral pharmacology experiments were conducted to examine descending inhibition of both evoked (thermal stimulation) and spontaneous pain behavior (formalin pain). The results revealed that the inhibitory effect of depression on evoked pain was eliminated following repeated thermal stimuli. Avoidance behavior in the tone-laser conditioning task was reduced in UCMS rats, relative to controls. However, avoidance motivation for formalin pain in the UCMS group was similar to controls. 5-HT1A receptor antagonism interfered with inhibition of pain responses over time. The present study demonstrated that the inhibitory effect of depression on evoked pain dissipates with increased nociception and that the sensory-discriminative and affective-motivational components of pain are jointly involved in the divergent effects of depression on pain. PMID:27733820

  2. Inhibitory effect of melatonin on testosterone synthesis is mediated via GATA-4/SF-1 transcription factors.

    PubMed

    Qin, Fenju; Zhang, Jie; Zan, Linsen; Guo, Weiqiang; Wang, Jin; Chen, Lili; Cao, Yi; Shen, Ouxi; Tong, Jian

    2015-11-01

    The aim of the present study was to elucidate whether the GATA-4/SF-1 signalling pathway is involved in the inhibitory effects of melatonin on testosterone production in both the TM3 Leydig cell line and in C57BL/6J mice. In-vitro experiments demonstrated that melatonin treatment significantly reduced testosterone levels in cell culture medium (P < 0.05 or P < 0.01); and decreased intracellular cyclic adenosine monophospha accumulation (P < 0.05 or P < 0.01) and mRNA/protein expression of GATA-4, SF-1 (NR5A1), StAR, P450SCC (CYP11A1) and 3β-HSD (P < 0.05 or P < 0.01). These effects were blocked by N-acetyl-2-benzyltryptamin, a melatonin receptor antagonist. Similar effects of melatonin on testosterone production (P < 0.05 or P < 0.01) and down-regulation of transcription factors GATA-4 and SF-1 (P < 0.01) were also observed in mice treated with intratesticular injections of melatonin. Overall, the data suggest that the inhibitory effects of melatonin on testosterone production are mediated via down-regulation of GATA-4 and SF-1 expression.

  3. Effect of Zn2+ on the proteolytic inhibitory action of insulin and biguanide antihyperglycemic drugs.

    PubMed

    Thorne, D P; Lockwood, T D

    1991-05-01

    The involvement of Zn2+ in the inhibitory action of insulin and phenformin on bulk proteolysis was studied in the Langendorff rat heart with a Zn(2+)-buffering perfusate (0.1 mM citrate, physiological complete amino acids and 0.2% albumin). Proteins were biosynthetically labeled in vitro for 10 min with [3H]leucine. Rapidly degraded proteins were eliminated during a 3-h preliminary degradation without insulin or added Zn2+ (2 mM nonradioactive leucine). Insulin (5 nM), the lysosomal inhibitor chloroquine (30 microM), and the biguanide antihyperglycemic agent phenformin (2 microns) each caused a sustained 35-40% inhibition of [3H]leucine release beginning within 1-2 min and reaching a maximum at 1-1.5 h. When these agents were combined, their simultaneous proteolytic inhibitory effects were not appreciably greater than the effect of chloroquine alone. Infusion of supraphysiological perfusate Zn2+ (greater than 15 microM) mimicked the inhibitory effect of insulin and chloroquine on lysosomal proteolysis. Infusion of supraphysiological Co2+, Mn2+, Fe2+, and Cr3+ (30 microM, 0.5 h) caused no change in proteolysis; however, 30 microM Cu2+ caused a slight inhibition. Presumptive chelation of the background (approximately 20 nM) Zn2+ by infusion of 3 microM CaNa2 EDTA caused no change in protein degradation over 1-2 h. The infusion of a physiological concentration of 1 or 5 microM Zn2+ (as ZnCl2) caused no change in protein degradation over 1-2 h. Biguanides are known to reversibly form a Zn2+ complex with affinity less than that of Zn2+ for EDTA. Prior infusion of 3 microM CaNa2 EDTA inactivated the proteolytic inhibitory effect of maximal (2 microM) phenformin over at least 1.25 h of concurrent infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. New secoiridoids from the fruits of Ligustrum lucidum Ait with triglyceride accumulation inhibitory effects.

    PubMed

    Zhang, Yi; Liu, Lili; Gao, Jing; Wu, Chunhua; Han, Lifeng; Liu, Erwei; Shi, Pingping; Gao, Xiumei; Wang, Tao

    2013-12-01

    Five new secoiridoids, nuzhenal C (1), 6'-O-trans-cinnamoyl iso-8-epikingisidic acid (2), ligulucidumosides A (3), B (4), and C (5), were obtained from the fruits of Ligustrum lucidum Ait. Their structures were elucidated by chemical and spectroscopic methods (UV, IR, HRESI-TOF-MS, 1D and 2D NMR). Among them, compound 3 is the first 1-OCH3 substituent secoiridoid obtained from plant kingdom. Furthermore, activity screening results showed that all of the isolates had triglyceride accumulation inhibitory effects in HepG2 cells. PMID:24001714

  5. Effect of inhibitory species on electrochemical corrosion of high copper amalgam.

    PubMed

    Naguib, E A

    1994-07-01

    This investigation evaluates the corrosion potential of high copper amalgam containing inhibitory species, sodium phosphate and sodium citrate, in artificial saliva at different pH levels. The data revealed that the phosphate incorporated in high copper amalgam leads to increase in passivation of the alloy as compared to less or even negative effect of citrate incorporation. The linear steady potential of the amalgam was closer to the reversible potentials corresponding to hydrogen evolution and tin oxide formation. The corrosion potential does not respond reversibly to pH of the saliva solution due to the pronounced passivation of the high pH levels. PMID:9588156

  6. Selective LXR{alpha} inhibitory effects observed in plant extracts of MEH184 (Parthenocissua tricuspidata) and MEH185 (Euscaphis japonica)

    SciTech Connect

    Kim, Kang Ho; Choi, Seung Hyun; Lee, Thomas S.; Oh, Won Keun; Kim, Dong Sun; Kim, Jae Bum . E-mail: jaebkim@snu.ac.kr

    2006-10-20

    Liver X receptors (LXRs) are nuclear hormone receptors that behave as lipid sensors of cellular cholesterol and fatty acid. Although LXR activation can alleviate hypercholesterolemia by inducing cholesterol efflux, it also results in undesirable effects of fatty acid synthesis, resulting in hepatic steatosis and hyperlipidemia. Therefore, it is critical to identify LXR{alpha} inhibitory agents that would repress fatty acid synthesis and hepatic lipid accumulation. In current study, screening of plant extracts used for traditional oriental medicine resulted in the identification of two candidates demonstrating selective LXR{alpha} inhibitory activity. These were whole leaf methanol extracts of Parthenocissua tricuspidata (MEH184) and Euscaphis japonica (MEH185). Both MEH184 and MEH185 decreased transcriptional activity of LXR{alpha} and the expression of LXR{alpha} target genes, such as FAS and ADD1/SREBP1c. Additionally, MEH184 and MEH184 significantly reduced lipogenesis and adipocyte differentiation. Together, the data imply that MEH184 and MEH185 possess selective antagonistic properties on LXR{alpha} to downregulate lipogenesis.

  7. Identification of benzoquinones in pretreated lignocellulosic feedstocks and inhibitory effects on yeast.

    PubMed

    Stagge, Stefan; Cavka, Adnan; Jönsson, Leif J

    2015-12-01

    Pretreatment of lignocellulosic biomass under acidic conditions gives rise to by-products that inhibit fermenting microorganisms. An analytical procedure for identification of p-benzoquinone (BQ) and 2,6-dimethoxybenzoquinone (DMBQ) in pretreated biomass was developed, and the inhibitory effects of BQ and DMBQ on the yeast Saccharomyces cerevisiae were assessed. The benzoquinones were analyzed using ultra-high performance liquid chromatography-electrospray ionization-triple quadrupole-mass spectrometry after derivatization with 2,4-dinitrophenylhydrazine. Pretreatment liquids examined with regard to the presence of BQ and DMBQ originated from six different lignocellulosic feedstocks covering agricultural residues, hardwood, and softwood, and were produced through impregnation with sulfuric acid or sulfur dioxide at varying pretreatment temperature (165-204 °C) and residence time (6-20 min). BQ was detected in all six pretreatment liquids in concentrations ranging up to 6 mg/l, while DMBQ was detected in four pretreatment liquids in concentrations ranging up to 0.5 mg/l. The result indicates that benzoquinones are ubiquitous as by-products of acid pretreatment of lignocellulose, regardless of feedstock and pretreatment conditions. Fermentation experiments with BQ and DMBQ covered the concentration ranges 2 mg/l to 1 g/l and 20 mg/l to 1 g/l, respectively. Even the lowest BQ concentration tested (2 mg/l) was strongly inhibitory to yeast, while 20 mg/l DMBQ gave a slight negative effect on ethanol formation. This work shows that benzoquinones should be regarded as potent and widespread inhibitors in lignocellulosic hydrolysates, and that they warrant attention besides more well-studied inhibitory substances, such as aliphatic carboxylic acids, phenols, and furan aldehydes. PMID:26384342

  8. Inhibitory effect of curcuminoids and tetrahydrocurcuminoids on equine activated neutrophils and myeloperoxidase activity.

    PubMed

    Franck, T; Kohnen, S; Grulke, S; Neven, P; Goutman, Y; Peters, F; Pirotte, B; Deby-Dupont, G; Serteyn, D

    2008-01-01

    In the horse, the inflammation response to various pathologies (intestinal strangulations, laminitis, etc.) involves an excessive stimulation of the polymorphonuclear neutrophils releasing reactive oxygen species (ROS) and myeloperoxidase (MPO). The aim of the present work was to study the effect of natural polyphenols, curcuminoids and tetrahydrocurcuminoids (THC) on isolated stimulated equine neutrophils and on the activity of purified MPO. The ROS production and the release of MPO by activated neutrophils were measured by chemiluminescence and ELISA techniques, respectively. The activity of purified MPO was measured by studying its nitration, chlorination or oxidation capacity and by using an original method called SIEFED allowing the study of drug interaction with the enzyme without interferences of the medium. Curcuminoids and THC had dose-dependent inhibitory effects on ROS production and MPO release by activated neutrophils and on purified MPO activity. We suggest that the higher efficacy of curcuminoids versus THC could be explained, at least partially, by its chemical structure: the conjugated double bounds and the plane structure of curcuminoids made easier the neutralization of the radical species generated by activated neutrophils and the interaction of the drug with the active site of MPO. These inhibitory effects of curcuminoids on the oxidant activity of equine neutrophils and on MPO activity open therapeutic perspectives in equine pathologies with excessive inflammatory reactions.

  9. Dopamine transporter inhibitory and antiparkinsonian effect of common flowering quince extract.

    PubMed

    Zhao, Gang; Jiang, Zhi-Hua; Zheng, Xiang-Wei; Zang, Shao-Yun; Guo, Li-He

    2008-09-01

    Common flowering quince (FQ) is the fruit of Chaenomeles speciosa (Sweet) Nakai. FQ-containing cocktails have been applied to the treatment of neuralgia, migraine, and depression in traditional Chinese medicine. The present study assessed whether FQ is effective in dopamine transporter (DAT) regulation and antiparkinsonism by utilizing in vitro and in vivo assays, respectively. FQ at concentrations of 1-1000 microg/ml concentration-dependently inhibited dopamine uptake by Chinese hamster ovary (CHO) cells stably expressing DAT (D8 cells) and by synaptosomes. FQ had a slight inhibitory action on norepinephrine uptake by CHO cells expressing the norepinephrine transporter and no inhibitory effect on gamma-aminobutyric acid (GABA) uptake by CHO cells expressing GABA transporter-1 or serotonin uptake by the serotonin transporter. A viability assay showed that FQ mitigated 1-methyl-4-phenylpyridinium-induced toxicity in D8 cells. Furthermore, in behavioral studies, FQ alleviated rotational behavior in 6-hydroxydopamine-treated rats and improved deficits in endurance performance in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. Furthermore, immunohistochemistry revealed that FQ markedly reduced the loss of tyrosine hydroxylase-positive neurons in the substantia nigra in MPTP-treated mice. In summary, FQ is a selective, potent DAT inhibitor and has antiparkinsonian-like effects that are mediated possibly by DAT suppression. FQ has the potential to be further developed for Parkinson's disease treatment.

  10. The effects of inhibitory control training for preschoolers on reasoning ability and neural activity.

    PubMed

    Liu, Qian; Zhu, Xinyi; Ziegler, Albert; Shi, Jiannong

    2015-09-23

    Inhibitory control (including response inhibition and interference control) develops rapidly during the preschool period and is important for early cognitive development. This study aimed to determine the training and transfer effects on response inhibition in young children. Children in the training group (N = 20; 12 boys, mean age 4.87 ± 0.26 years) played "Fruit Ninja" on a tablet computer for 15 min/day, 4 days/week, for 3 weeks. Children in the active control group (N = 20; 10 boys, mean age 4.88 ± 0.20 years) played a coloring game on a tablet computer for 10 min/day, 1-2 days/week, for 3 weeks. Several cognitive tasks (involving inhibitory control, working memory, and fluid intelligence) were used to evaluate the transfer effects, and electroencephalography (EEG) was performed during a go/no-go task. Progress on the trained game was significant, while performance on a reasoning task (Raven's Progressive Matrices) revealed a trend-level improvement from pre- to post-test. EEG indicated that the N2 effect of the go/no-go task was enhanced after training for girls. This study is the first to show that pure response inhibition training can potentially improve reasoning ability. Furthermore, gender differences in the training-induced changes in neural activity were found in preschoolers.

  11. Inhibitory Effects of Spices on Biogenic Amine Accumulation during Fish Sauce Fermentation.

    PubMed

    Zhou, Xuxia; Qiu, Mengting; Zhao, Dandan; Lu, Fei; Ding, Yuting

    2016-04-01

    The presence of high levels of biogenic amines is detrimental to the quality and safety of fish sauce. This study investigated the effects of ethanol extracts of spices, including garlic, ginger, cinnamon, and star anise extracts, in reducing the accumulation of biogenic amines during fish sauce fermentation. The concentrations of biogenic amines, which include histamine, putrescine, tyramine, and spermidine, all increased during fish sauce fermentation. When compared with the samples without spices, the garlic and star anise extracts significantly reduced these increases. The greatest inhibitory effect was observed for the garlic ethanolic extracts. When compared with controls, the histamine, putrescine, tyramine, and spermidine contents and the overall biogenic amine levels of the garlic extract-treated samples were reduced by 30.49%, 17.65%, 26.03%, 37.20%, and 27.17%, respectively. The garlic, cinnamon, and star anise extracts showed significant inhibitory effects on aerobic bacteria counts. Furthermore, the garlic and star anise extracts showed antimicrobial activity against amine producers. These findings may be helpful for enhancing the safety of fish sauce.

  12. The α-amylase and α-glucosidase inhibitory effects of Irish seaweed extracts.

    PubMed

    Lordan, Sinéad; Smyth, Thomas J; Soler-Vila, Anna; Stanton, Catherine; Ross, R Paul

    2013-12-01

    To date, numerous studies have reported on the antidiabetic properties of various plant extracts through inhibition of carbohydrate-hydrolysing enzymes. The objective of this research was to evaluate extracts of seaweeds for α-amylase and α-glucosidase inhibitory effects. Cold water and ethanol extracts of 15 seaweeds were initially screened and from this, five brown seaweed species were chosen. The cold water and ethanol extracts of Ascophyllum nodosum had the strongest α-amylase inhibitory effect with IC50 values of 53.6 and 44.7 μg/ml, respectively. Moreover, the extracts of Fucus vesiculosus Linnaeus were found to be potent inhibitors of α-glucosidase with IC50 values of 0.32 and 0.49 μg/ml. The observed effects were associated with the phenolic content and antioxidant activity of the extracts, and the concentrations used were below cytotoxic levels. Overall, our findings suggest that brown seaweed extracts may limit the release of simple sugars from the gut and thereby alleviate postprandial hyperglycaemia.

  13. The α-amylase and α-glucosidase inhibitory effects of Irish seaweed extracts.

    PubMed

    Lordan, Sinéad; Smyth, Thomas J; Soler-Vila, Anna; Stanton, Catherine; Ross, R Paul

    2013-12-01

    To date, numerous studies have reported on the antidiabetic properties of various plant extracts through inhibition of carbohydrate-hydrolysing enzymes. The objective of this research was to evaluate extracts of seaweeds for α-amylase and α-glucosidase inhibitory effects. Cold water and ethanol extracts of 15 seaweeds were initially screened and from this, five brown seaweed species were chosen. The cold water and ethanol extracts of Ascophyllum nodosum had the strongest α-amylase inhibitory effect with IC50 values of 53.6 and 44.7 μg/ml, respectively. Moreover, the extracts of Fucus vesiculosus Linnaeus were found to be potent inhibitors of α-glucosidase with IC50 values of 0.32 and 0.49 μg/ml. The observed effects were associated with the phenolic content and antioxidant activity of the extracts, and the concentrations used were below cytotoxic levels. Overall, our findings suggest that brown seaweed extracts may limit the release of simple sugars from the gut and thereby alleviate postprandial hyperglycaemia. PMID:23870944

  14. Picture-word interference reveals inhibitory effects of syllable frequency on lexical selection.

    PubMed

    Farrell, Meagan T; Abrams, Lise

    2014-01-01

    While previous research has shown that high syllable frequency can facilitate speech production at the level of phonological/phonetic encoding, little is known about its influence on prephonological processes, specifically lexical selection. The current study used a picture-word interference (PWI) task to (a) shed light on the stages of lexical access where syllable frequency is relevant, and (b) inform as to whether lexical selection is accomplished via competition among activated word options. Participants named pictures whose names had high-frequency (HF) and low-frequency (LF) first syllables while ignoring phonologically related (same first syllable) or unrelated distractor words that were presented simultaneously. Word frequency was also manipulated, as half of the targets were HF words, and half were LF words. Results revealed inhibitory syllable frequency effects in all conditions, such that targets with HF first syllables were named more slowly than targets with LF first syllables. However, inhibitory syllable frequency effects were exacerbated in conditions thought to reflect heightened lexical competition, specifically in the presence of phonologically related distractors and for targets with low word frequency. These findings reveal novel evidence for first-syllable frequency effects on lexical selection and offer further support for models proposing delays at lexical selection due to activation of nontarget competitors. PMID:23931573

  15. Inhibitory effects of neferine on Nav1.5 channels expressed in HEK293 cells.

    PubMed

    Wang, Chen; Wang, Huan; Xiao, Jun-Hua; Wang, Jia-Ling; Xiang, Ji-Zhou; Tang, Qiang

    2016-08-01

    Neferine, a bisbenzylisoquinoline alkaloid in Lotus Plumule, was proved to have a wide range of biological activities. In the present study, using whole-cell patch-clamp technique, we investigated the effects of neferine on Nav1.5 channels that are stably expressed in HEK 293 cells. We found that neferine potently and reversibly inhibited Nav1.5 currents in a concentration dependent manner with a half-maximal inhibition (IC50) being 26.15 μmol/L. The inhibitory effects of neferine on Nav1.5 currents were weaker than those of quinidine at the same concentration. The steady-state inactivation curve was significantly shifted towards hyperpolarizing direction in the presence of 30 μmol/L neferine, while the voltage-dependent activation was unaltered. Neferine prolonged the time to peak of activation, increased the inactivation time constants of Nav1.5 currents and markedly slowed the recovery from inactivation. The inhibitory effect of neferine could be potentiated in a frequency-dependent manner. These results suggested that neferine can block Nav1.5 channels under the open state and inactivating state and it is an open channel blocker of Nav1.5 channels. PMID:27465321

  16. Inhibitory effects of amines from Citrus reticulata on bleomycin-induced pulmonary fibrosis in rats.

    PubMed

    Zhou, Xian-Mei; Cao, Zhen-Dong; Xiao, Na; Shen, Qi; Li, Jian-Xin

    2016-02-01

    Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal lung disease for which, thus far, there are no effective treatments. The pericarp of Citrus reticulata, as a traditional herbal drug, has been used for the clinical treatment of lung-related diseases in China for many years. In the present study, the amines from the pericarp of Citrus reticulata were isolated, and their hydrochlorides were prepared. The results of screening using cultured human embryonic lung fibroblasts (hELFs) revealed that, of the amines, 4-methoxyphenethylamine hydrochloride (designated as amine hydrochloride 1) possessed the most potent inhibitory effect. Further in vivo experiments using a rat model of bleomycin-induced pulmonary fibrosis demonstrated that the oral administration of amine hydrochloride 1 significantly lowered the hydroxyproline content in both serum and lung tissue, and alleviated pulmonary alveolitis and fibrosis. Immunohistochemical analysis revealed that amine hydrochloride 1 exerted its inhibitory effect against IPF through the downregulation of lung transforming growth factor (TGF)-β1 protein expression. Our results demonstrated that amine hydrochloride 1 prevented the development of bleomycin‑induced lung fibrosis in rats. Thus, our data suggest that the amines from the pericarp of Citrus reticulata have therapeutic potential for use in the treatment of IPF. PMID:26675886

  17. Inhibitory effects of amines from Citrus reticulata on bleomycin-induced pulmonary fibrosis in rats

    PubMed Central

    ZHOU, XIAN-MEI; CAO, ZHEN-DONG; XIAO, NA; SHEN, QI; LI, JIAN-XIN

    2016-01-01

    Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal lung disease for which, thus far, there are no effective treatments. The pericarp of Citrus reticulata, as a traditional herbal drug, has been used for the clinical treatment of lung-related diseases in China for many years. In the present study, the amines from the pericarp of Citrus reticulata were isolated, and their hydrochlorides were prepared. The results of screening using cultured human embryonic lung fibroblasts (hELFs) revealed that, of the amines, 4-methoxyphenethylamine hydrochloride (designated as amine hydrochloride 1) possessed the most potent inhibitory effect. Further in vivo experiments using a rat model of bleomycin-induced pulmonary fibrosis demonstrated that the oral administration of amine hydrochloride 1 significantly lowered the hydroxyproline content in both serum and lung tissue, and alleviated pulmonary alveolitis and fibrosis. Immunohistochemical analysis revealed that amine hydrochloride 1 exerted its inhibitory effect against IPF through the downregulation of lung transforming growth factor (TGF)-β1 protein expression. Our results demonstrated that amine hydrochloride 1 prevented the development of bleomycin-induced lung fibrosis in rats. Thus, our data suggest that the amines from the pericarp of Citrus reticulata have therapeutic potential for use in the treatment of IPF. PMID:26675886

  18. The effects of inhibitory control training for preschoolers on reasoning ability and neural activity

    PubMed Central

    Liu, Qian; Zhu, Xinyi; Ziegler, Albert; Shi, Jiannong

    2015-01-01

    Inhibitory control (including response inhibition and interference control) develops rapidly during the preschool period and is important for early cognitive development. This study aimed to determine the training and transfer effects on response inhibition in young children. Children in the training group (N = 20; 12 boys, mean age 4.87 ± 0.26 years) played “Fruit Ninja” on a tablet computer for 15 min/day, 4 days/week, for 3 weeks. Children in the active control group (N = 20; 10 boys, mean age 4.88 ± 0.20 years) played a coloring game on a tablet computer for 10 min/day, 1–2 days/week, for 3 weeks. Several cognitive tasks (involving inhibitory control, working memory, and fluid intelligence) were used to evaluate the transfer effects, and electroencephalography (EEG) was performed during a go/no-go task. Progress on the trained game was significant, while performance on a reasoning task (Raven’s Progressive Matrices) revealed a trend-level improvement from pre- to post-test. EEG indicated that the N2 effect of the go/no-go task was enhanced after training for girls. This study is the first to show that pure response inhibition training can potentially improve reasoning ability. Furthermore, gender differences in the training-induced changes in neural activity were found in preschoolers. PMID:26395158

  19. Inhibitory effect of midkine-binding peptide on tumor proliferation and migration

    PubMed Central

    Huang, Hui-Lian; Shen, Jian-Fen; Min, Li-Shan; Ping, Jin-Liang; Lu, Yong-Liang; Dai, Li-Cheng

    2015-01-01

    Background: To investigate the inhibitory effect of midkine-binding peptides on human umbilical vein endothelial cells (HUVECs) proliferation and angiogenesis of xenograft tumor. Methods: The midkine-binding peptides were panned by Ph.D.-7™ Phage Display Peptide Library Kit, and the specific binding activities of positive clones to target protein were examined by phage ELISA. The effect of midkine-binding peptides on proliferation of HUVECs was confirmed by MTT test. The xenograft tumor model was formed in BALB/c mice with the murine hepatocarcinoma cells H22 (H22). Microvessel density (MVD) was analyzed by immunohistochemistry of factor VIII staining. Results: Midkine-binding peptides have the inhibitory effects on tumor angiogenesis, a proliferation assay using human umbilical vein endothelial cells (HUVECs) indicated that particular midkine-binding peptides significantly inhibited the proliferation of the HUVECs. Midkine-binding peptides were also observed to efficiently suppress angiogenesis induced by murine hepatocarcinoma H22 cells in BALB/c nude mice. Conclusion: The midkine-binding peptides can inhibit solid tumor growth by retarding the formation of new blood vessels. The results indicate that midkine-binding peptides may represent potent anti-angiogenesis agents in vivo. PMID:26191241

  20. Inhibitory Effects of Spices on Biogenic Amine Accumulation during Fish Sauce Fermentation.

    PubMed

    Zhou, Xuxia; Qiu, Mengting; Zhao, Dandan; Lu, Fei; Ding, Yuting

    2016-04-01

    The presence of high levels of biogenic amines is detrimental to the quality and safety of fish sauce. This study investigated the effects of ethanol extracts of spices, including garlic, ginger, cinnamon, and star anise extracts, in reducing the accumulation of biogenic amines during fish sauce fermentation. The concentrations of biogenic amines, which include histamine, putrescine, tyramine, and spermidine, all increased during fish sauce fermentation. When compared with the samples without spices, the garlic and star anise extracts significantly reduced these increases. The greatest inhibitory effect was observed for the garlic ethanolic extracts. When compared with controls, the histamine, putrescine, tyramine, and spermidine contents and the overall biogenic amine levels of the garlic extract-treated samples were reduced by 30.49%, 17.65%, 26.03%, 37.20%, and 27.17%, respectively. The garlic, cinnamon, and star anise extracts showed significant inhibitory effects on aerobic bacteria counts. Furthermore, the garlic and star anise extracts showed antimicrobial activity against amine producers. These findings may be helpful for enhancing the safety of fish sauce. PMID:26953496

  1. Inhibitory effect of tocotrienol on eukaryotic DNA polymerase {lambda} and angiogenesis

    SciTech Connect

    Mizushina, Yoshiyuki . E-mail: mizushin@nutr.kobegakuin.ac.jp; Nakagawa, Kiyotaka; Shibata, Akira; Awata, Yasutoshi; Kuriyama, Isoko; Shimazaki, Noriko; Koiwai, Osamu; Uchiyama, Yukinobu; Sakaguchi, Kengo; Miyazawa, Teruo; Yoshida, Hiromi

    2006-01-20

    Tocotrienols, vitamin E compounds that have an unsaturated side chain with three double bonds, selectively inhibited the activity of mammalian DNA polymerase {lambda} (pol {lambda}) in vitro. These compounds did not influence the activities of replicative pols such as {alpha}, {delta}, and {epsilon}, or even the activity of pol {beta} which is thought to have a very similar three-dimensional structure to the pol {beta}-like region of pol {lambda}. Since {delta}-tocotrienol had the strongest inhibitory effect among the four ({alpha}- to {delta}-) tocotrienols, the isomer's structure might be an important factor in the inhibition of pol {lambda}. The inhibitory effect of {delta}-tocotrienol on both intact pol {lambda} (residues 1-575) and a truncated pol {lambda} lacking the N-terminal BRCA1 C-terminus (BRCT) domain (residues 133-575, del-1 pol {lambda}) was dose-dependent, with 50% inhibition observed at a concentration of 18.4 and 90.1 {mu}M, respectively. However, del-2 pol {lambda} (residues 245-575) containing the C-terminal pol {beta}-like region was unaffected. Tocotrienols also inhibited the proliferation of and formation of tubes by bovine aortic endothelial cells, with {delta}-tocotrienol having the greatest effect. These results indicated that tocotrienols targeted both pol {lambda} and angiogenesis as anti-cancer agents. The relationship between the inhibition of pol {lambda} and anti-angiogenesis by {delta}-tocotrienol was discussed.

  2. The effects of inhibitory control training for preschoolers on reasoning ability and neural activity.

    PubMed

    Liu, Qian; Zhu, Xinyi; Ziegler, Albert; Shi, Jiannong

    2015-01-01

    Inhibitory control (including response inhibition and interference control) develops rapidly during the preschool period and is important for early cognitive development. This study aimed to determine the training and transfer effects on response inhibition in young children. Children in the training group (N = 20; 12 boys, mean age 4.87 ± 0.26 years) played "Fruit Ninja" on a tablet computer for 15 min/day, 4 days/week, for 3 weeks. Children in the active control group (N = 20; 10 boys, mean age 4.88 ± 0.20 years) played a coloring game on a tablet computer for 10 min/day, 1-2 days/week, for 3 weeks. Several cognitive tasks (involving inhibitory control, working memory, and fluid intelligence) were used to evaluate the transfer effects, and electroencephalography (EEG) was performed during a go/no-go task. Progress on the trained game was significant, while performance on a reasoning task (Raven's Progressive Matrices) revealed a trend-level improvement from pre- to post-test. EEG indicated that the N2 effect of the go/no-go task was enhanced after training for girls. This study is the first to show that pure response inhibition training can potentially improve reasoning ability. Furthermore, gender differences in the training-induced changes in neural activity were found in preschoolers. PMID:26395158

  3. Inhibitory effects of extracellular products from oral bacteria on human fibroblasts and stimulated lymphocytes.

    PubMed Central

    Higerd, T B; Vesole, D H; Goust, J M

    1978-01-01

    Extracellular products of 12 strains of Streptococcus mutans and 5 additional species of oral bacteria were analyzed for their ability to inhibit proliferation of fibroblastoid cells (HeLa and AV3) and blast transformation of human peripheral blood lymphocytes obtained from normal individuals. Products from S. mutans strains AHT and BHT, Streptococcus intermedius, and Actinomyces viscosus inhibited [3H]thymidine uptake by fibroblastoid cells and phytohemagglutinin-stimulated lymphocytes. Products from S. mutans E49, Streptococcus salivarius, and Actinomyces naeslundii inhibited blast transformation of human lymphocytes but did not significantly inhibit the growth of fibroblastoid cells. Preparations from S. intermedius gave the greatest inhibitory activity against both target cell types; initial characterization of this preparation suggested a single factor active in both assays, in that the heat lability and Sephadex G-200 elution profile were similar for the inhibitory activity seen with the two cell types. The molecular weight of the inhibitor, estimated by gel filtration on Sephadex G-200 and Ultragel AcA34, was approximately 160,000. The results strongly suggest that oral bacteria produce heat-labile substances that interfere with fibroblast proliferation and alter the lymphocytic immunological response. Images PMID:689736

  4. Inhibitory effects of extracellular products from oral bacteria on human fibroblasts and stimulated lymphocytes.

    PubMed

    Higerd, T B; Vesole, D H; Goust, J M

    1978-08-01

    Extracellular products of 12 strains of Streptococcus mutans and 5 additional species of oral bacteria were analyzed for their ability to inhibit proliferation of fibroblastoid cells (HeLa and AV3) and blast transformation of human peripheral blood lymphocytes obtained from normal individuals. Products from S. mutans strains AHT and BHT, Streptococcus intermedius, and Actinomyces viscosus inhibited [3H]thymidine uptake by fibroblastoid cells and phytohemagglutinin-stimulated lymphocytes. Products from S. mutans E49, Streptococcus salivarius, and Actinomyces naeslundii inhibited blast transformation of human lymphocytes but did not significantly inhibit the growth of fibroblastoid cells. Preparations from S. intermedius gave the greatest inhibitory activity against both target cell types; initial characterization of this preparation suggested a single factor active in both assays, in that the heat lability and Sephadex G-200 elution profile were similar for the inhibitory activity seen with the two cell types. The molecular weight of the inhibitor, estimated by gel filtration on Sephadex G-200 and Ultragel AcA34, was approximately 160,000. The results strongly suggest that oral bacteria produce heat-labile substances that interfere with fibroblast proliferation and alter the lymphocytic immunological response. PMID:689736

  5. Effective Suppression of Pathological Synchronization in Cortical Networks by Highly Heterogeneous Distribution of Inhibitory Connections

    PubMed Central

    Kada, Hisashi; Teramae, Jun-Nosuke; Tokuda, Isao T.

    2016-01-01

    Even without external random input, cortical networks in vivo sustain asynchronous irregular firing with low firing rate. In addition to detailed balance between excitatory and inhibitory activities, recent theoretical studies have revealed that another feature commonly observed in cortical networks, i.e., long-tailed distribution of excitatory synapses implying coexistence of many weak and a few extremely strong excitatory synapses, plays an essential role in realizing the self-sustained activity in recurrent networks of biologically plausible spiking neurons. The previous studies, however, have not considered highly non-random features of the synaptic connectivity, namely, bidirectional connections between cortical neurons are more common than expected by chance and strengths of synapses are positively correlated between pre- and postsynaptic neurons. The positive correlation of synaptic connections may destabilize asynchronous activity of networks with the long-tailed synaptic distribution and induce pathological synchronized firing among neurons. It remains unclear how the cortical network avoids such pathological synchronization. Here, we demonstrate that introduction of the correlated connections indeed gives rise to synchronized firings in a cortical network model with the long-tailed distribution. By using a simplified feed-forward network model of spiking neurons, we clarify the underlying mechanism of the synchronization. We then show that the synchronization can be efficiently suppressed by highly heterogeneous distribution, typically a lognormal distribution, of inhibitory-to-excitatory connection strengths in a recurrent network model of cortical neurons. PMID:27803659

  6. [The Xanthine Oxidase Inhibitory Activity and Hypouricemic Effects of Crude Drugs Obtained from the Silkworm in Mice].

    PubMed

    Tanaka, Ryuichirou; Miyata, Yuuma; Minakuchi, Naoki; Murakami, Ayako; Sakazaki, Fumitoshi

    2015-01-01

    This study evaluated the effects of crude drugs obtained from the silkworm in mice with oxonic acid-induced hyperuricemia using xanthine oxidase inhibitory activity and plasma uric acid levels. The plasma uric acid level was analyzed using an improved HPLC with UV detection (HPLC-UV) method, which enabled high-sensitivity analysis of a microliter of plasma. Using this method, we evaluated natural products administered orally to the hypouricemic mice. The plasma uric acid level of mice administered a water-soluble extract from silkworm larvae with botrytis (used in traditional Chinese medicine to reduce wind, lower blood pressure, and change platelet coagulation) was significantly lower than in the control group 1, 2, and 3 h after treatment. In addition, water soluble extracts from a fungus (NBRC 31161) metabolite and silkworm pupae and larvae reduced the plasma uric acid levels in mice compared with the control group.

  7. Stromal Cells from Human Decidua Exert a Strong Inhibitory Effect on NK Cell Function and Dendritic Cell Differentiation

    PubMed Central

    Canegallo, Francesca; Conte, Romana; Venturini, Pier Luigi; Moretta, Lorenzo; Mingari, Maria Cristina

    2014-01-01

    Stromal cells (SC) are an important component of decidual tissues where they are in strict proximity with both NK and CD14+ myelomonocytic cells that play a role in the maintenance of pregnancy. In this study we analyzed whether decidual SC (DSC) could exert a regulatory role on NK and CD14+ cells that migrate from peripheral blood (PB) to decidua during pregnancy. We show that DSCs inhibit the IL15-mediated up-regulation of major activating NK receptors in PB-derived NK cells. In addition, the IL15-induced NK cell proliferation, cytolytic activity and IFN-γ production were severely impaired. DSCs sharply inhibited dendritic cells differentiation and their ability to induce allogeneic T cell proliferation. Indoleamine 2,3-dioxygenase (IDO) and prostaglandin E2 (PGE2) mediated the inhibitory effect of DSCs. Our results strongly suggest an important role of DSCs in preventing potentially dangerous immune response, thus contributing to maintenance of pregnancy. PMID:24586479

  8. [The Xanthine Oxidase Inhibitory Activity and Hypouricemic Effects of Crude Drugs Obtained from the Silkworm in Mice].

    PubMed

    Tanaka, Ryuichirou; Miyata, Yuuma; Minakuchi, Naoki; Murakami, Ayako; Sakazaki, Fumitoshi

    2015-01-01

    This study evaluated the effects of crude drugs obtained from the silkworm in mice with oxonic acid-induced hyperuricemia using xanthine oxidase inhibitory activity and plasma uric acid levels. The plasma uric acid level was analyzed using an improved HPLC with UV detection (HPLC-UV) method, which enabled high-sensitivity analysis of a microliter of plasma. Using this method, we evaluated natural products administered orally to the hypouricemic mice. The plasma uric acid level of mice administered a water-soluble extract from silkworm larvae with botrytis (used in traditional Chinese medicine to reduce wind, lower blood pressure, and change platelet coagulation) was significantly lower than in the control group 1, 2, and 3 h after treatment. In addition, water soluble extracts from a fungus (NBRC 31161) metabolite and silkworm pupae and larvae reduced the plasma uric acid levels in mice compared with the control group. PMID:26423873

  9. Glucose level determines excitatory or inhibitory effects of adiponectin on arcuate POMC neuron activity and feeding.

    PubMed

    Suyama, Shigetomo; Maekawa, Fumihiko; Maejima, Yuko; Kubota, Naoto; Kadowaki, Takashi; Yada, Toshihiko

    2016-01-01

    Adiponectin regulates glucose and lipid metabolism, acting against metabolic syndrome and atherosclerosis. Accumulating evidence suggest that adiponectin acts on the brain including hypothalamic arcuate nucleus (ARC), where proopiomelanocortin (POMC) neurons play key roles in feeding regulation. Several studies have examined intracerebroventricular (ICV) injection of adiponectin and reported opposite effects, increase or decrease of food intake. These reports used different nutritional states. The present study aimed to clarify whether adiponectin exerts distinct effects on food intake and ARC POMC neurons depending on the glucose concentration. Adiponectin was ICV injected with or without glucose for feeding experiments and administered to ARC slices with high or low glucose for patch clamp experiments. We found that adiponectin at high glucose inhibited POMC neurons and increased food intake while at low glucose it exerted opposite effects. The results demonstrate that glucose level determines excitatory or inhibitory effects of adiponectin on arcuate POMC neuron activity and feeding. PMID:27503800

  10. Glucose level determines excitatory or inhibitory effects of adiponectin on arcuate POMC neuron activity and feeding

    PubMed Central

    Suyama, Shigetomo; Maekawa, Fumihiko; Maejima, Yuko; Kubota, Naoto; Kadowaki, Takashi; Yada, Toshihiko

    2016-01-01

    Adiponectin regulates glucose and lipid metabolism, acting against metabolic syndrome and atherosclerosis. Accumulating evidence suggest that adiponectin acts on the brain including hypothalamic arcuate nucleus (ARC), where proopiomelanocortin (POMC) neurons play key roles in feeding regulation. Several studies have examined intracerebroventricular (ICV) injection of adiponectin and reported opposite effects, increase or decrease of food intake. These reports used different nutritional states. The present study aimed to clarify whether adiponectin exerts distinct effects on food intake and ARC POMC neurons depending on the glucose concentration. Adiponectin was ICV injected with or without glucose for feeding experiments and administered to ARC slices with high or low glucose for patch clamp experiments. We found that adiponectin at high glucose inhibited POMC neurons and increased food intake while at low glucose it exerted opposite effects. The results demonstrate that glucose level determines excitatory or inhibitory effects of adiponectin on arcuate POMC neuron activity and feeding. PMID:27503800

  11. Inhibitory effects of indomethacin on growth and proliferation of gastric carcinoma cells KATO III.

    PubMed

    Fujiwara, Y; Tarnawski, A; Fujiwara, K; Arakawa, T; Kobayashi, K

    1993-06-01

    The effects of indomethacin on growth and proliferation of gastric carcinoma cells KATO III were examined. Indomethacin (10(-4) and 10(-3) M) significantly inhibited cell growth and these effects were not affected by treatment with 16,16-dimethyl prostaglandin E2 (3 x 10(-7) M and 3 x 10(-6) M). Indomethacin 10(-3) M significantly reduced cell viability and completely inhibited cell growth. Indomethacin 10(-4) M did not affect cell viability and its inhibitory effect of cell growth became apparent on the fifth day of culture. Indomethacin 10(-4) M reduced BrdU labeling index within 2 hours. These results suggest that indomethacin inhibited growth and proliferation of gastric carcinoma cells KATO III. This effect is not mediated by prostaglandins. PMID:8358051

  12. Inhibitory effects of volatile antioxidants found in various beans on malonaldehyde formation in horse blood plasma.

    PubMed

    Lee, Seung-Joo; Lee, Kwang-Geun

    2005-04-01

    The inhibitory effect of aroma extracts isolated from dried soybeans, mung beans, kidney beans, and azuki beans on malonaldehyde (MA) formation from horse blood plasma oxidized with Fenton's reagent was determined by gas chromatography (GC) coupled with nitrogen-phosphorus detector (NPD). Aroma chemicals such as maltol, eugenol, benzyl alcohol, 1-octen-3-ol, butyrolactone, and 1-methyl-2-pyrrolidone, found in the aroma extracts of beans, were also examined for their inhibitory effect on the same system. Among the four aroma extracts tested, the aroma extract of soybeans exhibited the strongest antioxidant activity. Extracts of soybeans, mung beans, azuki beans, and kidney beans inhibited MA formation by 58%, 47%, 40%, and 23%, respectively, at the level of 400 microg/mL, whereas, alpha-tocopherol and BHT inhibited MA formation by 52% and 70%, respectively, at the same level. Among the tested aroma chemicals, the antioxidant activity decreased in the following order: eugenol>maltol>1-octen-3-ol>benzyl alcohol>butyrolactone>1-methyl-2-pyrrolidone.

  13. Antiobesity and Antidiabetes Effects of a Cudrania tricuspidata Hydrophilic Extract Presenting PTP1B Inhibitory Potential.

    PubMed

    Kim, Dae Hoon; Lee, Sooung; Chung, Youn Wook; Kim, Byeong Mo; Kim, Hanseul; Kim, Kunhong; Yang, Kyung Mi

    2016-01-01

    Diabetes and obesity represent the major health problems and the most age-related metabolic diseases. Protein-tyrosine phosphatase 1B (PTP1B) has emerged as an important regulator of insulin signal transduction and is regarded as a pharmaceutical target for metabolic disorders. To find novel natural materials presenting therapeutic activities against diabetes and obesity, we screened various herb extracts using a chip screening allowing the determination of PTP1B inhibitory effects of the tested compounds using insulin receptor (IR) as the substrate. Cudrania tricuspidata leaves (CTe) had a strong inhibitory effect on PTP1B activity and substantially inhibited fat accumulation in 3T3-L1 cells. CTe was orally administrated to diet-induced obesity (DIO) mice once daily for 3 weeks after which changes in glucose, insulin metabolism, and fat accumulation were examined. Hepatic enzyme markers (aspartate aminotransferase, AST, and alanine aminotransferase, ALT) and total fat mass and triglyceride levels decreased in CTe-treated mice, whereas body weight and total cholesterol concentration slightly decreased. CTe increased the phosphorylation of IRS-1 and Akt in liver tissue. Furthermore, CTe treatment significantly lowered blood glucose levels and improved insulin secretion in DIO mice. Our results strongly suggest that CTe may represent a promising therapeutic substance against diabetes and obesity. PMID:26989693

  14. Inhibitory effects of nobiletin on hepatocellular carcinoma in vitro and in vivo.

    PubMed

    Ma, Xiuying; Jin, Shaoju; Zhang, Yuanyuan; Wan, Lihong; Zhao, Yanyan; Zhou, Liming

    2014-04-01

    Nobiletin (5, 6, 7, 8, 3' 4'-hexamethoxyflavone) is a major anticancer component in juice from zhishi (Rutaceae). This study aimed to investigate the inhibitory effect of Nobiletin on hepatic cancer cells both in vitro and in vivo. The 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), growth curve, and clonogenic assay showed that nobiletin inhibited the proliferation of SMMC-7721 cells in vitro. Hoechst staining observed the characteristics of cell apoptosis in nobiletin-treated cells, and the apoptotic rates of treated groups were increased in a dose-dependent manner. Flow cytometric analysis demonstrated that nobiletin could block the cell cycle arrested at G2 phase. Cell cycle analysis was performed using flow cytometry. Results showed that cell cycle phase distribution analysis showed G2 arrest. It was found that nobiletin downregulated the expressions of Bcl-2 and COX-2 and up-regulated the expressions of Bax and caspase-3 in SMMC-7721 cells by western blotting. The experiment in vivo demonstrated that nobiletin significantly inhibited the growth of H22 transplantable tumor, downregulated the expressions of COX-2, up-regulated the expressions of Bax and caspase-3 detected by immunohistochemistry and western blotting, and the ratios of Bcl-2/Bax were decreased. Our results suggest that nobiletin has significant inhibitory effects on hepatocellular carcinoma both in vitro and in vivo.

  15. Inhibitory effects of volatile antioxidants found in various beans on malonaldehyde formation in horse blood plasma.

    PubMed

    Lee, Seung-Joo; Lee, Kwang-Geun

    2005-04-01

    The inhibitory effect of aroma extracts isolated from dried soybeans, mung beans, kidney beans, and azuki beans on malonaldehyde (MA) formation from horse blood plasma oxidized with Fenton's reagent was determined by gas chromatography (GC) coupled with nitrogen-phosphorus detector (NPD). Aroma chemicals such as maltol, eugenol, benzyl alcohol, 1-octen-3-ol, butyrolactone, and 1-methyl-2-pyrrolidone, found in the aroma extracts of beans, were also examined for their inhibitory effect on the same system. Among the four aroma extracts tested, the aroma extract of soybeans exhibited the strongest antioxidant activity. Extracts of soybeans, mung beans, azuki beans, and kidney beans inhibited MA formation by 58%, 47%, 40%, and 23%, respectively, at the level of 400 microg/mL, whereas, alpha-tocopherol and BHT inhibited MA formation by 52% and 70%, respectively, at the same level. Among the tested aroma chemicals, the antioxidant activity decreased in the following order: eugenol>maltol>1-octen-3-ol>benzyl alcohol>butyrolactone>1-methyl-2-pyrrolidone. PMID:15721197

  16. Antiobesity and Antidiabetes Effects of a Cudrania tricuspidata Hydrophilic Extract Presenting PTP1B Inhibitory Potential

    PubMed Central

    Kim, Dae Hoon; Lee, Sooung; Chung, Youn Wook; Kim, Byeong Mo; Kim, Hanseul; Kim, Kunhong; Yang, Kyung Mi

    2016-01-01

    Diabetes and obesity represent the major health problems and the most age-related metabolic diseases. Protein-tyrosine phosphatase 1B (PTP1B) has emerged as an important regulator of insulin signal transduction and is regarded as a pharmaceutical target for metabolic disorders. To find novel natural materials presenting therapeutic activities against diabetes and obesity, we screened various herb extracts using a chip screening allowing the determination of PTP1B inhibitory effects of the tested compounds using insulin receptor (IR) as the substrate. Cudrania tricuspidata leaves (CTe) had a strong inhibitory effect on PTP1B activity and substantially inhibited fat accumulation in 3T3-L1 cells. CTe was orally administrated to diet-induced obesity (DIO) mice once daily for 3 weeks after which changes in glucose, insulin metabolism, and fat accumulation were examined. Hepatic enzyme markers (aspartate aminotransferase, AST, and alanine aminotransferase, ALT) and total fat mass and triglyceride levels decreased in CTe-treated mice, whereas body weight and total cholesterol concentration slightly decreased. CTe increased the phosphorylation of IRS-1 and Akt in liver tissue. Furthermore, CTe treatment significantly lowered blood glucose levels and improved insulin secretion in DIO mice. Our results strongly suggest that CTe may represent a promising therapeutic substance against diabetes and obesity. PMID:26989693

  17. Aromatase inhibiting and combined estrogenic effects of parabens and estrogenic effects of other additives in cosmetics

    SciTech Connect

    Meeuwen, J.A. van Son, O. van; Piersma, A.H.; Jong, P.C. de; Berg, M. van den

    2008-08-01

    There is concern widely on the increase in human exposure to exogenous (anti)estrogenic compounds. Typical are certain ingredients in cosmetic consumer products such as musks, phthalates and parabens. Monitoring a variety of human samples revealed that these ingredients, including the ones that generally are considered to undergo rapid metabolism, are present at low levels. In this in vitro research individual compounds and combinations of parabens and endogenous estradiol (E{sub 2}) were investigated in the MCF-7 cell proliferation assay. The experimental design applied a concentration addition model (CA). Data were analyzed with the estrogen equivalency (EEQ) and method of isoboles approach. In addition, the catalytic inhibitory properties of parabens on an enzyme involved in a rate limiting step in steroid genesis (aromatase) were studied in human placental microsomes. Our results point to an additive estrogenic effect in a CA model for parabens. In addition, it was found that parabens inhibit aromatase. Noticeably, the effective levels in both our in vitro systems were far higher than the levels detected in human samples. However, estrogenic compounds may contribute in a cumulative way to the circulating estrogen burden. Our calculation for the extra estrogen burden due to exposure to parabens, phthalates and polycyclic musks indicates an insignificant estrogenic load relative to the endogenous or therapeutic estrogen burden.

  18. Aromatase inhibiting and combined estrogenic effects of parabens and estrogenic effects of other additives in cosmetics.

    PubMed

    van Meeuwen, J A; van Son, O; Piersma, A H; de Jong, P C; van den Berg, M

    2008-08-01

    There is concern widely on the increase in human exposure to exogenous (anti)estrogenic compounds. Typical are certain ingredients in cosmetic consumer products such as musks, phthalates and parabens. Monitoring a variety of human samples revealed that these ingredients, including the ones that generally are considered to undergo rapid metabolism, are present at low levels. In this in vitro research individual compounds and combinations of parabens and endogenous estradiol (E(2)) were investigated in the MCF-7 cell proliferation assay. The experimental design applied a concentration addition model (CA). Data were analyzed with the estrogen equivalency (EEQ) and method of isoboles approach. In addition, the catalytic inhibitory properties of parabens on an enzyme involved in a rate limiting step in steroid genesis (aromatase) were studied in human placental microsomes. Our results point to an additive estrogenic effect in a CA model for parabens. In addition, it was found that parabens inhibit aromatase. Noticeably, the effective levels in both our in vitro systems were far higher than the levels detected in human samples. However, estrogenic compounds may contribute in a cumulative way to the circulating estrogen burden. Our calculation for the extra estrogen burden due to exposure to parabens, phthalates and polycyclic musks indicates an insignificant estrogenic load relative to the endogenous or therapeutic estrogen burden.

  19. Sesquiterpenes from an Egyptian herbal medicine, Pulicaria undulate, with inhibitory effects on nitric oxide production in RAW264.7 macrophage cells.

    PubMed

    Hegazy, Mohamed-Elamir F; Matsuda, Hisashi; Nakamura, Seikou; Yabe, Mikuko; Matsumoto, Tomoko; Yoshikawa, Masayuki

    2012-01-01

    The methylene chloride-methanol (1 : 1) extract from the air-dried aerial parts of wild Pulicaria undulata collected in North Sinia, Egypt, showed inhibitory effects on lipopolysaccharide (LPS)-induced production of nitric oxide (NO) in RAW264.7 macrophages. From the extract, three new sesquiterpenes named 5α-hydroperoxyivalin, 8-epi-xanthanol, and 8-epi-isoxanthanol were isolated together with four known sesquiterpenes. The structure of each new sesquiterpenes was determined on the basis of physicochemical and chemical evidence. In addition, all the sesquiterpenoids significantly inhibited the production of NO. Ivalin (IC50=2.0 μM) and 2α-hydroxyalantolactone (1.8 μM) showed particularly strong inhibitory effects, but had strong cytotoxic effects as well. Furthermore, ivalin and 2α-hydroxyalantolactone concentration-dependently reduced inducible NO synthase (iNOS) protein levels in RAW264.7 cells.

  20. Angiotensin-I Converting Enzyme (ACE) Inhibitory and Anti-Hypertensive Effect of Protein Hydrolysate from Actinopyga lecanora (Sea Cucumber) in Rats

    PubMed Central

    Sadegh Vishkaei, Mahdokht; Ebrahimpour, Afshin; Abdul-Hamid, Azizah; Ismail, Amin; Saari, Nazamid

    2016-01-01

    Food protein hydrolysates are known to exhibit angiotensin converting enzyme (ACE) inhibitory properties and can be used as a novel functional food for prevention of hypertension. This study evaluated the ACE inhibitory potentials of Actinopyga lecanora proteolysate (ALP) in vivo. The pre-fed rats with ALP at various doses (200, 400, 800 mg/kg body weight) exhibited a significant (p ≤ 0.05) suppression effect after inducing hypertension. To determine the optimum effective dose that will produce maximal reduction in blood pressure, ALP at three doses was fed to the rats after inducing hypertension. The results showed that the 800 mg/kg body weight dose significantly reduced blood pressure without noticeable negative physiological effect. In addition, there were no observable changes in the rats’ heart rate after oral administration of the ALP. It was concluded that Actinopyga lecanora proteolysate could potentially be used for the development of functional foods and nutraceuticals for prevention and treatment of hypertension. PMID:27706040

  1. Duration of the inhibitory effect of calcium on non-haem iron absorption in man.

    PubMed

    Gleerup, A; Rossander-Hultén, L; Hallberg, L

    1993-12-01

    We investigated the duration of the inhibitory effect of calcium from milk and cheese (340 mg) in a breakfast meal on non-haem iron absorption from a hamburger meal eaten 2 or 4 h after the breakfast. The effect of calcium on iron absorption was studied in 21 human subjects by using paired observations and a dual-radioisotope method (55Fe and 59Fe). No duration effect of calcium on iron absorption was observed in this study. The present findings offer an opportunity for theoretical improvement of iron nutrition by a redistribution of the daily intake of calcium to the meals with a minor iron content, i.e. breakfast and the evening meal.

  2. Inhibitory effects of Lactobacillus fermentum on microbial growth and biofilm formation.

    PubMed

    Rybalchenko, Oxana V; Bondarenko, Viktor M; Orlova, Olga G; Markov, Alexander G; Amasheh, S

    2015-10-01

    Beneficial effects of Lactobacilli have been reported, and lactic bacteria are employed for conservation of foods. Therefore, the effects of a Lactobacillus fermentum strain were analyzed regarding inhibitory effects on staphylococci, Candida albicans and enterotoxigenic enterobacteria by transmission electron microscopy (TEM). TEM of bacterial biofilms was performed using cocultures of bacteriocin-producing L. fermentum 97 with different enterotoxigenic strains: Staphylococcus epidermidis expressing the ica gene responsible for biofilm formation, Staphylococcus aureus producing enterotoxin type A, Citrobacter freundii, Enterobacter cloaceae, Klebsiella oxytoca, Proteus mirabilis producing thermolabile and thermostable enterotoxins determined by elt or est genes, and Candida albicans. L. fermentum 97 changed morphological features and suppressed biofilm formation of staphylococci, enterotoxigenic enterobacteria and Candida albicans; a marked transition to resting states, a degradation of the cell walls and cytoplasm, and a disruption of mature bacterial biofilms were observed, the latter indicating efficiency even in the phase of higher cell density.

  3. Inhibitory effect of substituted dextrans on MCF7 human breast cancer cell growth in vitro.

    PubMed

    Morere, J F; Letourneur, D; Planchon, P; Avramoglou, T; Jozefonvicz, J; Israel, L; Crepin, M

    1992-12-01

    Substituted dextrans can reproduce some of the properties of heparin and can thus be used to alter cellular growth. We studied the effect of heparin (H108), dextran (D), carboxymethylbenzylamide dextran (CMDB) and carboxymethylbenzylamide sulfonate dextran (CMDBS) on the growth of human mammary cells of the MCF7 tumor line. The cells were cultured in minimum Eagle's medium containing 2% fetal calf serum without biopolymer, or with increasing concentrations of H108, D, CMDB or CMDBS. Growth curves were accurately based on cell counting using a Coulter counter. Cell distribution in the various phases of the cycle was analyzed by flow cytometry. Dose-dependent growth inhibitory effects (400-4000 micrograms/ml) were observed. The effect on MCF7 tumor cells was most apparent with CMDBS. The percentage of cells in the S phase decreased with preferential blocking in the G0/G1 phase. Pre-clinical studies can be anticipated as there is an absence of in vivo toxicity.

  4. The effects of environmental enrichment and age-related differences on inhibitory avoidance in zebrafish (Danio rerio Hamilton).

    PubMed

    Manuel, Remy; Gorissen, Marnix; Stokkermans, Mitchel; Zethof, Jan; Ebbesson, Lars O E; van de Vis, Hans; Flik, Gert; van den Bos, Ruud

    2015-04-01

    The inhibitory avoidance paradigm allows the study of mechanisms underlying learning and memory formation in zebrafish (Danio rerio Hamilton). For zebrafish, the physiology and behavior associated with this paradigm are as yet poorly understood. We therefore assessed the effects of environmental enrichment and fish age on inhibitory avoidance learning. Fish raised in an environmentally enriched tank showed decreased anxiety-like behavior and increased exploration. Enrichment greatly reduced inhibitory avoidance in 6-month (6M)- and 12-month (12 M)-old fish. Following inhibitory avoidance, telencephalic mRNA levels of proliferating cell nuclear antigen (pcna), neurogenic differentiation (neurod), cocaine- and amphetamine-regulated transcript 4 (cart4), and cannabinoid receptor 1 (cnr1) were lower in enriched-housed fish, while the ratios of mineralocorticoid receptor (nr3c2)/glucocorticoid receptor α [nr3c1(α)] and glucocorticoid receptor β [nr3c1(β)]/glucocorticoid receptor α [nr3c1(α)] were higher. This was observed for 6M-old fish only, not for 24-month (24 M) old fish. Instead, 24 M-old fish showed delayed inhibitory avoidance, no effects of enrichment, and reduced expression of neuroplasticity genes. Overall, our data show strong differences in inhibitory avoidance behavior between zebrafish of different ages and a clear reduction in avoidance behavior following housing under environmental enrichment.

  5. Inhibitory effect of beta3-adrenoceptor agonist in lower esophageal sphincter smooth muscle: in vitro studies.

    PubMed

    Sarma, D N K; Banwait, Kuldip; Basak, Ashim; DiMarino, Anthony J; Rattan, Satish

    2003-01-01

    We investigated the effects of (R,R)-5-[2-[2-3-chlorophenyl)-2-hydroxyethyl] - amino]propyl] - 1,3 - benzodioxole - 2, 2 - dicarboxylate (CL 316243) (a typical beta3-agonist) on the spontaneously tonic smooth muscle of the lower esophageal sphincter (LES). Studies were carried out in smooth muscle strips and smooth muscle cells (SMCs) of opossum LES. Isometric tension was recorded in the basal state and after CL 316243, and before and after beta3-antagonist (S)-N-[4-[2-[[3-[-(acetamidomethyl)phenoxy]-2-hydroxypropyl]amino]ethyl]phenyl]benzenesulfonamide (L 748337) and nonselective antagonist propranolol. In some experiments, the effects of nonadrenergic noncholinergic (NANC) nerve activation by electrical field stimulation (EFS) were also examined. The effects of CL 316243 were compared with those of nonselective beta-agonist isoproterenol. CL 316243 caused a concentration-dependent relaxation of the LES smooth muscle. The relaxant action of CL 316243 was determined to be directly at the smooth muscle because it remained unmodified by the neurotoxin tetrodotoxin and other neurohumoral antagonists, and also was observed in the SMCs. L 748337 selectively antagonized the relaxant effect of CL 316243 and, conversely, had no significant effect on the inhibitory actions of isoproterenol. CL 316243 (1 x 10(-8) M) caused an augmentation of NANC relaxation in the LES. Another beta3-agonist, (S)-4-[hydroxy-3-phenoxy-propylamino-ethoxy]-N-(2-methoxyethyl)-phenoxyacetamide (ZD 7114), also caused concentration-dependent full relaxation of the LES that was selectively antagonized by beta3-anatagonist 3-(2-ethylphenoxy)-1-[(1S)1,2,3,4-tetrahydronaphth-1-ylaminol]-(2S)-2-propanol oxalate (SR 59230A). These studies defined the effects of characteristic inhibitory beta3-adrenoceptors in the spontaneously tonic LES smooth muscle and suggested a potential therapeutic role in the esophageal motility disorders characterized by hypertensive LES. PMID:12490574

  6. Increased training prevents the impairing effect of intra-amygdala infusion of the non-NMDA receptor antagonist CNQX on inhibitory avoidance expression.

    PubMed

    Roesler, R; Quevedo, J; Rodrigues, C; Madruga, M; Vianna, M R; Ferreira, M B

    1999-03-01

    Intra-amygdala infusion of the non-N-methyl-D-aspartate (NMDA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) prior to testing impairs inhibitory avoidance retention test performance. Increased training attenuates the impairing effects of amygdala lesions and intra-amygdala infusions of CNQX. The objective of the present study was to determine the effects of additional training on the impairing effects of intra-amygdala CNQX on expression of the inhibitory avoidance task. Adult female Wistar rats bilaterally implanted with cannulae into the border between the central and the basolateral nuclei of the amygdala were submitted to a single session or to three training sessions (0.2 mA, 24-h interval between sessions) in a step-down inhibitory avoidance task. A retention test session was held 48 h after the last training. Ten minutes prior to the retention test session, the animals received a 0.5-microliter infusion of CNQX (0.5 microgram) or its vehicle (25% dimethylsulfoxide in saline). The CNQX infusion impaired, but did not block, retention test performance in animals submitted to a single training session. Additional training prevented the impairing effect of CNQX. The results suggest that amygdaloid non-NMDA receptors may not be critical for memory expression in animals given increased training.

  7. Flavonoids from Machilus japonica Stems and Their Inhibitory Effects on LDL Oxidation

    PubMed Central

    Joo, Se-Jin; Park, Hee-Jung; Park, Ji-Hae; Cho, Jin-Gyeong; Kang, Ji-Hyun; Jeong, Tae-Sook; Kang, Hee Cheol; Lee, Dae-Young; Kim, Hack-Soo; Byun, Sang-Yo; Baek, Nam-In

    2014-01-01

    Stems of Machilus japonica were extracted with 80% aqueous methanol (MeOH) and the concentrated extract was successively extracted with ethyl acetate (EtOAc), normal butanol (n-BuOH), and water. Six flavonoids were isolated from the EtOAc fraction: (+)-taxifolin, afzelin, (−)-epicatechin, 5,3'-di-O-methyl-(−)-epicatechin, 5,7,3'-tri-O-methyl-(−)-epicatechin, and 5,7-di-O-methyl-3',4'-methylenedioxyflavan-3-ol. The chemical structures were identified using spectroscopic data including NMR, mass spectrometry and infrared spectroscopy. This is the first report of isolation of these six compounds from M. japonica. The compounds were evaluated for their diphenyl picryl hydrazinyl scavenging activity and inhibitory effects on low-density lipoprotein oxidation. Compounds 1 and 3–6 exhibited DPPH antioxidant activity equivalent with that of ascorbic acid, with half maximal inhibitory concentration (IC50) values of 0.16, 0.21, 0.17, 0.15 and 0.07 mM, respectively. The activity of compound 1 was similar to the positive control butylated hydroxytoluene, which had an IC50 value of 1.9 µM, while compounds 3 and 5 showed little activity. Compounds 1, 3, and 5 exhibited LDL antioxidant activity with IC50 values of 2.8, 7.1, and 4.6 µM, respectively. PMID:25229822

  8. β-Secretase (BACE1) inhibitory and neuroprotective effects of p-terphenyls from Polyozellus multiplex.

    PubMed

    Chon, So-Hyun; Yang, Eun-Ju; Lee, Taeho; Song, Kyung-Sik

    2016-09-14

    Alzheimer's disease (AD), a major neurodegenerative disorder, is associated with the enzymatic reaction of β-secretase (BACE1) on the amyloid precursor protein (APP) for the generation of neurotoxic amyloid-β (Aβ). Therefore, Aβ accumulation and oxidative stress-induced neuronal cell death are the pathogenic hallmarks of AD. In this study, we tried to identify BACE1 inhibitors and neuroprotectants from natural products, in particular, from the Korean mushroom Polyozellus multiplex. Four p-terphenyls were identified from the ethanolic extract of P. multiplex; polyozellin (1), thelephoric acid (2), polyozellic acid (3), and kynapcin-12 (4). Compounds 1-4 effectively inhibited BACE1 activity with a half-maximal inhibitory concentration (IC50) of 3.08, 3.50, 4.78, and 15.79 μM, respectively. Compounds 1-3 reduced the production of neurotoxic Aβ1-42 production in APPswe-N2a cells in a concentration-dependent manner. When HT22 cells were stressed with 5 mM glutamate, compounds 2 and 3 significantly recovered cell viability. It was correlated with their inhibitory properties against glutamate-mediated Ca(2+) influx, intracellular reactive oxygen species (ROS) generation, lipid peroxidation, reduction in Bcl-2 and Bid levels, and enhanced phosphorylation of mitogen-activated protein kinase (MAPK). Thus, P. multiplex and the isolated p-terphenyls might be useful in the development of lead compounds for the prevention of neurodegenerative diseases, especially AD.

  9. β-Secretase (BACE1) inhibitory and neuroprotective effects of p-terphenyls from Polyozellus multiplex.

    PubMed

    Chon, So-Hyun; Yang, Eun-Ju; Lee, Taeho; Song, Kyung-Sik

    2016-09-14

    Alzheimer's disease (AD), a major neurodegenerative disorder, is associated with the enzymatic reaction of β-secretase (BACE1) on the amyloid precursor protein (APP) for the generation of neurotoxic amyloid-β (Aβ). Therefore, Aβ accumulation and oxidative stress-induced neuronal cell death are the pathogenic hallmarks of AD. In this study, we tried to identify BACE1 inhibitors and neuroprotectants from natural products, in particular, from the Korean mushroom Polyozellus multiplex. Four p-terphenyls were identified from the ethanolic extract of P. multiplex; polyozellin (1), thelephoric acid (2), polyozellic acid (3), and kynapcin-12 (4). Compounds 1-4 effectively inhibited BACE1 activity with a half-maximal inhibitory concentration (IC50) of 3.08, 3.50, 4.78, and 15.79 μM, respectively. Compounds 1-3 reduced the production of neurotoxic Aβ1-42 production in APPswe-N2a cells in a concentration-dependent manner. When HT22 cells were stressed with 5 mM glutamate, compounds 2 and 3 significantly recovered cell viability. It was correlated with their inhibitory properties against glutamate-mediated Ca(2+) influx, intracellular reactive oxygen species (ROS) generation, lipid peroxidation, reduction in Bcl-2 and Bid levels, and enhanced phosphorylation of mitogen-activated protein kinase (MAPK). Thus, P. multiplex and the isolated p-terphenyls might be useful in the development of lead compounds for the prevention of neurodegenerative diseases, especially AD. PMID:27511641

  10. Inhibitory effects of polycyclic aromatic hydrocarbons (PAHs) on photosynthetic performance are not related to their aromaticity.

    PubMed

    Jajoo, Anjana; Mekala, Nageswara Rao; Tomar, Rupal Singh; Grieco, Michele; Tikkanen, Mikko; Aro, Eva-Mari

    2014-08-01

    Polycyclic aromatic hydrocarbons (PAHs) are very toxic and highly persistent environmental pollutants which accumulate in soil and affect growth of the plants adversely. This study aims to investigate inhibitory effects of 3 major PAH particularly on photosynthetic processes in Arabidopsis thaliana grown in soil treated with PAH. The 3 PAH chosen differ from each other in aromaticity (number of rings) comprising their structure (2 rings: naphthalene, 3 rings: anthracene and 4 rings: pyrene). Several growth parameters and Chlorophyll a fluorescence was monitored in PAH treated plants. BN-PAGe analysis was done in order to get information about change in the protein conformation. PAH treatment led to increased value of Fo which collaborated with increase in the amount of free LHC as seen through BN-Page analysis. Thus PAH were found to inhibit PS II photochemistry and caused distinct change in pigment composition. However the results led us to infer that 3-ring anthracence is more inhibitory as compared to 2-ring naphthalene and 4-ring pyrene. This indicates that aromaticity of PAH is unrelated to their response on photosynthetic processes.

  11. Influence of the spacer on the inhibitory effect of different polycarbophil-protease inhibitor conjugates.

    PubMed

    Marschütz, M K; Veronese, F M; Bernkop-Schnürch, A

    2001-09-01

    Within the present study various polycarbophil (PCP)-serine protease inhibitor conjugates were synthesized and the influence of different spacers on their inhibitory efficacy was evaluated in vitro. Results demonstrated that 4.2+/-0.15 units (n=3; +/-SD) of alpha-chymotrypsin were inhibited by 50% utilizing 0.86% (w/v) of a PCP-tetramethylenediamine (TMDA)-chymostatin 20:1 conjugate. In contrast, only 0.6+/-0.05 units (n=3; +/-SD) of alpha-chymotrypsin were inhibited by a corresponding PCP-poly(ethylene glycol) (PEG)-chymostatin conjugate. Inhibitory effects of PCP-TMDA-antipain and -elastatinal conjugates towards trypsin and elastase, respectively, were also significantly higher (P<0.05) than those of corresponding PCP-PEG-inhibitor conjugates. Hence, the great impact of the molecular size as well as the structure of the spacer on resulting polymer-inhibitor conjugates could be demonstrated. The small and rigid C4-spacer TMDA (molecular weight (MW) 161.1) was thereby shown to be highly advantageous over a long, hydrophilic and flexible PEG-diamine spacer (MW 3400). Results obtained should provide helpful basic knowledge for the development of mucoadhesive polymer-inhibitor conjugates used as auxiliary agents for the oral administration of peptide drugs.

  12. The inhibitory effect of natural bioactives on the growth of pathogenic bacteria

    PubMed Central

    Kim, Ji-Sun

    2007-01-01

    The objective of this study was to evaluate the inhibitory activity of natural products, against growth of Escherichia coli (ATCC 25922) and Salmonella typhimurium (KCCM 11862). Chitosan, epigallocatechin gallate (EGCG), and garlic were used as natural bioactives for antibacterial activity. The testing method was carried out according to the disk diffusion method. All of chitosan, EGCG, and garlic showed inhibitory effect against the growth of E. coli and Salmonella typhi. To evaluate the antibacterial activity of natural products during storage, chicken skins were inoculated with 106 of E. coli or Salmonella typhi. The inoculated chicken skins, treated with 0.5, 1, or 2% natural bioactives, were stored during 8 day at 4℃. The numbers of microorganisms were measured at 8 day. Both chitosan and EGCG showed significant decrease in the number of E. coli and Salmonella typhi in dose dependent manner (P < 0.05). These results suggest that natural bioactives such as chitosan, EGCG may be possible to be used as antimicrobial agents for the improvement of food safety. PMID:20368950

  13. Flavonoids from Machilus japonica stems and their inhibitory effects on LDL oxidation.

    PubMed

    Joo, Se-Jin; Park, Hee-Jung; Park, Ji-Hae; Cho, Jin-Gyeong; Kang, Ji-Hyun; Jeong, Tae-Sook; Kang, Hee Cheol; Lee, Dae-Young; Kim, Hack-Soo; Byun, Sang-Yo; Baek, Nam-In

    2014-01-01

    Stems of Machilus japonica were extracted with 80% aqueous methanol (MeOH) and the concentrated extract was successively extracted with ethyl acetate (EtOAc), normal butanol (n-BuOH), and water. Six flavonoids were isolated from the EtOAc fraction: (+)-taxifolin, afzelin, (-)-epicatechin, 5,3'-di-O-methyl-(-)-epicatechin, 5,7,3'-tri-O-methyl-(-)-epicatechin, and 5,7-di-O-methyl-3',4'-methylenedioxyflavan-3-ol. The chemical structures were identified using spectroscopic data including NMR, mass spectrometry and infrared spectroscopy. This is the first report of isolation of these six compounds from M. japonica. The compounds were evaluated for their diphenyl picryl hydrazinyl scavenging activity and inhibitory effects on low-density lipoprotein oxidation. Compounds 1 and 3-6 exhibited DPPH antioxidant activity equivalent with that of ascorbic acid, with half maximal inhibitory concentration (IC50) values of 0.16, 0.21, 0.17, 0.15 and 0.07 mM, respectively. The activity of compound 1 was similar to the positive control butylated hydroxytoluene, which had an IC50 value of 1.9 µM, while compounds 3 and 5 showed little activity. Compounds 1, 3, and 5 exhibited LDL antioxidant activity with IC50 values of 2.8, 7.1, and 4.6 µM, respectively. PMID:25229822

  14. Growth inhibitory effects of endotoxins from Bacteroides gingivalis and intermedius on human gingival fibroblasts in vitro

    SciTech Connect

    Layman, D.L.; Diedrich, D.L.

    1987-06-01

    Purified endotoxin or lipopolysaccharide from Bacteroides gingivalis and Bacteroides intermedius caused a similar dose-dependent inhibition of growth of cultured human gingival fibroblasts as determined by /sup 3/H-thymidine incorporation and direct cell count. Approximately 200 micrograms/ml endotoxin caused a 50% reduction in /sup 3/H-thymidine uptake of logarithmically growing cells. Inhibition of growth was similar in cultures of fibroblasts derived from either healthy or diseased human gingiva. When examining the change in cell number with time of exposure in culture, the rate of proliferation was significantly suppressed during the logarithmic phase of growth. However, the cells recovered so that the rate of proliferation, although reduced, was sufficient to produce a cell density similar to the control cells with prolonged culture. The endotoxins were characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The profiles of the Bacteroides endotoxins were different. B. gingivalis endotoxin showed a wide range of distinct bands indicating a heterogeneous distribution of molecular species. Endotoxin from B. intermedius exhibited a few discrete low molecular weight bands, but the majority of the lipopolysaccharides electrophoresed as a diffuse band of high molecular weight material. The apparent heterogeneity of the two Bacteroides endotoxins and the similarity in growth inhibitory capacity suggest that growth inhibitory effects of these substances cannot be attributed to any polysaccharide species of endotoxin.

  15. Inhibitory effect of Disulfiram/copper complex on non-small cell lung cancer cells.

    PubMed

    Duan, Lincan; Shen, Hongmei; Zhao, Guangqiang; Yang, Runxiang; Cai, Xinyi; Zhang, Lijuan; Jin, Congguo; Huang, Yunchao

    2014-04-18

    Non-small cell lung cancer (NSCLC) is the most common cause of cancer-related death in both men and women worldwide. Recently, Disulfiram has been reported to be able to inhibit glioblastoma, prostate, or breast cancer cell proliferation. In this study, the synergistic effect of Disulfiram and copper on NSCLC cell growth was investigated. Inhibition of cancer cell proliferation was detected by 1-(4,5-Dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT) assay and cell cycle analysis. Liquid colony formation and tumor spheroid formation assays were used to evaluate their effect on cancer cell clonogenicity. Real-time PCR was performed to test the mRNA level of cancer stem cell related genes. We found that Disulfiram or copper alone did not potently inhibit NSCLC cell proliferation in vitro. However, the presence of copper significantly enhanced inhibitory effect of Disulfiram on NSCLC cell growth, indicating a synergistic effect between Disulfiram and copper. Cell cycle analysis showed that Disulfiram/copper complex caused NSCLC cell cycle arrest in G2/M phase. Furthermore, Disulfiram/copper significantly increased the sensitivity of cisplatin in NSCLC cells tested by MTT assay. Liquid colony formation assay revealed that copper dramatically increased the inhibitory effect of Disulfiram on NSCLC cell colony forming ability. Disulfiram combined with copper significantly attenuated NSCLC cell spheroid formation and recuded the mRNA expression of lung cancer stem cell related genes. Our data suggest that Disulfiram/copper complex alone or combined with other chemotherapy is a potential therapeutic strategy for NSCLC patients.

  16. Inhibitory effect of Disulfiram/copper complex on non-small cell lung cancer cells

    SciTech Connect

    Duan, Lincan; Shen, Hongmei; Zhao, Guangqiang; Yang, Runxiang; Cai, Xinyi; Zhang, Lijuan; Jin, Congguo; Huang, Yunchao

    2014-04-18

    Highlights: • Disulfiram and copper synergistically inhibit lung cancer cell proliferation. • Lung cancer cell colony formation ability is inhibited by Disulfiram/copper. • Disulfiram/copper increases the sensitivity of cisplatin to lung cancer cells. • Lung cancer stem cells are specifically targeted by Disulfiram/copper complex. - Abstract: Non-small cell lung cancer (NSCLC) is the most common cause of cancer-related death in both men and women worldwide. Recently, Disulfiram has been reported to be able to inhibit glioblastoma, prostate, or breast cancer cell proliferation. In this study, the synergistic effect of Disulfiram and copper on NSCLC cell growth was investigated. Inhibition of cancer cell proliferation was detected by 1-(4,5-Dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT) assay and cell cycle analysis. Liquid colony formation and tumor spheroid formation assays were used to evaluate their effect on cancer cell clonogenicity. Real-time PCR was performed to test the mRNA level of cancer stem cell related genes. We found that Disulfiram or copper alone did not potently inhibit NSCLC cell proliferation in vitro. However, the presence of copper significantly enhanced inhibitory effect of Disulfiram on NSCLC cell growth, indicating a synergistic effect between Disulfiram and copper. Cell cycle analysis showed that Disulfiram/copper complex caused NSCLC cell cycle arrest in G2/M phase. Furthermore, Disulfiram/copper significantly increased the sensitivity of cisplatin in NSCLC cells tested by MTT assay. Liquid colony formation assay revealed that copper dramatically increased the inhibitory effect of Disulfiram on NSCLC cell colony forming ability. Disulfiram combined with copper significantly attenuated NSCLC cell spheroid formation and recuded the mRNA expression of lung cancer stem cell related genes. Our data suggest that Disulfiram/copper complex alone or combined with other chemotherapy is a potential therapeutic strategy for NSCLC patients.

  17. Inhibitory effects of sweet cherry anthocyanins on the obesity development in C57BL/6 mice.

    PubMed

    Wu, Tao; Tang, Qiong; Yu, Zhuoping; Gao, Zichun; Hu, Hao; Chen, Wei; Zheng, Xiaodong; Yu, Ting

    2014-05-01

    In the present study, purified sweet cherry anthocyanins (CACN) were evaluated to determine their inhibitory effects on adipocyte differentiation of 3T3-L1 cells and their anti-obesity properties in male C57BL/6 mice fed with high-fat diet (HFD). CACN prevented HFD-induced obesity in C57BL/6 mice. In vivo experiment revealed that 40 and 200 mg/kg of CACN in food reduced the body weight by 5.2% and 11.2%, respectively. CACN supplementation could also reduce the size of adipocytes, leptin secretion, serum glucose, triglyceride, total cholesterol, LDL-cholesterol and liver triglycerides. Furthermore, CACN could effectively reduce the expression levels of IL-6 and TNFα genes, markedly increase the SOD and GPx activity. Our results indicated that CACN slowed down the development of HFD-induced obesity in male C57BL/6 mice. PMID:24224922

  18. Inhibitory effect of pinaverium bromide on gastrointestinal contractile activity in conscious dogs.

    PubMed

    Itoh, Z; Takahashi, I

    1981-01-01

    The inhibitory effect of 4-(6-bromoveratryl)-4-(2-[2-(6,6-dimethyl-2-norpinyl)-ethoxy]-ethyl)-morpholinium hydroxide (pinaverium bromide), a quaternary ammonium derivative, on the contractile activity of the gastrointestinal tract from the stomach to the colon was investigated in six conscious dogs. Gastrointestinal motor activity was monitored by means of chronically implanted force transducers. Pinaverium bromide was continuously administered i.v. for 30 min in doses of 10 and 20 mg/kg/h during both the digestive and interdigestive states. It was found that pinaverium bromide strongly inhibited gastrointestinal contractile activity during both the digestive and interdigestive states; contractions in the stomach were most strongly inhibited; however, those in the small and large bowels were also significantly inhibited. No significant side effects in the circulatory and respiratory systems and the gastrointestinal tract such as nausea, vomiting or diarrhea were observed during and after the infusion of this agent. PMID:7197953

  19. Inhibitory effects of macelignan isolated from Myristica fragrans HOUTT. on melanin biosynthesis.

    PubMed

    Cho, Yumi; Kim, Kyu-Hoi; Shim, Jae-Seok; Hwang, Jae-Kwan

    2008-05-01

    The aim of this study was to investigate the in vitro inhibitory effects of macelignan isolated from Myristica fragrans HOUTT. on melanogenesis and its related enzymes such as tyrosinase, tyrosinase-related protein-1 (TRP-1), and tyrosinase-related protein-2 (TRP-2) in melan-a murine melanocytes. The IC50 values of macelignan for melanogenesis and tyrosinase were 13 microM and 30 microM, respectively, while those of arbutin as a positive control were 990 microM and 660 microM, respectively. In Western blot analysis, macelignan also significantly decreased tyrosinase, TRP-1, and TRP-2 protein expression. These results indicate that macelignan effectively inhibits melanin biosynthesis and thus could be employed as a new skin-whitening agent.

  20. Inhibitory Effects and Mechanisms of Luteolin on Proliferation and Migration of Vascular Smooth Muscle Cells

    PubMed Central

    Jiang, Dehua; Li, Dongye; Wu, Wanling

    2013-01-01

    Atherosclerosis (AS) is a complicated progress, involving many types of cells. Although the exact mechanisms of progression of atherosclerosis are uncertain, the balance of vascular smooth muscle cells (VSMCs) proliferation and apoptosis appears to play a pivotal role in the pathogenesis and progression of atherosclerosis, and much discussion has been undertaken to elucidate the detailed mechanisms, relevant gene expression and transduction pathways. Drug treatment has focused on ameliorating atherosclerosis. Some researchers have indicated that inhibiting VSMCs proliferation is involved in attenuating atherosclerosis. Luteolin is a kind of flavonoids naturally occurring in many plants and possesses beneficial effects on cardiovascular diseases. Luteolin can reduce VSMCs’ proliferation and migration and this reduction is stimulated by several factors. The aim of this review is to summarize the existing inhibitory effects and mechanisms of luteolin on proliferation and migration of VSMCs, and consider whether luteolin may be a potential candidate for preventing and treating atherosclerosis. PMID:23686014

  1. Carbon tetrachloride-induced hepatic and renal damages in rat: inhibitory effects of cacao polyphenol.

    PubMed

    Suzuki, Koichiro; Nakagawa, Kiyotaka; Yamamoto, Takayuki; Miyazawa, Taiki; Kimura, Fumiko; Kamei, Masanori; Miyazawa, Teruo

    2015-01-01

    Here, we investigated the protective effect of cacao polyphenol extract (CPE) on carbon tetrachloride (CCl4)-induced hepato-renal oxidative stress in rats. Rats were administered CPE for 7 days and then received intraperitoneal injection of CCl4. Two hours after injection, we found that CCl4 treatment significantly increased biochemical injury markers, lipid peroxides (phosphatidylcholine hydroperoxide (PCOOH) and malondialdehyde (MDA)) and decreased glutathione peroxidase activity in kidney rather than liver, suggesting that kidney is more vulnerable to oxidative stress under the present experimental conditions. CPE supplementation significantly reduced these changes, indicating that this compound has antioxidant properties against CCl4-induced oxidative stress. An inhibitory effect of CPE on CCl4-induced CYP2E1 mRNA degradation may provide an explanation for CPE antioxidant property. Together, these results provide quantitative evidence of the in vivo antioxidant properties of CPE, especially in terms of PCOOH and MDA levels in the kidneys of CCl4-treated rats.

  2. Inhibitory effect for proliferation of oral bacteria in dogs by tooth brushing and application of toothpaste

    PubMed Central

    WATANABE, Kazuhiro; KIJIMA, Saku; NONAKA, Chie; MATSUKAWA, Yuki; YAMAZOE, Kazuaki

    2016-01-01

    To investigate inhibitory effect for oral bacterial proliferation, we divided 12 dogs into 3 groups; scaling alone (C; control group), brushing (B) and application of toothpaste (P). Before scaling (Pre) and at 0 to 8 weeks after scaling (0–8 w), we collected oral bacteria from the dental surface every week and counted them using a bacterial counter. The results demonstrated a significant reduction in the number of oral bacteria for group B relative to Pre and group C, as well as for group P relative to group C at 5–7 w. Consequently, brushing may inhibit an increase in the number of oral bacteria, and toothpaste may be effective at a certain level, although not more than that of brushing. PMID:27062999

  3. Carbon tetrachloride-induced hepatic and renal damages in rat: inhibitory effects of cacao polyphenol.

    PubMed

    Suzuki, Koichiro; Nakagawa, Kiyotaka; Yamamoto, Takayuki; Miyazawa, Taiki; Kimura, Fumiko; Kamei, Masanori; Miyazawa, Teruo

    2015-01-01

    Here, we investigated the protective effect of cacao polyphenol extract (CPE) on carbon tetrachloride (CCl4)-induced hepato-renal oxidative stress in rats. Rats were administered CPE for 7 days and then received intraperitoneal injection of CCl4. Two hours after injection, we found that CCl4 treatment significantly increased biochemical injury markers, lipid peroxides (phosphatidylcholine hydroperoxide (PCOOH) and malondialdehyde (MDA)) and decreased glutathione peroxidase activity in kidney rather than liver, suggesting that kidney is more vulnerable to oxidative stress under the present experimental conditions. CPE supplementation significantly reduced these changes, indicating that this compound has antioxidant properties against CCl4-induced oxidative stress. An inhibitory effect of CPE on CCl4-induced CYP2E1 mRNA degradation may provide an explanation for CPE antioxidant property. Together, these results provide quantitative evidence of the in vivo antioxidant properties of CPE, especially in terms of PCOOH and MDA levels in the kidneys of CCl4-treated rats. PMID:25996516

  4. Inhibitory effects of bovine lactoferrin on the adherence of enterotoxigenic Escherichia coli to host cells.

    PubMed

    Kawasaki, Y; Tazume, S; Shimizu, K; Matsuzawa, H; Dosako, S; Isoda, H; Tsukiji, M; Fujimura, R; Muranaka, Y; Isihida, H

    2000-02-01

    Adherence is an essential and prerequisite step for the colonization of mucosal surfaces by enterotoxigenic Escherichia coli (ETEC). We studied the effect of bovine lactoferrin (BLF) on the adherence of ETEC to human epithelial cells in vitro, and to intestinal mucosa of ICR germfree mice in vivo. In the in vitro study, BLF was found to inhibit the adherence of ETEC. This adhesion-inhibiting activity of BLF was found to lessen with decreasing BLF concentration, but the data obtained suggest a positive inhibitory effect of BLF against the adhesion of ETEC cells. In the in vivo study, the counts of adherent bacteria in various sections of the intestinal tract (duodenum, jejunoileum, and large intestine) were lower in the BLF group than in the control group, suggesting the possible action of BLF as an intestinal tract adherence-blocking agent with regards to ETEC.

  5. Anti-oxidative and cholinesterase inhibitory effects of leaf extracts and their isolated compounds from two closely related Croton species.

    PubMed

    Ndhlala, Ashwell R; Aderogba, Mutalib A; Ncube, Bhekumthetho; Van Staden, Johannes

    2013-02-01

    A comparative evaluation of the antioxidant and acetylcholinesterase inhibitory activity of the leaf extracts of Croton gratissimus and Croton zambesicus (subgratissimus) and compounds isolated from the extracts was carried out to determine their potential and suitability or otherwise as a substitute for each other in the management of oxidative and neurodegenerative conditions. Different antioxidant assays (DPPH, FRAP, β-carotene-linoleic and the lipid peroxidation models) and the microplate assay for acetylcholinesterase (AChE) inhibition were carried out separately to study the activities of the crude leaf extracts and four solvent fractions from each of the two Croton species. Bioassay guided fractionation was used to target antioxidant constituents of the crude extracts and ethyl acetate fractions of 20% aqueous methanol extract of C. gratissimus on silica gel and Sephadex LH-20 columns resulted in the isolation of kaempferol-3-O-β-6''(p-coumaroyl) glucopyranoside (tiliroside, 2), apigenin-6-C-glucoside (isovitexin, 3) and kampferol (4). The extract of C. zambesicus yielded quercetin-3-O-β-6''(p-coumaroyl) glucopyranoside-3'-methyl ether (helichrysoside- 3'-methyl ether, 1), kaempferol-3-O-β-6''(p-coumaroyl) glucopyranoside (tiliroside, 2) and apigenin-6-C-glucoside (isovitexin, 3). Three of the isolated compounds and their different combinations were also included in the bioassays. In all the assays performed, the antioxidant capacity and AChE inhibitory effects of C. zambesicus extracts were weaker than those of C. gratissimus. This suggests that C. gratissimus may not be substituted by C. zambesicus, despite the similarity in some of their constituents. Generally, the combinations made from the isolated compounds showed better activities in most of the assays compared to the individual isolated compounds. This suggests mechanisms such as synergism and/or additive effects to be taking place. This study established low, moderate and high antioxidant

  6. The effect of gastric inhibitory polypeptide on intestinal glucose absorption and intestinal motility in mice

    SciTech Connect

    Ogawa, Eiichi; Hosokawa, Masaya; Harada, Norio; Yamane, Shunsuke; Hamasaki, Akihiro; Toyoda, Kentaro; Fujimoto, Shimpei; Fujita, Yoshihito; Fukuda, Kazuhito; Tsukiyama, Katsushi; Yamada, Yuichiro; Seino, Yutaka; Inagaki, Nobuya

    2011-01-07

    Research highlights: {yields} Exogenous GIP inhibits intestinal motility through a somatostatin-mediated pathway. {yields} Exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility. {yields} The GIP-receptor-mediated action in intestine does not involve in GLP-1-mediated pathway. -- Abstract: Gastric inhibitory polypeptide (GIP) is released from the small intestine upon meal ingestion and increases insulin secretion from pancreatic {beta} cells. Although the GIP receptor is known to be expressed in small intestine, the effects of GIP in small intestine are not fully understood. This study was designed to clarify the effect of GIP on intestinal glucose absorption and intestinal motility. Intestinal glucose absorption in vivo was measured by single-pass perfusion method. Incorporation of [{sup 14}C]-glucose into everted jejunal rings in vitro was used to evaluate the effect of GIP on sodium-glucose co-transporter (SGLT). Motility of small intestine was measured by intestinal transit after oral administration of a non-absorbed marker. Intraperitoneal administration of GIP inhibited glucose absorption in wild-type mice in a concentration-dependent manner, showing maximum decrease at the dosage of 50 nmol/kg body weight. In glucagon-like-peptide-1 (GLP-1) receptor-deficient mice, GIP inhibited glucose absorption as in wild-type mice. In vitro examination of [{sup 14}C]-glucose uptake revealed that 100 nM GIP did not change SGLT-dependent glucose uptake in wild-type mice. After intraperitoneal administration of GIP (50 nmol/kg body weight), small intestinal transit was inhibited to 40% in both wild-type and GLP-1 receptor-deficient mice. Furthermore, a somatostatin receptor antagonist, cyclosomatostatin, reduced the inhibitory effect of GIP on both intestinal transit and glucose absorption in wild-type mice. These results demonstrate that exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility through a somatostatin

  7. High potassium intake enhances the inhibitory effect of 11,12-EET on ENaC.

    PubMed

    Sun, Peng; Lin, Dao-Hong; Yue, Peng; Jiang, Houli; Gotlinger, Katherine H; Schwartzman, Michal L; Falck, John R; Goli, Mohan; Wang, Wen-Hui

    2010-10-01

    High dietary potassium stimulates the renal expression of cytochrome P450 (CYP) epoxygenase 2C23, which metabolizes arachidonic acid (AA). Because the AA metabolite 11,12-epoxyeicosatrienoic acid (11,12-EET) can inhibit the epithelial sodium channel (ENaC) in the cortical collecting duct, we tested whether dietary potassium modulates ENaC function. High dietary potassium increased 11,12-EET in the isolated cortical collecting duct, an effect mimicked by inhibiting the angiotensin II type I receptor with valsartan. In patch-clamp experiments, a high potassium intake or treatment with valsartan enhanced AA-induced inhibition of ENaC, an effect mediated by a CYP-epoxygenase-dependent pathway. Moreover, high dietary potassium and valsartan each augmented the inhibitory effect of 11,12-EET on ENaC. Liquid chromatography/mass spectrometry showed that the rate of EET conversion to dihydroxyeicosatrienoic acids (DHET) was lower in renal tissue obtained from rats on a high-potassium diet than from those on a control diet, but this was not a result of altered expression of soluble epoxide hydrolase (sEH). Instead, suppression of sEH activity seemed to be responsible for the 11,12-EET-mediated enhanced inhibition of ENaC in animals on a high-potassium diet. Patch-clamp experiments demonstrated that 11,12-DHET was a weak inhibitor of ENaC compared with 11,12-EET, whereas 8,9- and 14,15-DHET were not. Furthermore, inhibition of sEH enhanced the 11,12-EET-induced inhibition of ENaC similar to high dietary potassium. In conclusion, high dietary potassium enhances the inhibitory effect of AA and 11,12-EET on ENaC by increasing CYP epoxygenase activity and decreasing sEH activity, respectively.

  8. Chemical characterization, antioxidant and inhibitory effects of some marine sponges against carbohydrate metabolizing enzymes

    PubMed Central

    2012-01-01

    Background More than 15,000 marine products have been described up to now; Sponges are champion producers, concerning the diversity of products that have been found. Most bioactive compounds from sponges were classified into anti-inflammatory, antitumor, immuno- or neurosurpressive, antiviral, antimalarial, antibiotic, or antifouling. Evaluation of in vitro inhibitory effects of different extracts from four marine sponges versus some antioxidants indices and carbohydrate hydrolyzing enzymes concerned with diabetes mellitus was studied. The chemical characterizations for the extracts of the predominating sponges; SP1 and SP3 were discussed. Methods All chemicals served in the biological study were of analytical grade and purchased from Sigma, Merck and Aldrich. All kits were the products of Biosystems (Spain), Sigma Chemical Company (USA), Biodiagnostic (Egypt). Carbohydrate metabolizing enzymes; α-amylase, α-glucosidase, and β-galactosidase (EC3.2.1.1, EC3.2.1.20, and EC3.2.1.23, respectively) were obtained from Sigma Chemical Company (USA). Results Four marine sponges; Smenospongia (SP1), Callyspongia (SP2), Niphates (SP3), and Stylissa (SP4), were collected from the Red Sea at Egyptian coasts, and taxonomically characterized. The sponges' extracts exhibited diverse inhibitory effects on oxidative stress indices and carbohydrate hydrolyzing enzymes in linear relationships to some extent with concentration of inhibitors (dose dependant). The extracts of sponges (3, 1, and 2) showed, respectively, potent-reducing power. Purification and Chemical characterization of sponge 1 using NMR and mass spectroscopy, recognized the existence of di-isobutyl phthalate (1), di-n-butyl phthalate (2), linoleic acid (3), β-sitosterol (4), and cholesterol (5). Sponge 3 produced bis-[2-ethyl]-hexyl-phthylester (6) and triglyceride fatty acid ester (7). Conclusion Marine sponges are promising sources for delivering of bioactive compounds. Four marine sponges, collected from

  9. Inhibitory effect of Xenorhabdus nematophila TB on plant pathogens Phytophthora capsici and Botrytis cinerea in vitro and in planta.

    PubMed

    Fang, Xiangling; Zhang, Manrang; Tang, Qian; Wang, Yonghong; Zhang, Xing

    2014-01-01

    Entomopathogenic bacteria Xenorhabdus spp. produce secondary metabolites with potential antimicrobial activity for use in agricultural productions. This study evaluated the inhibitory effect of X. nematophila TB culture on plant pathogens Botrytis cinerea and Phytophthora capsici. The cell-free filtrate of TB culture showed strong inhibitory effects (>90%) on mycelial growth of both pathogens. The methanol-extracted bioactive compounds (methanol extract) of TB culture also had strong inhibitory effects on mycelial growth and spore germinations of both pathogens. The methanol extract (1000 μg/mL) and cell-free filtrate both showed strong therapeutic and protective effects (>70%) on grey mold both in detached tomato fruits and plants, and leaf scorch in pepper plants. This study demonstrates X. nematophila TB produces antimicrobial metabolites of strong activity on plant pathogens, with great potential for controlling tomato grey mold and pepper leaf scorch and being used in integrated disease control to reduce chemical application. PMID:24599183

  10. Inhibitory effect of corcin on aggregation of 1N/4R human tau protein in vitro

    PubMed Central

    Karakani, Ali Mohammadi; Riazi, Gholamhossein; Mahmood Ghaffari, Seyed; Ahmadian, Shahin; Mokhtari, Farzad; Jalili Firuzi, Mahshad; Zahra Bathaie, Seyedeh

    2015-01-01

    Objective(s): Alzheimer’s disease (AD) is the most common age-related neurodegenerative disorder. One of the hallmarks of AD is an abnormal accumulation of fibril forms of tau protein which is known as a microtubule associated protein. In this regard, inhibition of tau aggregation has been documented to be a potent therapeutic approach in AD and tauopathies. Unfortunately, the available synthetic drugs have modest beneficial efficacy with several side effects. Therefore, pipeline drugs from natural sources with anti-aggregation properties can be useful in the prevention and treatment of AD. Among medicinal plants, saffron (Crocus sativus, L.), as a traditional herbal medicine has different pharmacological properties and can be used as treatment for several nervous system impairment including depression and dementia. Crocin as a major constituent of saffron is the glycosylated form of crocetin. Materials and Methods: In this study, we investigated the inhibitory effect of crocin on aggregation of recombinant human tau protein 1N/4R isoform using biochemical methods and cell culture. Results: Results revealed that tau protein under the fibrillation condition and in the presence of crocin had enough stability with low tendency for aggregation. Crocin inhibited tau aggregation with IC50 of 100 µg/ml. Furthermore, transmission electron microscopy images confirmed that crocin could suppress the formation of tau protein filaments. Conclusion: Inhibitory effect of crocin could be related to its interference with nucleation phase that led to increases in monomer species of tau protein. Based on our results, crocin is recommended as a proper candidate to be used in AD treatment. PMID:26124935

  11. Comparison of inhibitory effects between acetaminophen-glutathione conjugate and reduced glutathione in human glutathione reductase.

    PubMed

    Nýdlová, Erika; Vrbová, Martina; Cesla, Petr; Jankovičová, Barbora; Ventura, Karel; Roušar, Tomáš

    2014-09-01

    Acetaminophen overdose is the most frequent cause of acute liver injury. The main mechanism of acetaminophen toxicity has been attributed to oxidation of acetaminophen. The oxidation product is very reactive and reacts with glutathione generating acetaminophen-glutathione conjugate (APAP-SG). Although this conjugate has been recognized to be generally nontoxic, we have found recently that APAP-SG could produce a toxic effect. Therefore, the aim of our study was to estimate the toxicity of purified APAP-SG by characterizing the inhibitory effect in human glutathione reductase (GR) and comparing that to the inhibitory effect of the natural inhibitor reduced glutathione. We used two types of human GR: recombinant and freshly purified from red blood cells. Our results show that GR was significantly inhibited in the presence of both APAP-SG and reduced glutathione. For example, the enzyme activity of recombinant and purified GR was reduced in the presence of 4 mm APAP-SG (with 0.5 mm glutathione disulfide) by 28% and 22%, respectively. The type of enzyme inhibition was observed to be competitive in the cases of both APAP-SG and glutathione. As glutathione inhibits GR activity in cells under physiological conditions, the rate of enzyme inhibition ought to be weaker in the case of glutathione depletion that is typical of acetaminophen overdose. Notably, however, enzyme activity likely remains inhibited due to the presence of APAP-SG, which might enhance the pro-oxidative status in the cell. We conclude that our finding could reflect some other pathological mechanism that may contribute to the toxicity of acetaminophen.

  12. In vitro inhibitory effect on pancreatic lipase activity of subfractions from ethanol extracts of fermented Oats (Avena sativa L.) and synergistic effect of three phenolic acids.

    PubMed

    Cai, Shengbao; Wang, Ou; Wang, Mengqian; He, Jianfeng; Wang, Yong; Zhang, Di; Zhou, Feng; Ji, Baoping

    2012-07-25

    The purpose of the present work is to study the pancreatic lipase inhibitory effects of different subfractions (n-hexane, ethyl acetate (EA), n-butanol, and water) from ethanol extracts of nonfermented and fungi-fermented oats and to delineate the interactions of three primary phenolic acids in the EA subfractions. The EA subfraction showed the highest inhibitory effect on pancreatic lipase activity at 1.5 mg/mL compared to the other subfractions, regardless of whether the oats were fermented. Meanwhile, both of the EA subfractions of two fungi-fermented oats demonstrated more effective inhibitory activity than that of nonfermented oats. A positive correlation between the total phenolics content and inhibitory activity was found. The inhibitory ability of the EA subfraction from nonfermented or fermented oats also displayed a dose-dependent effect. The standards of caffeic, ferulic, and p-coumaric acids, mainly included in EA subfractions of fermented oats, also displayed a dose-dependent inhibitory effect. A synergistic effect of each binary combination of p-coumaric, ferulic, and caffeic acids was observed, especially at 150.0 μg/mL. Those results indicate that fungi-fermented oats have a more effective inhibitory ability on pancreatic lipase and polyphenols may be the most effective component and could be potentially used for dietary therapy of obesity.

  13. Inhibitory effect of iron withdrawal by chelation on the growth of human and murine mammary carcinoma and fibrosarcoma cells.

    PubMed

    Power Coombs, Melanie R; Grant, Taryn; Greenshields, Anna L; Arsenault, Daniel J; Holbein, Bruce E; Hoskin, David W

    2015-10-01

    Since iron uptake is essential for cell growth, rapidly dividing cancer cells are sensitive to iron depletion. To explore the effect of iron withdrawal on cancer cell growth, mouse and human mammary carcinoma cells (4T1 and MDA-MB-468, respectively) and mouse and human fibrosarcoma cells (L929 and HT1080, respectively) were cultured in the absence or presence of DIBI, a novel iron-chelating polymer containing hydroxypyridinone iron-ligand functionality. Cell growth was measured by a colorimetric assay for cell metabolic activity. DIBI-treated 4T1, MDA-MB-468, L929 and HT1080 cells, as well as their normal counterparts, showed a dose- and time-dependent reduction in growth that was selective for human cancer cells and mouse fibrosarcoma cells. The inhibitory effect of DIBI on fibrosarcoma and mammary carcinoma cell growth was reversed by addition of exogenous iron in the form of iron (III) citrate, confirming the iron selectivity of DIBI and that its inhibitory activity was iron-related. Fibrosarcoma and mammary carcinoma cell growth inhibition by DIBI was associated with S-phase cell cycle arrest and low to moderate levels of cell death by apoptosis. Consistent with apoptosis induction following DIBI-mediated iron withdrawal, fibrosarcoma and mammary carcinoma cells exhibited mitochondrial membrane permeabilization. A comparison of DIBI to other iron chelators showed that DIBI was superior to deferiprone and similar to or better than deferoxamine for inhibition of fibrosarcoma and mammary carcinoma cell growth. These findings suggest that iron withdrawal from the tumor microenvironment with a selective and potent iron chelator such as DIBI may prevent or inhibit tumor progression.

  14. Inhibitory Effect of Furanic and Phenolic Compounds on Exoelectrogenesis in a Microbial Electrolysis Cell Bioanode

    DOE PAGES

    Zeng, Xiaofei; Borole, Abhijeet P.; Pavlostathis, Spyros G.

    2016-09-09

    Furanic and phenolic compounds are 20 lignocellulose-derived compounds known to inhibit to H2- and ethanol- producing microorganisms in dark fermentation. Bioelectrochemical conversion of furanic and phenolic compounds to electricity or H2 has recently been demonstrated as a productive method to use these compounds. However, potential inhibitory effect of furanic and phenolic compounds on exoelectrogenesis in bioelectrochemical systems is not well understood. This study systematically investigated the inhibitory effect of furfural (FF), 5-hydroxymethylfurfural (HMF), syringic acid (SA), vanillic acid (VA), and 4-hydroxybenzoic acid (HBA) on exoelectrogenesis in the bioanode of a microbial electrolysis cell. A mixture of these five compounds atmore » an increasing initial total concentration from 0.8 to 8.0 g/L resulted in current decrease up to 91%. The observed inhibition primarily affected exoelectrogenesis, instead of non-exoelectrogenic biotransformation pathways (e.g., fermentation) of the five compounds. Furthermore, the parent compounds at a high concentration, as opposed to their biotransformation products, were responsible for the observed inhibition. Tests with individual compounds show that all five parent compounds contributed to the observed inhibition by the mixture. The IC50 (concentration resulting in 50% current decrease) was estimated as 2.7 g/L for FF, 3.0 g/L for HMF, 1.9 g/L for SA, 2.1 g/L for VA and 2.0 g/L for HBA. Nevertheless, these compounds below their non-inhibitory concentrations jointly resulted in significant inhibition as a mixture. Catechol and phenol, which were persistent biotransformation products of the mixture, inhibited exoelectrogens at high concentrations, but to a lesser extent than the parent compounds. Recovery of exoelectrogenesis from inhibition by all compounds was observed, except for catechol, which resulted in irreversible inhibition. The reversibility of inhibition, as well as the observed difference in recovery

  15. Inhibitory effect of peroxyacetyl nitrate on cyclic photophosphorylation by chloroplasts from black valentine bean leaves.

    PubMed

    Koukol, J; Dugger, W M; Palmer, R L

    1967-10-01

    The inhibitory effect of peroxyacetyl nitrate on the cyclic photophosphorylation of chloroplasts isolated from Black Valentine variety bean leaves (Phaseolis vulgaris L.) has been studied. Peroxyacetyl nitrate caused inhibition to photophosphorylation, in either the dark or the light, by affecting the chloroplast. Evidence is presented which suggests that peroxyacetyl nitrate could oxidize sulfhydryl groups on enzymes necessary for photophosphorylation. The inhibition to photophosphorylation caused by peroxyacetyl nitrate cannot be reversed by glutathione, even when added in large amounts, whereas the inhibition to photophosphorylation caused by para-chloromercuriphenylsulfonic acid is easily reversed by small quantities of glutathione. This suggests that if peroxyacetyl nitrate is oxidizing sulfhydryl groups necessary for photophosphorylation, this oxidation is proceeding beyond the disulfide state.

  16. The inhibitory effect of metals and other ions on acid phosphatase activity from Vigna aconitifolia seeds.

    PubMed

    Srivastava, Pramod Kumar; Anand, Asha

    2015-01-01

    Sensitivity of acid phosphatase from Vigna aconitifolia seeds to metal ions, fluoride, and phosphate was examined. All the effectors had different degree of inhibitory effect on the enzyme. Among metal ions, molybdate and ferric ion were observed to be most potent inhibitors and both exhibited mixed type of inhibition. Acid phosphatase activity was inhibited by Cu2+ in a noncompetitive manner. Zn and Mn showed mild inhibition on the enzyme activity. Inhibition kinetics analysis explored molybdate as a potent inhibitor for acid phosphatase in comparison with other effectors used in this study. Fluoride was the next most strong inhibitor for the enzyme activity, and caused a mixed type of inhibition. Phosphate inhibited the enzyme competitively, which demonstrates that inhibition due to phosphate is one of the regulatory factors for enzyme activity.

  17. Inhibitory effect of plant Manilkara subsericea against biological activities of Lachesis muta snake venom.

    PubMed

    De Oliveira, Eduardo Coriolano; Fernandes, Caio Pinho; Sanchez, Eladio Flores; Rocha, Leandro; Fuly, André Lopes

    2014-01-01

    Snake venom is composed of a mixture of substances that caused in victims a variety of pathophysiological effects. Besides antivenom, literature has described plants able to inhibit injuries and lethal activities induced by snake venoms. This work describes the inhibitory potential of ethanol, hexane, ethyl acetate, or dichloromethane extracts and fractions from stem and leaves of Manilkara subsericea against in vivo (hemorrhagic and edema) and in vitro (clotting, hemolysis, and proteolysis) activities caused by Lachesis muta venom. All the tested activities were totally or at least partially reduced by M. subsericea. However, when L. muta venom was injected into mice 15 min first or after the materials, hemorrhage and edema were not inhibited. Thus, M. subsericea could be used as antivenom in snakebites of L. muta. And, this work also highlights Brazilian flora as a rich source of molecules with antivenom properties.

  18. Inhibitory Effect of Plant Manilkara subsericea against Biological Activities of Lachesis muta Snake Venom

    PubMed Central

    De Oliveira, Eduardo Coriolano; Fernandes, Caio Pinho; Sanchez, Eladio Flores; Fuly, André Lopes

    2014-01-01

    Snake venom is composed of a mixture of substances that caused in victims a variety of pathophysiological effects. Besides antivenom, literature has described plants able to inhibit injuries and lethal activities induced by snake venoms. This work describes the inhibitory potential of ethanol, hexane, ethyl acetate, or dichloromethane extracts and fractions from stem and leaves of Manilkara subsericea against in vivo (hemorrhagic and edema) and in vitro (clotting, hemolysis, and proteolysis) activities caused by Lachesis muta venom. All the tested activities were totally or at least partially reduced by M. subsericea. However, when L. muta venom was injected into mice 15 min first or after the materials, hemorrhage and edema were not inhibited. Thus, M. subsericea could be used as antivenom in snakebites of L. muta. And, this work also highlights Brazilian flora as a rich source of molecules with antivenom properties. PMID:24511532

  19. Inhibitory effect of tea polyphenols on local tissue damage induced by snake venoms.

    PubMed

    Pithayanukul, P; Leanpolchareanchai, J; Bavovada, R

    2010-01-01

    The methanolic extract of fresh tea leaves of Camellia sinensis L. (Theaceae) (CS) was assayed for its potential to inhibit enzymes with hydrolytic activity in Naja naja kaouthia Lesson (Elapidae) and Calloselasma rhodostoma Kuhl (Viperidae) venoms. These snake venom enzymes are responsible for the early effects of envenomation, such as local tissue damage and inflammation. The CS extract inhibited phospholipase A(2), proteases, hyaluronidase and L-amino acid oxidase in both venoms by in vitro neutralization and inhibited the hemorrhagic and the dermonecrotic activities of the venoms in vivo. It is suggested that the inhibitory potential of the CS extract against local tissue damage induced by snake venoms may be attributed to complexation and chelation between the venom proteins and the phenolic contents of the extract.

  20. Fungichromin: a substance from Streptomyces padanus with inhibitory effects on Rhizoctonia solani.

    PubMed

    Shih, Hsin-Der; Liu, Yung-Chuan; Hsu, Fen-Lin; Mulabagal, Vanisree; Dodda, Rajasekhar; Huang, Jenn-Wen

    2003-01-01

    Streptomyces padanus strain PMS-702 is an antagonist of Rhizoctonia solani AG-4, the causal agent of damping-off of cabbage. Treatment of cabbage seeds with the culture filtrate of S. padanus strain PMS-702 was effective in reducing the incidence of damping-off of cabbage. The major active ingredient from the culture filtrate of S. padanus strain PMS-702 was purified by silica gel column chromatography and identified as the polyene macrolide, fungichromin, by NMR and mass spectral data. Bioassay studies showed that fungichromin had a strong antifungal activity against R. solani AG-4, and its minimum inhibitory concentration (over 90% inhibition) was found to be 72 microg/mL. This is the first report of fungichromin from S. padanus as an active ingredient for the control of Rhizoctonia damping-off of cabbage.

  1. Inhibitory effects of whisky polyphenols on melanogenesis in mouse B16 melanoma cells.

    PubMed

    Yoshioka, Sayaka; Terashita, Takao; Yoshizumi, Hajime; Shirasaka, Norifumi

    2011-01-01

    Whisky exerts an inhibitory effect on melanogenesis in B16 cells, the anti-melanogenic activity being positively correlated with the aging period and anti-oxidative activity of whisky. We examined the correlation between the inhibition of melanogenesis and the concentration of each compound in various whiskies to evaluate the importance of 11 different whisky polyphenols, including ellagic acid, gallic acid and lyoniresinol, in the anti-melanogenic activity of whisky. The concentration of all the compounds was positively correlated with the anti-melanogenic activity of whisky. Ellagic acid, gallic acid and lyoniresinol were the predominant polyphenols in the whiskies measured by HPLC. These three compounds also significantly inhibited the melanogenesis and tyrosinase activity in B16 cells. Ellagic acid, gallic acid and lyoniresinol were confirmed as the major participants in the anti-melanogenic activity of whisky.

  2. [Inhibitory effect of DMPP on soil nitrification as affected by soil moisture content, pH and organic matter].

    PubMed

    Xue, Yan; Wu, Zhi-Jie; Zhang, Li-Li; Gong, Ping; Dong, Xin-Xin; Nie, Yan-Xia

    2012-10-01

    A laboratory incubation test with meadow brown soil was conducted to study the inhibitory effect of 3,4-dimethylpyrazole phosphate (DMPP) on soil nitrification as affected by soil moisture content (40%, 60% and 80% of the maximum field capacity), pH (4, 7 and 10), and organic matter (retained and removal). With the decrease of soil moisture content, the degradation of DMPP in soil tended to slow down, and the oxidation of soil NH4+ was more inhibited. At pH 10, more DMPP was remained in soil, and had the greatest inhibitory effect; at pH 7 and pH 4, the DMPP was lesser remained, with a smaller inhibitory effect. The removal of organic matter prolonged the remaining time of DMPP in soil, and decreased the apparent soil nitrification rate significantly.

  3. Potent inhibitory effects of N-aryl S-alkylthiocarbamate derivatives on the dopa oxidase activity of mushroom tyrosinase.

    PubMed

    Lee, Kun Ho; Koketsu, Mamoru; Choi, Sang Yoon; Lee, Kang Jin; Lee, Pyeongjae; Ishihara, Hideharu; Kim, Sun Yeou

    2005-07-01

    This study reports the potent inhibitory effect of N-aryl S-alkylthiocarbamate derivatives on mushroom tyrosinase (MT) activity. N-Aryl S-alkylthiocarbamate derivatives were found to exhibit a potent inhibitory effect on the dopa (3,4-dihydroxyphenylalanine) oxidase activity of mushroom tyrosinase. Most of the N-aryl S-alkylthiocarbamate derivatives (compounds from A to J) exhibited higher inhibitory effects than kojic acid (IC50=318 microM), a well known tyrosinase inhibitor. Tyrosinase was the most inhibited by S-phenetyl N-phenylthiocarbamate (compound E, IC50=7.25 microM), and this inhibition was 44 times stronger than that of kojic acid. Compound E exhibited 95.0% of inhibition at 100 microM. A kinetic study of MT inhibition by compound E using the Lineweaver-Burk plots analysis was performed. And the kinetics profiles observed suggest that compound E competitively inhibits MT.

  4. Inhibitory effects of Persicariae Rhizoma aqueous extracts on experimental periodontitis and alveolar bone loss in Sprague-Dawley rats

    PubMed Central

    Kang, Su Jin; Lee, Eun Kyung; Han, Chang Hyun; Lee, Bong Hyo; Lee, Young Joon; Ku, Sae Kwang

    2016-01-01

    Persicariae Rhizoma (PR) is the dried stem parts of Persicaria tinctoria H. Gross (Polygonaceae), and has been traditionally used as anti-inflammatory and detoxifying agent. In the present study, the effects of PR aqueous extracts on ligation-induced experimental periodontitis (EPD) and associated alveolar bone loss in rats were examined. Following the induction of EPD in rats, PR extracts were orally administered once a day for 10 days, and the changes and gains in body weight, alveolar bone loss and total aerobic bacterial counts of buccal gingiva were observed with histopathological analysis. In addition, anti-inflammatory effects were evaluated by monitoring myeloperoxidase (MPO) activities, and interleukin (IL)-1β and tumor necrosis factor (TNF)-α contents, and anti-oxidant effects were investigated by measuring inducible nitric oxide synthase (iNOS) activities and malondialdehyde (MDA) levels. Bacterial proliferation, periodontitis and associated alveolar bone loss induced by ligature placement were significantly and dose-dependently inhibited by the treatment with PR extracts. The inhibitory effects of 200 mg/kg PR were similar to those of 5 mg/kg indomethacin on ligation-induced periodontitis and associated alveolar bone losses in this study. The results suggest that PR effectively inhibits ligature placement-induced periodontitis and alveolar bone loss in rats via antibacterial, antioxidative and anti-inflammatory activities. PMID:27588077

  5. In vitro inhibitory effects of asiaticoside and madecassoside on human cytochrome P450.

    PubMed

    Winitthana, T; Niwattisaiwong, N; Patarapanich, C; Tantisira, M H; Lawanprasert, S

    2011-06-01

    The inhibitory effects and types of inhibition of asiaticoside and madecassoside on human CYPs were studied in vitro using recombinant human CYPs. The median inhibitory concentrations (IC50) of asiaticoside and madecassoside were determined for CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4. Asiaticoside inhibited CYP2C19 (IC50 = 412.68 ± 15.44 μM) and CYP3A4 (IC50=343.35 ± 29.35 μM). Madecassoside also inhibited CYP2C19 (IC50 = 539.04 ± 14.18 μM) and CYP3A4 (IC50 = 453.32 ± 39.33 μM). Asiaticoside and madecassoside had no effect on the activities of CYP1A2, CYP2C9 and CYP2D6 and CYP2E1. Assessment of mechanism-based inhibition and the type of inhibition were performed for asiaticoside and madecassoside with CYP2C19 and CYP3A4. These results suggested that madecassoside is a mechanism-based inhibitor of CYP2C19 and CYP3A4. Assessment of mechanism-based inhibition by asiaticoside was limited by its low solubility. Asiaticoside exhibited non-competitive inhibition of CYP2C19 (Ki=385.24 ± 8.75 μM) and CYP3A4 (Ki = 535.93 ± 18.99 μM). Madecassoside also showed non-competitive inhibition of CYP2C19 (Ki = 109.62 ± 6.14 μM) and CYP3A4 (Ki = 456.84 ± 16.43 μM). These results suggest that asiaticoside and madecassoside could cause drug-drug interactions via inhibition of CYP2C19 and CYP3A4. An in vivo study is needed to examine this further.

  6. Inhibitory effects of French pine bark extract, Pycnogenol®, on alveolar bone resorption and on the osteoclast differentiation.

    PubMed

    Sugimoto, Hideki; Watanabe, Kiyoko; Toyama, Toshizo; Takahashi, Shun-suke; Sugiyama, Shuta; Lee, Masaichi-Chang-il; Hamada, Nobushiro

    2015-02-01

    Pycnogenol(®) (PYC) is a standardized bark extract from French maritime pine (Pinus pinaster Aiton). We examined the inhibitory effects of PYC on alveolar bone resorption, which is a characteristic feature of periodontitis, induced by Porphyromonas gingivalis (P. gingivalis) and osteoclast differentiation. In rat periodontitis model, rats were divided into four groups: group A served as the non-infected control, group B was infected orally with P. gingivalis ATCC 33277, group C was administered PYC in the diet (0.025%: w/w), and group D was infected with P. gingivalis and administered PYC. Administration of PYC along with P. gingivalis infection significantly reduced alveolar bone resorption. Treatment of P. gingivalis with 1 µg/ml PYC reduced the number of viable bacterial cells. Addition of PYC to epithelial cells inhibited adhesion and invasion by P. gingivalis. The effect of PYC on osteoclast formation was confirmed by tartrate-resistant acid phosphatase staining. PYC treatment significantly inhibited osteoclast formation. Addition of PYC (1-100 µg/ml) to purified osteoclasts culture induced cell apoptosis. These results suggest that PYC may prevent alveolar bone resorption through its antibacterial activity against P. gingivalis and by suppressing osteoclastogenesis. Therefore, PYC may be useful as a therapeutic and preventative agent for bone diseases such as periodontitis.

  7. Inhibitory effects on phospholipase A2 and antivenin activity of melanin extracted from Thea sinensis Linn.

    PubMed

    Hung, Yao-Ching; Sava, Vasyl; Hong, Meng-Yen; Huang, G Steven

    2004-03-01

    Antivenin activity of melanin extracted from black tea (MEBT) was reported for the first time. The antagonistic effect of MEBT was evaluated for Agkistrodon contortrix laticinctus (broadbanded copperhead), Agkistrodon halys blomhoffii (Japanese mamushi), and Crotalus atrox (western diamondback rattlesnake) snake venoms administered i.p. to ICR mice. MEBT was injected i.p. immediately after the venom administration in dose of 3 mg per mouse in the same place of venom injection. MEBT demonstrated neutralization effect against all venoms tested. The greatest antivenin effect of MEBT was found against Japanese mamushi snake venom. In this case, half the mice died within 2.5 +/- 0.7 h after injection of 0.9 mg/kg of venom. An immediate injection of MEBT substantially reduced the toxic effect of venom and extended time at the 50% level of survival up to 52.3 +/- 2.3 h. The antivenin activity of MEBT is due to chelating of Ca++ and non-specific binding of phospholipase A2. The inhibitory effect of MEBT on phospholipase A2 assessed for different venoms was similar to that obtained with pure enzyme. Low toxicity of MEBT in combination with its antagonistic activity against different venoms may allow effective life-saving treatment against snakebites. Such application of MEBT is important when identification of the snake is impossible or if specific treatment is unavailable.

  8. [Inhibitory effect of imperatorin and isoimperatorin on activity of cytochrome P450 enzyme in human and rat liver microsomes].

    PubMed

    Cao, Yan; Zhong, Yu-Huan; Yuan, Mei; Li, Hua; Zhao, Chun-Jie

    2013-04-01

    Imperatorin (IM) and isoimperatorin (ISOIM) are major active components of common herbal medicines from Umbelliferae plants, and widely used in clinic. This article studies the inhibitory effect of IM and ISOIM on the activity of cytochrome P450 (CYP) enzyme, and assesses their potential drug-drug interaction. IM and ISOIM were incubated separately with human or rat liver microsomes for 30 min, with phenacetin, bupropion, tolbutamide, S-mephenytoin, dextromethorphan and midazolam as probe substrates. Metabolites of the CYP probe substrates were determined by LC-MS/MS, and IC50 values were calculated to assess the inhibitory effect of the two drugs on human CYP1A2, 2B6, 2C9, 2C19, 2D6 and 3A4 enzymes, as well as on rat CYP1A2, 2B6, 2D2 and 3A1/2, and grade their inhibitory intensity. In human liver microsomes, IM and ISOIM showed different inhibitory effects on all of the six CYP isoenzymes. They were strong inhibitors for 1A2 and 2B6. The IC50 values were 0.05 and 0.20 micromol x L(-1) for 1A2, and 0.18 and 1.07 micromol x L(-1) for 2B6, respectively. They also showed moderate inhibitory effect on 2C19, and weak effect on 2C9, 2D6 and 3A4. In rat liver microsomes, IM and ISOIM were identified as moderate inhibitors for 1A2, with IC50 values of 1.95 and 2.98 micromol x L(-1). They were moderate and weak inhibitors for 2B6, with IC50 values of 6.22 and 21.71 micromol x L(-1), respectively. They also had weaker inhibitory effect on 2D2 and 3A1/2. The results indicated that IM and ISOIM had extensive inhibitory effects on human CYP enzymes. They are strong inhibitors of CYP1 A2 and 2B6 enzymes. However, it is worth noting the interaction arising from the inhibitory effect of CYP enzymes in clinic.

  9. The Effect of Inhibitory Control on General Mathematics Achievement and Fraction Comparison in Middle School Children

    ERIC Educational Resources Information Center

    Gómez, David Maximiliano; Jiménez, Abelino; Bobadilla, Roberto; Reyes, Cristián; Dartnell, Pablo

    2015-01-01

    Individual differences in inhibitory control have been shown to relate to general mathematics achievement, but whether this relation varies for specific areas within mathematics is a question that remains open. Here, we evaluate if inhibitory processes play a specific role in the particular case of fraction comparison, where learners must ignore…

  10. Multilingual Stroop Performance: Effects of Trilingualism and Proficiency on Inhibitory Control

    ERIC Educational Resources Information Center

    Marian, Viorica; Blumenfeld, Henrike K.; Mizrahi, Elena; Kania, Ursula; Cordes, Anne-Kristin

    2013-01-01

    Previous research suggests that multilinguals' languages are constantly co-activated and that experience managing this co-activation changes inhibitory control function. The present study examined language interaction and inhibitory control using a colour-word Stroop task. Multilingual participants were tested in their three most proficient…

  11. Inhibitory effect of commercial green tea and rosemary leaf powders on the growth of foodborne pathogens in laboratory media and oriental-style rice cakes.

    PubMed

    Lee, Sun-Young; Gwon, So-Young; Kim, Seung-Ju; Moon, Bo Kyung

    2009-05-01

    The antimicrobial effects of green tea and rosemary added to foods as antagonists to foodborne pathogens were determined in laboratory media and oriental-style rice cakes. The growth of each pathogen (Bacillus cereus, Salmonella Typhimurium, Enterobacter sakazakii, Escherichia coli O157:H7, Staphylococcus aureus, and Listeria monocytogenes) in tryptic soy broth or rice cake with or without addition of green tea or rosemary leaf powders before autoclaving or cooking, respectively, was investigated after inoculation. The addition of 1% green tea or rosemary produced similar results for inhibiting the growth of pathogens in tryptic soy broth. However, green tea was more effective than rosemary for inhibiting the growth of L. monocytogenes. Both botanicals had inhibitory effects against all pathogens tested in this study. Green tea was particularly effective against B. cereus, S. aureus, and L. monocytogenes, and rosemary was strongly inhibitory against B. cereus and S. aureus. The addition of 1 or 3% green tea or rosemary to rice cakes did not significantly reduce total aerobic counts; however, levels of B. cereus and S. aureus were significantly reduced in rice cakes stored for 3 days at room temperature (22 degrees C). The order of antimicrobial activities against B. cereus in rice cake was 1% rosemary < 1% green tea < 3% rosemary = 3% green tea. These results indicate that the use of natural plant materials such as green tea and rosemary could improve the microbial quality of foods in addition to their functional properties.

  12. Chemo-enzymatic synthesis of vinyl and l-ascorbyl phenolates and their inhibitory effects on advanced glycation end products.

    PubMed

    Hwang, Seung Hwan; Wang, Zhiqiang; Lim, Soon Sung

    2017-01-01

    This study successfully established the feasibility of a two-step chemo-enzymatic synthesis of l-ascorbyl phenolates. Intermediate vinyl phenolates were first chemically produced and then underwent trans-esterification with l-ascorbic acid in the presence of Novozyme 435® (Candida Antarctica lipase B) as a catalyst. Twenty vinyl phenolates and 11 ascorbyl phenolates were subjected to in vitro bioassays to investigate their inhibitory activity against advanced glycation end products (AGEs). Among them, vinyl 4-hydroxycinnamate (17VP), vinyl 4-hydroxy-3-methoxycinnamate (18VP), vinyl 4-hydroxy-3,5-dimethoxycinnamate (20VP), ascorbyl 4-hydroxy-3-methoxycinnamate (18AP) and ascorbyl 3,4-dimethoxycinnamate (19AP) showed 2-10 times stronger inhibitory activities than positive control (aminoguanidine and its precursors). These results indicated that chemo-enzymatically synthesized compounds have AGE inhibitory effect and thus are effective in either preventing or retarding glycation protein formation. PMID:27507531

  13. Inhibitory effects of selected Turkish spices and oregano components on some foodborne fungi.

    PubMed

    Akgül, A; Kivanç, M

    1988-05-01

    The inhibitory effects of 10 selected Turkish spices, oregano essential oil, thymol and carvacrol towards growth of 9 foodborne fungi were investigated in culture media with pH 3.5 and 5.5. The antifungal effects of sodium chloride, sorbic acid and sodium benzoate and the combined use of oregano with sodium chloride were also tested under the same conditions for comparison. Of the spices tested, only sodium chloride were also tested under the same conditions for comparison. Of the spices tested, only oregano at 1.0, 1.5, 2.0% (w/v) levels showed effect on all fungi. 8% (w/v) sodium chloride was less effective than oregano. Oregano essential oil, thymol or carvacrol at concentrations of 0.025% and 0.05% completely inhibited the growth of all fungi, showing greater inhibition than sorbic acid at the same concentrations. The combined use of oregano and sodium chloride exhibited a synergistic antifungal effect. PMID:2978951

  14. Toxic and inhibitory effects of trichloroethylene aerobic co-metabolism on phenol-grown aerobic granules.

    PubMed

    Zhang, Yi; Tay, JooHwa

    2015-04-01

    Aerobic granule, a form of microbial aggregate, exhibits good potential in degrading toxic and recalcitrant substances. In this study, the inhibitory and toxic effects of trichloroethylene (TCE), a model compound for aerobic co-metabolism, on phenol-grown aerobic granules were systematically studied, using respiratory activities after exposure to TCE as indicators. High TCE concentration did not exert positive or negative effects on the subsequent endogenous respiration rate or phenol dependent specific oxygen utilization rate (SOUR), indicating the absence of solvent stress and induction effect on phenol-hydroxylase. Phenol-grown aerobic granules exhibited a unique response to TCE transformation product toxicity, that small amount of TCE transformation enhanced the subsequent phenol SOUR. Granules that had transformed between 1.3 and 3.7 mg TCE gSS(-1) showed at most 53% increase in the subsequent phenol SOUR, and only when the transformation exceeded 6.6 mg TCE gSS(-1) did the SOUR dropped below that of the control. This enhancing effect was found to sustain throughout several phenol dosages, and TCE transformation below the toxicity threshold also lessened the granules' sensitivity to higher phenol concentration. The unique toxic effect was possibly caused by the granule's compact structure as a protection barrier against the diffusive transformation product(s) of TCE co-metabolism.

  15. Effect of adrenalectomy on miniature inhibitory postsynaptic currents in the paraventricular nucleus of the hypothalamus.

    PubMed

    Verkuyl, J M; Joëls, M

    2003-01-01

    Within the rat paraventricular nucleus of the hypothalamus two types of neurons have been distinguished based on morphological appearance, i.e., parvocellular and magnocellular neurons. The parvocellular neurons play a key role in regulating the activity of the hypothalamo-pituitary-adrenal axis, which is activated, e.g., after stress exposure. These neurons receive humoral negative feedback via the adrenal hormone corticosterone but also neuronal inhibitory input, either directly or transsynaptically relayed via GABAergic interneurons. In the present study we examined to what extent the neuronal GABAergic input is influenced by the humoral signal. To this end, miniature inhibitory postsynaptic currents (mIPSCs) were recorded in parvo- and magnocellular neurons of adrenalectomized rats, which lack corticosterone, and in sham-operated controls. Under visual control neurons in coronal slices containing the paraventricular nucleus were designated as putative parvocellular or magnocellular neurons: the former were located in the medial part of the nucleus and displayed a small fusiform soma; the latter were mostly located in the lateral part and were recognized by their large round soma. Compared with putative magnocellular neurons, parvocellular neurons generally exhibited a lower membrane capacitance, lower mIPSC frequency, and smaller mIPSC amplitude. Following adrenalectomy, the mIPSC frequency was significantly enhanced in parvo- but not magnocellular neurons. Other properties of the cells were not affected. In a second series of experiments we examined whether the increase in mIPSC frequency was due to the absence of corticosterone or caused by other effects related to adrenalectomy. The data support the former explanation since implantation of a corticosterone releasing pellet after adrenalectomy fully prevented the change in mIPSC frequency. We conclude that, in the absence of humoral negative feedback, local GABAergic input of parvocellular neurons in the

  16. Is harsh caregiving effective in toddlers with low inhibitory control? An experimental study in the food domain.

    PubMed

    Rigal, Natalie; Rubio, Bérengère; Monnery-Patris, Sandrine

    2016-05-01

    The aim of our study is to evaluate the validity of the "Caregiving×Temperament Paradigm" in the food domain. In this study, two prototypes of caregiving control have been contrasted: Harsh (forceful measures to curve the child's behavior) versus Gentle control (supportive measures to direct the child's behavior). In food domain, the most effective control to help a child to overcome initial dislike is repeated exposure. Our first objective was to test whether the repeated exposure displayed in a gentle context has a more benefical effect on dislike shifting than the one displayed in a harsh context. Our second objective was to assess whether this effect was moderated by a temperamental characteristic (child's inhibitory control). A randomized experimental protocol was used in day care-centers, involving 98 children aged 21-41 months. Children were asked to consume an initially rejected target food on five occasions either with a Gentle or a Harsh instruction. Children's dislike for the target food was assessed via intake before and after the familiarization phase. Inhibitory control level was measured in 78 of these children using validated questionnaire. Four groups were created: Instructions (Gentle vs Harsh)×Inhibitory control (Lower vs Higher). After the familiarization phase, the consumption of the target food increased in all groups, but with a higher increase in children with high Inhibitory control with Gentle instruction, than for children with low Inhibitory control with Harsh instruction, the two other groups being in between. Our data fit a model of cumulative effects, and show that both gentle control strategies and high inhibitory control in children contribute to regulate disgusts experienced in some feeding contexts. PMID:27043272

  17. Competition and cooperation among similar representations: toward a unified account of facilitative and inhibitory effects of lexical neighbors.

    PubMed

    Chen, Qi; Mirman, Daniel

    2012-04-01

    One of the core principles of how the mind works is the graded, parallel activation of multiple related or similar representations. Parallel activation of multiple representations has been particularly important in the development of theories and models of language processing, where coactivated representations (neighbors) have been shown to exhibit both facilitative and inhibitory effects on word recognition and production. Researchers generally ascribe these effects to interactive activation and competition, but there is no unified explanation for why the effects are facilitative in some cases and inhibitory in others. We present a series of simulations of a simple domain-general interactive activation and competition model that is broadly consistent with more specialized domain-specific models of lexical processing. The results showed that interactive activation and competition can indeed account for the complex pattern of reversals. Critically, the simulations revealed a core computational principle that determines whether neighbor effects are facilitative or inhibitory: strongly active neighbors exert a net inhibitory effect, and weakly active neighbors exert a net facilitative effect.

  18. Inhibitory effect of synthetic cannabinoids on CYP1A activity in mouse liver microsomes.

    PubMed

    Ashino, Takashi; Hakukawa, Kanae; Itoh, Yuka; Numazawa, Satoshi

    2014-01-01

    Synthetic cannabinoids developed by chemical modification are believed to bind to cannabinoid receptors and cause neurological effects similar to cannabis; however, their effects on drug metabolizing enzymes are unknown. This study aimed to elucidate the effect of synthetic cannabinoids on cytochrome P450 1A activity. Naphthoylindole, a basic structure of the major synthetic cannabinoids, strongly inhibited CYP1A activity in a competitive manner; the apparent Ki value was 0.40 μM. The N-Alkylated derivatives of naphthoylindole, MAM-2201 and JWH-019, also inhibited CYP1A activity in a concentration-dependent manner; however, their inhibitory effects were weaker than naphthoylindole. An adamantylamidoindole derivative, STS-135, showed inhibition of CYP1A activity in a concentrationdependent manner, but the adamantoylindole derivatives, AB-001 and AM-1248, did not. A tetramethylcyclopropanoylindole derivative, UR-144, showed a weak inhibition of CYP1A activity at high concentrations. These results suggest that synthetic cannabinoids and their basic molecules are capable of inhibiting CYP1A enzymatic activity.

  19. Inhibitory effect of synthetic cannabinoids on CYP1A activity in mouse liver microsomes.

    PubMed

    Ashino, Takashi; Hakukawa, Kanae; Itoh, Yuka; Numazawa, Satoshi

    2014-01-01

    Synthetic cannabinoids developed by chemical modification are believed to bind to cannabinoid receptors and cause neurological effects similar to cannabis; however, their effects on drug metabolizing enzymes are unknown. This study aimed to elucidate the effect of synthetic cannabinoids on cytochrome P450 1A activity. Naphthoylindole, a basic structure of the major synthetic cannabinoids, strongly inhibited CYP1A activity in a competitive manner; the apparent Ki value was 0.40 μM. The N-Alkylated derivatives of naphthoylindole, MAM-2201 and JWH-019, also inhibited CYP1A activity in a concentration-dependent manner; however, their inhibitory effects were weaker than naphthoylindole. An adamantylamidoindole derivative, STS-135, showed inhibition of CYP1A activity in a concentrationdependent manner, but the adamantoylindole derivatives, AB-001 and AM-1248, did not. A tetramethylcyclopropanoylindole derivative, UR-144, showed a weak inhibition of CYP1A activity at high concentrations. These results suggest that synthetic cannabinoids and their basic molecules are capable of inhibiting CYP1A enzymatic activity. PMID:25374372

  20. Inhibitory effect of a phosphatidyl ethanolamine derivative on LPS-induced sepsis.

    PubMed

    Lee, Chunghyun; An, Hyun-Jung; Kim, Jung-Ln; Lee, Hayyoung; Paik, Sang-Gi

    2009-02-28

    Sepsis is the leading cause of death in critically ill patients. Today, around 60% of all cases of sepsis are caused by Gram-negative bacteria. The cell wall component lipopoly-saccharide (LPS) is the main initiator of the cascade of cellular reactions in Gram-negative infections. The core receptors for LPS are toll-like receptor 4 (TLR4), MD-2 and CD14. Attempts have been made to antagonize the toxic effect of endotoxin using monoclonal antibodies against CD14 and synthetic lipopolysaccharides but there is as yet no effective treatment for septic syndrome. Here, we describe an inhibitory effect of a phosphatidylethanolamine derivative, PE-DTPA (phosphatidylethanolamine diethyl-enetriaminepentaacetate) on LPS recognition. PE-DTPA bound strongly to CD14 (K ( d ), 9.52 x 10(-8) M). It dose dependency inhibited LPS-mediated activation of human myeloid cells, mouse macrophage cells and human whole blood as measured by the production of tumor necrosis factor-a (TNF-alpha) and nitric oxide, whereas other phospho-lipids including phosphatidylserine and phosphatidylethanolamine had little effect. PE-DTPA also inhibited transcription dependent on NF-kappaB activation when it was added together with LPS, and it rescued LPS-primed mice from septic death. These results suggest that PE-DTPA is a potent antagonist of LPS, and that it acts by competing for binding to CD14. PMID:19277509

  1. Inhibitory Effect of Crocin(s) on Lens α-Crystallin Glycation and Aggregation, Results in the Decrease of the Risk of Diabetic Cataract.

    PubMed

    Bahmani, Fereshteh; Bathaie, Seyedeh Zahra; Aldavood, Seyed Javid; Ghahghaei, Arezou

    2016-01-26

    The current study investigates the inhibitory effect of crocin(s), also known as saffron apocarotenoids, on protein glycation and aggregation in diabetic rats, and α-crystallin glycation. Thus, crocin(s) were administered by intraperitoneal injection to normal and streptozotocin-induced diabetic rats. The cataract progression was recorded regularly every two weeks and was classified into four stages. After eight weeks, the animals were sacrificed and the parameters involved in the cataract formation were measured in the animal lenses. Some parameters were also determined in the serum and blood of the rats. In addition, the effect of crocin(s) on the structure and chaperone activity of α-crystallin in the presence of glucose was studied by different methods. Crocin(s) lowered serum glucose levels of diabetic rats and effectively maintained plasma total antioxidants, glutathione levels and catalase activity in the lens of the animals. In the in vitro study, crocin(s) inhibited α-crystallin glycation and aggregation. Advanced glycation end products fluorescence, hydrophobicity and protein cross-links were also decreased in the presence of crocin(s). In addition, the decreased chaperone activity of α-crystallin in the presence of glucose changed and became close to the native value by the addition of crocin(s) in the medium. Crocin(s) thus showed a powerful inhibitory effect on α-crystallin glycation and preserved the structure-function of this protein. Crocin(s) also showed the beneficial effects on prevention of diabetic cataract.

  2. Different pH requirements are associated with divergent inhibitory effects of chloroquine on human and avian influenza A viruses

    PubMed Central

    Di Trani, Livia; Savarino, Andrea; Campitelli, Laura; Norelli, Sandro; Puzelli, Simona; D'Ostilio, Daniela; Vignolo, Edoardo; Donatelli, Isabella; Cassone, Antonio

    2007-01-01

    Chloroquine is a 4-aminoquinoline previously used in malaria therapy and now becoming an emerging investigational antiviral drug due to its broad spectrum of antiviral activities. To explore whether the low pH-dependency of influenza A viruses might affect the antiviral effects of chloroquine at clinically achievable concentrations, we tested the antiviral effects of this drug on selected human and avian viruses belonging to different subtypes and displaying different pH requirements. Results showed a correlation between the responses to chloroquine and NH4Cl, a lysosomotropic agent known to increase the pH of intracellular vesicles. Time-of-addition experiments showed that the inhibitory effect of chloroquine was maximal when the drug had been added at the time of infection and was lost after 2 h post-infection. This timing approximately corresponds to that of virus/cell fusion. Moreover, there was a clear correlation between the EC50 of chloroquine in vitro and the electrostatic potential of the HA subunit (HA2) mediating the virus/cell fusion process. Overall, the present study highlights the critical importance of a host cell factor such as intravesicular pH in determining the anti-influenza activity of chloroquine and other lysosomotropic agents. PMID:17477867

  3. Inhibitory effect of cinnamon powder on pathogen growth in laboratory media and oriental-style rice cakes (sulgidduk).

    PubMed

    Hong, Yu-Jin; Bae, Young-Min; Moon, Bokyung; Lee, Sun-Young

    2013-01-01

    There has been an increasing interest in the use of natural plant materials as alternative food preservatives. We examined the antimicrobial effects of natural plant materials used as additives against foodborne pathogens in laboratory media and Sulgidduk, oriental-style rice cakes. Cinnamon, mugwort, and garlic powder solutions (3%) were tested for their antimicrobial activities against pathogens in laboratory media. Sulgidduk prepared with different amounts of cinnamon powder (1, 3, and 6%) was inoculated with a Staphylococcus aureus or Bacillus cereus cocktail. The samples were air or vacuum packaged and stored at 22 ± 1°C for 72 h, and microbial growth was determined. Cinnamon powder showed more inhibitory properties against pathogens such as Salmonella enterica serovar Typhimurium, Escherichia coli O157:H7, Listeria monocytogenes, S. aureus, and B. cereus than did mugwort or garlic powder. The populations of S. aureus and B. cereus in Sulgidduk containing cinnamon powder were significantly lower than in the control during storage time. Different packaging methods did not result in a significant difference in pathogen growth. In a sensory evaluation, Sulgidduk containing 1 and 3% cinnamon powder did not significantly differ from the control sample in any of the attributes tested other than flavor. These results indicate that natural plant materials such as cinnamon powder could be used as food additives to improve the microbiological stability of rice cakes.

  4. Sesquiterpenoids from the Rhizomes of Curcuma phaeocaulis and Their Inhibitory Effects on LPS-Induced TLR4 Activation.

    PubMed

    Jang, Hyun-Jae; Kim, Jin-Han; Oh, Hyun-Mee; Kim, Min-Suk; Jo, Jin Ha; Jung, Kyungsook; Lee, Soyoung; Kim, Young-Ho; Lee, Woo Song; Lee, Seung Woong; Rho, Mun-Chual

    2016-01-01

    Two new guaiane-type (2, 6) and one new furanogermacrane-type (11) sesquiterpenoids have been isolated along with twelve known compounds from an EtOAc-soluble extract of Curcuma phaeocaulis rhizomes. The structures of the isolated compounds were elucidated using a combination of NMR, MS, and circular dichroism (CD) spectra. The inhibitory effects of each compound on lipopolysaccharide (LPS)-induced Toll-like receptor 4 (TLR4) activation in THP-1-Blue cells were assessed, and compound 4 showed more potent inhibitory activity against LPS-stimulated TLR4 activation. PMID:27373668

  5. New constituents from Crinum latifolium with inhibitory effects against tube-like formation of human umbilical venous endothelial cells.

    PubMed

    Nam, Nguyen-Hai; Kim, Yong; You, Young-Jae; Hong, Dong-Ho; Kim, Hwan-Mook; Ahn, Byung-Zun

    2004-12-01

    Six compounds (1-6) were isolated from the methanol extract of Crinum latifolium by bioassay-guided separation. Among the six isolates, compounds 2 and 6 were new metabolites. Their structures were established as 4-senecioyloxymethyl-3,4-dimethoxycoumarin (2) and 5,6,3'-trihydroxy-7,8,4'-trimethoxyflavone (6) based on spectroscopic analyses. Compound 2 was found to be strongly inhibitory against the in vitro tube-like formation of human umbilical venous endothelial cells (HUVECs) while manifesting no cytotoxicity in tumor cell lines (B16F10, HCT116). Significant inhibitory activity (inhibition percentage, 53.5%) was still observed at concentrations as low as 1 microg/mL. Compound 6 showed a modest inhibitory effect on the tube-like formation of HUVECs. Other compounds, including cycloartenol (1), 4',7-dihydroxy-3'-methoxyflavan (3), 4',7-dihydroxyflavan (4), and 2',4',7-trihydroxydihydrochalcone (5) were found to be nearly inactive.

  6. Inhibitory Effect of Sophorolipid on Candida albicans Biofilm Formation and Hyphal Growth

    PubMed Central

    Haque, Farazul; Alfatah, Md.; Ganesan, K.; Bhattacharyya, Mani Shankar

    2016-01-01

    Candida albicans causes superficial and life-threatening systemic infections. These are difficult to treat often due to drug resistance, particularly because C. albicans biofilms are inherently resistant to most antifungals. Sophorolipid (SL), a glycolipid biosurfactant, has been shown to have antimicrobial and anticancer properties. In this study, we investigated the effect of SL on C. albicans biofilm formation and preformed biofilms. SL was found to inhibit C. albicans biofilm formation as well as reduce the viability of preformed biofilms. Moreover, SL, when used along with amphotericin B (AmB) or fluconazole (FLZ), was found to act synergistically against biofilm formation and preformed biofilms. Effect of SL on C. albicans biofilm formation was further visualized by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM), which revealed absence of hyphae, typical biofilm architecture and alteration in the morphology of biofilm cells. We also found that SL downregulates the expression of hypha specific genes HWP1, ALS1, ALS3, ECE1 and SAP4, which possibly explains the inhibitory effect of SL on hyphae and biofilm formation. PMID:27030404

  7. The effect of aging on fronto-striatal reactive and proactive inhibitory control.

    PubMed

    Kleerekooper, Iris; van Rooij, Sanne J H; van den Wildenberg, Wery P M; de Leeuw, Max; Kahn, Rene S; Vink, Matthijs

    2016-05-15

    Inhibitory control, like most cognitive processes, is subject to an age-related decline. The effect of age on neurofunctional inhibition processing remains uncertain, with age-related increases as well as decreases in activation being reported. This is possibly because reactive (i.e., outright stopping) and proactive inhibition (i.e., anticipation of stopping) have not been evaluated separately. Here, we investigate the effects of aging on reactive as well as proactive inhibition, using functional MRI in 73 healthy subjects aged 30-70years. We found reactive inhibition to slow down with advancing age, which was paralleled by increased activation in the motor cortex. Behaviorally, older adults did not exercise increased proactive inhibition strategies compared to younger adults. However, the pattern of activation in the right inferior frontal gyrus (rIFG) showed a clear age-effect on proactive inhibition: rather than flexibly engaging the rIFG in response to varying stop-signal probabilities, older subjects showed an overall hyperactivation. Whole-brain analyses revealed similar hyperactivations in various other frontal and parietal brain regions. These results are in line with the neural compensation hypothesis of aging: processing becomes less flexible and efficient with advancing age, which is compensated for by overall enhanced activation. Moreover, by disentangling reactive and proactive inhibition, we can show for the first time that the age-related increase in activation during inhibition that is reported generally by prior studies may be the result of compensation for reduced neural flexibility related to proactive control strategies.

  8. The inhibitory effect of vitamin K on RANKL-induced osteoclast differentiation and bone resorption.

    PubMed

    Wu, Wei-Jie; Kim, Min Seuk; Ahn, Byung-Yong

    2015-10-01

    To further understand the correlation between vitamin K and bone metabolism, the effects of vitamins K1, menaquinone-4 (MK-4), and menaquinone-7 (MK-7) on RANKL-induced osteoclast differentiation and bone resorption were comparatively investigated. Vitamin K2 groups (MK-4 and MK-7) were found to significantly inhibit RANKL-medicated osteoclast cell formation of bone marrow macrophages (BMMs) in a dose-dependent manner, without any evidence of cytotoxicity. The mRNA expression of specific osteoclast differentiation markers, such as c-Fos, NFATc1, OSCAR, and TRAP, as well as NFATc1 protein expression and TRAP activity in RANKL-treated BMMs were inhibited by vitamin K2, although MK-4 exhibited a significantly greater efficiency compared to MK-7. In contrast, the same dose of vitamin K1 had no inhibitory effect on RANKL-induced osteoclast cell formation, but increased the expression of major osteoclastogenic genes. Interestingly, vitamins K1, MK-4 and MK-7 all strongly inhibited osteoclastic bone resorption (p < 0.01) in a dose dependent manner. These results suggest that vitamins K1, MK-4 and MK-7 have anti-osteoporotic properties, while their regulation effects on osteoclastogenesis are somewhat different.

  9. Inhibitory avoidance learning in CD1 mice: Effects of chronic social defeat stress.

    PubMed

    Monleón, Santiago; Duque, Aranzazu; Vinader-Caerols, Concepción

    2015-06-01

    Chronic social defeat stress (CSDS) is an animal model widely used to determine the neurobiological mechanisms of stress and its associated pathologies. In this study, the effects of CSDS on inhibitory avoidance (IA) were evaluated in post-pubertal and adult male CD1 mice, instead of the C57BL/6J strain used in the CSDS standard protocol. CSDS consisted of daily 5-min (experiments 1 and 2) or 10-min (experiment 3) agonistic encounters on 21 consecutive days. Twenty four hours after the last session of CSDS, all the mice were tested for IA. They were also evaluated in an elevated plus-maze, obtaining complementary measures of locomotor activity and emotionality. In experiments 1 and 2, IA learning was confirmed in both non-stressed and stressed groups, showing stressed post-pubertal mice higher test latencies than controls. In experiment 3, IA was confirmed in the non-stressed but not in the stressed group. In conclusion, a moderate degree of CSDS (5-min encounters) enhances memory in post-pubertal but not in adult mice, while a high degree (10-min encounters) prevents the memory formation of IA in mice. These effects of CSDS on memory are not secondary to motor or emotional effects of stress. Furthermore, CD1 has been shown to be a valid strain for the stressed mice in the CSDS model. PMID:25745884

  10. Inhibitory effect of essential oils against Trichosporon ovoides causing Piedra Hair Infection.

    PubMed

    Saxena, Seema; Uniyal, Veena; Bhatt, R P

    2012-10-01

    Piedra, is an asymptomatic fungal infection of the hair shaft, resulting in the formation of nodules of different hardness on the infected hair. The infection also known as Trichomycosis nodularis is a superficial fungal infection arising from the pathogen being restricted to the stratum corneum with little or no tissue reaction. The nodules are a concretion of hyphae and fruiting bodies of the fungus. Two varieties of Piedra may be seen, Black Piedra and White Piedra. The fungus Trichosporon ovoides is involved in the occurrence of both types of Piedras. The purpose of this study was to examine the effectiveness of selected essential oils for the control of growth of the fungus and to determine whether the antifungal effect was due to the major compounds of the oils. Two screening methods viz. Agar well diffusion assay and Minimum Inhibitory Concentration were adopted for the study. MIC and MFC were determined by tube dilution method. Essential oils from Eucalyptus, Ocimum basilicum, Mentha piperita, Cymbopogon flexuosus, Cymbopogon winterians, Trachyspermum ammi, Zingiber officinalis, Citrus limon, Cinnamomon zeylanicum, Salvia sclarea, Citrus aurantifolia, Melaleuca alternifolia, Citrus aurantium, Citrus bergamia, Pogostemon pathchouli, Cedrus atlantica, Jasminum officinale, Juniperus communis, Abelmoschus moschatus, Cyperus scariosus, Palargonium graveolens, Boswellia carterii, Rosa damascene, Veteveria zizanoides and Commiphora myrrha were evaluated. The essential oils of Cymbopogon winterians, Mentha piperita, Cinnamomum zeylanicum, Melaleuca alternifolia and Eucalyptus globulus were proved to be most effective against the fungus Trichosporon ovoides.

  11. Inhibitory effect of essential oils against Trichosporon ovoides causing Piedra Hair Infection.

    PubMed

    Saxena, Seema; Uniyal, Veena; Bhatt, R P

    2012-10-01

    Piedra, is an asymptomatic fungal infection of the hair shaft, resulting in the formation of nodules of different hardness on the infected hair. The infection also known as Trichomycosis nodularis is a superficial fungal infection arising from the pathogen being restricted to the stratum corneum with little or no tissue reaction. The nodules are a concretion of hyphae and fruiting bodies of the fungus. Two varieties of Piedra may be seen, Black Piedra and White Piedra. The fungus Trichosporon ovoides is involved in the occurrence of both types of Piedras. The purpose of this study was to examine the effectiveness of selected essential oils for the control of growth of the fungus and to determine whether the antifungal effect was due to the major compounds of the oils. Two screening methods viz. Agar well diffusion assay and Minimum Inhibitory Concentration were adopted for the study. MIC and MFC were determined by tube dilution method. Essential oils from Eucalyptus, Ocimum basilicum, Mentha piperita, Cymbopogon flexuosus, Cymbopogon winterians, Trachyspermum ammi, Zingiber officinalis, Citrus limon, Cinnamomon zeylanicum, Salvia sclarea, Citrus aurantifolia, Melaleuca alternifolia, Citrus aurantium, Citrus bergamia, Pogostemon pathchouli, Cedrus atlantica, Jasminum officinale, Juniperus communis, Abelmoschus moschatus, Cyperus scariosus, Palargonium graveolens, Boswellia carterii, Rosa damascene, Veteveria zizanoides and Commiphora myrrha were evaluated. The essential oils of Cymbopogon winterians, Mentha piperita, Cinnamomum zeylanicum, Melaleuca alternifolia and Eucalyptus globulus were proved to be most effective against the fungus Trichosporon ovoides. PMID:24031963

  12. Flavonoids from Millettia nitida var. hirsutissima with their anticoagulative activities and inhibitory effects on NO production.

    PubMed

    Liao, Xiao-Lin; Luo, Jian-Guang; Kong, Ling-Yi

    2013-10-01

    Two new compounds, (2R)-7,3'-dihydroxy-6,4'-methoxyflavan (1) and (3R)-7,4'-dihydroxy-2'-methoxyisoflavan (2), along with 12 known flavonoids (3-14), were isolated from the vine stems of Millettia nitida var. hirsutissima. The structures of the isolated compounds were elucidated based on spectroscopic analyses and comparison of literature data. All of the isolates were evaluated for their effects on in-vitro anticoagulative assay and on nitric oxide (NO) production in lipopolysaccharide (LPS)-activated RAW264.7 macrophages. As a result, all compounds showed weak antiplatelet aggregation activities and compounds 4, 5, 7, 8 and 9 demonstrated antithrombin activity with a good dose-effect relationship from 5 to 100 μg mL⁻¹ in rabbit plasma. Compounds 8, 9, 10 and 14 exhibited inhibitory effects on LPS-induced NO production in RAW264.7 macrophages with IC₅₀ values of 4.79 ± 0.20, 8.23 ± 0.35, 5.23 ± 0.11 and 6.30 ± 0.30 μg mL⁻¹, respectively. PMID:23359229

  13. Inhibitory effect of an intellectual task on breathing after voluntary hyperventilation.

    PubMed

    Chin, K; Ohi, M; Fukui, M; Kita, H; Tsuboi, T; Noguchi, T; Otsuka, N; Hirata, H; Mishima, M; Kuno, K

    1996-09-01

    We investigated the effects of an intellectual task on posthyperventilation (PHV) breathing by using a video game. Eight normal subjects were placed in a supine positions. The game task by itself led to increase ventilation compared with the control tasks via an increase in the average inspiratory flow rate (P < 0.01) and the respiratory frequency (P < 0.001). After hypocapnic voluntary hyperventilation (VHV), the task led to a decrease in the 1-min PHV breathing level compared with the control tasks after VHV [after VHV, first 60 s average minute ventilation while watching television and while playing a video game are 5.54 +/- 2.91 (SD) and 2.05 +/- 1.40 l/min, respectively; P < 0.01]. Only one subject showed PHV apnea for at least 10 s during the control protocol, whereas seven of the same eight subjects showed PHV apnea while performing the task. After isocapnic VHV, the task still led to a decrease in PHV breathing compared with the control tasks. However, this decrease was smaller than in the hypocapnic studies and was only significant during the first 15 s of recovery. These results suggest that increased activity in the higher centers of the central nervous system has an inhibitory effect on PHV breathing at a time when the effects of short-term potentiation after VHV, hypocapnia, and perhaps other mechanisms would be expected to be acting on breathing.

  14. Inhibitory effect of essential oils against Trichosporon ovoides causing Piedra Hair Infection

    PubMed Central

    Saxena, Seema; Uniyal, Veena; Bhatt, R.P.

    2012-01-01

    Piedra, is an asymptomatic fungal infection of the hair shaft, resulting in the formation of nodules of different hardness on the infected hair. The infection also known as Trichomycosis nodularis is a superficial fungal infection arising from the pathogen being restricted to the stratum corneum with little or no tissue reaction. The nodules are a concretion of hyphae and fruiting bodies of the fungus. Two varieties of Piedra may be seen, Black Piedra and White Piedra. The fungus Trichosporon ovoides is involved in the occurrence of both types of Piedras. The purpose of this study was to examine the effectiveness of selected essential oils for the control of growth of the fungus and to determine whether the antifungal effect was due to the major compounds of the oils. Two screening methods viz. Agar well diffusion assay and Minimum Inhibitory Concentration were adopted for the study. MIC and MFC were determined by tube dilution method. Essential oils from Eucalyptus, Ocimum basilicum, Mentha piperita, Cymbopogon flexuosus, Cymbopogon winterians, Trachyspermum ammi, Zingiber officinalis, Citrus limon, Cinnamomon zeylanicum, Salvia sclarea, Citrus aurantifolia, Melaleuca alternifolia, Citrus aurantium, Citrus bergamia, Pogostemon pathchouli, Cedrus atlantica, Jasminum officinale, Juniperus communis, Abelmoschus moschatus, Cyperus scariosus, Palargonium graveolens, Boswellia carterii, Rosa damascene, Veteveria zizanoides and Commiphora myrrha were evaluated. The essential oils of Cymbopogon winterians, Mentha piperita, Cinnamomum zeylanicum, Melaleuca alternifolia and Eucalyptus globulus were proved to be most effective against the fungus Trichosporon ovoides. PMID:24031963

  15. Modelling inhibitory effects of long chain fatty acids in the anaerobic digestion process.

    PubMed

    Zonta, Z; Alves, M M; Flotats, X; Palatsi, J

    2013-03-01

    Mathematical modelling of anaerobic digestion process has been used to give new insights regarding dynamics of the long chain fatty acids (LCFA) inhibition. Previously published experimental data, including batch tests with clay mineral bentonite additions, were used for parameter identification. New kinetics were considered to describe the bio-physics of the inhibitory process, including: i) adsorption of LCFA over granular biomass and ii) specific LCFA substrate (saturated/unsaturated) and LCFA-degrading populations. Furthermore, iii) a new variable was introduced to describe the state of damage of the acetoclastic methanogens in order to account for the loss of cell-functionality (inhibition) induced by the adsorbed LCFAs. The proposed model modifications are state compatible and easy to be integrated into the International Water Association's Anaerobic Digestion Model N°1 (ADM1) framework. Practical identifiability of model parameters was assessed with a global sensitivity analysis, while calibration and model structure validation were performed on independent data sets. A reliable simulation of the LCFA-inhibition process can be achieved, if the model includes the description of the adsorptive nature of the LCFAs and the LCFA-damage over specific biomass. The importance of microbial population structure (saturated/unsaturated LCFA-degraders) and the high sensitivity of acetoclastic population to LCFA are evidenced, providing a plausible explanation of experimental based hypothesis. PMID:23276428

  16. Global marine pollutants inhibit P-glycoprotein: Environmental levels, inhibitory effects, and cocrystal structure

    PubMed Central

    Nicklisch, Sascha C. T.; Rees, Steven D.; McGrath, Aaron P.; Gökirmak, Tufan; Bonito, Lindsay T.; Vermeer, Lydia M.; Cregger, Cristina; Loewen, Greg; Sandin, Stuart; Chang, Geoffrey; Hamdoun, Amro

    2016-01-01

    The world’s oceans are a global reservoir of persistent organic pollutants to which humans and other animals are exposed. Although it is well known that these pollutants are potentially hazardous to human and environmental health, their impacts remain incompletely understood. We examined how persistent organic pollutants interact with the drug efflux transporter P-glycoprotein (P-gp), an evolutionarily conserved defense protein that is essential for protection against environmental toxicants. We identified specific congeners of organochlorine pesticides, polychlorinated biphenyls, and polybrominated diphenyl ethers that inhibit mouse and human P-gp, and determined their environmental levels in yellowfin tuna from the Gulf of Mexico. In addition, we solved the cocrystal structure of P-gp bound to one of these inhibitory pollutants, PBDE (polybrominated diphenyl ether)–100, providing the first view of pollutant binding to a drug transporter. The results demonstrate the potential for specific binding and inhibition of mammalian P-gp by ubiquitous congeners of persistent organic pollutants present in fish and other foods, and argue for further consideration of transporter inhibition in the assessment of the risk of exposure to these chemicals. PMID:27152359

  17. Global marine pollutants inhibit P-glycoprotein: Environmental levels, inhibitory effects, and cocrystal structure.

    PubMed

    Nicklisch, Sascha C T; Rees, Steven D; McGrath, Aaron P; Gökirmak, Tufan; Bonito, Lindsay T; Vermeer, Lydia M; Cregger, Cristina; Loewen, Greg; Sandin, Stuart; Chang, Geoffrey; Hamdoun, Amro

    2016-04-01

    The world's oceans are a global reservoir of persistent organic pollutants to which humans and other animals are exposed. Although it is well known that these pollutants are potentially hazardous to human and environmental health, their impacts remain incompletely understood. We examined how persistent organic pollutants interact with the drug efflux transporter P-glycoprotein (P-gp), an evolutionarily conserved defense protein that is essential for protection against environmental toxicants. We identified specific congeners of organochlorine pesticides, polychlorinated biphenyls, and polybrominated diphenyl ethers that inhibit mouse and human P-gp, and determined their environmental levels in yellowfin tuna from the Gulf of Mexico. In addition, we solved the cocrystal structure of P-gp bound to one of these inhibitory pollutants, PBDE (polybrominated diphenyl ether)-100, providing the first view of pollutant binding to a drug transporter. The results demonstrate the potential for specific binding and inhibition of mammalian P-gp by ubiquitous congeners of persistent organic pollutants present in fish and other foods, and argue for further consideration of transporter inhibition in the assessment of the risk of exposure to these chemicals. PMID:27152359

  18. Inhibitory effect of apixaban compared with rivaroxaban and dabigatran on thrombin generation assay.

    PubMed

    Wong, Pancras C; White, Andrew; Luettgen, Joseph

    2013-02-01

    The effect of the oral direct activated factor X (factor Xa) inhibitor apixaban on tissue factor-induced thrombin generation in human plasma was investigated in vitro using the calibrated automated thrombogram (CAT) method and compared with the oral direct factor Xa inhibitor rivaroxaban and the direct thrombin inhibitor dabigatran. Pooled citrated, anticoagulated, platelet-poor human plasma was spiked with apixaban, rivaroxaban, or dabigatran at concentrations of 0.01 to 10 μM. The inhibitory potencies of the compounds were quantified by 5 CAT parameters: the control thrombin lag time (LT) and time to thrombin peak (TTP) for the doubling of inhibitor concentration (IC2x); and the control endogenous thrombin potential (ETP), thrombin peak, and maximum rate of thrombin generation (Vmax) for the inhibitor concentration, which inhibited 50% (IC50). The inhibitors modified CAT concentration dependently. Their inhibitory potencies, expressed as IC2x LT, IC2x TTP, IC50 ETP, IC50 peak thrombin, and IC50 Vmax, were as follows: 0.10 ± 0.01, 0.19 ± 0.02, 0.65 ± 0.11, 0.089 ± 0.019, and 0.049 ± 0.007 μM for apixaban; 0.049 ± 0.007, 0.070 ± 0.009, 0.43 ± 0.07, 0.048 ± 0.008, and 0.022 ± 0.005 μM for rivaroxaban; and 0.063 ± 0.019, 0.18 ± 0.06, 0.50 ± 0.08, 0.55 ± 0.06, and 0.57 ± 0.27 μM for dabigatran. In summary, apixaban, rivaroxaban, and dabigatran have similar potencies in the prolongation of LT and TTP. The CAT parameters that are related to the rate of thrombin generation during the propagation phase (ie, peak thrombin and Vmax) are more sensitive to activities of apixaban and rivaroxaban than dabigatran. The ETP is the least sensitive parameter for measuring the activities of these inhibitors. Recombinant activated factor VII at 5 and 50 μg/mL reversed the anticoagulant effects of apixaban more at 0.2 μM than at 2 μM. Our study suggests that the CAT method is a sensitive assay to monitor the pharmacodynamic and pharmacokinetic properties of

  19. [Inhibitory effects of liquor cultured with Nelumbo nucifera and Nymphaea tetragona on the growth of Microcystis aeruginosa].

    PubMed

    Li, Lei; Hou, Wen-hua

    2007-10-01

    The inhibitory effects of liquor cultured with Nelumbo nucifera and Nymphaea tetragona on the growth of Microcystis aeruginosa have been investigated by measuring the cell number and the chlorophyll a content of Microcystis aeruginosa of culture in the laboratory. The results showed that the inhibitory effects on the growth of Microcystis aeruginosa with different concentration of the liquor cultured with Nelumbo nucifera and Nymphaea tetragona were dissimilar, and an evident phenomenon appeared that low concentrations could promote the growth of Microcystis aeruginosa. However, the inhibitory effects on the growth of Microcystis aeruginosa with continuous liquor cultured with Nelumbo nucifera and Nymphaea tetragona were obvious, which made the algal cell almost lose the capability of photosynthesis, and the inhibitory effects of liquor cultured with Nymphaea tetragona were better than those of Nelumbo nucifera. The scale-up experiment demonstrated that the algal cell received menace and damage by measuring the activities of peroxidase (SOD) and the accumulated contents of malondialdehyde (MDA) of Microcystis aeruginosa in the co-culture. Sterilization methods influenced the algal growth inhibition experiment so that high temperature couldn't replace micropore filter, which explained that the matter excreted by Nelumbo nucifera and Nymphaea tetragona may contain thermally-instabe matter.

  20. [Inhibitory effects of liquor cultured with Nelumbo nucifera and Nymphaea tetragona on the growth of Microcystis aeruginosa].

    PubMed

    Li, Lei; Hou, Wen-hua

    2007-10-01

    The inhibitory effects of liquor cultured with Nelumbo nucifera and Nymphaea tetragona on the growth of Microcystis aeruginosa have been investigated by measuring the cell number and the chlorophyll a content of Microcystis aeruginosa of culture in the laboratory. The results showed that the inhibitory effects on the growth of Microcystis aeruginosa with different concentration of the liquor cultured with Nelumbo nucifera and Nymphaea tetragona were dissimilar, and an evident phenomenon appeared that low concentrations could promote the growth of Microcystis aeruginosa. However, the inhibitory effects on the growth of Microcystis aeruginosa with continuous liquor cultured with Nelumbo nucifera and Nymphaea tetragona were obvious, which made the algal cell almost lose the capability of photosynthesis, and the inhibitory effects of liquor cultured with Nymphaea tetragona were better than those of Nelumbo nucifera. The scale-up experiment demonstrated that the algal cell received menace and damage by measuring the activities of peroxidase (SOD) and the accumulated contents of malondialdehyde (MDA) of Microcystis aeruginosa in the co-culture. Sterilization methods influenced the algal growth inhibition experiment so that high temperature couldn't replace micropore filter, which explained that the matter excreted by Nelumbo nucifera and Nymphaea tetragona may contain thermally-instabe matter. PMID:18268975

  1. Phenylethanoids in the herb of Plantago lanceolata and inhibitory effect on arachidonic acid-induced mouse ear edema.

    PubMed

    Murai, M; Tamayama, Y; Nishibe, S

    1995-10-01

    The five phenylethanoids, acteoside (1), cistanoside F (2), lavandulifolioside (3), plantamajoside (4) and isoacteoside (5) were isolated from the herb of Plantago lanceolata L. (Plantaginaceae). Compounds 1, the major phenylethanoid in the herb of P. lanceolata L., and 4, the major phenylethanoid in the herb of P. asiatica L., showed inhibitory effects on arachidonic acid-induced mouse ear edema. PMID:7480214

  2. Phenylethanoids in the herb of Plantago lanceolata and inhibitory effect on arachidonic acid-induced mouse ear edema.

    PubMed

    Murai, M; Tamayama, Y; Nishibe, S

    1995-10-01

    The five phenylethanoids, acteoside (1), cistanoside F (2), lavandulifolioside (3), plantamajoside (4) and isoacteoside (5) were isolated from the herb of Plantago lanceolata L. (Plantaginaceae). Compounds 1, the major phenylethanoid in the herb of P. lanceolata L., and 4, the major phenylethanoid in the herb of P. asiatica L., showed inhibitory effects on arachidonic acid-induced mouse ear edema.

  3. Estimation of inhibitory effects of hemicellulosic wood hydrolysate inhibitors on PHA production by Burkholderia cepacia ATCC 17759 using response surface methodology.

    PubMed

    Pan, Wenyang; Nomura, Christopher T; Nakas, James P

    2012-12-01

    Sugar maple hemicellulosic hydrolysate was utilized as a renewable feedstock for polyhydroxyalkanoates production by Burkholderia cepacia ATCC 17759. To estimate inhibitory effects of the hydrolysate, response surface methodology was utilized to analyze cell growth and PHA accumulation in the presence of multiple inhibitors. Mixture design was employed to study the correlation between the proportion of phenolics and total inhibition. The resultant models (R(2) as 92.42% and 93.14% for cell growth and PHA production, respectively) indicated syringic acid was the most inhibitory among three phenolics and synergistic inhibition was observed for the combinations of vanillin/syringic acid and vanillic acid/syringic acid. When furfural, levulinic acid, and acetate were also present during the fermentation, central composite design was employed. The regression model using 48 h cell growth as the response surface (R(2)=87.82%) showed acetate was the most inhibitory. Additionally, strong synergistic effects were observed for the combinations of acetate/phenolics and levulinic acid/furfural. PMID:23037882

  4. Effects of leukemia inhibitory factor on 3T3-L1 adipocytes.

    PubMed

    Hogan, Jessica C; Stephens, Jacqueline M

    2005-06-01

    Leukemia inhibitory factor (LIF) is a member of the gp130 cytokine family and signals through the receptor complex of gp130 and the LIF receptor (LIFR) to activate the JAK/STAT signaling cascade. Since LIF activates STATs 1 and 3 in adipocytes, we examined the effects of LIF on 3T3-L1 adipocytes. Our studies clearly demonstrate that LIF treatment had minimal effects on adipocyte differentiation as judged by marker gene expression, but did inhibit triacylglyceride (TAG) accumulation during adipogenesis. Acute treatment with LIF resulted in increased expression of suppressors of cytokine signaling-3 (SOCS3) and CCAAT/enhancer-binding protein-delta (C/EBPdelta) mRNA in 3T3-L1 adipocytes. Moreover, the upregulation of C/EBPdelta correlated with binding to three sites in the C/EBPdelta promoter by LIF-activated protein complexes that contained STAT1 and not STAT3. Chronic treatment with LIF resulted in decreased protein levels of sterol regulatory element binding protein-1 (SREBP1) and fatty acid synthase (FAS), but had no effect on the expression of other adipocyte marker proteins or on TAG levels in mature 3T3-L1 adipocytes. LIF had a small effect on insulin-stimulated glucose uptake in 3T3-L1 adipocytes, but did not cause insulin resistance following chronic treatment. These findings indicate that LIF has similar and distinct effects in comparison with the effects of other gp130 cytokines on cultured fat cells. In summary, our results support a role for LIF in the regulation of proteins involved in lipid synthesis and in the modulation of signal transduction pathways in 3T3-L1 adipocytes.

  5. Effect of nitrous oxide on excitatory and inhibitory synaptic transmission in hippocampal cultures.

    PubMed

    Mennerick, S; Jevtovic-Todorovic, V; Todorovic, S M; Shen, W; Olney, J W; Zorumski, C F

    1998-12-01

    Nitrous oxide (N2O; laughing gas) has been a widely used anesthetic/analgesic since the 19th century, although its cellular mechanism of action is not understood. Here we characterize the effects of N2O on excitatory and inhibitory synaptic transmission in microcultures of rat hippocampal neurons, a preparation in which anesthetic effects on monosynaptic communication can be examined in a setting free of polysynaptic network variables. Eighty percent N2O occludes peak NMDA receptor-mediated (NMDAR) excitatory autaptic currents (EACs) with no effect on the NMDAR EAC decay time course. N2O also mildly depresses AMPA receptor-mediated (AMPAR) EACs. We find that N2O inhibits both NMDA and non-NMDA receptor-mediated responses to exogenous agonist. The postsynaptic blockade of NMDA receptors exhibits slight apparent voltage dependence, whereas the blockade of AMPA receptors is not voltage dependent. Although the degree of ketamine and Mg2+ blockade of NMDA-induced responses is dependent on permeant ion concentration, the degree of N2O blockade is not. We also observe a slight and variable prolongation of GABAA receptor-mediated (GABAR) postsynaptic currents likely caused by previously reported effects of N2O on GABAA receptors. Despite the effects of N2O on both NMDA and non-NMDA ionotropic receptors, glial glutamate transporter currents and metabotropic glutamate receptor-mediated synaptic depression are not affected. Paired-pulse depression, the frequency of spontaneous miniature excitatory synaptic currents, and high-voltage-activated calcium currents are not affected by N2O. Our results suggest that the effects of N2O on synaptic transmission are confined to postsynaptic targets. PMID:9822732

  6. Metabolic Profile Changes of CCl₄-Liver Fibrosis and Inhibitory Effects of Jiaqi Ganxian Granule.

    PubMed

    Wang, Ge; Li, Zehao; Li, Hao; Li, Lidan; Li, Jian; Yu, Changyuan

    2016-01-01

    Jiaqi Ganxian Granule (JGG) is a famous traditional Chinese medicine, which has been long used in clinical practice for treating liver fibrosis. However, the mechanism underlying its anti-hepatic fibrosis is still not clear. In this study, an Ultra-Performance Liquid Chromatography-Time-Of-Flight Mass Spectrometry (UPLC-TOF-MS)-based metabolomics strategy was used to profile the metabolic characteristic of serum obtained from a carbon tetrachloride (CCl₄)-induced hepatic fibrosis model in Sprague-Dawley (SD) rats with JGG treatment. Through Principal Component Analysis (PCA) and Partial Least Square Discriminant Analysis (PLS-DA), it was shown that metabolic perturbations induced by CCl₄ were inhibited after treatment of JGG, for 17 different metabolites related to CCl₄. Among these compounds, the change tendency of eight potential drug targets was restored after the intervention with JGG. The current study indicates that JGG has a significant anti-fibrosis effect on CCl₄-induced liver fibrosis in rats, which might be by regulating the dysfunction of sphingolipid metabolism, glycerophospholipid metabolism, N-acylethanolamine biosynthesis, fat digestion and absorption, while glycerophospholipid metabolism played vital roles in the inhibitory effects of JGG on hepatic fibrosis according to Metabolic Pathway Analysis (MetPA). Our findings indicated that the metabolomics approach may provide a useful tool for exploring potential biomarkers involved in hepatic fibrosis and elucidate the mechanisms underlying the action of therapies used in traditional Chinese medicine. PMID:27248993

  7. [Inhibitory effects of fifteen kinds of Chinese herbal drugs, vegetables and chemicals on SOS response].

    PubMed

    Jin, Z C; Qian, J

    1994-05-01

    Effects of 15 kinds of herbal drugs, vegetables and chemicals on lex-dependent sfi-SOS response were determined by micropersistent and/or pulse models induced by 4-Nitroquinoline-N-oxide (4NQO) and Mitomycin C (MMC) in Escherichia coli(E. coli) PQ37 and PQ35, respectively. Results showed the water extract of Rhizoma Polygonati (RP), Fructus Chebulae (FC), Radix Polygoni Multiflori (RPM), Fructus Ligustri Lucidi (FLL), Bulbus Fritillariae Thunbergii (BFT), shell of water chestnut with a pedicle, Chinese chives juice, and solutions of 5-Fluorouracil, Tannic acid and garlicin could inhibit SOS responses with a dose-response relationship and suggested the inhibitory effects took place both inside and outside E. coli cells. Water extract of FC, FLL, BFT, shell of water chestnut with a pedicle, Chinese chives juice and solution of 5-Fluorouracil and Tannic acid could intracellularly inhibit SOS responses induced by MMC in E. coli PQ35, and acetone extract of Grifola Frondosa (GF) could extracellularly inhibit SOS responses in E. coli PQ37 and intracellularly in PQ35 induced by 4NQO or MMC. Water extract of raw hawthorn. Radix Angelicae Duhuricae (RAD), Radix Ophiopogonis (RO), and 5-Fluorodeoxyuridine could extracellularly inhibit SOS responses induced by 4NQO in E coli PQ37. The possible mechanisms of intracellular inhibition and antidamage repair were discussed in the paper.

  8. Effect of polymorphism in the leukemia inhibitory factor gene on litter size in Large White pigs.

    PubMed

    Lin, H C; Liu, G F; Wang, A G; Kong, L J; Wang, X F; Fu, J L

    2009-09-01

    DNA polymorphism of the porcine leukemia inhibitory factory (LIF) was investigated and used to study the effects on litter size in Large White pigs. A total of 2,167 litter records from 420 sows genotyped at two SNP loci (LIF1 and LIF2) within LIF gene were analyzed to determine whether LIF influenced total number born (TNB) and number born alive (NBA). The results indicated that B allele at LIF1 locus and A allele at LIF2 locus seem to have advantageous effects on litter size. However, the combined analyzed results demonstrated that genotype AAAA, ABBB, and BBBB are better than genotype AAAB, AABB, and ABAB for TNB and NBA in either third to eighth parity or all parities. In all parities, the sows with AAAA genotype had an advantage of 1.76 piglets (P < 0.001) for TNB and 1.44 piglets (P < 0.01) for NBA per litter over the AAAB sows, respectively. The results in this study demonstrated that LIF gene was significantly associated with litter size in pigs. PMID:19002603

  9. Inhibitory effect of oat products on non-haem iron absorption in man.

    PubMed

    Rossander-Hulthén, L; Gleerup, A; Hallberg, L

    1990-11-01

    Oat products are increasingly used in human nutrition due to the rather high content of soluble fibre. Oat products, however, have a high content of phytate which may interfere with the absorption of non-haem iron. The iron balance situation is critical in several groups, especially in children, teenagers and women in their fertile years. It is therefore important to examine the effect of oat products on non-haem iron absorption in man. The present studies showed that oat bran and oat porridge markedly inhibited the absorption of non-haem iron. The inhibition can be explained by the high phytate content of oat products. This is partly due to a high resistance of oat phytate against exogenous phytase and partly to an inactivation of the endogenous phytase in oats caused by the usual heat treatment of oats which is made to prevent rancidity of oat lipids during storage. The inhibitory effect of oat products on iron absorption is sufficiently marked to be a serious consideration if such products are more regularly consumed.

  10. Composition Analysis and Inhibitory Effect of Sterculia lychnophora against Biofilm Formation by Streptococcus mutans.

    PubMed

    Yang, Yang; Park, Bok-Im; Hwang, Eun-Hee; You, Yong-Ouk

    2016-01-01

    Pangdahai is a traditional Chinese drug, specifically described in the Chinese Pharmacopoeia as the seeds of Sterculia lychnophora Hance. Here, we separated S. lychnophora husk and kernel, analyzed the nutrient contents, and investigated the inhibitory effects of S. lychnophora ethanol extracts on cariogenic properties of Streptococcus mutans, important bacteria in dental caries and plaque formation. Ethanol extracts of S. lychnophora showed dose-dependent antibacterial activity against S. mutans with significant inhibition at concentrations higher than 0.01 mg/mL compared with the control group (p < 0.05). Furthermore, biofilm formation was decreased by S. lychnophora at concentrations > 0.03 mg/mL, while bacterial viability was decreased dose-dependently at high concentrations (0.04, 0.08, 0.16, and 0.32 mg/mL). Preliminary phytochemical analysis of the ethanol extract revealed a strong presence of alkaloid, phenolics, glycosides, and peptides while the presence of steroids, terpenoids, flavonoids, and organic acids was low. The S. lychnophora husk had higher moisture and ash content than the kernel, while the protein and fat content of the husk were lower (p < 0.05) than those of the kernel. These results indicate that S. lychnophora may have antibacterial effects against S. mutans, which are likely related to the alkaloid, phenolics, glycosides, and peptides, the major components of S. lychnophora. PMID:27190540

  11. Inhibitory effect of recombinant adenovirus carrying immunocaspase-3 on hepatocellular carcinoma

    SciTech Connect

    Li, Xiaohua; Fan, Rui; Zou, Xue; Gao, Lin; Jin, Haifeng; Du, Rui; Xia, Lin; Fan, Daiming . E-mail: fandaim@yahoo.com.cn

    2007-06-29

    Previously, Srinivasula devised a contiguous molecule (C-cp-3 or immunocaspase-3) containing the small and large subunits similar to that in the active form of caspas-3 and found C-cp-3 had similar cleavage activity to the active form of caspase-3. To search for a new clinical application of C-cp-3 to treat hepatocellular carcinoma, recombinant adenoviruses carrying the C-cp-3 and a-fetoprotein (AFP) promoter (Ad-rAFP-C-cp-3) were constructed through a bacterial homologous recombinant system. The efficiency of adenovirus-mediated gene transfer and the inhibitory effect of Ad-rAFP-C-cp-3 on the proliferation of hepatocarcinoma cells were determined by X-gal stain and MTT assay, respectively. The tumorigenicity of hepatocarcinoma cells transfected by Ad-rAFP-C-cp-3 and the antitumor effect of Ad-rAFP-C-cp-3 on transplanted tumor in nude mice were detected in vivo. The results suggested that Ad-rAFP-C-cp-3 can inhibit specifically proliferation of AFP-producing human hepatocarcinoma cells in vitro and in vivo and adenovirus-mediated C-cp-3 transfer could be used as a new method to treat human hepatocarcinoma.

  12. In vivo inhibitory effects of puerarin on selected rat cytochrome P450 isoenzymes.

    PubMed

    Guo, Yu-Jin; Liang, Dong-Lou; Xu, Zhi-Sheng; Ye, Qiang

    2014-05-01

    Puerarin, the major bioactive constituent in kudzu root, is used widely in China for the treatment of cardiovascular diseases and diabetes. The purpose of this study was to find out whether puerarin influences the effect on rat cytochrome P450 (CYP) enzymes (CYP2B6, CYP2C9 and CYP3A4) by using cocktail probe drugs in vivo. A cocktail solution at a dose of 5 mL/kg, which contained bupropion (20 mg/kg), tolbutamide (5 mg/kg) and midazolam (20 mg/kg), was given as oral administration to rats treated with 10 days oral administration of puerarin. Blood samples were collected at a series of time-points and the concentrations of probe drugs in plasma were determined by HPLC-MS/MS. The results showed that treatment with multiple doses of puerarin had inhibitory effects on rat CYP2B6, CYP2C9 and CYP3A4 enzyme activities. Therefore, caution is needed when puerarin is co-administered with CYP substrates, in view of herb-drug interactions.

  13. Preliminary investigation of the inhibitory effects of mechanical stress in tumor growth

    NASA Astrophysics Data System (ADS)

    Garg, Ishita; Miga, Michael I.

    2008-03-01

    In the past years different models have been formulated to explain the growth of gliomas in the brain. The most accepted model is based on a reaction-diffusion equation that describes the growth of the tumor as two separate components- a proliferative component and an invasive component. While many improvements have been made to this basic model, the work exploring the factors that naturally inhibit growth is insufficient. It is known that stress fields affect the growth of normal tissue. Due to the rigid skull surrounding the brain, mechanical stress might be an important factor in inhibiting the growth of gliomas. A realistic model of glioma growth would have to take that inhibitory effect into account. In this work a mathematical model based on the reaction-diffusion equation was used to describe tumor growth, and the affect of mechanical stresses caused by the mass effect of tumor cells was studied. An initial tumor cell concentration with a Gaussian distribution was assumed and tumor growth was simulated for two cases- one where growth was solely governed by the reaction-diffusion equation and second where mechanical stress inhibits growth by affecting the diffusivity. All the simulations were performed using the finite difference method. The results of simulations show that the proposed mechanism of inhibition could have a significant affect on tumor growth predictions. This could have implications for varied applications in the imaging field that use growth models, such as registration and model updated surgery.

  14. Growth inhibitory effect of grape phenolics against wine spoilage yeasts and acetic acid bacteria.

    PubMed

    Pastorkova, E; Zakova, T; Landa, P; Novakova, J; Vadlejch, J; Kokoska, L

    2013-02-15

    This paper investigates the in vitro antimicrobial potential of 15 grape phenolic compounds of various chemical classes (phenolic acids, stilbenes and flavonoids) using the broth microdilution method against yeasts and acetic acid bacteria frequently occurring in deteriorated wine. Pterostilbene (MICs=32-128 μg/mL), resveratrol (MICs=256-512 μg/mL) and luteolin (MICs=256-512 μg/mL) are among six active compounds that possessed the strongest inhibitory effects against all microorganisms tested. In the case of phenolic acids, myricetin, p-coumaric and ferulic acids exhibited selective antimicrobial activity (MICs=256-512 μg/mL), depending upon yeasts and bacteria tested. In comparison with potassium metabisulphite, all microorganisms tested were more susceptible to the phenolics. The results revealed the antibacterial and antiyeast effects against wine spoilage microorganisms of several highly potent phenolics naturally occurring in grapes. These findings also provide arguments for further investigation of stilbenes as prospective compounds reducing the need for the use of sulphites in winemaking.

  15. The inhibitory effects of Escherichia coli maltose binding protein on β-amyloid aggregation and cytotoxicity.

    PubMed

    Sharoar, Md Golam; Shahnawaz, Md; Islam, Md Imamul; Ramasamy, Vijay Sankar; Shin, Song Yub; Park, Il-Seon

    2013-10-01

    The aggregation of β-amyloid (Aβ) peptide from its monomeric to its fibrillar form importantly contributes to the development of Alzheimer's disease. Here, we investigated the effects of Escherichia coli maltose binding protein (MBP), which has been previously used as a fusion protein, on Aβ42 fibrillization, in order to improve understanding of the self-assembly process and the cytotoxic mechanism of Aβ42. MBP, at a sub-stoichiometric ratio with respect to Aβ42, was found to have chaperone-like inhibitory effects on β-sheet fibril formation, due to the accumulation of Aβ42 aggregates by sequestration of active Aβ42 species as Aβ42-MBP complexes. Furthermore, MBP increased the lag time of Aβ42 polymerization, decreased the growth rate of fibril extension, and suppressed Aβ42 mediated toxicity in human neuroblastoma SH-SY5Y cells. It appears that MBP decreases the active concentration of Aβ42 by sequestering it as Aβ42-MBP complex, and that this sequestration suppresses ongoing nucleation and retards the growth rate of Aβ42 species required for fibril formation. We speculate that inhibition of the growth rate of potent Aβ42 species by MBP suppresses Aβ42-mediated toxicity in SH-SY5Y cells. PMID:23948569

  16. Inhibitory effects of Iranian Thymus vulgaris extracts on in vitro growth of Entamoeba histolytica.

    PubMed

    Behnia, Maryam; Haghighi, Ali; Komeylizadeh, Hossein; Tabaei, Seyyed-Javadi Seyyed; Abadi, Alireza

    2008-09-01

    One of the most common drugs used against a wide variety of anaerobic protozoan parasites is metronidazole. However, this drug is mutagenic for bacteria and is a potent carcinogen for rodents. Thymus vulgaris is used for cough suppression and relief of dyspepsia. Also it has antibacterial and antifungal properties. The aim of this study was to investigate antiamebic effect of Thymus vulgaris against Entamoeba histolytica in comparison with metronidazole. One hundred gram air-dried T. vulgaris plant was obtained and macerated at 25 degrees C for 14 days using n-hexane and a mixture of ethanol and water. For essential oil isolation T. vulgaris was subjected to hydrodistillation using a clevenger-type apparatus for 3 hr. E. histolytica, HM-1: IMSS strain was used in all experiments. It was found that the minimal inhibitory concentration (MIC) for T. vulgaris hydroalcoholic, hexanic extracts, and the essential oil after 24 hr was 4 mg/mL, 4 mg/mL, and 0.7 mg/mL, respectively. After 48 hr the MIC for T. vulgaris hydroalcoholic and hexanic extracts was 3 and 3 mg/mL, respectively. Therefore, it can be concluded that the Iranian T. vulgaris is effective against the trophozoites of E. histolytica.

  17. Inhibitory Effects of Amorphigenin on the Mitochondrial Complex I of Culex pipiens pallens Coquillett (Diptera: Culicidae)

    PubMed Central

    Ji, Mingshan; Liang, Yaping; Gu, Zumin; Li, Xiuwei

    2015-01-01

    Previous studies in our laboratory found that the extract from seeds of Amorpha fruticosa in the Leguminosae family had lethal effects against mosquito larvae, and an insecticidal compound amorphigenin was isolated. In this study, the inhibitory effects of amorphigenin against the mitochondrial complex I of Culex pipiens pallens (Diptera: Culicidae) were investigated and compared with that of rotenone. The results showed that amorphigenin and rotenone can decrease the mitochondrial complex I activity both in vivo and in vitro as the in vivo IC50 values (the inhibitor concentrations leading to 50% of the enzyme activity lost) were determined to be 2.4329 and 2.5232 μmol/L, respectively, while the in vitro IC50 values were 2.8592 and 3.1375 μmol/L, respectively. Both amorphigenin and rotenone were shown to be reversible and mixed-I type inhibitors of the mitochondrial complex I of Cx. pipiens pallens, indicating that amorphigenin and rotenone inhibited the enzyme activity not only by binding with the free enzyme but also with the enzyme-substrate complex, and the values of KI and KIS for amorphigenin were determined to be 20.58 and 87.55 μM, respectively, while the values for rotenone were 14.04 and 69.23 μM, respectively. PMID:26307964

  18. Composition Analysis and Inhibitory Effect of Sterculia lychnophora against Biofilm Formation by Streptococcus mutans

    PubMed Central

    Yang, Yang; Park, Bok-Im; Hwang, Eun-Hee; You, Yong-Ouk

    2016-01-01

    Pangdahai is a traditional Chinese drug, specifically described in the Chinese Pharmacopoeia as the seeds of Sterculia lychnophora Hance. Here, we separated S. lychnophora husk and kernel, analyzed the nutrient contents, and investigated the inhibitory effects of S. lychnophora ethanol extracts on cariogenic properties of Streptococcus mutans, important bacteria in dental caries and plaque formation. Ethanol extracts of S. lychnophora showed dose-dependent antibacterial activity against S. mutans with significant inhibition at concentrations higher than 0.01 mg/mL compared with the control group (p < 0.05). Furthermore, biofilm formation was decreased by S. lychnophora at concentrations > 0.03 mg/mL, while bacterial viability was decreased dose-dependently at high concentrations (0.04, 0.08, 0.16, and 0.32 mg/mL). Preliminary phytochemical analysis of the ethanol extract revealed a strong presence of alkaloid, phenolics, glycosides, and peptides while the presence of steroids, terpenoids, flavonoids, and organic acids was low. The S. lychnophora husk had higher moisture and ash content than the kernel, while the protein and fat content of the husk were lower (p < 0.05) than those of the kernel. These results indicate that S. lychnophora may have antibacterial effects against S. mutans, which are likely related to the alkaloid, phenolics, glycosides, and peptides, the major components of S. lychnophora. PMID:27190540

  19. Inhibitory effects of capsaicin on hepatic stellate cells and liver fibrosis.

    PubMed

    Yu, Fu-Xiang; Teng, Yin-Yan; Zhu, Qian-Dong; Zhang, Qi-Yu; Tang, Yin-He

    2014-10-01

    Hepatic stellate cells (HSCs) play an important role in the process of liver fibrosis. In this study, we investigated the inhibitory effects of capsaicin on HSCs and liver fibrosis. Cultured HSCs were incubated with various concentrations of capsaicin. Cell proliferation was examined using a cell counting kit. Production of hydrogen peroxide was determined using a 2',7'-dichlorofluorescin diacetate (DCFH-DA) assay. The mRNA and protein expression of target genes was analyzed by reverse transcription PCR and Western blot analysis, respectively. Cell apoptosis was evaluated by annexin V-FITC and propidium iodide (PI) costaining followed by flow cytometric analysis. A CCl4 rat liver fibrosis model was used to assess in vivo effects of capsaicin by histological examination and measurement of liver fibrosis markers, including hydroxyproline content, serum type III collagen, and hyaluronic acid (HA) levels. Our results show that capsaicin dose-dependently inhibited cell proliferation, suppressed cell activation, and decreased hydrogen peroxide production in cultured HSCs. Capsaicin reduced the mRNA levels of tissue inhibitors of metalloproteinase 1 (TIMP-1) and transforming growth factor-β1 (TGF-β1) in HSCs. Moreover, capsaicin-induced cell apoptosis was associated with increased expression of Bax, cytochrome c (cyt c), and caspase-3, but reduced levels of Bcl-2. The animal studies further revealed that capsaicin efficiently reduced the extent of liver fibrosis, inhibited HSC proliferation, and promoted cell apoptosis. Our findings suggest that capsaicin might inhibit fibrogenesis by inhibiting the activities of HSCs.

  20. Matrix metalloproteinases (MMPs) inhibitory effects of an octameric oligopeptide isolated from abalone Haliotis discus hannai.

    PubMed

    Nguyen, Van-Tinh; Qian, Zhong-Ji; Ryu, Bomi; Kim, Kil-Nam; Kim, Daekyung; Kim, Young-Mog; Jeon, You-Jin; Park, Won Sun; Choi, Il-Whan; Kim, Geun Hyung; Je, Jae-Young; Jung, Won-Kyo

    2013-11-01

    Abalone (Haliotis discus hannai) is a marine gastropod, and an important fishery and food industrial resource that is massively maricultured in Asia, Africa, Australia and America. However, its health benefits have rarely been studied for nutraceutical and pharmaceutical application. In this study, the purified abalone oligopeptide (AOP) with anti-matrix metalloproteinases (anti-MMPs) effects was isolated from the digests of abalone intestine using recycle HPLC with a JAI W253 column and an OHpak SB-803 HQ column. The AOP was identified as Ala-Glu-Leu-Pro-Ser-Leu-Pro-Gly (MW=782.4 Da) with a de novo peptide sequencing technique using a tandem mass spectrometer. The AOP exhibited a specific inhibitory effect against MMP-2/-9 activity and attenuated protein expression of p50 and p65 in the human fibrosarcoma (HT1080) cells, dose-dependently. The results presented illustrate that the AOP could inhibit MMP-2/-9 expression in HT1080 cells via the nuclear factor-kappaB (NF-κB)-mediated pathway. This data suggest that the AOP from H. discus hannai intestine may possess therapeutic and preventive potential for the treatment of MMPs-related disorders such as angiogenesis and cardiovascular diseases.

  1. The inhibitory effects of silver nanoparticles, silver ions, and silver chloride colloids on microbial growth.

    PubMed

    Choi, Okkyoung; Deng, Kathy Kanjun; Kim, Nam-Jung; Ross, Louis; Surampalli, Rao Y; Hu, Zhiqiang

    2008-06-01

    Emerging nanomaterials are of great concern to wastewater treatment utilities and the environment. The inhibitory effects of silver nanoparticles (Ag NPs) and other important Ag species on microbial growth were evaluated using extant respirometry and an automatic microtiter fluorescence assay. Using autotrophic nitrifying organisms from a well-controlled continuously operated bioreactor, Ag NPs (average size=14+/-6 nm), Ag(+) ions (AgNO(3)), and AgCl colloids (average size=0.25 microm), all at 1mg/L Ag, inhibited respiration by 86+/-3%, 42+/-7%, and 46+/-4%, respectively. Based on a prolonged microtiter assay, at about 0.5mg/L Ag, the inhibitions on the growth of Escherichia coli PHL628-gfp by Ag NPs, Ag(+) ions, and AgCl colloids were 55+/-8%, 100%, and 66+/-6%, respectively. Cell membrane integrity was not compromised under the treatment of test Ag species by using a LIVE/DEAD Baclight bacterial viability assay. However, electron micrographs demonstrated that Ag NPs attached to the microbial cells, probably causing cell wall pitting. The results suggest that nitrifying bacteria are especially susceptible to inhibition by Ag NPs, and the accumulation of Ag NPs could have detrimental effects on the microorganisms in wastewater treatment.

  2. Fish Oil and Adjuvant-Induced Arthritis: Inhibitory Effect on Leukocyte Recruitment.

    PubMed

    Estevão-Silva, Camila Fernanda; Ames, Franciele Queiroz; Silva-Comar, Francielli Maria de Souza; Kummer, Raquel; Tronco, Rafael Prizon; Cuman, Roberto Kenji Nakamura; Bersani-Amado, Ciomar Aparecida

    2016-02-01

    Fish oil, a rich source of n-3 fatty acids, has been studied for its beneficial effects in many diseases. Recent studies have shown the robust anti-inflammatory activity of fish oil (FO), when administered orally to rats, in models of acute inflammation. Herein, we investigated if treatment with fish oil preparation (FOP) could interfere with the recruitment of leukocytes into the joint cavity of arthritic rats. We also evaluated the effect of treatment on rolling behavior and leukocyte adhesion in vivo and on leukocyte chemotaxis in vitro. Treatment with FOP (75, 150, and 300 mg/kg) initiated on the day of induction of arthritis (day 0) and maintained for 21 days reduced the total number of leukocytes recruited into the joint cavity, the number of rolling and adhered leukocytes in arthritic rats, and leukocyte migration in response to stimulation with N-formyl-methionyl-leucyl-phenylalanine (fMLP) and leukotriene B4 (LTB4). Together, our data provide evidence that FOP plays an important inhibitory role in the recruitment of leukocytes into the joint cavity of arthritic rats. PMID:26378008

  3. Chemokines and chemokine receptors as novel therapeutic targets in rheumatoid arthritis (RA): inhibitory effects of traditional Chinese medicinal components.

    PubMed

    Chen, Xin; Oppenheim, Joost J; Howard, O M Zack

    2004-10-01

    Chemokines belong to a large family of inflammatory cytokines responsible for migration and accumulation of leukocytes at inflammatory sites. Over the past decade, accumulating evidence indicated a crucial role for chemokines and chemokine receptors in the pathophysiology of rheumatoid arthritis (RA). RA is a chronic autoimmune disease in which the synovial tissue is heavily infiltrated by leukocytes. Chemokines play an important role in the infiltration, localization, retention of infiltrating leukocytes and generation of ectopic germinal centers in the inflamed synovium. Recent evidence also suggests that identification of inhibitors directly targeting chemokines or their receptors may provide a novel therapeutic strategy in RA. Traditional Chinese medicines (TCMs) have a long history in the treatment of inflammatory joint disease. The basis for the clinical benefits of TCM remains largely unclear. Our studies have led to the identification of numerous novel chemokine/chemokine receptor inhibitors present in anti-inflammatory TCMs. All of these inhibitors were previously reported by other researchers to have anti-arthritic effect, which may be attributable, at least in part, to their inhibitory effect on chemokine and/or chemokine receptor. Therefore, identification of agents capable of targeting chemokine/chemokine receptor interactions has suggested a mechanism of action for several TCM components and provided a means of identifying additional anti-RA TCM. Thus, this approach may lead to the discovery of new inhibitors of chemokines or chemokine receptors that can be used to treat diseases associated with inappropriately overactive chemokine mediated inflammatory reactions.

  4. Inhibitory and toxic effects of extracellular self-DNA in litter: a mechanism for negative plant-soil feedbacks?

    PubMed

    Mazzoleni, Stefano; Bonanomi, Giuliano; Incerti, Guido; Chiusano, Maria Luisa; Termolino, Pasquale; Mingo, Antonio; Senatore, Mauro; Giannino, Francesco; Cartenì, Fabrizio; Rietkerk, Max; Lanzotti, Virginia

    2015-02-01

    Plant-soil negative feedback (NF) is recognized as an important factor affecting plant communities. The objectives of this work were to assess the effects of litter phytotoxicity and autotoxicity on root proliferation, and to test the hypothesis that DNA is a driver of litter autotoxicity and plant-soil NF. The inhibitory effect of decomposed litter was studied in different bioassays. Litter biochemical changes were evaluated with nuclear magnetic resonance (NMR) spectroscopy. DNA accumulation in litter and soil was measured and DNA toxicity was assessed in laboratory experiments. Undecomposed litter caused nonspecific inhibition of root growth, while autotoxicity was produced by aged litter. The addition of activated carbon (AC) removed phytotoxicity, but was ineffective against autotoxicity. Phytotoxicity was related to known labile allelopathic compounds. Restricted (13) C NMR signals related to nucleic acids were the only ones negatively correlated with root growth on conspecific substrates. DNA accumulation was observed in both litter decomposition and soil history experiments. Extracted total DNA showed evident species-specific toxicity. Results indicate a general occurrence of litter autotoxicity related to the exposure to fragmented self-DNA. The evidence also suggests the involvement of accumulated extracellular DNA in plant-soil NF. Further studies are needed to further investigate this unexpected function of extracellular DNA at the ecosystem level and related cellular and molecular mechanisms. PMID:25354164

  5. Inhibitory effect of mitragynine on human cytochrome P450 enzyme activities

    PubMed Central

    Hanapi, N. A.; Ismail, S.; Mansor, S. M.

    2013-01-01

    Context: To date, many findings reveal that most of the modern drugs have the ability to interact with herbal drugs. Aims: This study was conducted to determine the inhibitory effects of mitragynine on cytochrome P450 2C9, 2D6 and 3A4 activities. Methods and Material: The in vitro study was conducted using a high-throughput luminescence assay. Statistical Analysis: Statistical analysis was conducted using one-way ANOVA and Dunnett's test with P < 0.05 vs. control. The IC50 values were calculated using the GraphPad Prism® 5 (Version 5.01, GraphPad Software, Inc., USA). Results: Assessment using recombinant enzymes showed that mitragynine gave the strongest inhibitory effect on CYP2D6 with an IC50 value of 0.45±0.33 mM, followed by CYP2C9 and CYP3A4 with IC50 values of 9.70±4.80 and 41.32±6.74 μM respectively. Positive inhibitors appropriate for CYP2C9, CYP2D6, and CYP3A4 which are sulfaphenazole, quinidine and ketoconazole were used respectively. Vmax values of CYP2C9, CYP2D6 and CYP3A4 were 0.0005, 0.01155 and 0.0137 μM luciferin formed/pmol/min respectively. Km values of CYP2C9, CYP2D6, and CYP3A4 were 32.65, 56.01, and 103.30 μM respectively. Mitragynine noncompetitively inhibits CYP2C9 and CYP2D6 activities with the Ki values of 61.48 and 12.86 μM respectively. On the other hand, mitragynine inhibits CYP3A4 competitively with a Ki value of 379.18 μM. Conclusions: The findings of this study reveal that mitragynine might inhibit cytochrome P450 enzyme activities, specifically CYP2D6. Therefore, administration of mitragynine together with herbal or modern drugs which follow the same metabolic pathway may contribute to herb-drug interactions. PMID:24174816

  6. Effects of support unloading on inhibitory processes in motoneurons pools of postural muscles

    NASA Astrophysics Data System (ADS)

    Shigueva, Tatiana; Zakirova, Albina; Tomilovskaya, Elena

    The purpose of the study was to investigate the effect of support unloading on characteristics of shin extensor muscles (m.soleus and m.gastrocnemius lat.) motor units` (MU) activity evoked by electrical stimulation and intensity of spinal inhibitory processes. Conditions of support unloading were reproduced by "dry" immersion (DI), that it seen to be is the most adequate ground simulation model of weightlessness [Shulzhenko E.B. et al, 1976]. The experiments were performed with participation of 10 healthy men of 20-27 years old. The subjects were divided into 2 groups. In the first one (control group) the subjects stayed in DI for 3 days without any other influences; in the second one (experimental group) in the course of DI the mechanical stimulation of soles’ support zones in the regimen of locomotion was applied daily for 20 min at the beginning of each hour for 6 hours per day [Kozlovskaya I.B., 2007]. MUs’ activity of shin muscles (mm. gastrocnemius lat. and soleus) was recorded with needle concentric electrodes during execution of the task of maintaining a small plantar flexion effort (not stronger than 7% of maximal voluntary contraction force). Single electrical pulses 0,1 ms duration were applied to n.tibialis during spontaneous MU activity. The duration of silent period (SP) following H-reflex response and presence of rebound phenomenon - an increase of MU activity at the end of SP, that is usually observed under normal conditions and reflects trace of inhibitory and excitatory processes in motoneurons pools, were analyzed [Person R.S., 1985]. Experiments were performed before, on the 2nd and 3d day of DI and on the 2nd day after its accomplishment. The Wilcoxon nonparametric criteria were used for statistical data analysis. Exposure to the conditions of support unloading was followed by significant decline of SP duration. The mean of SP duration in shin muscles before DI was 227±31,4 ms. On the 2nd and 3rd days of DI in the control group it

  7. Acute effects of alcohol on inhibitory control and information processing in high and low sensation-seekers

    PubMed Central

    Fillmore, Mark T.; Ostling, Erik W.; Martin, Catherine A.; Kelly, Thomas H.

    2009-01-01

    Sensation-seeking is a personality characteristic that has been associated with drug abuse. Some evidence suggests that sensation-seekers might experience increased rewarding effects from drugs of abuse, possibly contributing to the association between sensation-seeking and risk for drug abuse. The present study examined the effects of three doses of alcohol (0.0 g/kg, 0.45 g/kg, and 0.65 g/kg) on inhibitory control, information processing, and subjective ratings in a group of high sensation-seekers and a group of low sensation-seekers (N = 20). Inhibitory control was measured by a cued go/no-go task and speed of information processing was assessed by the Rapid Information Processing (RIP) task. Alcohol impaired inhibitory control and information processing. Group differences were also observed. Compared with their low sensation-seeking counterparts, high sensation-seekers demonstrated increased sensitivity to the subjective rewarding effects of alcohol and a poorer degree of inhibitory control that was further impaired by alcohol. The findings highlight reward- and cognitive-based mechanisms by which sensation-seeking could operate to increase risk for alcohol abuse. PMID:19004578

  8. Inhibitory and inductive effects of Phikud Navakot extract on human cytochrome P450.

    PubMed

    Chiangsom, Abhiruj; Lawanprasert, Somsong; Oda, Shingo; Kulthong, Kornphimol; Luechapudiporn, Rataya; Yokoi, Tsuyoshi; Maniratanachote, Rawiwan

    2016-06-01

    Effects of the hydroethanolic extract of Phikud Navakot (PN), a Thai traditional remedy, on human cytochrome P450s (CYPs) were investigated in vitro. Selective substrates of CYPs were used to investigate the effects and kinetics of PN on CYP inhibition using human liver microsomes. Primary human hepatocytes were used to assess the inductive effects of PN on CYP enzyme activities and protein expressions. The results showed that PN inhibited the activities of CYP1A2, CYP2C9, CYP2D6, and CYP3A4 with half maximal inhibitory concentration (IC50) values of 13, 62, 67, and 88 μg/mL, respectively. Meanwhile, it had no effect on the activities of CYP2C19 and CYP2E1 (IC50 > 1 mg/mL). PN exhibited competitive inhibition of CYP1A2 (Ki = 34 μg/mL), mixed type inhibition of CYP2C9 and CYP2D6 (Ki = 80 and 12 μg/mL, respectively), and uncompetitive inhibition of CYP3A4 (Ki = 150 μg/mL). PN did not have an inductive effect on CYP1A2, CYP2C9, CYP2C19 and CYP3A4 in primary human hepatocytes, which is an advantageous characteristic of the extract. However the extract may cause herb-drug interactions via inhibition of CYP1A2, CYP2C9, CYP2D6 and CYP3A4, and precautions should be taken when PN is coadministered with drugs that are metabolized by these CYP enzymes. PMID:27212065

  9. Effect of combination on the antioxidant and inhibitory properties of tropical pepper varieties against α-amylase and α-glucosidase activities in vitro.

    PubMed

    Oboh, Ganiyu; Ademiluyi, Adedayo O; Faloye, Yetunde M

    2011-10-01

    Pepper used as a spice for food preparations is usually a single type or a combination of several different varieties. This choice is usually based on individual preferences, without consideration of health benefits. Therefore, the present study investigated the health benefits of a combination of 3 pepper varieties commonly consumed in Nigeria. Aqueous extracts (1:100 w/v) of Capsicum annuum var. grossum, C. annuum var. abbreviatum, and C. annuum var. accuminatum and a combination of the 3 varieties (1:1:1) were assayed for phenolic content (total phenol and flavonoid), antioxidant activities (reducing power and 1,1-diphenyl-2-picrylhydrazyl radical-scavenging abilities), inhibitory effect on Fe²⁺-induced lipid peroxidation in rat pancreas in vitro, and the ability of the extracts to inhibit key enzymes linked with type 2 diabetes (α-amylase and α-glucosidase). The combination of peppers showed additive effects in their phenolic content and displayed antioxidant properties. However, the inhibition of pancreatic α-amylase activity showed an additive effect, whereas α-glucosidase inhibitory activity was antagonistic with the combination. C. annuum var. accuminatum contributed most to the activities of the combined peppers. Strong inhibitory activities of the peppers against key enzymes linked to type 2 diabetes and Fe²⁺-induced lipid peroxidation in rat pancreas in vitro, coupled with their antioxidant properties, suggest that pepper could be used in the prevention and management of type 2 diabetes. The pepper combination showed additive tendencies of these properties.

  10. Effect of in vitro irradiation and cell cycle-inhibitory drugs on the spontaneous human IgE synthesis in vitro

    SciTech Connect

    Del Prete, G.F.; Vercelli, D.; Tiri, A.; Maggi, E.; Rossi, O.; Romagnani, S.; Ricci, M.

    1987-01-01

    The in vitro effects of radiation, diterpine forskolin (FK), and hydrocortisone (HC) on the in vitro spontaneous IgE synthesis by peripheral blood B-lymphocytes from atopic patients were investigated. Without affecting cell viability, in vitro irradiation inhibited in a dose-dependent fashion de novo IgE synthesis in vitro by B cells from all patients examined with a mean 40% reduction of in vitro IgE product after treatment with 100 rads. In contrast, the in vitro IgE production by the U266 myeloma cell line was unaffected, even by irradiation with 1600 rads. The addition to B cell cultures from atopic patients of FK consistently resulted in a dose-dependent inhibition of the spontaneous IgE production in vitro. The addition to cultures of 10(-5) and 10(-6) molar concentrations of HC was also usually inhibitory, whereas lower HC concentrations were uneffective or even enhanced the spontaneous in vitro IgE synthesis. When 10(-6) molar concentrations of both HC and FK were combined in culture, a summation inhibitory effect on the spontaneous IgE synthesis was observed. In contrast, neither FK nor HC had inhibitory effect on the in vitro spontaneous IgE synthesis by the U266 myeloma cell line. The spontaneous in vitro IgE synthesis by B cells from patients with Hodgkin's disease, demonstrating high levels of serum IgE, was strongly reduced or virtually abolished after patients underwent total nodal irradiation to prevent the spread of the disease. In addition, the in vitro spontaneous IgE synthesis by B cells from atopic patients was markedly decreased or abolished by in vivo administration of betamethasone.

  11. Synergistic inhibitory effect of scopoletin and bisdemethoxycurcumin on Tetranychus cinnabarinus (Boisduval) (Acari: Tetranychidae).

    PubMed

    Zhang, Yong-Qiang; Yang, Zhen-Guo; Ding, Wei; Luo, Jin-Xiang

    2016-01-01

    The study aimed to investigate the synergistic activity of scopoletin and bisdemethoxycurcumin (BDMC) against the carmine spider mite Tetranychus cinnabarinus. The acaricidal activities of mixtures of scopoletin and BDMC against T. cinnabarinus female adults were measured via slide dipping and leaf disc dipping. A mathematical model was established by SPSS software. Bioassays for multiple effects including contact, ovicidal, cowpea root intake, repellency and oviposition inhibitory activity were carried out. The optimal mass ratio of the mixture of scopoletin and BDMC (at their respective LC(50)), the median lethal concentration (LC(50)) and the co-toxicity coefficient were 7:6, 0.19 mg/mL and 129, respectively. LC(50) values of contact activities of the mixture at optimal ratio against adults, nymphs, larvae, and eggs were 0.19, 0.18, 0.06, and 1.52 mg/mL, respectively. LC(50) values of cowpea root intake activity against adults and nymphs were 5.62 and 6.52 mg/mL, respectively. The highest repellent rates against adults and nymphs were 69.5% and 72.5%, respectively. The mixture of scopoletin and BDMC at the optimal mass ratio possessed strong acaricidal activity against T. cinnabarinus at various developmental stages. PMID:26824978

  12. Inhibitory effect of Allium sativum and Zingiber officinale extracts on clinically important drug resistant pathogenic bacteria

    PubMed Central

    2012-01-01

    Background Herbs and spices are very important and useful as therapeutic agent against many pathological infections. Increasing multidrug resistance of pathogens forces to find alternative compounds for treatment of infectious diseases. Methods In the present study the antimicrobial potency of garlic and ginger has been investigated against eight local clinical bacterial isolates. Three types of extracts of each garlic and ginger including aqueous extract, methanol extract and ethanol extract had been assayed separately against drug resistant Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, Staphylococcus aureus, Klebsiella pneumoniae, Shigella sonnei, Staphylococcusepidermidis and Salmonella typhi. The antibacterial activity was determined by disc diffusion method. Results All tested bacterial strains were most susceptible to the garlic aqueous extract and showed poor susceptibility to the ginger aqueous extract. The (minimum inhibitory concentration) MIC of different bacterial species varied from 0.05 mg/ml to 1.0 mg/ml. Conclusion In the light of several socioeconomic factors of Pakistan mainly poverty and poor hygienic condition, present study encourages the use of spices as alternative or supplementary medicine to reduce the burden of high cost, side effects and progressively increasing drug resistance of pathogens. PMID:22540232

  13. Lignan from Thyme Possesses Inhibitory Effect on ASIC3 Channel Current*

    PubMed Central

    Dubinnyi, Maxim A.; Osmakov, Dmitry I.; Koshelev, Sergey G.; Kozlov, Sergey A.; Andreev, Yaroslav A.; Zakaryan, Naira A.; Dyachenko, Igor A.; Bondarenko, Dmitry A.; Arseniev, Alexander S.; Grishin, Eugene V.

    2012-01-01

    A novel compound was identified in the acidic extract of Thymus armeniacus collected in the Lake Sevan region of Armenia. This compound, named “sevanol,” to our knowledge is the first low molecular weight natural molecule that has a reversible inhibition effect on both the transient and the sustained current of human ASIC3 channels expressed in Xenopus laevis oocytes. Sevanol completely blocked the transient component (IC50 353 ± 23 μm) and partially (∼45%) inhibited the amplitude of the sustained component (IC50 of 234 ± 53 μm). Other types of acid-sensing ion channel (ASIC) channels were intact to sevanol application, except ASIC1a, which showed more than six times less affinity to it as compared with the inhibitory action on the ASIC3 channel. To elucidate the structure of sevanol, the set of NMR spectra in two solvents (d6-DMSO and D2O) was collected, and the complete chemical structure was confirmed by liquid chromatography-mass spectrometry with electrospray ionization (LC-ESI+-MS) fragmentation. This compound is a new lignan built up of epiphyllic acid and two isocitryl esters in positions 9 and 10. In vivo administration of sevanol (1–10 mg/kg) significantly reversed thermal hyperalgesia induced by complete Freund's adjuvant injection and reduced response to acid in a writhing test. Thus, we assume the probable considerable role of sevanol in known analgesic and anti-inflammatory properties of thyme. PMID:22854960

  14. In vitro inhibitory effects of plant-derived by-products against Cryptosporidium parvum.

    PubMed

    Teichmann, Klaus; Kuliberda, Maxime; Schatzmayr, Gerd; Pacher, Thomas; Zitterl-Eglseer, Karin; Joachim, Anja; Hadacek, Franz

    2016-01-01

    Disposal of organic plant wastes and by-products from the food or pharmaceutical industries usually involves high costs. In the present study, 42 samples derived from such by-products were screened in vitro against Cryptosporidium parvum, a protozoan parasite that may contaminate drinking water and cause diarrhoea. The novel bioassay was previously established in the microtitre plate format. Human ileocaecal adenocarcinoma (HCT-8) cell cultures were seeded with C. parvum oocysts and parasite development was monitored by an indirect fluorescent antibody technique (IFAT) and microscopic assessment for clusters of secondary infection (CSI). Minimum inhibitory concentrations (MICs) and potential detrimental effects on the host cells were determined. An ethanolic extract from olive (Olea europaea) pomace, after oil pressing and phenol recovery, reproducibly inhibited C. parvum development (MIC = 250-500 μg mL(-1), IC50 = 361 (279-438) μg mL(-1), IC90 = 467 (398-615) μg mL(-1)). Accordingly, tyrosol, hydroxytyrosol, trans-coniferyl alcohol and oleuropein were selected as reference test compounds, but their contributions to the observed activity of the olive pomace extract were insignificant. The established test system proved to be a fast and efficient assay for identifying anti-cryptosporidial activities in biological waste material and comparison with selected reference compounds.

  15. Antifungal properties and inhibitory effects upon aflatoxin production of Thymus vulgaris L. by Aspergillus flavus Link.

    PubMed

    Kohiyama, Cássia Yumie; Yamamoto Ribeiro, Milene Mayumi; Mossini, Simone Aparecida Galerani; Bando, Erika; Bomfim, Natália da Silva; Nerilo, Samuel Botião; Rocha, Gustavo Henrique Oliveira; Grespan, Renata; Mikcha, Jane Martha Graton; Machinski, Miguel

    2015-04-15

    The antifungal and antiaflatoxigenic properties of Thymus vulgaris essential oil (TEO) were evaluated upon Aspergillus flavus "in vitro". Suspension containing 10(6) of A. flavus were cultivated with TEO in concentrations ranging from 50 to 500 μg/mL. TEO reached minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) at 250 μg/mL. Inhibition of ergosterol biosynthesis was detected at a concentration of 100 μg/mL of TEO. Morphological evaluation performed by both light microscopy and scanning electron microscopy showed that antifungal activity of TEO could be detected starting at a concentration of 50 μg/mL and the fungicide effect at a concentration of 250 μg/mL. TEO completely inhibited production of both B1 and B2 aflatoxins (AFB1 and AFB2) at a concentration of 150 μg/mL. This way, fungal biomass development and aflatoxin production were dependent on TEO concentration. Therefore, TEO was capable of controlling the growth of A. flavus and its production of aflatoxins.

  16. In vitro inhibitory effects of plant-derived by-products against Cryptosporidium parvum

    PubMed Central

    Teichmann, Klaus; Kuliberda, Maxime; Schatzmayr, Gerd; Pacher, Thomas; Zitterl-Eglseer, Karin; Joachim, Anja; Hadacek, Franz

    2016-01-01

    Disposal of organic plant wastes and by-products from the food or pharmaceutical industries usually involves high costs. In the present study, 42 samples derived from such by-products were screened in vitro against Cryptosporidium parvum, a protozoan parasite that may contaminate drinking water and cause diarrhoea. The novel bioassay was previously established in the microtitre plate format. Human ileocaecal adenocarcinoma (HCT-8) cell cultures were seeded with C. parvum oocysts and parasite development was monitored by an indirect fluorescent antibody technique (IFAT) and microscopic assessment for clusters of secondary infection (CSI). Minimum inhibitory concentrations (MICs) and potential detrimental effects on the host cells were determined. An ethanolic extract from olive (Olea europaea) pomace, after oil pressing and phenol recovery, reproducibly inhibited C. parvum development (MIC = 250–500 μg mL−1, IC50 = 361 (279–438) μg mL−1, IC90 = 467 (398–615) μg mL−1). Accordingly, tyrosol, hydroxytyrosol, trans-coniferyl alcohol and oleuropein were selected as reference test compounds, but their contributions to the observed activity of the olive pomace extract were insignificant. The established test system proved to be a fast and efficient assay for identifying anti-cryptosporidial activities in biological waste material and comparison with selected reference compounds. PMID:27627637

  17. Inhibitory effects of seaweed extracts on the growth of the vaginal bacterium Gardnerella vaginalis.

    PubMed

    Ha, Yu-Mi; Choi, Jae-Suk; Lee, Bo-Bae; Moon, Hye Eun; Cho, Kwang Keun; Choi, In Soon

    2014-05-01

    Of 44 species of seaweed screened for potential anti-Gardnerella vaginalis activity, 27 (61.4%) showed antimicrobial activity by the agar disk-diffusion method. Among them, the strongest activities against the pathogen were exhibited by Chlorophyta, with Ulva pertusa producing an 11.3-mm zone of inhibition at 5 mg disk⁻¹. The MIC values of U. pertusa extracts against both G. vaginalis KCTC 5096 and KCTC 5097, the main cause of vaginosis, were 312 μg ml⁻¹, while the MIC values against both Candida albicans KCTC 7270 and KCTC 7965, the main cause of candidiasis, were 2.5 mg ml⁻¹. Against Lactobacillus gasseri KCTC 3173 and Lactobacillus jensenii KCTC 5194, members of the normal vaginal microflora, no inhibitory effect was seen even at 10 mg ml⁻¹. To identify the primary active compounds, a U. pertusa powder was successively fractionated according to polarity, and the main active agents against G. vaginalis KCTC 5096 were determined to be nitrogenous compounds (156 μg ml⁻¹ of the MIC value). According to these results, it was suggested that extracts of the seaweed U. pertusa are valuable for the development of natural therapeutic agents for treating women with bacterial vaginosis.

  18. Antifungal properties and inhibitory effects upon aflatoxin production of Thymus vulgaris L. by Aspergillus flavus Link.

    PubMed

    Kohiyama, Cássia Yumie; Yamamoto Ribeiro, Milene Mayumi; Mossini, Simone Aparecida Galerani; Bando, Erika; Bomfim, Natália da Silva; Nerilo, Samuel Botião; Rocha, Gustavo Henrique Oliveira; Grespan, Renata; Mikcha, Jane Martha Graton; Machinski, Miguel

    2015-04-15

    The antifungal and antiaflatoxigenic properties of Thymus vulgaris essential oil (TEO) were evaluated upon Aspergillus flavus "in vitro". Suspension containing 10(6) of A. flavus were cultivated with TEO in concentrations ranging from 50 to 500 μg/mL. TEO reached minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) at 250 μg/mL. Inhibition of ergosterol biosynthesis was detected at a concentration of 100 μg/mL of TEO. Morphological evaluation performed by both light microscopy and scanning electron microscopy showed that antifungal activity of TEO could be detected starting at a concentration of 50 μg/mL and the fungicide effect at a concentration of 250 μg/mL. TEO completely inhibited production of both B1 and B2 aflatoxins (AFB1 and AFB2) at a concentration of 150 μg/mL. This way, fungal biomass development and aflatoxin production were dependent on TEO concentration. Therefore, TEO was capable of controlling the growth of A. flavus and its production of aflatoxins. PMID:25466118

  19. A novel polyherbal microbicide with inhibitory effect on bacterial, fungal and viral genital pathogens.

    PubMed

    Talwar, G P; Dar, Sajad A; Rai, Mahendra K; Reddy, K V R; Mitra, Debashis; Kulkarni, Sujata V; Doncel, Gustavo F; Buck, Christopher B; Schiller, John T; Muralidhar, Sumathi; Bala, Manju; Agrawal, S S; Bansal, Kavita; Verma, Jitendra K

    2008-08-01

    A polyherbal cream (Basant) has been formulated using diferuloylmethane (curcumin), purified extracts of Emblica officinalis (Amla), purified saponins from Sapindus mukorossi, Aloe vera and rose water along with pharmacopoeially approved excipients and preservatives. Basant inhibits the growth of WHO strains and clinical isolates of Neisseria gonorrhoeae, including those resistant to penicillin, tetracycline, nalidixic acid and ciprofloxacin. It has pronounced inhibitory action against Candida glabrata, Candida albicans and Candida tropicalis isolated from women with vulvovaginal candidiasis, including three isolates resistant to azole drugs and amphotericin B. Basant displayed a high virucidal action against human immunodeficiency virus HIV-1NL4.3 in CEM-GFP reporter T and P4 (Hela-CD4-LTR-betaGal) cell lines with a 50% effective concentration (EC50) of 1:20000 dilution and nearly complete (98-99%) inhibition at 1:1000 dilution. It also prevented the entry of HIV-1(IIIB) virus into P4-CCR5 cells (EC50 approximately 1:2492). Two ingredients, Aloe and Amla, inhibited the transduction of human papillomavirus type 16 (HPV-16) pseudovirus in HeLa cells at concentrations far below those that are cytotoxic and those used in the formulation. Basant was found to be totally safe according to pre-clinical toxicology carried out on rabbit vagina after application for 7 consecutive days or twice daily for 3 weeks. Basant has the potential of regressing vulvovaginal candidiasis and preventing N. gonorrhoeae, HIV and HPV infections. PMID:18571386

  20. Inhibitory effects of apoptotic cell ingestion upon endotoxin-driven myeloid dendritic cell maturation.

    PubMed

    Stuart, Lynda M; Lucas, Mark; Simpson, Cathy; Lamb, Jonathan; Savill, John; Lacy-Hulbert, Adam

    2002-02-15

    Dendritic cells (DCs) are the sentinels of the immune system, able to interact with both naive and memory T cells. The recent observation that DCs can ingest cells dying by apoptosis has raised the possibility that DCs may, in fact, present self-derived Ags, initiating both autoimmunity and tumor-specific responses, especially if associated with appropriate danger signals. Although the process of ingestion of apoptotic cells has not been shown to induce DC maturation, the exact fate of these phagocytosing DCs remains unclear. In this paper we demonstrate that DCs that ingest apoptotic cells are able to produce TNF-alpha but have a diminished ability to produce IL-12 in response to external stimuli, a property that corresponds to a failure to up-regulate CD86. By single-cell analysis we demonstrate that these inhibitory effects are restricted to those DCs that have engulfed apoptotic cells, with bystander DCs remaining unaffected. These changes were independent of the production of anti-inflammatory cytokines TGF-beta1 and IL-10 and corresponded with a diminished capacity to stimulate naive T cells. Thus, the ingestion of apoptotic cells is not an immunologically null event but is capable of modulating DC maturation. These results have important implications for our understanding of the role of clearance of dying cells by DCs not only in the normal resolution of inflammation but also in control of subsequent immune responses to apoptotic cell-derived Ags.

  1. In vitro inhibitory effects of plant-derived by-products against Cryptosporidium parvum.

    PubMed

    Teichmann, Klaus; Kuliberda, Maxime; Schatzmayr, Gerd; Pacher, Thomas; Zitterl-Eglseer, Karin; Joachim, Anja; Hadacek, Franz

    2016-01-01

    Disposal of organic plant wastes and by-products from the food or pharmaceutical industries usually involves high costs. In the present study, 42 samples derived from such by-products were screened in vitro against Cryptosporidium parvum, a protozoan parasite that may contaminate drinking water and cause diarrhoea. The novel bioassay was previously established in the microtitre plate format. Human ileocaecal adenocarcinoma (HCT-8) cell cultures were seeded with C. parvum oocysts and parasite development was monitored by an indirect fluorescent antibody technique (IFAT) and microscopic assessment for clusters of secondary infection (CSI). Minimum inhibitory concentrations (MICs) and potential detrimental effects on the host cells were determined. An ethanolic extract from olive (Olea europaea) pomace, after oil pressing and phenol recovery, reproducibly inhibited C. parvum development (MIC = 250-500 μg mL(-1), IC50 = 361 (279-438) μg mL(-1), IC90 = 467 (398-615) μg mL(-1)). Accordingly, tyrosol, hydroxytyrosol, trans-coniferyl alcohol and oleuropein were selected as reference test compounds, but their contributions to the observed activity of the olive pomace extract were insignificant. The established test system proved to be a fast and efficient assay for identifying anti-cryptosporidial activities in biological waste material and comparison with selected reference compounds. PMID:27627637

  2. Synthesis of 4-(2-substituted hydrazinyl)benzenesulfonamides and their carbonic anhydrase inhibitory effects.

    PubMed

    Gul, Halise Inci; Kucukoglu, Kaan; Yamali, Cem; Bilginer, Sinan; Yuca, Hafize; Ozturk, Iknur; Taslimi, Parham; Gulcin, Ilhami; Supuran, Claudiu T

    2016-08-01

    In this study, 4-(2-substituted hydrazinyl)benzenesulfonamides were synthesized by microwave irradiation and their chemical structures were confirmed by (1)H NMR, (13)CNMR, and HRMS. Ketones used were: Acetophenone (S1), 4-methylacetophenone (S2), 4-chloroacetophenone (S3), 4-fluoroacetophenone (S4), 4-bromoacetophenone (S5), 4-methoxyacetophenone (S6), 4-nitroacetophenone (S7), 2-acetylthiophene (S8), 2-acetylfuran (S9), 1-indanone (S10), 2-indanone (S11). The compounds S9, S10 and S11 were reported for the first time, while S1-S8 was synthesized by different method than literature reported using microwave irradiation method instead of conventional heating in this study. The inhibitory effects of 4-(2-substituted hydrazinyl)benzenesulfonamide derivatives (S1-S11) against hCA I and II were studied. Cytosolic hCA I and II isoenzymes were potently inhibited by new synthesized sulphonamide derivatives with Kis in the range of 1.79 ± 0.22-2.73 ± 0.08 nM against hCA I and in the range of 1.72 ± 0.58-11.64 ± 5.21 nM against hCA II, respectively.

  3. Inhibitory effect of leonurine on the formation of advanced glycation end products.

    PubMed

    Huang, Lianqi; Yang, Xin; Peng, Anlin; Wang, Hui; Lei, Xiang; Zheng, Ling; Huang, Kun

    2015-02-01

    Long-term hyperglycemia is a typical symptom of diabetes mellitus (DM) which can cause a high level of protein glycation and lead to the formation of advanced glycation end products (AGEs). The accumulation of AGEs in turn deteriorates DM and its complications. Insulin, the only hormone that directly decreases blood sugar in vivo, is vulnerable to glycation which causes the loss of its biological activity. In this study, we used a porcine insulin (PI)-methylglyoxal (MGO) model to investigate the inhibitory effect of leonurine (LN), a natural alkaloid extracted from Herba leonuri, on AGE formation. Assays including AGE-specific fluorescence, and fructosamine level and carbonyl group content determination showed that LN can dose-dependently suppress PI glycation. A significantly decreased cross-linking level on the glycated PI was also proven by SDS-PAGE electrophoresis. A further liquid chromatography-mass spectrometry study suggested that LN may inhibit PI glycation through trapping MGO and keeping it from reacting with PI. Our results thus indicate that LN is a promising anti-glycation agent for the prevention of diabetes and its complications via inhibiting AGE formation.

  4. The inhibitory effects of interleukin-1 on growth hormone action during catabolic illness.

    PubMed

    Cooney, Robert N; Shumate, Margaret

    2006-01-01

    Growth hormone (GH) induces the expression of the anabolic genes responsible for growth, metabolism, and differentiation. Normally, GH stimulates the synthesis of circulating insulin-like growth factor-I (IGF-I) by liver, which upregulates protein synthesis in many tissues. The development of GH resistance during catabolic illness or inflammation contributes to loss of body protein, resulting in multiple complications that prolong recovery and cause death. In septic patients, increased levels of proinflammatory cytokines and GH resistance are commonly observed together. Numerous studies have provided evidence that the inhibitory effects of cytokines on skeletal muscle protein synthesis during sepsis and inflammation are mediated indirectly by changes in the GH/IGF-I system. Interleukin (IL)-1, a member of the family of proinflammatory cytokines, interacts with most cell types and is an important mediator of the inflammatory response. Infusion of a specific IL-1 receptor antagonist (IL-1Ra) ameliorates protein catabolism and GH resistance during systemic infection. This suggests that IL-1 is an important mediator of GH resistance during systemic infection or inflammation. Consequently, a better understanding of the interaction between GH, IL-1, and the regulation of protein metabolism is of great importance for the care of the patient.

  5. Transcriptome analysis of phycocyanin inhibitory effects on SKOV-3 cell proliferation.

    PubMed

    Ying, Jun; Wang, Jian; Ji, Huijuan; Lin, Chaoqing; Pan, Ruowang; Zhou, Li; Song, Yulong; Zhang, Enyong; Ren, Ping; Chen, Jishun; Liu, Qian; Xu, Teng; Yi, Huiguang; Li, Jinsong; Bao, Qiyu; Hu, Yunliang; Li, Peizhen

    2016-07-01

    Phycocyanin (PC) from Spirulina platensis has inhibitory effects on tumor cell growth. In this research, the transcriptome study was designed to investigate the underlying molecular mechanisms of PC inhibition on human ovarian cancer cell SKOV-3 proliferation. The PC IC50 was 216.6μM and 163.8μM for 24h and 48h exposure, respectively, as determined by CCK-8 assay. The morphological changes of SKOV-3 cells after PC exposure were recorded using HE staining. Cells arrested in G2/M stages as determined by flow cytometry. The transcriptome analysis showed that 2031 genes (with > three-fold differences) were differentially expressed between the untreated and the PC-treated cells, including 1065 up-regulated and 966 down-regulated genes. Gene ontology and KEGG pathway analysis identified 18 classical pathways that were remarkably enriched, such as neurotrophin signaling pathway, VEGF signaling pathway and P53 signaling pathway. qPCR results further showed that PTPN12, S100A2, RPL26, and LAMA3 increased while HNRNPA1P10 decreased in PC-treated cells. Molecules and genes in those pathways may be potential targets to develop treatments for ovarian cancer. PMID:26995654

  6. sup 15 NO sub 3 assimilation and its inhibitory effect on symbiotic nitrogen fixation in peanut

    SciTech Connect

    Stanfill, S.B.; Wells, R.; Israel, D.W.; Rufty, T.W. )

    1990-05-01

    To assess the inhibitory effect of nitrate on the contribution of symbiotic N fixation to total plant N, cultivars of different nodulation capacity were monitored in a growth chamber study. Plants inoculated with Bradyrhizobium sp. (Arachis) strain NC 70.1 were grown in a nutrient solution containing 0, 2.5, 5 or 10 mM NO{sub 3} enriched with 2.5 atom % {sup 15}N. Plant harvests at 30 and 60 DAP provided tissue for measurement of growth, total N, NO{sub 3} and {sup 15}N partitioning. Nitrogenase activity was estimated via C{sub 2}H{sub 2} reduction. Data indicates that plant growth was associated to NO{sub 3} concentration. Average nodule weight and N plant{sup {minus}1} decreased in excess of 2.5mM NO{sub 3}. Specific nitrogenase activity diminished markedly with application of NO{sub 3} with a decline from 40.2 to 25.0 {mu}moles C{sub 2}H{sub 2} g hr{sup {minus}1} at 0 and 2.5mM NO{sub 3}, respectively. Nitrate and fixed N assimilation patterns will be elucidated by {sup 15}N analysis.

  7. Inhibitory effects of tetradecanoylphorbol acetate and diacylglycerol on erythropoietin production in human renal carcinoma cell cultures

    SciTech Connect

    Hagiwara, Masamichi; Nagakura, Kazuhiko; Ueno, Munehisa; Fisher, J.W. )

    1987-11-01

    A human renal carcinoma from a patient with an erythrocytosis, serially transplanted into athymic nude mice, was grown in primary monolayer cell cultures. After reaching confluency the cultured cells formed multicellular hemicysts (domes) which became more abundant as the cultures approached saturation density. Erythropoietin (Ep) production by this renal carcinoma in culture was only slightly increased at the time of semiconfluency but showed a marked increase in Ep levels in the culture medium after the cultures reached confluency, in parallel with an increase in dome formation. The phorbol ester tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) showed a significant dose-related inhibitory effect on Ep production and dome formation in the renal carcinoma cell cultures, suggesting an important role of protein kinase C, the only known receptor for TPA, in inhibiting the expression of differentiated phenotypes in the renal carcinoma cells. These studies suggest a role of the inositol-lipid second messenger path and protein kinase C in the regulation of Ep production.

  8. Inhibitory effect of prolactin on Toxoplasma proliferation in peripheral blood mononuclear cells from patients with hyperprolactinemia.

    PubMed

    Dzitko, K; Lawnicka, H; Gatkowska, J; Dziadek, B; Komorowski, J; Długońska, H

    2012-06-01

    Despite many years of studies on the mechanisms of immunological defence responses induced in host organisms by Toxoplasma, no satisfactory immunoprophylaxis or chemotherapy have yet been established for humans. Thus, alternative methods to prevent toxoplasmosis and to enhance the efficacy of currently used antitoxoplasmic drugs are under evaluation. In this work, we strove to determine the influence of human prolactin (endogenous present in serum--sPRL and recombinant--rhPRL) on the course of Toxoplasma infection of peripheral blood mononuclear cells (PBMC) originating from female hyperprolactinemia patients. This study revealed that exogenous rhPRL as well as autologous sPRL from inactivated sera significantly restricted intracellular growth of Toxoplasma in PBMC cultures. Moreover, analysis of IL-10 production by PBMC infected with Toxoplasma and cultured in the presence of sPRL showed a positive correlation between sPRL concentration and the level of IL-10. The obtained results could indicate the possible protective action of PRL in a host organism infected with Toxoplasma and suggest that a significant increase in the serum PRL level, during pregnancy for instance, might significantly limit the risk of Toxoplasma spreading and could play an important role in natural protection against toxoplasmosis. The mechanism of inhibitory effect of PRL needs further detailed study.

  9. Inhibitory control in bilinguals and musicians: event related potential (ERP) evidence for experience-specific effects.

    PubMed

    Moreno, Sylvain; Wodniecka, Zofia; Tays, William; Alain, Claude; Bialystok, Ellen

    2014-01-01

    Bilinguals and musicians exhibit behavioral advantages on tasks with high demands on executive functioning, particularly inhibitory control, but the brain mechanisms supporting these differences are unclear. Of key interest is whether these forms of experience influence cognition through similar or distinct information processing mechanisms. Here, we recorded event-related potentials (ERPs) in three groups - bilinguals, musicians, and controls - who completed a visual go-nogo task that involved the withholding of key presses to rare targets. Participants in each group achieved similar accuracy rates and responses times but the analysis of cortical responses revealed significant differences in ERP waveforms. Success in withholding a prepotent response was associated with enhanced stimulus-locked N2 and P3 wave amplitude relative to go trials. For nogo trials, there were altered timing-specific ERP differences and graded amplitude differences observed in the neural responses across groups. Specifically, musicians showed an enhanced early P2 response accompanied by reduced N2 amplitude whereas bilinguals showed increased N2 amplitude coupled with an increased late positivity wave relative to controls. These findings demonstrate that bilingualism and music training have differential effects on the brain networks supporting executive control over behavior.

  10. Inhibitory Control in Bilinguals and Musicians: Event Related Potential (ERP) Evidence for Experience-Specific Effects

    PubMed Central

    Moreno, Sylvain; Wodniecka, Zofia; Tays, William; Alain, Claude; Bialystok, Ellen

    2014-01-01

    Bilinguals and musicians exhibit behavioral advantages on tasks with high demands on executive functioning, particularly inhibitory control, but the brain mechanisms supporting these differences are unclear. Of key interest is whether these forms of experience influence cognition through similar or distinct information processing mechanisms. Here, we recorded event-related potentials (ERPs) in three groups – bilinguals, musicians, and controls – who completed a visual go-nogo task that involved the withholding of key presses to rare targets. Participants in each group achieved similar accuracy rates and responses times but the analysis of cortical responses revealed significant differences in ERP waveforms. Success in withholding a prepotent response was associated with enhanced stimulus-locked N2 and P3 wave amplitude relative to go trials. For nogo trials, there were altered timing-specific ERP differences and graded amplitude differences observed in the neural responses across groups. Specifically, musicians showed an enhanced early P2 response accompanied by reduced N2 amplitude whereas bilinguals showed increased N2 amplitude coupled with an increased late positivity wave relative to controls. These findings demonstrate that bilingualism and music training have differential effects on the brain networks supporting executive control over behavior. PMID:24743321

  11. Lanostane Triterpenes from the Tibetan Medicinal Mushroom Ganoderma leucocontextum and Their Inhibitory Effects on HMG-CoA Reductase and α-Glucosidase.

    PubMed

    Wang, Kai; Bao, Li; Xiong, Weiping; Ma, Ke; Han, Junjie; Wang, Wenzhao; Yin, Wenbing; Liu, Hongwei

    2015-08-28

    Sixteen new lanostane triterpenes, ganoleucoins A-P (1-16), together with 10 known tripterpenes (17-26), were isolated from the cultivated fruiting bodies of Ganoderma leucocontextum, a new member of the Ganoderma lucidum complex. The structures of the new compounds were elucidated by extensive spectroscopic analysis and chemical transformation. The inhibitory effects of 1-26 on HMG-CoA reductase and α-glucosidase were tested in vitro. Compounds 1, 3, 6, 10-14, 17, 18, 23, 25, and 26 showed much stronger inhibitory activity against HMG-CoA reductase than the positive control atorvastatin. Compounds 13, 14, and 16 presented potent inhibitory activity against α-glucosidase from yeast with IC₅₀ values of 13.6, 2.5, and 5.9 μM, respectively. In addition, the cytotoxicity of 1-26 was evaluated against the K562 and PC-3 cell lines by the MTT assay. Compounds 1, 2, 6, 7, 10, 12, 16, 18, and 25 exhibited cytotoxicity against K562 cells with IC₅₀ values in the range 10-20 μM. Paclitaxel was used as the positive control with an IC₅₀ value of 0.9 μM. This is the first report of secondary metabolites from this medicinal mushroom.

  12. Sodium phenylacetate enhances the inhibitory effect of dextran derivative on breast cancer cell growth in vitro and in nude mice.

    PubMed

    Di Benedetto, M; Kourbali, Y; Starzec, A; Vassy, R; Jozefonvicz, J; Perret, G; Crepin, M; Kraemer, M

    2001-09-14

    Sodium phenylacetate (NaPa) and carboxymethyl benzylamide dextran derivative (CMDB(LS4)) are able to inhibit growth of breast tumour cells. In this study, we explored whether the combination of NaPa and CMDB(LS4)may enhance their respective inhibitory effects on the MCF-7ras cell growth in vitro and in vivo. NaPa inhibited MCF-7ras cell proliferation by reducing the DNA replication concomitantly with a recruitment of cells in G0/G1 phase and by inducing apoptosis in a dose- and time-dependent manner. The addition of CMDB(LS4)potentiated the NaPa antiproliferative effect in the manner dependent on the ratio of CMDB(LS4)and NaPa concentrations. In nude mice, CMDB(LS4)(150 mg kg(-1)) or NaPa (40 mg kg(-1)) administrated twice a week, for 7 weeks inhibited MCF-7ras xenograft growth by 40% and 60%, respectively. The treatment by both, CMDB(LS4)and NaPa, decreased tumour growth by 83% without any toxicity. To better understand the mechanism of NaPa and CMDB(LS4)action we assessed their effect on mitogenic activity of MCF-7ras conditioned medium (CM) on BALBC/3T3 fibroblasts. CMDB(LS4)added to the CM, inhibited its mitogenic activity whereas NaPa had an anti-mitogenic effect when CM was prepared from MCF-7ras cells pretreated with NaPa. Thus, the antiproliferative effects of NaPa and CMDB(LS4)involve 2 different mechanisms explaining, at least in part, the possible synergism between them. Overall, this study points to the potential use of a combination of dextran derivatives with NaPa to inhibit the breast tumour growth.

  13. Sodium phenylacetate enhances the inhibitory effect of dextran derivative on breast cancer cell growth in vitro and in nude mice

    PubMed Central

    Benedetto, M Di; Kourbali, Y; Starzec, A; Vassy, R; Jozefonvicz, J; Perret, G; Crepin, M; Kraemer, M

    2001-01-01

    Sodium phenylacetate (NaPa) and carboxymethyl benzylamide dextran derivative (CMDBLS4) are able to inhibit growth of breast tumour cells. In this study, we explored whether the combination of NaPa and CMDBLS4 may enhance their respective inhibitory effects on the MCF-7ras cell growth in vitro and in vivo. NaPa inhibited MCF-7ras cell proliferation by reducing the DNA replication concomitantly with a recruitment of cells in G0/G1 phase and by inducing apoptosis in a dose- and time-dependent manner. The addition of CMDBLS4 potentiated the NaPa antiproliferative effect in the manner dependent on the ratio of CMDBLS4 and NaPa concentrations. In nude mice, CMDBLS4 (150 mg kg−1) or NaPa (40 mg kg−1) administrated twice a week, for 7 weeks inhibited MCF-7ras xenograft growth by 40% and 60%, respectively. The treatment by both, CMDBLS4 and NaPa, decreased tumour growth by 83% without any toxicity. To better understand the mechanism of NaPa and CMDBLS4 action we assessed their effect on mitogenic activity of MCF-7ras conditioned medium (CM) on BALBC/3T3 fibroblasts. CMDBLS4 added to the CM, inhibited its mitogenic activity whereas NaPa had an anti-mitogenic effect when CM was prepared from MCF-7ras cells pretreated with NaPa. Thus, the antiproliferative effects of NaPa and CMDBLS4 involve 2 different mechanisms explaining, at least in part, the possible synergism between them. Overall, this study points to the potential use of a combination of dextran derivatives with NaPa to inhibit the breast tumour growth. © 2001 Cancer Research Campaignhttp://www.bjcancer.com PMID:11556846

  14. Inhibitory effect of benzene metabolites on nuclear DNA synthesis in bone marrow cells

    SciTech Connect

    Lee, E.W.; Johnson, J.T.; Garner, C.D. )

    1989-01-01

    Effects of endogenously produced and exogenously added benzene metabolites on the nuclear DNA synthetic activity were investigated using a culture system of mouse bone marrow cells. Effects of the metabolites were evaluated by a 30-min incorporation of ({sup 3}H)thymidine into DNA following a 30-min interaction with the cells in McCoy's 5a medium with 10% fetal calf serum. Phenol and muconic acid did not inhibit nuclear DNA synthesis. However, catechol, 1,2,4-benzenetriol, hydroquinone, and p-benzoquinone were able to inhibit 52, 64, 79, and 98% of the nuclear DNA synthetic activity, respectively, at 24 {mu}M. In a cell-free DNA synthetic system, catechol and hydroquinone did not inhibit the incorporation of ({sup 3}H)thymidine triphosphate into DNA up to 24 {mu}M but 1,2,4-benzenetriol and p-benzoquinone did. The effect of the latter two benzene metabolites was completely blocked in the presence of 1,4-dithiothreitol (1 mM) in the cell-free assay system. Furthermore, when DNA polymerase {alpha}, which requires a sulfhydryl (SH) group as an active site, was replaced by DNA polymerase 1, which does not require an SH group for its catalytic activity, p-benzoquinone and 1,2,4-benzenetriol were unable to inhibit DNA synthesis. Thus, the data imply the p-benzoquinone and 1,2,4-benzenetriol inhibited DNA polymerase {alpha}, consequently resulting in inhibition of DNA synthesis in both cellular and cell-free DNA synthetic systems. The present study identifies catechol, hydroquinone, p-benzoquinone, and 1,2,4-benzenetriol as toxic benzene metabolites in bone marrow cells and also suggests that their inhibitory action on DNA synthesis is mediated by mechanism(s) other than that involving DNA damage as a primary cause.

  15. The effect of aging on fronto-striatal reactive and proactive inhibitory control.

    PubMed

    Kleerekooper, Iris; van Rooij, Sanne J H; van den Wildenberg, Wery P M; de Leeuw, Max; Kahn, Rene S; Vink, Matthijs

    2016-05-15

    Inhibitory control, like most cognitive processes, is subject to an age-related decline. The effect of age on neurofunctional inhibition processing remains uncertain, with age-related increases as well as decreases in activation being reported. This is possibly because reactive (i.e., outright stopping) and proactive inhibition (i.e., anticipation of stopping) have not been evaluated separately. Here, we investigate the effects of aging on reactive as well as proactive inhibition, using functional MRI in 73 healthy subjects aged 30-70years. We found reactive inhibition to slow down with advancing age, which was paralleled by increased activation in the motor cortex. Behaviorally, older adults did not exercise increased proactive inhibition strategies compared to younger adults. However, the pattern of activation in the right inferior frontal gyrus (rIFG) showed a clear age-effect on proactive inhibition: rather than flexibly engaging the rIFG in response to varying stop-signal probabilities, older subjects showed an overall hyperactivation. Whole-brain analyses revealed similar hyperactivations in various other frontal and parietal brain regions. These results are in line with the neural compensation hypothesis of aging: processing becomes less flexible and efficient with advancing age, which is compensated for by overall enhanced activation. Moreover, by disentangling reactive and proactive inhibition, we can show for the first time that the age-related increase in activation during inhibition that is reported generally by prior studies may be the result of compensation for reduced neural flexibility related to proactive control strategies. PMID:26899783

  16. Inhibitory effect of CuSO₄ on α-glucosidase activity in ddY mice.

    PubMed

    Yoshikawa, Yutaka; Hirata, Ryoko; Yasui, Hiroyuki; Hattori, Masakazu; Sakurai, Hiromu

    2010-01-01

    We investigated the effects of divalent alkaline earth and first-row transition metal and zinc ions on α-glucosidase activity in vitro and in vivo. CuSO₄ and ZnSO₄ exhibited a high α-glucosidase inhibitory effect in vitro. The IC(50) values of CuSO₄ were 0.77 ± 0.01 (substrate; maltose) and 0.78 ± 0.01 (substrate; sucrose), and those of ZnSO₄ were 5.49 ± 0.14 (substrate; maltose) and 4.70 ± 0.06 (substrate; sucrose) for yeast α-glucosidase. On the basis of Lineweaver-Burk plots, both CuSO₄ and ZnSO₄ exhibited different modes of inhibition against α-glucosidase. Subsequently, oral glucose and sucrose tolerance tests (OGTT and OSTT) were performed on non-diabetic ddY mice to examine the effect of the metal ions on their blood glucose levels. As a result of single oral administration of CuSO₄ in non-diabetic ddY mice, a significant and potent lowering of the blood glycemic response toward disaccharide, sucrose, ingestion was observed at 45 min after doses of 0.08 and 0.24 mmol kg(-1) body weight. In contrast, the CuSO₄ administration showed no suppression of the elevation of blood glucose levels in mice after a monosaccharide, glucose, administration. These results indicate that CuSO₄ suppresses disaccharide digestion by inhibiting α-glucosidase activity in the epithelium of the small intestine, suggesting that antidiabetic Cu complexes with some ligands have a similar action mechanism to that of α-glucosidase inhibitor, acarbose, currently used for clinical purposes. PMID:21072376

  17. CYP450 Enzyme-Mediated Metabolism of TCAS and Its Inhibitory and Induced Effects on Metabolized Enzymes in Vitro.

    PubMed

    Shen, Guolin; Wang, Cheng; Zhou, Lili; Li, Lei; Chen, Huiming; Yu, Wenlian; Li, Haishan

    2015-09-02

    In this study, we investigated the enzymes catalyzing the phase I metabolism of thiacalixarene (TCAS) based on in vitro system including cDNA-expressed P450 enzymes, human liver microsomes plus inhibitors and monoclonal antibodies. In addition, the inhibitory potential of TCAS on major CYP450 drug metabolizing enzymes (CYP1A2, CYP2C9, CYP2B6, CYP2D6 and CYP3A4) was assessed. The results showed that CYP1A2 and CYP2C9 mediated TCAS hydroxylation. IC50 values for TCAS in rat and human liver microsomes were greater than 50 µM, and it demonstrated a weak inhibition of rat and human CYP450 enzymes. Finally, sandwiched hepatocytes were used to evaluate the induction of CYP1A and CYP3A to define the function of TCAS in vivo. The results showed that incubation of TCAS at different concentrations for 72 h failed to induce CYP1A and CYP3A. However, incubation of the cells with 50 and 100 µM TCAS caused a profound decrease in the activities of CYP1A and CYP3A, which was probably due to cytotoxic effects, suggesting that exposure to TCAS might be a health concern.

  18. Inhibitory Effect of Biocides on the Viable Masses and Matrices of Staphylococcus aureus and Pseudomonas aeruginosa Biofilms▿

    PubMed Central

    Toté, K.; Horemans, T.; Berghe, D. Vanden; Maes, L.; Cos, P.

    2010-01-01

    Bacteria and matrix are essential for the development of biofilms, and assays should therefore target both components. The current European guidelines for biocidal efficacy testing are not adequate for sessile microorganisms; hence, alternative discriminatory test protocols should be used. The activities of a broad range of biocides on Staphylococcus aureus and Pseudomonas aeruginosa biofilms were evaluated using such in vitro assays. Nearly all selected biocides showed a significant decrease in S. aureus biofilm viability, with sodium hypochlorite and peracetic acid as the most active biocides. Only hydrogen peroxide and sodium hypochlorite showed some inhibitory effect on the matrix. Treatment of P. aeruginosa biofilms was roughly comparable to that of S. aureus biofilms. Peracetic acid was the most active on viable mass within 1 min of contact. Isopropanol ensured a greater than 99.999% reduction of P. aeruginosa viability after at least 30 min of contact. Comparable to results with S. aureus, sodium hypochlorite and hydrogen peroxide markedly reduced the P. aeruginosa matrix. This study clearly demonstrated that despite their aspecific mechanisms of action, most biocides were active only against biofilm bacteria, leaving the matrix undisturbed. Only hydrogen peroxide and sodium hypochlorite were active on both the biofilm matrix and the viable mass, making them the better antibiofilm agents. In addition, this study emphasizes the need for updated and standardized guidelines for biofilm susceptibility testing of biocides. PMID:20363795

  19. CYP450 Enzyme-Mediated Metabolism of TCAS and Its Inhibitory and Induced Effects on Metabolized Enzymes in Vitro

    PubMed Central

    Shen, Guolin; Wang, Cheng; Zhou, Lili; Li, Lei; Chen, Huiming; Yu, Wenlian; Li, Haishan

    2015-01-01

    In this study, we investigated the enzymes catalyzing the phaseⅠmetabolism of thiacalixarene (TCAS) based on in vitro system including cDNA-expressed P450 enzymes, human liver microsomes plus inhibitors and monoclonal antibodies. In addition, the inhibitory potential of TCAS on major CYP450 drug metabolizing enzymes (CYP1A2, CYP2C9, CYP2B6, CYP2D6 and CYP3A4) was assessed. The results showed that CYP1A2 and CYP2C9 mediated TCAS hydroxylation. IC50 values for TCAS in rat and human liver microsomes were greater than 50 µM, and it demonstrated a weak inhibition of rat and human CYP450 enzymes. Finally, sandwiched hepatocytes were used to evaluate the induction of CYP1A and CYP3A to define the function of TCAS in vivo. The results showed that incubation of TCAS at different concentrations for 72 h failed to induce CYP1A and CYP3A. However, incubation of the cells with 50 and 100 µM TCAS caused a profound decrease in the activities of CYP1A and CYP3A, which was probably due to cytotoxic effects, suggesting that exposure to TCAS might be a health concern. PMID:26404338

  20. Establishing equivalence for microbial-growth-inhibitory effects ("iso-hurdle rules") by analyzing disparate listeria monocytogenes data with a gamma-type predictive model.

    PubMed

    Pujol, Laure; Kan-King-Yu, Denis; Le Marc, Yvan; Johnston, Moira D; Rama-Heuzard, Florence; Guillou, Sandrine; McClure, Peter; Membré, Jeanne-Marie

    2012-02-01

    Preservative factors act as hurdles against microorganisms by inhibiting their growth; these are essential control measures for particular food-borne pathogens. Different combinations of hurdles can be quantified and compared to each other in terms of their inhibitory effect ("iso-hurdle"). We present here a methodology for establishing microbial iso-hurdle rules in three steps: (i) developing a predictive model based on existing but disparate data sets, (ii) building an experimental design focused on the iso-hurdles using the model output, and (iii) validating the model and the iso-hurdle rules with new data. The methodology is illustrated with Listeria monocytogenes. Existing data from industry, a public database, and the literature were collected and analyzed, after which a total of 650 growth rates were retained. A gamma-type model was developed for the factors temperature, pH, a(w), and acetic, lactic, and sorbic acids. Three iso-hurdle rules were assessed (40 logcount curves generated): salt replacement by addition of organic acids, sorbic acid replacement by addition of acetic and lactic acid, and sorbic acid replacement by addition of lactic/acetic acid and salt. For the three rules, the growth rates were equivalent in the whole experimental domain (γ from 0.1 to 0.5). The lag times were also equivalent in the case of mild inhibitory conditions (γ ≥ 0.2), while they were longer in the presence of salt than acids under stress conditions (γ < 0.2). This methodology allows an assessment of the equivalence of inhibitory effects without intensive data generation; it could be applied to develop milder formulations which guarantee microbial safety and stability.

  1. Mycobacterium-Specific γ9δ2 T Cells Mediate Both Pathogen-Inhibitory and CD40 Ligand-Dependent Antigen Presentation Effects Important for Tuberculosis Immunity.

    PubMed

    Abate, Getahun; Spencer, Charles T; Hamzabegovic, Fahreta; Blazevic, Azra; Xia, Mei; Hoft, Daniel F

    2016-02-01

    Numerous pathogens, including Mycobacterium tuberculosis, can activate human γ9δ2 T cells to proliferate and express effector mechanisms. γ9δ2 T cells can directly inhibit the growth of intracellular mycobacteria and may also act as antigen-presenting cells (APC). Despite evidence for γδ T cells having the capacity to function as APC, the mechanisms involved and importance of these effects on overall tuberculosis (TB) immunity are unknown. We prepared M. tuberculosis-specific γ9δ2 T cell lines to study their direct protective effects and APC functions for M. tuberculosis-specific αβ T cells. The direct inhibitory effects on intracellular mycobacteria were measured, and the enhancing effects on proliferative and effector responses of αβ T cells assessed. Furthermore, the importance of cell-to-cell contact and soluble products for γ9δ2 T cell effector responses and APC functions were investigated. We demonstrate, in addition to direct inhibitory effects on intracellular mycobacteria, the following: (i) γ9δ2 T cells enhance the expansion of M. tuberculosis-specific αβ T cells and increase the ability of αβ T cells to inhibit intracellular mycobacteria; (ii) although soluble mediators are critical for the direct inhibitory effects of γ9δ2 T cells, their APC functions do not require soluble mediators; (iii) the APC functions of γ9δ2 T cells involve cell-to-cell contact that is dependent on CD40-CD40 ligand (CD40L) interactions; and (iv) fully activated CD4(+) αβ T cells and γ9δ2 T cells provide similar immune enhancing/APC functions for M. tuberculosis-specific T cells. These effector and helper effects of γ9δ2 T cells further indicate that these T cells should be considered important new targets for new TB vaccines.

  2. Implementation of Complexity Analyzing Based on Additional Effect

    NASA Astrophysics Data System (ADS)

    Zhang, Peng; Li, Na; Liang, Yanhong; Liu, Fang

    According to the Complexity Theory, there is complexity in the system when the functional requirement is not be satisfied. There are several study performances for Complexity Theory based on Axiomatic Design. However, they focus on reducing the complexity in their study and no one focus on method of analyzing the complexity in the system. Therefore, this paper put forth a method of analyzing the complexity which is sought to make up the deficiency of the researches. In order to discussing the method of analyzing the complexity based on additional effect, this paper put forth two concepts which are ideal effect and additional effect. The method of analyzing complexity based on additional effect combines Complexity Theory with Theory of Inventive Problem Solving (TRIZ). It is helpful for designers to analyze the complexity by using additional effect. A case study shows the application of the process.

  3. Effect of additives on the purification of urease

    NASA Astrophysics Data System (ADS)

    Yu, X.; Wang, J.; Ulrich, J.

    2015-12-01

    The effect of additives on the purification of proteins was investigated. The target protein studied here is the enzyme urease. Studies on the purification of urease from jack bean meal were carried out. 32% (v/v) acetone was utilized to extract urease from the jack bean meal. Further purification by crystallization with the addition of 2-mercaptoethanol and EDTA disodium salt dehydrate was carried out. It was found out that the presence of additives can affect the selectivity of the crystallization. Increases in both purity and yield of the urease after crystallization were observed in the presence of additives, which were proven using both SDS-PAGE and activity. Urease crystals with a yield of 69.9% and a purity of 85.1% were obtained in one crystallization step in the presence of additives. Furthermore, the effect of additives on the thermodynamics and kinetics of urease crystallization was studied.

  4. Inhibitory effect of emodin and Astragalus polysaccharide on the replication of HBV

    PubMed Central

    Dang, Shuang-Suo; Jia, Xiao-Li; Song, Ping; Cheng, Yan-An; Zhang, Xin; Sun, Ming-Zhu; Liu, En-Qi

    2009-01-01

    AIM: To evaluate the anti-viral effect of emodin plus Astragalus polysaccharide (APS) in hepatitis B virus (HBV) transgenic mice. METHODS: Sixty HBV transgenic mice (HBV TGM) whose weight varied between 18 and 24 g were randomly divided into 3 groups, with 20 mice in each group. Group A was the normal control, where the mice were treated with physiological saline; group B was the positive control where the mice were treated with lamivudine solution (100 mL/kg per day). Group C was the experimental group where the mice were treated with physiological saline containing emodin and APS (57.59 mg/kg per day and 287.95 mg/kg per day, respectively). The mice were treated daily for 3 wk. After 1 wk recovery time, the mice were sacrificed and serum as well as liver tissues were collected for ELISA and histological examination. RESULTS: After 21 d treatment, HBV DNA levels in group B and group C significantly declined when compared with group A (P < 0.05). However, a significant increase in HBV DNA content was observed in group B, whereas this phenomenon was not observed in group C. A reduction in the contents of HBsAg, HBeAg and HBcAg in the mice from group B and C was observed when compared with group A. CONCLUSION: Emodin and APS have a weak but persistent inhibitory effect on HBV replication in vivo, which may function as a supplementary modality in the treatment of hepatitis B infection. PMID:19960563

  5. Extracellular vesicles from malignant effusions induce tumor cell migration: inhibitory effect of LMWH tinzaparin.

    PubMed

    Gamperl, Hans; Plattfaut, Corinna; Freund, Annika; Quecke, Tabea; Theophil, Friederike; Gieseler, Frank

    2016-10-01

    Elevated levels of extracellular vesicles (EVs) have been correlated with inflammatory diseases as well as progressive and metastatic cancer. By presenting tissue factor (TF) on their membrane surface, cellular microparticles (MPs) activate both the coagulation system and cell-signaling pathways such as the PAR/ERK pathway. We have shown before that malignant effusions are a rich source of tumor cell-derived EVs. Here, we used EVs from malignant effusions from three different patients after serial low-speed centrifugation steps as recommended by the ISTH (lsEV). Significant migration of human pancreatic carcinoma cells could be induced by lsEVs and was effectively inhibited by pre-incubation with tinzaparin, a low-molecular-weight heparin. Tinzaparin induced tissue factor pathway inhibitor (TFPI) release from tumor cells, and recombinant TFPI inhibited EV-induced tumor cell migration. EVs also induced ERK phosphorylation, whereas inhibitors of PAR2 and ERK suppressed EV-induced tumor cell migration. LsEVs have been characterized by high-resolution flow cytometry and, after elimination of smaller vesicles including exosomes, by further high-speed centrifugation (hsEV). The remaining population consisting primarily of MPs is indeed the main migration-inducing population with tenase activity. Compared to other LMWHs, tinzaparin is suggested to have high potency to induce TFPI release from epithelial cells. The migration-inhibitory effect of TFPI and the interruption of tumor cell migration by inhibitors of PAR2 and ERK suggest that lsEVs induce tumor cell migration by activating the PAR2 signaling pathway. Tinzaparin might inhibit this process at least partly by inducing the release of TFPI from tumor cells, which blocks PAR-activating TF complexes. The clinical relevance of the results is discussed.

  6. Inhibitory effects of regorafenib, a multiple tyrosine kinase inhibitor, on corneal neovascularization

    PubMed Central

    Onder, Halil Ibrahim; Erdurmus, Mesut; Bucak, Yasin Yücel; Simavli, Hüseyin; Oktay, Murat; Kukner, Ahmet Sahap

    2014-01-01

    AIM To evaluate the inhibitory effects of regorafenib (BAY 73-4506), a multikinase inhibitor, on corneal neovascularization (NV). METHODS Thirty adult male Sprague-Dawley rats weighing 250-300 g, were used. Corneal NV was induced by NaOH in the left eyes of each rat. Following the establishment of alkali burn, the animals were randomized into five groups according to topical treatment. Group 1 (n = 6) received 0.9% NaCl, Group 2 (n = 6) received dimethyl sulfoxide, Group 3 (n = 6) received regorafenib 1 mg/mL, Group 4 (n =6) received bevacizumab 5 mg/mL and Group 5 (n = 6) received 0.1% dexamethasone phosphate. On the 7d, the corneal surface covered with neovascular vessels was measured on photographs as the percentage of the cornea's total area using computer-imaging analysis. The corneas obtained from rats were semiquantitatively evaluated for caspase-3 and vascular endothelial growth factor by immunostaining. RESULTS A statistically significant difference in the percent area of corneal NV was found among the groups (P <0.001). Although the Group 5 had the smallest percent area of corneal NV, there was no difference among Groups 3, 4 and 5 (P >0.005). There was a statistically significant difference among the groups in apoptotic cell density (P = 0.002). The staining intensity of vascular endothelial growth factor in the epithelial and endothelial layers of cornea was significantly different among the groups (P <0.05). The staining intensity of epithelial and endothelial vascular endothelial growth factor was significantly weaker in Groups 3, 4 and 5 than in Groups 1 and 2. CONCLUSION Topical administration of regorafenib 1 mg/mL is partly effective for preventing alkali-induced corneal NV in rats. PMID:24790861

  7. Inhibitory Effect of Endostar on Specific Angiogenesis Induced by Human Hepatocellular Carcinoma

    PubMed Central

    Ye, Qing; Qin, Shukui; Liu, Yanhong; Feng, Jundong; Wu, Qiong; Qu, Wenshu; Yin, Xiaojin

    2015-01-01

    To investigate the effect of endostar on specific angiogenesis induced by human hepatocellular carcinoma, this research systematically elucidated the inhibitory effect on HepG2-induced angiogenesis by endostar from 50 ng/mL to 50000 ng/mL. We employed fluorescence quantitative Boyden chamber analysis, wound-healing assay, flow cytometry examination using a coculture system, quantitative analysis of tube formation, and in vivo Matrigel plug assay induced by HCC conditioned media (HCM) and HepG2 compared with normal hepatocyte conditioned media (NCM) and L02. Then, we found that endostar as a tumor angiogenesis inhibitor could potently inhibit human umbilical vein endothelial cell (HUVEC) migration in response to HCM after four- to six-hour action, inhibit HCM-induced HUVEC migration to the lesion part in a dose-dependent manner between 50 ng/mL and 5000 ng/mL at 24 hours, and reduce HUVEC proliferation in a dose-dependent fashion. Endostar inhibited HepG2-induced tube formation of HUVECs which peaked at 50 ng/mL. In vivo Matrigel plug formation was also significantly reduced by endostar in HepG2 inducing system rather than in L02 inducing system. It could be concluded that, at cell level, endostar inhibited the angiogenesis-related biological behaviors of HUVEC in response to HCC, including migration, adhesion proliferation, and tube formation. At animal level, endostar inhibited the angiogenesis in response to HCC in Matrigel matrix. PMID:25983751

  8. Inhibitory effects of docosyl p-coumarate on DNA topoisomerase activity and human cancer cell growth.

    PubMed

    Mizushina, Yoshiyuki; Nishimura, Katsumi; Takenaka, Yukiko; Takeuchi, Toshifumi; Sugawara, Fumio; Yoshida, Hiromi; Tanahashi, Takao

    2010-10-01

    We previously found six compounds of alkyl p-coumarates from a composite plant Artemisia annua L., and chemically synthesized these compounds (cis-isomer of C20, C22 and C24, and trans-isomer of C20, C22 and C24 of p-coumarates are compounds 1-6, respectively). This report describes the inhibitory activities of these alkyl p-coumarates against DNA polymerase (pol), DNA topoisomerase (topo), and human cancer cell growth. Among the compounds tested, compounds 1 and 4 weakly inhibited repair-related pol beta activity, but no compound influenced the activity of replicative pol alpha. Compounds 4-6 and compounds 2 and 5 were potent inhibitors of human topos I and II, respectively. Compounds 2, 4, 5 and 6 also suppressed the growth of human colon carcinoma cell line, HCT116, with or without p53, suggesting that cell growth inhibition had the same tendency as the inhibition of topos rather than pols. Compound 5 (docosyl p-coumarate), which was the strongest inhibitor of topo II and cancer cell growth in the compounds tested, halted HCT116 p53(+/+) cells in G2/M phases, and induced apoptosis, although this compound did not affect the cell cycle of HCT116 p53(-/-) cells. These results suggest that the effect of p53-dependent cell cycle arrest may be effective for topo inhibition by com-pound 5. From these findings, the action mode of alkyl p-coumarates as an anti-cancer agent is discussed. PMID:20811721

  9. Extracellular vesicles from malignant effusions induce tumor cell migration: inhibitory effect of LMWH tinzaparin.

    PubMed

    Gamperl, Hans; Plattfaut, Corinna; Freund, Annika; Quecke, Tabea; Theophil, Friederike; Gieseler, Frank

    2016-10-01

    Elevated levels of extracellular vesicles (EVs) have been correlated with inflammatory diseases as well as progressive and metastatic cancer. By presenting tissue factor (TF) on their membrane surface, cellular microparticles (MPs) activate both the coagulation system and cell-signaling pathways such as the PAR/ERK pathway. We have shown before that malignant effusions are a rich source of tumor cell-derived EVs. Here, we used EVs from malignant effusions from three different patients after serial low-speed centrifugation steps as recommended by the ISTH (lsEV). Significant migration of human pancreatic carcinoma cells could be induced by lsEVs and was effectively inhibited by pre-incubation with tinzaparin, a low-molecular-weight heparin. Tinzaparin induced tissue factor pathway inhibitor (TFPI) release from tumor cells, and recombinant TFPI inhibited EV-induced tumor cell migration. EVs also induced ERK phosphorylation, whereas inhibitors of PAR2 and ERK suppressed EV-induced tumor cell migration. LsEVs have been characterized by high-resolution flow cytometry and, after elimination of smaller vesicles including exosomes, by further high-speed centrifugation (hsEV). The remaining population consisting primarily of MPs is indeed the main migration-inducing population with tenase activity. Compared to other LMWHs, tinzaparin is suggested to have high potency to induce TFPI release from epithelial cells. The migration-inhibitory effect of TFPI and the interruption of tumor cell migration by inhibitors of PAR2 and ERK suggest that lsEVs induce tumor cell migration by activating the PAR2 signaling pathway. Tinzaparin might inhibit this process at least partly by inducing the release of TFPI from tumor cells, which blocks PAR-activating TF complexes. The clinical relevance of the results is discussed. PMID:27435911

  10. Lipase inhibition attenuates the acute inhibitory effects of oral fat on food intake in healthy subjects.

    PubMed

    O'Donovan, Deirdre; Feinle-Bisset, Christine; Wishart, Judith; Horowitz, Michael

    2003-11-01

    The lipase inhibitor, orlistat, is used in the treatment of obesity and reduces fat absorption by about 30%. However, the mean weight loss induced by orlistat is less than expected for the degree of fat malabsorption. It was hypothesised that lipase inhibition with orlistat attenuates the suppressive effects of oral fat on subsequent energy intake in normal-weight subjects. Fourteen healthy, lean subjects (nine males, five females; aged 25 +/- 1.3 years) were studied twice, in a double-blind fashion. The subjects received a high-fat yoghurt 'preload' (males 400 g (2562 kJ); females 300 g (1923 kJ)), containing orlistat (120 mg) on one study day (and no orlistat on the other 'control' day), 30 min before ad libitum access to food and drinks; energy intake was assessed during the following 8 h. Blood samples were taken at regular intervals for the measurement of plasma cholecystokinin (CCK). Each subject performed a 3 d faecal fat collection following each study. Energy intake during the day was greater following orlistat (10,220 (SEM 928) kJ) v. control (9405 (SEM 824) kJ) (P=0.02). On both days plasma CCK increased (P<0.05) after the preload. Plasma CCK 20 min following ingestion of the preload was less after orlistat (4.1 (SEM 0.9) pmol/l) v. control (5.3 (SEM 0.9) pmol/l (P=0.028); however there was no difference in the area under the curve 0-510 min between the two study days. Fat excretion was greater following orlistat (1017 (SEM 168) kJ) v. control (484 (SEM 90) kJ) (P=0.004). In conclusion, in healthy, lean subjects the acute inhibitory effect of fat on subsequent energy intake is attenuated by orlistat and the increase in energy intake approximates the energy lost due to fat malabsorption. PMID:14667178

  11. Molecular Understanding of Growth Inhibitory Effect from Irradiated to Bystander Tumor Cells in Mouse Fibrosarcoma Tumor Model.

    PubMed

    Desai, Sejal; Srambikkal, Nishad; Yadav, Hansa D; Shetake, Neena; Balla, Murali M S; Kumar, Amit; Ray, Pritha; Ghosh, Anu; Pandey, B N

    2016-01-01

    Even though bystander effects pertaining to radiation risk assessment has been extensively studied, the molecular players of radiation induced bystander effect (RIBE) in the context of cancer radiotherapy are poorly known. In this regard, the present study is aimed to investigate the effect of irradiated tumor cells on the bystander counterparts in mouse fibrosarcoma (WEHI 164 cells) tumor model. Mice co-implanted with WEHI 164 cells γ-irradiated with a lethal dose of 15 Gy and unirradiated (bystander) WEHI 164 cells showed inhibited tumor growth, which was measured in terms of tumor volume and Luc+WEHI 164 cells based bioluminescence in vivo imaging. Histopathological analysis and other assays revealed decreased mitotic index, increased apoptosis and senescence in these tumor tissues. In addition, poor angiogenesis was observed in these tumor tissues, which was further confirmed by fluorescence imaging of tumor vascularisation and CD31 expression by immuno-histochemistry. Interestingly, the growth inhibitory bystander effect was exerted more prominently by soluble factors obtained from the irradiated tumor cells than the cellular fraction. Cytokine profiling of the supernatants obtained from the irradiated tumor cells showed increased levels of VEGF, Rantes, PDGF, GMCSF and IL-2 and decreased levels of IL-6 and SCF. Comparative proteomic analysis of the supernatants from the irradiated tumor cells showed differential expression of total 24 protein spots (21 up- and 3 down-regulated) when compared with the supernatant from the unirradiated control cells. The proteins which showed substantially higher level in the supernatant from the irradiated cells included diphosphate kinase B, heat shock cognate, annexin A1, angiopoietin-2, actin (cytoplasmic 1/2) and stress induced phosphoprotein 1. However, the levels of proteins like annexin A2, protein S100 A4 and cofilin was found to be lower in this supernatant. In conclusion, our results provided deeper insight about

  12. Molecular Understanding of Growth Inhibitory Effect from Irradiated to Bystander Tumor Cells in Mouse Fibrosarcoma Tumor Model.

    PubMed

    Desai, Sejal; Srambikkal, Nishad; Yadav, Hansa D; Shetake, Neena; Balla, Murali M S; Kumar, Amit; Ray, Pritha; Ghosh, Anu; Pandey, B N

    2016-01-01

    Even though bystander effects pertaining to radiation risk assessment has been extensively studied, the molecular players of radiation induced bystander effect (RIBE) in the context of cancer radiotherapy are poorly known. In this regard, the present study is aimed to investigate the effect of irradiated tumor cells on the bystander counterparts in mouse fibrosarcoma (WEHI 164 cells) tumor model. Mice co-implanted with WEHI 164 cells γ-irradiated with a lethal dose of 15 Gy and unirradiated (bystander) WEHI 164 cells showed inhibited tumor growth, which was measured in terms of tumor volume and Luc+WEHI 164 cells based bioluminescence in vivo imaging. Histopathological analysis and other assays revealed decreased mitotic index, increased apoptosis and senescence in these tumor tissues. In addition, poor angiogenesis was observed in these tumor tissues, which was further confirmed by fluorescence imaging of tumor vascularisation and CD31 expression by immuno-histochemistry. Interestingly, the growth inhibitory bystander effect was exerted more prominently by soluble factors obtained from the irradiated tumor cells than the cellular fraction. Cytokine profiling of the supernatants obtained from the irradiated tumor cells showed increased levels of VEGF, Rantes, PDGF, GMCSF and IL-2 and decreased levels of IL-6 and SCF. Comparative proteomic analysis of the supernatants from the irradiated tumor cells showed differential expression of total 24 protein spots (21 up- and 3 down-regulated) when compared with the supernatant from the unirradiated control cells. The proteins which showed substantially higher level in the supernatant from the irradiated cells included diphosphate kinase B, heat shock cognate, annexin A1, angiopoietin-2, actin (cytoplasmic 1/2) and stress induced phosphoprotein 1. However, the levels of proteins like annexin A2, protein S100 A4 and cofilin was found to be lower in this supernatant. In conclusion, our results provided deeper insight about

  13. Molecular Understanding of Growth Inhibitory Effect from Irradiated to Bystander Tumor Cells in Mouse Fibrosarcoma Tumor Model

    PubMed Central

    Desai, Sejal; Srambikkal, Nishad; Yadav, Hansa D.; Shetake, Neena; Balla, Murali M. S.; Kumar, Amit; Ray, Pritha; Ghosh, Anu

    2016-01-01

    Even though bystander effects pertaining to radiation risk assessment has been extensively studied, the molecular players of radiation induced bystander effect (RIBE) in the context of cancer radiotherapy are poorly known. In this regard, the present study is aimed to investigate the effect of irradiated tumor cells on the bystander counterparts in mouse fibrosarcoma (WEHI 164 cells) tumor model. Mice co-implanted with WEHI 164 cells γ-irradiated with a lethal dose of 15 Gy and unirradiated (bystander) WEHI 164 cells showed inhibited tumor growth, which was measured in terms of tumor volume and Luc+WEHI 164 cells based bioluminescence in vivo imaging. Histopathological analysis and other assays revealed decreased mitotic index, increased apoptosis and senescence in these tumor tissues. In addition, poor angiogenesis was observed in these tumor tissues, which was further confirmed by fluorescence imaging of tumor vascularisation and CD31 expression by immuno-histochemistry. Interestingly, the growth inhibitory bystander effect was exerted more prominently by soluble factors obtained from the irradiated tumor cells than the cellular fraction. Cytokine profiling of the supernatants obtained from the irradiated tumor cells showed increased levels of VEGF, Rantes, PDGF, GMCSF and IL-2 and decreased levels of IL-6 and SCF. Comparative proteomic analysis of the supernatants from the irradiated tumor cells showed differential expression of total 24 protein spots (21 up- and 3 down-regulated) when compared with the supernatant from the unirradiated control cells. The proteins which showed substantially higher level in the supernatant from the irradiated cells included diphosphate kinase B, heat shock cognate, annexin A1, angiopoietin-2, actin (cytoplasmic 1/2) and stress induced phosphoprotein 1. However, the levels of proteins like annexin A2, protein S100 A4 and cofilin was found to be lower in this supernatant. In conclusion, our results provided deeper insight about

  14. Inhibitory effect of unconjugated bile acids on the intestinal transport of 5-methyltetrahydrofolate in rat jejunum in vitro.

    PubMed Central

    Said, H M; Hollander, D; Strum, W B

    1984-01-01

    The effect of the unconjugated bile acids, cholic, deoxycholic, chenodeoxycholic, and ursodeoxycholic acids, and of the conjugated bile acid taurocholic acid on the mucosal-to-serosal transport and tissue uptake of the naturally occurring folate derivative, 5-methyltetrahydrofolate (5-CH3H4PteGlu) was examined in everted sacs of rat jejunum. Each of the unconjugated bile acids examined inhibited the transport and tissue uptake of 5-CH3H4PteGlu in a concentration dependent manner. At low concentrations (0.01-0.1 mM) of cholic and deoxycholic acids, no structural or functional damage to the intestinal mucosa occurred and the transport of 5-CH3H4PteGlu was inhibited competitively with Ki values of 0.114 mM and 0.055 mM for cholic and deoxycholic acids, respectively. The greater inhibition of 5-CH3H4PteGlu transport by unconjugated bile acids at 1 mM can be attributed to observed structural and functional damage to the intestinal mucosa. The addition of 2 mM lecithin to the mucosal medium failed to prevent the inhibitory effect of 0.1 mM deoxycholic acid on the transport of 0.5 microM 5-CH3H4PteGlu. Compared with the effect of unconjugated bile acids, the conjugated bile acid taurocholic acid (0.01-5 mM) showed no effect on the transport and tissue uptake of 5-CH3H4PteGlu. The results of this study show that intestinal transport and tissue uptake of 5-CH3H4PteGlu are inhibited by unconjugated bile acids in a dose-dependent fashion. The clinical and physiological implications of these observations are discussed. PMID:6510770

  15. [Inhibitory effects of methyl o-(4-hydroxy-3-methoxycinnamoyl) reserpate (CD-3400) on the central nervous system (author's transl)].

    PubMed

    Shika, K; Nakata, C; Ogura, M; Tamada, T; Fujimoto, Y

    1977-10-01

    Effects of methyl o-(4-hydroxy-3-methoxycinnamoyl) reserpate (CD-3400) on the central nervous system in mice, rats and cats were investigated, and a comparison was made with such effects of reserpine and rescinamine. Inhibitory effects of CD-3400 on spontaneous motor activity and conditioned avoidance response were weaker and shorter than those of reserpine and rescinnamine. In the experiments of the inhibitory effects of the central actions such as ptosis, hypothermia, decrease in motor ability, potentiation of hexobarbital and taming, reserpine was found to be the most potent followed by rescinnamine and CD-3400, respectively. High doses of CD-3400 exhibited inhibitory effects on methamphetamine-induced hyperactivity in mice and this action was weaker than those of reserpine and rescinnamine. CD-3400, 80-160 mg/kg p.o., showed no significant effects on morphine-induced analgesia, while a slight inhibition was observed on the Straub-tail reaction using morphine. Reserpine, 0.5 mg/kg i.v., resulted in a drowsy pattern in the spontaneous EEG activity and the EEG arousal response was depressed, while with CD-3400, 5 mg/kg i.v., there was no drowsy pattern. CD-3400 as well as rescinnamine and reserpine remarkably depleted 5-HT levels in brain, heart and plasma and the potency of CD-3400, particularly in the brain, was weaker than the potency of reserpine and rescinnamine. These results indicate that CD-3400 is an antihypertensive agent with a low toxicity and a weak central action.

  16. Antihypertensive effect of an angiotensin converting enzyme inhibitory peptide from enzyme modified cheese.

    PubMed

    Tonouchi, Hidekazu; Suzuki, Masayuki; Uchida, Masayuki; Oda, Munehiro

    2008-08-01

    Two angiotensin converting enzyme (ACE)-inhibitory peptides were isolated from enzyme modified cheese (EMC) and their amino acid sequences were identified as Leu-Gln-Pro and Met-Ala-Pro. The EMC was prepared by a combination of Protease N, Umamizyme, and Flavourzyme 500L. Both peptides were derived from beta-casein, f 88-90 and f 102-104, respectively. Met-Ala-Pro showed strong ACE inhibitory activity (IC50=0.8 mum) and antihypertensive activity in spontaneously hypertensive rats (SHR) after single oral administration. The IC50 value of Met-Ala-Pro was not affected by pre-incubation with ACE, suggesting that this peptide was a true ACE-inhibitory peptide. We report here, for the first time antihypertensive peptides from EMC.

  17. Polymer Photooxidation: An Experiment to Demonstrate the Effect of Additives.

    ERIC Educational Resources Information Center

    Allen, Norman S.; McKellar, John F.

    1979-01-01

    This undergraduate experiment shows that the inclusion of an appropriate additive can have a very marked effect on the physical properties of a polymer. The polymer used is polypropylene and the additives are 2-hydroxy-4-octyloxy-benzophenone and benzophenone. (BB)

  18. Growth inhibitory effect of KYKZL-1 on Hep G{sub 2} cells via inhibition of AA metabolites and caspase-3 pathway and cell cycle arrest

    SciTech Connect

    Cheng, Jing; Du, Yi-Fang; Xiao, Zhi-Yi; Pan, Li-Li; Li, Wei; Huan, Lin; Gong, Zhu-Nan; Wei, Shao-Hua; Huang, Shi-Qian; Xun, Wei; Zhang, Yi; Chang, Lei-Lei; Xie, Meng-Yu; Ao, Gui-Zhen; Cai, Jie; Qiu, Ting; Wu, Hao; Sun, Ting; Xu, Guang-Lin

    2014-01-01

    KYKZL-1, a newly synthesized compound with COX/5-LOX dual inhibition, was subjected to the inhibitory activity test on Hep G{sub 2} growth. We found that KYKZL-1 inhibited the growth of Hep G{sub 2} cells via inducing apoptosis. Further studies showed that KYKZL-1 activated caspase-3 through cytochrome c release from mitochondria and down regulation of Bcl-2/Bax ratio and reduced the high level of COX-2 and 5-LOX. As shown in its anti-inflammatory effect, KYKZL-1 also exhibited inhibitory effect on the PGE{sub 2} and LTB{sub 4} production in Hep G{sub 2} cells. Accordingly, exogenous addition of PGE{sub 2} or LTB{sub 4} reversed the decreases in cell viability. In addition, KYKZL-1 caused cell cycle arrest at the S–G{sub 2} checkpoint via the activation of p21{sup CIP1} protein and down-regulation of cyclin A expression. These data indicate that the growth inhibitory effect of KYKZL-1 is associated with inhibition of AA metabolites and caspase-3 pathway and cell cycle arrest. Combined with our previous findings, KYKZL-1 exhibiting COX/5-LOX inhibition may be a promising potential agent not only for inflammation control but also for cancer prevention/therapy with an enhanced gastric safety profile. - Highlights: • KYKZL-1 is designed to exhibit COX/5-LOX dual inhibition. • KYKZL-1 resulted in apoptosis of Hep G{sub 2} cells. • KYKZL-1 activated caspase-3 through cytochrome c and bcl-2/bax ratio. • KYKZL-1 caused cell cycle arrest via modulation of p21{sup CIP1} and cyclin A level.

  19. Fermentation of purple Jerusalem artichoke extract to improve the α-glucosidase inhibitory effect in vitro and ameliorate blood glucose in db/db mice

    PubMed Central

    Wang, Zhiqiang; Hwang, Seung Hwan; Lee, Sun Youb

    2016-01-01

    BACKGROUND/OBJECTIVES Jerusalem artichoke has inhibitory activity against α-glucosidase and decreases fasting serum glucose levels, which may be related to its fructan content. The biological activity of fructan can be influenced by the degree of polymerization. Thus, in this study, the inhibitory effects of original and fermented purple Jerusalem artichoke (PJA) on α-glucosidase were compared in vitro. Additionally, the anti-diabetes effect of Lactobacillus plantarum-fermented PJA (LJA) was studied in a non-insulin-dependent diabetes mellitus animal model (C57BIKsJ db/db). MATERIALS/METHODS The water extract of PJA was fermented by L. plantarum, and two strains of Bacillus subtilis to compare their anti-α-glucosidase activities in vitro by α-glucosidase assays. The anti-diabetes effect of LJA was studied in a non-insulin-dependent diabetes mellitus animal model (C57BIKsJ db/db) for seven weeks. During the experiment, food intake, body weight, and fasting blood glucose were measured every week. At the end of the treatment period, several diabetic parameters and the intestinal α-glucosidase activity were measured. RESULTS The LJA showed the highest α-glucosidase inhibitory activity in vitro. In the in vivo study, it resulted in a significantly lower blood glucose concentration than the control. Serum insulin and HDL cholesterol levels were significantly higher and the concentrations of triglycerides, non-esterified fatty acids, and total cholesterol were significant lower in mice treated with LJA after seven weeks. In addition, the intestinal α-glucosidase activity was partially inhibited. CONCLUSIONS These results suggested that LJA regulates blood glucose and has potential use as a dietary supplement. PMID:27247724

  20. Unraveling Additive from Nonadditive Effects Using Genomic Relationship Matrices

    PubMed Central

    Muñoz, Patricio R.; Resende, Marcio F. R.; Gezan, Salvador A.; Resende, Marcos Deon Vilela; de los Campos, Gustavo; Kirst, Matias; Huber, Dudley; Peter, Gary F.

    2014-01-01

    The application of quantitative genetics in plant and animal breeding has largely focused on additive models, which may also capture dominance and epistatic effects. Partitioning genetic variance into its additive and nonadditive components using pedigree-based models (P-genomic best linear unbiased predictor) (P-BLUP) is difficult with most commonly available family structures. However, the availability of dense panels of molecular markers makes possible the use of additive- and dominance-realized genomic relationships for the estimation of variance components and the prediction of genetic values (G-BLUP). We evaluated height data from a multifamily population of the tree species Pinus taeda with a systematic series of models accounting for additive, dominance, and first-order epistatic interactions (additive by additive, dominance by dominance, and additive by dominance), using either pedigree- or marker-based information. We show that, compared with the pedigree, use of realized genomic relationships in marker-based models yields a substantially more precise separation of additive and nonadditive components of genetic variance. We conclude that the marker-based relationship matrices in a model including additive and nonadditive effects performed better, improving breeding value prediction. Moreover, our results suggest that, for tree height in this population, the additive and nonadditive components of genetic variance are similar in magnitude. This novel result improves our current understanding of the genetic control and architecture of a quantitative trait and should be considered when developing breeding strategies. PMID:25324160

  1. The effect of domestication on inhibitory control: wolves and dogs compared.

    PubMed

    Marshall-Pescini, Sarah; Virányi, Zsófia; Range, Friederike

    2015-01-01

    Inhibitory control i.e. blocking an impulsive or prepotent response in favour of a more appropriate alternative, has been suggested to play an important role in cooperative behaviour. Interestingly, while dogs and wolves show a similar social organization, they differ in their intraspecific cooperation tendencies in that wolves rely more heavily on group coordination in regard to hunting and pup-rearing compared to dogs. Hence, based on the 'canine cooperation' hypothesis wolves should show better inhibitory control than dogs. On the other hand, through the domestication process, dogs may have been selected for cooperative tendencies towards humans and/or a less reactive temperament, which may in turn have affected their inhibitory control abilities. Hence, based on the latter hypothesis, we would expect dogs to show a higher performance in tasks requiring inhibitory control. To test the predictive value of these alternative hypotheses, in the current study two tasks; the 'cylinder task' and the 'detour task', which are designed to assess inhibitory control, were used to evaluate the performance of identically raised pack dogs and wolves. Results from the cylinder task showed a significantly poorer performance in wolves than identically-raised pack dogs (and showed that pack-dogs performed similarly to pet dogs with different training experiences), however contrary results emerged in the detour task, with wolves showing a shorter latency to success and less perseverative behaviour at the fence. Results are discussed in relation to previous studies using these paradigms and in terms of the validity of these two methods in assessing inhibitory control.

  2. The Effect of Domestication on Inhibitory Control: Wolves and Dogs Compared

    PubMed Central

    Marshall-Pescini, Sarah; Virányi, Zsófia; Range, Friederike

    2015-01-01

    Inhibitory control i.e. blocking an impulsive or prepotent response in favour of a more appropriate alternative, has been suggested to play an important role in cooperative behaviour. Interestingly, while dogs and wolves show a similar social organization, they differ in their intraspecific cooperation tendencies in that wolves rely more heavily on group coordination in regard to hunting and pup-rearing compared to dogs. Hence, based on the ‘canine cooperation’ hypothesis wolves should show better inhibitory control than dogs. On the other hand, through the domestication process, dogs may have been selected for cooperative tendencies towards humans and/or a less reactive temperament, which may in turn have affected their inhibitory control abilities. Hence, based on the latter hypothesis, we would expect dogs to show a higher performance in tasks requiring inhibitory control. To test the predictive value of these alternative hypotheses, in the current study two tasks; the ‘cylinder task’ and the ‘detour task’, which are designed to assess inhibitory control, were used to evaluate the performance of identically raised pack dogs and wolves. Results from the cylinder task showed a significantly poorer performance in wolves than identically-raised pack dogs (and showed that pack-dogs performed similarly to pet dogs with different training experiences), however contrary results emerged in the detour task, with wolves showing a shorter latency to success and less perseverative behaviour at the fence. Results are discussed in relation to previous studies using these paradigms and in terms of the validity of these two methods in assessing inhibitory control. PMID:25714840

  3. The effect of domestication on inhibitory control: wolves and dogs compared.

    PubMed

    Marshall-Pescini, Sarah; Virányi, Zsófia; Range, Friederike

    2015-01-01

    Inhibitory control i.e. blocking an impulsive or prepotent response in favour of a more appropriate alternative, has been suggested to play an important role in cooperative behaviour. Interestingly, while dogs and wolves show a similar social organization, they differ in their intraspecific cooperation tendencies in that wolves rely more heavily on group coordination in regard to hunting and pup-rearing compared to dogs. Hence, based on the 'canine cooperation' hypothesis wolves should show better inhibitory control than dogs. On the other hand, through the domestication process, dogs may have been selected for cooperative tendencies towards humans and/or a less reactive temperament, which may in turn have affected their inhibitory control abilities. Hence, based on the latter hypothesis, we would expect dogs to show a higher performance in tasks requiring inhibitory control. To test the predictive value of these alternative hypotheses, in the current study two tasks; the 'cylinder task' and the 'detour task', which are designed to assess inhibitory control, were used to evaluate the performance of identically raised pack dogs and wolves. Results from the cylinder task showed a significantly poorer performance in wolves than identically-raised pack dogs (and showed that pack-dogs performed similarly to pet dogs with different training experiences), however contrary results emerged in the detour task, with wolves showing a shorter latency to success and less perseverative behaviour at the fence. Results are discussed in relation to previous studies using these paradigms and in terms of the validity of these two methods in assessing inhibitory control. PMID:25714840

  4. Inhibitory effects of Stephania tetrandra S. Moore on free radical-induced lysis of rat red blood cells.

    PubMed

    Sekiya, Nobuyasu; Hikiami, Hiroaki; Yokoyama, Koichi; Kouta, Kazufumi; Sakakibara, Iwao; Shimada, Yutaka; Terasawa, Katsutoshi

    2005-04-01

    Crude preparations of Stephania tetrandra S. MOORE (ST), a traditional herbal medicine, have been used safely for arthritis and silicosis in China. In this study, we demonstrated that ST in vitro protects red blood cells from 2,2-azo-bis (2-amidinopropane) dihydrochloride (AAPH)-induced hemolysis. The inhibitory effect was dose-dependent at concentrations of 10 to 1000 microg/ml. Moreover, tests were carried out to identify the main ingredient of ST that exerts a scavenging effect on free-radicals. Three representative alkaloids, tetrandrine, fangchinoline, and cyclanoline, isolated from ST, were found to have inhibitory activities against AAPH-induced lysis of red blood cells (RBC). Furthermore, the ingestion of 200 mg of ST extract was associated with a significant increase in free-radical scavenging effect of plasma in rats. These results suggest that ST as antioxidant inhibits AAPH-induced hemolysis of RBC both in vitro and in vivo. PMID:15802807

  5. Sex-specific effect of the anabolic steroid, 17α-methyltestosterone, on inhibitory avoidance learning in periadolescent rats.

    PubMed

    Ramos-Pratts, Keyla; Rosa-González, Dariana; Pérez-Acevedo, Nivia L; Cintrón-López, Dahima; Barreto-Estrada, Jennifer L

    2013-10-01

    The illicit use of anabolic androgenic steroids (AAS) has gained popularity among adolescents in the last decade. However, although it is known that exposure to AAS impairs cognition in adult animal models, the cognitive effects during adolescence remain undetermined. An inhibitory avoidance task (IAT) was used to assess the effect of AAS (17α-methyltestosterone; 17α-meT--7.5 mg/kg) in male and female periadolescent rats. A single injection of 17α-meT immediately before the footshock produced significant impairment of inhibitory avoidance learning in males but not females. Generalized anxiety, locomotion, and risk assessment behaviors (RAB) were not affected. Our results show that exposure to a single pharmacological dose of 17α-meT during periadolescence exerts sex-specific cognitive effects without affecting anxiety. Thus, disruption of the hormonal milieu during this early developmental period might have negative impact on learning and memory.

  6. Sex-specific effect of the anabolic steroid, 17α-methyltestosterone, on inhibitory avoidance learning in periadolescent rats

    PubMed Central

    Ramos-Pratts, Keyla; Rosa-González, Dariana; Pérez-Acevedo, Nivia L.; Cintrón-López, Dahima; Barreto-Estrada, Jennifer L.

    2013-01-01

    The illicit use of anabolic androgenic steroids (AAS) has gained popularity among adolescents in the last decade. However, although it is known that exposure to AAS impairs cognition in adult animal models, the cognitive effects during adolescence remain undetermined. An inhibitory avoidance task (IAT) was used to assess the effect of AAS (17α-methyltestosterone; 17α-meT-7.5 mg/kg) in male and female periadolescent rats. A single injection of 17α-meT immediately before the footshock produced significant impairment of inhibitory avoidance learning in males but not females. Generalized anxiety, locomotion, and risk assessment behaviors (RAB) were not affected. Our results show that exposure to a single pharmacological dose of 17α-meT during periadolescence exerts sex-specific cognitive effects without affecting anxiety. Thus, disruption of the hormonal milieu during this early developmental period might have negative impact on learning and memory. PMID:23792034

  7. Synthesis and carbonic anhydrase inhibitory effects of new N-glycosylsulfonamides incorporating the phenol moiety.

    PubMed

    Riafrecha, Leonardo E; Bua, Silvia; Supuran, Claudiu T; Colinas, Pedro A

    2016-08-15

    A small series of N-glycosylsulfonamides incorporating the phenol moiety has been prepared by Ferrier sulfonamidoglycosylation of d-glycals. N-Glycosides were tested for the inhibition of four isoforms of carbonic anhydrase. In this study, all compounds showed good inhibitory activity against hCA I and II, with selectivity against the cytosolic hCA II versus the tumor associated isozymes. These results confirm that attaching carbohydrate moieties to CA phenol pharmacophore improves and enhances its inhibitory activity. PMID:27423482

  8. Interactive effects of nutrient additions and predation on infaunal communities

    USGS Publications Warehouse

    Posey, M.H.; Alphin, T.D.; Cahoon, L.; Lindquist, D.; Becker, M.E.

    1999-01-01

    Nutrient additions represent an important anthropogenic stress on coastal ecosystems. At moderate levels, increased nutrients may lead to increased primary production and, possibly, to increased biomass of consumers although complex trophic interactions may modify or mask these effects. We examined the influence of nutrient additions and interactive effects of trophic interactions (predation) on benthic infaunal composition and abundances through small-scale field experiments in 2 estuaries that differed in ambient nutrient conditions. A blocked experimental design was used that allowed an assessment of direct nutrient effects in the presence and absence of predation by epibenthic predators as well as an assessment of the independent effects of predation. Benthic microalgal production increased with experimental nutrient additions and was greater when infaunal abundances were lower, but there were no significant interactions between these factors. Increased abundances of one infaunal taxa, Laeonereis culveri, as well as the grazer feeding guild were observed with nutrient additions and a number of taxa exhibited higher abundances with predator exclusion. In contrast to results from freshwater systems there were no significant interactive effects between nutrient additions and predator exclusion as was predicted. The infaunal responses observed here emphasize the importance of both bottom-up (nutrient addition and primary producer driven) and top-down (predation) controls in structuring benthic communities. These processes may work at different spatial and temporal scales, and affect different taxa, making observation of potential interactive effects difficult.

  9. [Kinetic analysis of additive effect on desulfurization activity].

    PubMed

    Han, Kui-hua; Zhao, Jian-li; Lu, Chun-mei; Wang, Yong-zheng; Zhao, Gai-ju; Cheng, Shi-qing

    2006-02-01

    The additive effects of A12O3, Fe2O3 and MnCO3 on CaO sulfation kinetics were investigated by thermogravimetic analysis method and modified grain model. The activation energy (Ea) and the pre-exponential factor (k0) of surface reaction, the activation energy (Ep) and the pre-exponential factor (D0) of product layer diffusion reaction were calculated according to the model. Additions of MnCO3 can enhance the initial reaction rate, product layer diffusion and the final CaO conversion of sorbents, the effect mechanism of which is similar to that of Fe2O3. The method based isokinetic temperature Ts and activation energy can not estimate the contribution of additive to the sulfation reactivity, the rate constant of the surface reaction (k), and the effective diffusivity of reactant in the product layer (Ds) under certain experimental conditions can reflect the effect of additives on the activation. Unstoichiometric metal oxide may catalyze the surface reaction and promote the diffusivity of reactant in the product layer by the crystal defect and distinct diffusion of cation and anion. According to the mechanism and effect of additive on the sulfation, the effective temperature and the stoichiometric relation of reaction, it is possible to improve the utilization of sorbent by compounding more additives to the calcium-based sorbent.

  10. In vitro α-amylase and α-glucosidase inhibitory effects and cytotoxic activity of Albizia antunesiana extracts

    PubMed Central

    Chipiti, Talent; Ibrahim, Mohammed Auwal; Singh, Moganavelli; Islam, Md. Shahidul

    2015-01-01

    Context: Diabetes mellitus is a chronic disease, and its incidence is tremendously increasing globally. Decreasing postprandial hyperglycemia by retarding glucose absorption through inhibiting carbohydrates digesting enzymes (α-amylase and α-glucosidase) is one of many approaches used for the management of this disease. Objectives: The leaf and root aqueous and ethanol extracts of Albizia antunesiana were investigated for α-amylase and α-glucosidase inhibitory and cytotoxic activity in vitro. Materials and Methods: The α-amylase and α-glucosidase activities were measured in the presence of aqueous and ethanol extracts of the plant parts using starch and p-nitrophenyl-D-glucopyranoside as substrates respectively. Furthermore, cytotoxic effects of the extracts were investigated on HEK (human embryonic kidney) 293 cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay. Results: The results showed that ethanolic root extract of A. antunesiana had mild α-amylase and strong α-glucosidase inhibitory activity with half-maximal inhibitory concentration values of 30.68 and 4.35 µg/mL, respectively. The aqueous root extract showed mild α-glucosidase but no α-amylase inhibitory activity. Cytotoxicity studies on the extracts using the MTT assay revealed that the ethanolic (leaf and root) extracts were relatively nontoxic at tested concentrations on the HEK 293 cell lines. However, the aqueous extracts (leaf and root) were cytotoxic at concentrations above 50 µg/mL. Conclusion: Data from this study suggest that the ethanolic root extract of A. antunesiana possess in vitro α-amylase and α-glucosidase inhibitory activities and are not cytotoxic at least in an in vitro condition. PMID:26664010

  11. SESN2/sestrin 2 induction-mediated autophagy and inhibitory effect of isorhapontigenin (ISO) on human bladder cancers.

    PubMed

    Liang, Yuguang; Zhu, Junlan; Huang, Haishan; Xiang, Daimin; Li, Yang; Zhang, Dongyun; Li, Jingxia; Wang, Yulei; Jin, Honglei; Jiang, Guosong; Liu, Zeyuan; Huang, Chuanshu

    2016-08-01

    Isorhapontigenin (ISO) is a new derivative of stilbene isolated from the Chinese herb Gnetum cleistostachyum. Our recent studies have revealed that ISO treatment at doses ranging from 20 to 80 μM triggers apoptosis in multiple human cancer cell lines. In the present study, we evaluated the potential effect of ISO on autophagy induction. We found that ISO treatment at sublethal doses induced autophagy effectively in human bladder cancer cells, which contributed to the inhibition of anchorage-independent growth of cancer cells. In addition, our studies revealed that ISO-mediated autophagy induction occurred in a SESN2 (sestrin 2)-dependent and BECN1 (Beclin 1, autophagy related)-independent manner. Furthermore, we identified that ISO treatment induced SESN2 expression via a MAPK8/JNK1 (mitogen-activated protein kinase 8)/JUN-dependent mechanism, in which ISO triggered MAPK8-dependent JUN activation and facilitated the binding of JUN to a consensus AP-1 binding site in the SESN2 promoter region, thereby led to a significant transcriptional induction of SESN2. Importantly, we found that SESN2 expression was dramatically downregulated or even lost in human bladder cancer tissues as compared to their paired adjacent normal tissues. Collectively, our results demonstrate that ISO treatment induces autophagy and inhibits bladder cancer growth through MAPK8-JUN-dependent transcriptional induction of SESN2, which provides a novel mechanistic insight into understanding the inhibitory effect of ISO on bladder cancers and suggests that ISO might act as a promising preventive and/or therapeutic drug against human bladder cancer. PMID:27171279

  12. Resveratrol exerts growth inhibitory effects on human SZ95 sebocytes through the inactivation of the PI3-K/Akt pathway.

    PubMed

    Kim, So Young; Hyun, Moo Yeol; Go, Kyung Chan; Zouboulis, Christos C; Kim, Beom Joon

    2015-04-01

    Resveratrol is known to be a naturally produced polyphenol that is able to reduce cell proliferation in several types of cancer cells and adipocytes. However, the antiproliferative effects of resveratrol on the growth of human sebocytes are not yet clear. In the present study, we investigated possible cellular pathways associated with these growth inhibitory effects on human SZ95 sebocytes. Our results revealed that resveratrol inhibited the proliferation of sebocytes, and that this resulted in disruption of the cell cycle. The inactivation of extracellular signal-regulated protein kinase (ERK), Akt and peroxisome proliferator-activated receptor (PPAR)-γ was also shown to be involved in the inhibition of sebocyte growth by resveratrol. To examine the antiproliferative effects of resveratrol, we determined the levels of cell cycle control proteins. Resveratrol inhibited cyclin D1 synthesis, whereas it stimulated p21WAF1/CIP1 (p21) and p27KIP1 (p27) synthesis. In addition, we demonstrated that the resveratrol-mediated cell cycle arrest resulted in an increase in the proportion of cells in the sub-G0/G1 phase. Moreover, we found that the growth inhibitory effects of resveratrol were enhanced by treatment with LY294002 [a phosphatidylinositol 3-kinase (PI3-K) inhibitor] more so than by treatment with PD98059 (a MEK inhibitor), which indicates that resveratrol exerts its inhibitory effects on sebocyte proliferation through the inhibition of Akt. Linoleic acid (LA) is a well-established lipid inducer in sebocytes and is known to stimulate sebocyte differentiation through the upregulation of PPAR-γ. In this study, resveratrol was found to decrease the lipid content and PPAR-γ expression during LA-stimulated lipogenesis. Our results indicate that resveratrol plays a critical role in the inhibition of sebocyte growth through the inactivation of the Akt pathway. The present data suggest that resveratrol may be used as a therapeutic agent for the treatment of acne vulgaris.

  13. The inhibitory effect of antimicrobial zeolite on the biofilm of Acidithiobacillus thiooxidans.

    PubMed

    Haile, Tesfaalem; Nakhla, George

    2010-02-01

    The inhibitory effect of antimicrobial zeolite coated concrete specimens (Z2) against Acidithiobacillus thiooxidans was studied by measuring biomass dry cell weight (DCW), biological sulphate generation, and oxygen uptake rates (OURs). Uncoated (UC), and blank zeolite coated without antimicrobial agent (ZC) concrete specimens were used as controls. The study was undertaken by exposing inoculated basal nutrient medium (BNM) to the various specimens. The coating material was prepared by mixing zeolite, epoxy and cure with ratios, by weight of 2:2:1. Concrete specimens were characterized before and after exposure to inoculated or sterile BNM by field emission-scanning electron microscopy (FE-SEM). Gypsum, which was absent in the other test concrete specimens, was detected in uncoated specimens exposed to the bacterium. In UC and ZC, the growth of the bacteria increased throughout the duration of the experiment. However, significant biomass inhibition was observed in experiments where Z2 was used. The overall biomass growth rate in suspension before the specimens were placed ranged from 3.18 to 3.5 mg DCW day(-1). After the bacterium was exposed to UC and ZC, growth continued with a corresponding value of 4 + or - 0.4 and 5.5 + or - 0.6 mg DCW day(-1), respectively. No biomass growth was observed upon exposure of the bacterium to Z2. Similarly, while biological sulphur oxidation rates in UC and ZC were 88 + or - 13 and 238 + or - 25 mg SO(4)(2-) day(-1), respectively, no sulphate production was observed in experiments where Z2 concrete specimens were used. Peak OURs for UC and ZC ranged from 2.6 to 5.2 mg l(-1) h(-1), and there was no oxygen uptake in those experiments where Z2 was used. The present study revealed that the antimicrobial zeolite inhibits the growth of both planktonic as well as biofilm populations of Acidithiobacillus thiooxidans. PMID:19618279

  14. Inhibitory effects of kiwifruit extract on human platelet aggregation and plasma angiotensin-converting enzyme activity.

    PubMed

    Dizdarevic, Lili L; Biswas, Dipankar; Uddin, M D Main; Jørgenesen, Aud; Falch, Eva; Bastani, Nasser E; Duttaroy, Asim K

    2014-01-01

    Previous human studies suggest that supplementation with kiwifruits lowers several cardiovascular risk factors such as platelet hyperactivity, blood pressure and plasma lipids. The cardiovascular health benefit of fruit and vegetables is usually attributed to the complex mixture of phytochemicals therein; however, kiwifruit's cardioprotective factors are not well studied. In this study, we investigated the effects of kiwifruit extract on human blood platelet aggregation and plasma angiotensin-converting enzyme (ACE) activity. A sugar-free, heat-stable aqueous extract with molecular mass less than 1000 Da was prepared from kiwifruits. Typically, 100 g kiwifruits produced 66.3 ± 5.8 mg (1.2 ± 0.1 mg CE) of sugar-free kiwifruit extract (KFE). KFE inhibited both human platelet aggregation and plasma ACE activity in a dose-dependent manner. KFE inhibited platelet aggregation in response to ADP, collagen and arachidonic acid, and inhibitory action was mediated in part by reducing TxA2 synthesis. The IC50 for ADP-induced platelet aggregation was 1.6 ± 0.2 mg/ml (29.0 ± 3.0 μg CE/ml), whereas IC50 for serum ACE was 0.6 ± 0.1 mg/ml (11.0 ± 1.2 μg CE/ml). Consuming 500 mg of KFE (9.0 mg CE) in 10 g margarine inhibited ex vivo platelet aggregation by 12.7%, 2 h after consumption by healthy volunteers (n = 9). All these data indicate that kiwifruit contains very potent antiplatelet and anti-ACE components. Consuming kiwifruits might be beneficial as both preventive and therapeutic regime in cardiovascular disease. PMID:24219176

  15. The inhibitory effect of antimicrobial zeolite on the biofilm of Acidithiobacillus thiooxidans.

    PubMed

    Haile, Tesfaalem; Nakhla, George

    2010-02-01

    The inhibitory effect of antimicrobial zeolite coated concrete specimens (Z2) against Acidithiobacillus thiooxidans was studied by measuring biomass dry cell weight (DCW), biological sulphate generation, and oxygen uptake rates (OURs). Uncoated (UC), and blank zeolite coated without antimicrobial agent (ZC) concrete specimens were used as controls. The study was undertaken by exposing inoculated basal nutrient medium (BNM) to the various specimens. The coating material was prepared by mixing zeolite, epoxy and cure with ratios, by weight of 2:2:1. Concrete specimens were characterized before and after exposure to inoculated or sterile BNM by field emission-scanning electron microscopy (FE-SEM). Gypsum, which was absent in the other test concrete specimens, was detected in uncoated specimens exposed to the bacterium. In UC and ZC, the growth of the bacteria increased throughout the duration of the experiment. However, significant biomass inhibition was observed in experiments where Z2 was used. The overall biomass growth rate in suspension before the specimens were placed ranged from 3.18 to 3.5 mg DCW day(-1). After the bacterium was exposed to UC and ZC, growth continued with a corresponding value of 4 + or - 0.4 and 5.5 + or - 0.6 mg DCW day(-1), respectively. No biomass growth was observed upon exposure of the bacterium to Z2. Similarly, while biological sulphur oxidation rates in UC and ZC were 88 + or - 13 and 238 + or - 25 mg SO(4)(2-) day(-1), respectively, no sulphate production was observed in experiments where Z2 concrete specimens were used. Peak OURs for UC and ZC ranged from 2.6 to 5.2 mg l(-1) h(-1), and there was no oxygen uptake in those experiments where Z2 was used. The present study revealed that the antimicrobial zeolite inhibits the growth of both planktonic as well as biofilm populations of Acidithiobacillus thiooxidans.

  16. Inhibitory effects of kiwifruit extract on human platelet aggregation and plasma angiotensin-converting enzyme activity.

    PubMed

    Dizdarevic, Lili L; Biswas, Dipankar; Uddin, M D Main; Jørgenesen, Aud; Falch, Eva; Bastani, Nasser E; Duttaroy, Asim K

    2014-01-01

    Previous human studies suggest that supplementation with kiwifruits lowers several cardiovascular risk factors such as platelet hyperactivity, blood pressure and plasma lipids. The cardiovascular health benefit of fruit and vegetables is usually attributed to the complex mixture of phytochemicals therein; however, kiwifruit's cardioprotective factors are not well studied. In this study, we investigated the effects of kiwifruit extract on human blood platelet aggregation and plasma angiotensin-converting enzyme (ACE) activity. A sugar-free, heat-stable aqueous extract with molecular mass less than 1000 Da was prepared from kiwifruits. Typically, 100 g kiwifruits produced 66.3 ± 5.8 mg (1.2 ± 0.1 mg CE) of sugar-free kiwifruit extract (KFE). KFE inhibited both human platelet aggregation and plasma ACE activity in a dose-dependent manner. KFE inhibited platelet aggregation in response to ADP, collagen and arachidonic acid, and inhibitory action was mediated in part by reducing TxA2 synthesis. The IC50 for ADP-induced platelet aggregation was 1.6 ± 0.2 mg/ml (29.0 ± 3.0 μg CE/ml), whereas IC50 for serum ACE was 0.6 ± 0.1 mg/ml (11.0 ± 1.2 μg CE/ml). Consuming 500 mg of KFE (9.0 mg CE) in 10 g margarine inhibited ex vivo platelet aggregation by 12.7%, 2 h after consumption by healthy volunteers (n = 9). All these data indicate that kiwifruit contains very potent antiplatelet and anti-ACE components. Consuming kiwifruits might be beneficial as both preventive and therapeutic regime in cardiovascular disease.

  17. The inhibitory effects of nor-oleanane triterpenoid saponins from Stauntonia brachyanthera towards UDP-glucuronosyltransferases.

    PubMed

    Liu, Dan; Li, Shuang; Qi, Jia-Qi; Meng, Da-Li; Cao, Yun-Feng

    2016-07-01

    The inhibition of UDP-glucuronosyltransferases (UGTs) by herbal components might be an important reason for clinical herb-drug interaction (HDI). The inhibitory effects on UGTs via nor-oleanane triterpenoid saponins, which were the bioactive ingredients from Stauntonia brachyanthera, a traditional Chinese folk medicines with highly biological values, were evaluated comprehensively with recombinant UGT isoforms as enzyme source and a nonspecific substrate 4-methylumbelliferone (4-MU) as substrate. The results showed that there are seven compounds, 2, 3, 4, 8, 9, 13 and 14, respectively, exhibited potential inhibitions towards UGT1A1, UGT1A3 and UGT1A10 among all 23 compounds isolated from the plants. The IC50 values were 17.1μM, 13.5μM, 9.5μM, 15.7μM, 16.3μM, 1.1μM, and 0.3μM, respectively. Data fitting using Dixon and Lineweaver-Burk plots demonstrated that the inhibition of UGT1A10, UGT1A1 and UGT1A3 was best fit to noncompetitive type and competitive, respectively. The inhibition kinetic parameter (Ki) was calculated to be 39μM, 17μM, 3.3μM, 10μM, 9.3μM, 0.19μM, and 0.016μM, respectively. All these experimental data suggested that HDI might occur when compounds containing herbs were co-administered with drugs which mainly undergo UGTs-mediated metabolism. PMID:27223851

  18. Inhibitory effects of Tripterygium wilfordii multiglycoside on benign prostatic hyperplasia in rats.

    PubMed

    Shen, Hai-Nan; Xu, Yuan; Jiang, Zhen-Zhou; Huang, Xin; Zhang, Lu-Yong; Wang, Tao

    2015-06-01

    The present study was designed to evaluate the inhibitory effects of Tripterygium wilfordii multiglycoside (GTW) against testosterone-induced benign prostatic hyperplasia (BPH) in rats. A total of 45 rats were randomly divided into five groups: Group I, vehicle control group (sham-operated and treated with vehicle); Group II, BPH group; Group III, BPH rats treated with finasteride at a dose of 5 mg·kg(-1); and Groups IV and V, BPH rats treated with GTW at dose levels of 10 and 20 mg·kg(-1), respectively. The drugs were administered orally once a day for 14 days. Prostate weight, prostatic index, and the testosterone and dihydrotestosterone (DHT) levels in serum and prostate, and the serum prostate specific antigen (PSA) levels were measured; prostate tissues were taken for histopathological examination; and serum biochemical analysis was also performed. The BPH rats displayed an increase in prostate weight, prostatic index with increased testosterone and DHT levels in both the serum and prostate, and increased serum PSA levels. GTW treatment at both doses resulted in significant reductions in prostate weight, prostatic index, testosterone and DHT levels in both the serum and prostate, and serum PSA levels, compared with BPH group. Histopathological examination also indicated that GTW treatment at both doses inhibited testosterone-induced prostatic hyperplasia. Serum biochemical analysis showed that the liver and renal functions were normal. In conclusion, GTW inhibited testosterone-induced prostatic hyperplasia in rats, without host toxicity, providing a basis for the development of GTW as a novel therapy for BPH. PMID:26073338

  19. Effects of some polymeric additives on the cocrystallization of caffeine

    NASA Astrophysics Data System (ADS)

    Chung, Jihae; Kim, Il Won

    2011-11-01

    Effects of polymeric additives on the model cocrystallization were examined. The model cocrystal was made from caffeine and oxalic acid, and poly(ethylene glycol) (PEG), poly( L-lactide) (PLLA), poly(ɛ-caprolactone) (PCL), and poly(acrylic acid) (PAA) were the additives. The cocrystals were formed as millimeter-sized crystals without additives, and they became microcrystals with PLLA and PCL, and nanocrystals with PAA. XRD and IR revealed that the cocrystal structure was unchanged despite the strong effects of the additives on the crystal morphology, although some decrease in crystallinity was observed with PAA as confirmed by DSC. The DSC study also showed that the cocrystal melted and recrystallized to form α-caffeine upon heating. The present study verified that the polymeric additives can be utilized to modulate the size and morphology of the cocrystals without interfering the intermolecular interactions essential to the integrity of the cocrystal structures.

  20. Additive effects on the toughening of unsaturated polyester resins

    SciTech Connect

    Suspene, L.; Yang, Y.S.; Pascault, J.P.

    1993-12-31

    An elastomer additive, carboxy-terminated acrylonitrile-butadiene copolymer, was used for toughening in the free radical cross-linking copolymerization of unsaturated polyester (UP) resins. For molded parts, Charpy impact behavior was generally enhanced and the number of catastrophic failures was reduced. The miscibility and interfacial properties of additive and resin blends play important roles in the toughening process. Phase-diagram studies showed that the elastomer additive is immiscible with the UP resin and is phase-separated from the resin matrix during curing. This phase-separation phenomenon is similar to that in the low-profile mechanism of UP resins. Additive-resin system miscibility greatly influences curing morphology. Microvoids occurred in the additive phase of cured resin because of shrinkage stress. The intrinsic inhomogeneity of the polyester network and the existence of microvoids in the final product limit the toughening effect of additives on unsaturated polyester resins. 49 refs., 13 figs., 3 tabs.

  1. Inhibitory Effect of Epinephrine on Insulin-stimulated Glucose Uptake by Rat Skeletal Muscle

    PubMed Central

    Chiasson, Jean-Louis; Shikama, Hisataka; Chu, David T. W.; Exton, John H.

    1981-01-01

    The effect of epinephrine on basal and insulin-stimulated glucose uptake in perfused hindlimbs of fed rats was studied. Insulin increased glucose uptake in a dose-dependent manner from a basal value of 1.5±0.3 up to a maximum value of 5.3±0.9 μmol/min per 100 g with 6 nM (1 m U/ml). Epinephrine at 10 nM and 0.1 μM also increased glucose uptake to 2.6±0.1 and 3.1±0.1 μmol/min per 100 g, respectively. These same concentrations of epinephrine, however, suppressed the insulin-stimulated glucose uptake to 3.2±0.3 μmol/min per 100 g. Both the stimulatory and inhibitory effects of epinephrine on glucose uptake were completely reversed by propranolol, but were not significantly altered by phentolamine. Uptake of 3-O-methylglucose and 2-deoxyglucose into thigh muscles of the perfused hindlimbs was stimulated fivefold by insulin, but was unaffected by epinephrine. Epinephrine also did not inhibit the stimulation of uptake by insulin. Epinephrine decreased the phosphorylation of 2-deoxyglucose, however, and caused the intracellular accumulation of free glucose. These last two effects were more prominent in the presence of insulin. Whereas epinephrine caused large rises in glucose-6-P and fructose-6-P, insulin did not alter the concentration of these metabolites either in the absence or presence of epinephrine. These data indicate that: (a) epinephrine has a stimulatory effect on glucose uptake by perfused rat hindlimbs that does not appear to be exerted on skeletal muscle; (b) epinephrine does not affect hexose transport in skeletal muscle; (c) epinephrine inhibits insulin-stimulated glucose uptake in skeletal muscle by inhibiting glucose phosphorylation. It is hypothesized that the inhibition of glucose phosphorylation is due to the stimulation of glycogenolysis, which leads to the accumulation of hexose phosphates, which inhibit hexokinase. PMID:6115864

  2. Effect of addition of Versagel on microbial, chemical, and physical properties of low-fat yogurt.

    PubMed

    Ramchandran, L; Shah, N P

    2008-09-01

    The objective of this study was to examine the effect of Versagel on the growth and proteolytic activity of Streptococcus thermophilus 1275 and Lactobacillus delbrueckii ssp. bulgaricus 1368 and angiotensin-I converting enzyme inhibitory activity of the peptides generated thereby as well as on the physical properties of low-fat yogurt during a storage period of 28 d at 4 degrees C. Three different types of low-fat yogurts, YV0, YV1, and YV2, were prepared using Versagel as a fat replacer. The fermentation time of the low-fat yogurts containing Versagel was less than that of the control yogurt (YV0). The starter cultures maintained their viability (8.68 to 8.81 log CFU/g of S. thermophilus and 8.51 to 8.81 log CFU/g of L. delbrueckii ssp. bulgaricus) in all the yogurts throughout the storage period. There was some decrease in the pH of the yogurts during storage and an increase in the concentration of lactic acid. However, the proteolytic and ACE-inhibitory potential of the starter cultures was suppressed in the presence of Versagel. On the other hand, the addition of Versagel had a positive impact on the physical properties of the low-fat yogurt, namely, spontaneous whey separation, firmness, and pseudoplastic properties.

  3. Effect of hyperoxaluria on the inhibitory activity of a 45-kD urinary protein.

    PubMed

    Selvam, Ramasamy; Balakrishnan, Selvakumar; Kalaiselvi, Periandavan

    2002-02-01

    Proteins are thought to play a major role in stone formation and structurally abnormal proteins have been reported to be present in the urine of stone formers. This study was aimed to determine whether hyperoxaluria modifies the kinetic properties of urinary inhibitory proteins. Hyperoxaluria was induced by feeding 1% ethylene glycol to rats. Oxalate, uric acid and calcium excretion were increased progressively during hyperoxaluria, while magnesium level was decreased. Urinary proteins were separated on a DEAE-cellulose column by eluting with stepwise increasing salt concentration in 0.05 M Tris-HCl buffer (pH 7.0). Each protein fraction was studied for its crystallization inhibitory potential by the spectrophotometric method. The protein eluted in 0.3 M NaCl containing buffer had the maximal nucleation as well as inhibitory activity. The protein had a molecular weight of 45 kD. In hyperoxaluria, the urinary excretion of this protein significantly increased. In the crystal growth assay, the control rat 45-kD protein inhibited nucleation by 75% and aggregation by 100%. In contrast, it is very interesting to note that the protein derived from 28th day hyperoxaluric urine, behaved as a promoter of nucleation (-113%, percentage inhibition) and weak inhibitor of aggregation (28%). A significantly high negative correlation (r = -0.97) between oxalate excretion and the inhibitory activity of the 45-kD protein was observed suggesting a modification of the protein by oxalate. PMID:11818706

  4. The Effect of Placement Instability on Adopted Children's Inhibitory Control Abilities and Oppositional Behavior

    ERIC Educational Resources Information Center

    Lewis, Erin E.; Dozier, Mary; Ackerman, John; Sepulveda-Kozakowski, Sandra

    2007-01-01

    This study assessed relations among placement instability, inhibitory control, and caregiver-rated child behavior. The sample included 33 adopted children who had experienced placement instability, 42 adopted children who had experienced 1 stable placement, and 27 children never placed in foster care. Five- and 6-year-old children completed the…

  5. Inhibitory effect of organic carbon on CO₂ fixing by non-photosynthetic microbial community isolated from the ocean.

    PubMed

    Hu, Jia-jun; Wang, Lei; Zhang, Shi-ping; Wang, Yuan-qing; Xi, Xue-fei

    2011-07-01

    The inhibitory effect of organic carbon on CO(2) fixation (CF) by the non-photosynthetic microbial community (NPMC) and its mechanism were studied. The results showed that different concentrations of glucose inhibited CF to some extent. However, when these microorganisms pre-cultured with glucose were re-cultured without organic carbon, their CF efficiency differed significantly from the control based on the glucose concentration in the pre-culture. ATP as bioenergy and NADH as reductant had no obvious inhibitory effect on CF; conversely, they improved CF efficiency to some extent, especially when both were present simultaneously. These results implied that not all organic materials inhibited CF by NPMC, and only those that acted as good carbon sources, such as glucose, inhibited CF. Moreover, some metabolites generated during the catabolism of glucose by heterotrophic metabolism of NPMC might inhibit CF, while other cumulated materials present in the cell interior, such as ATP and NADH, might improve CF.

  6. In vitro inhibitory effects of scutellarin on six human/rat cytochrome P450 enzymes and P-glycoprotein.

    PubMed

    Han, Yong-Long; Li, Dan; Yang, Quan-Jun; Zhou, Zhi-Yong; Liu, Li-Ya; Li, Bin; Lu, Jin; Guo, Cheng

    2014-05-05

    Inhibition of cytochrome P450 (CYP) and P-glycoprotein (P-gp) are regarded as the most frequent and clinically important pharmacokinetic causes among the various possible factors for drug-drug interactions. Scutellarin is a flavonoid which is widely used for the treatment of cardiovascular diseases. In this study, the in vitro inhibitory effects of scutellarin on six major human CYPs (CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4) and six rat CYPs (CYP1A2, CYP2C7, CYP2C11, CYP2C79, CYP2D4, and CYP3A2) activities were examined by using liquid chromatography-tandem mass spectrometry. Meanwhile, the inhibitory effects of scutellarin on P-gp activity were examined on a human metastatic malignant melanoma cell line WM-266-4 by calcein-AM fluorometry screening assay. Results demonstrated that scutellarin showed negligible inhibitory effects on the six major CYP isoenzymes in human/rat liver microsomes with almost all of the IC50 values exceeding 100 μM, whereas it showed values of 63.8 μM for CYP2C19 in human liver microsomes, and 63.1 and 85.6 μM for CYP2C7 and CYP2C79 in rat liver microsomes, respectively. Scutellarin also showed weak inhibitory effect on P-gp. In conclusion, this study demonstrates that scutellarin is unlikely to cause any clinically significant herb-drug interactions in humans when co-administered with substrates of the six CYPs (CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4) and P-gp.

  7. In Vitro Antioxidant, Anti-Diabetes, Anti-Dementia, and Inflammation Inhibitory Effect of Trametes pubescens Fruiting Body Extracts.

    PubMed

    Im, Kyung Hoan; Nguyen, Trung Kien; Choi, Jaehyuk; Lee, Tae Soo

    2016-01-01

    Trametes pubescens, white rot fungus, has been used for folk medicine in Asian countries to treat ailments such as cancer and gastrointestinal diseases. This study was initiated to evaluate the in vitro antioxidant, anti-diabetes, anti-dementia, and anti-inflammatory activities of T. pubescens fruiting bodies. The 1,1-diphenyl-2-picryl-hydrazyl (DPPH) free radical scavenging activities of T. pubescens methanol (ME) and hot water (HWE) extracts (2.0 mg/mL) were comparable to butylated hydroxytoluene (BHT), the positive control. However, the chelating effects of ME and HWE were significantly higher than that of BHT. The HWE (6 mg/mL) also showed comparable reducing power to BHT. Eleven phenol compounds were detected by high performance liquid chromatography (HPLC) analysis. The α-amylase and α-glucosidase inhibitory activities of the ME and HWE of the mushroom were lower than Acarbose, the standard reference; however, the inhibitory effects of the mushroom extracts at 2.0 mg/mL were moderate. The acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory effects of ME and HWE were moderate and comparable with galanthamine, the standard drug to treat early stages of Alzheimer's disease (AD). The ME had a neuroprotective effect against glutamate-induced PC-12 cell cytotoxicity at the concentration range of 2-40 μg/mL. The mushroom extracts also showed inflammation inhibitory activities such as production of nitric oxide (NO) and expression of inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-induced murine macrophage-like cell lines (RAW 264.7) and significantly suppressed the carrageenan-induced rat paw-edema. Therefore, fruiting body extracts of T. pubescens demonstrated antioxidant related anti-diabetes, anti-dementia and anti-inflammatory activities. PMID:27196881

  8. Structure of constituents isolated from the flower buds of Cananga odorata and their inhibitory effects on aldose reductase.

    PubMed

    Matsumoto, Takahiro; Nakamura, Seikou; Fujimoto, Katsuyoshi; Ohta, Tomoe; Ogawa, Keiko; Yoshikawa, Masayuki; Matsuda, Hisashi

    2014-10-01

    Three new terpenoid derivatives, canangaterpenes IV-VI, were isolated from the flower buds of Cananga odorata, cultivated in Thailand, together with eight known flavonoids. The chemical structures of the new compounds were elucidated on the basis of chemical and physicochemical evidence. The inhibitory effects of the isolated compounds on aldose reductase were also investigated. Several terpenoid derivatives and flavonoids were shown to inhibit aldose reductase. PMID:24816646

  9. Inhibitory control effects in adolescent binge eating and consumption of sugar-sweetened beverages and snacks.

    PubMed

    Ames, Susan L; Kisbu-Sakarya, Yasemin; Reynolds, Kim D; Boyle, Sarah; Cappelli, Christopher; Cox, Matthew G; Dust, Mark; Grenard, Jerry L; Mackinnon, David P; Stacy, Alan W

    2014-10-01

    Inhibitory control and sensitivity to reward are relevant to the food choices individuals make frequently. An imbalance of these systems can lead to deficits in decision-making that are relevant to food ingestion. This study evaluated the relationship between dietary behaviors - binge eating and consumption of sweetened beverages and snacks - and behavioral control processes among 198 adolescents, ages 14 to 17. Neurocognitive control processes were assessed with the Iowa Gambling Task (IGT), a generic Go/No-Go task, and a food-specific Go/No-Go task. The food-specific version directly ties the task to food cues that trigger responses, addressing an integral link between cue-habit processes. Diet was assessed with self-administered food frequency and binge eating questionnaires. Latent variable models revealed marked gender differences. Inhibitory problems on the food-specific and generic Go/No-Go tasks were significantly correlated with binge eating only in females, whereas inhibitory problems measured with these tasks were the strongest correlates of sweet snack consumption in males. Higher BMI percentile and sedentary behavior also predicted binge eating in females and sweet snack consumption in males. Inhibitory problems on the generic Go/No-Go, poorer affective decision-making on the IGT, and sedentary behavior were associated with sweetened beverage consumption in males, but not females. The food-specific Go/No-Go was not predictive in models evaluating sweetened beverage consumption, providing some initial discriminant validity for the task, which consisted of sweet/fatty snacks as no-go signals and no sugar-sweetened beverage signals. This work extends research findings, revealing gender differences in inhibitory function relevant to behavioral control. Further, the findings contribute to research implicating the relevance of cues in habitual behaviors and their relationship to snack food consumption in an understudied population of diverse adolescents not

  10. Inhibitory effect of tetrahydroswertianolin on tumor necrosis factor-alpha-dependent hepatic apoptosis in mice.

    PubMed

    Hase, K; Xiong, Q; Basnet, P; Namba, T; Kadota, S

    1999-06-15

    We investigated the effect of tetrahydroswertianolin (THS), a hepatoprotective agent from Swertia japonica, on tumor necrosis factor-alpha (TNF-alpha)-dependent hepatic apoptosis induced by D-galactosamine (D-GalN) (700 mg/kg, i.p.) and lipopolysaccharide (LPS) (10 microg/kg, i.p.) in mice. Apoptotic symptoms were observed at the initial stage of liver damage. By 5 hr after intoxication, hepatic DNA fragmentation had risen to 2123%, with the value in untreated mice set at 100%, without a significant elevation of serum alanine transaminase (ALT) activity. There was a parallel increase in hepatocytes undergoing chromatin condensation and apoptotic body formation. By 8 hr after intoxication, serum ALT activity had risen to 3707 U/L. Pretreatment with THS (50 mg/kg, p.o.) at 18 and 2 hr before intoxication significantly reduced DNA fragmentation to 821% of that in untreated mice and prevented the emergence of chromatin condensation and apoptotic body formation. A significant and dose-dependent reduction in serum ALT activity at 8 hr also was observed with THS pretreatment. These effects of THS were different from those observed from pretreatment with glycyrrhizin (GCR), which is a clinically used hepatoprotective agent with membrane-stabilizing activity. GCR pretreatment (100 mg/kg, p.o.) did not inhibit hepatic DNA fragmentation (1588% of untreated mice), although this compound significantly protected against serum ALT elevation (1463 U/L). These data suggest that an inhibitory effect on the progression of hepatic apoptosis prior to liver injury may be involved in the hepatoprotective mechanisms of THS, whereas it appears that GCR affects the processes after apoptosis. In a separate experiment, we found that the concentration of serum TNF-alpha rose to 2016 pg/mL at 1 hr after intoxication of mice with D-GalN and LPS, but this increase was suppressed by THS pretreatment (10, 50, or 200 mg/kg, p.o.) to 716, 454, or 406 pg/mL, respectively. Further study with a reverse

  11. Inhibitory effect of cadmium on estrogen signaling in zebrafish brain and protection by zinc.

    PubMed

    Chouchene, Lina; Pellegrini, Elisabeth; Gueguen, Marie-Madeleine; Hinfray, Nathalie; Brion, François; Piccini, Benjamin; Kah, Olivier; Saïd, Khaled; Messaoudi, Imed; Pakdel, Farzad

    2016-06-01

    The present study was conducted to assess the effects of Cd exposure on estrogen signaling in the zebrafish brain, as well as the potential protective role of Zn against Cd-induced toxicity. For this purpose, the effects on transcriptional activation of the estrogen receptors (ERs), aromatase B (Aro-B) protein expression and molecular expression of related genes were examined in vivo using wild-type and transgenic zebrafish embryos. For in vitro studies, an ER-negative glial cell line (U251MG) transfected with different zebrafish ER subtypes (ERα, ERβ1 and ERβ2) was also used. Embryos were exposed either to estradiol (E2 ), Cd, E2 +Cd or E2 +Cd+Zn for 72 h and cells were exposed to the same treatments for 30 h. Our results show that E2 treatment promoted the transcriptional activation of ERs and increased Aro-B expression, at both the protein and mRNA levels. Although exposure to Cd, does not affect the studied parameters when administered alone, it significantly abolished the E2 -stimulated transcriptional response of the reporter gene for the three ER subtypes in U251-MG cells, and clearly inhibited the E2 induction of Aro-B in radial glial cells of zebrafish embryos. These inhibitory effects were accompanied by a significant downregulation of the expression of esr1, esr2a, esr2b and cyp19a1b genes compared to the E2 -treated group used as a positive control. Zn administration during simultaneous exposure to E2 and Cd strongly stimulated zebrafish ERs transactivation and increased Aro-B protein expression, whereas mRNA levels of the three ERs as well as the cyp19a1b remained unchanged in comparison with Cd-treated embryos. In conclusion, our results clearly demonstrate that Cd acts as a potent anti-estrogen in vivo and in vitro, and that Cd-induced E2 antagonism can be reversed, at the protein level, by Zn supplement. Copyright © 2016 John Wiley & Sons, Ltd.

  12. The inhibitory effect of hypoxic cytotoxin on the expansion of cancer stem cells in ovarian cancer.

    PubMed

    Nozawa-Suzuki, Noriko; Nagasawa, Hideko; Ohnishi, Ken; Morishige, Ken-Ichirou

    2015-02-20

    While an increase in progression free survival time is seen when an angiogenesis inhibitor is used in the treatment of high-relapse rate ovarian cancer, it has little effect on overall survival. A possible cause of treatment-resistance to angiogenesis inhibitors is the growth of stem cells in a hypoxic microenvironment built inside the tumor tissue by angiogenesis inhibition. In this study, we examined the possible suppression of stem cell and cancer stem cell (CSC) expansion by hypoxic cytotoxin, TX-402. TX-402, an analogue of tirapazamine, has been developed as a hypoxia selective prodrug with inhibitory effects of HIF-1 and angiogenesis. We considered TX-402 as a possible molecular-target drug candidate for ovarian cancer due to its inhibition of CSC expansion. In this study, we found that the expressions of HIF-1α and HIF-2α were increased under hypoxia in serous ovarian cancer cell lines. The expressions of HIF-1α and HIF-2α induced under hypoxia were repressed by TX-402 in a dose-dependent manner. Next, we investigated the effects of hypoxia on the expression levels of stem cell factors, Oct4, Nanog, Sox2 and Lin28, and showed that their expressions were induced by hypoxia. It was also observed that the expressions of putative ovarian cancer stem cell markers, CD133 and CD44 were induced under hypoxia. Furthermore, TX-402 was found to dose-dependently inhibit the expressions of CSC markers and stem cell factors. Oct4 expression was repressed by HIF-2α silencing, but not by HIF-1α silencing, indicating that TX-402 may repress the expression of Oct4 by inhibiting HIF-2α. We constructed CaOV3 spheroids as a 3-dimensional hypoxia model, in which the internal hypoxic region contained CSC-like cells expressing Oct4. The internal hypoxic region, which contained Oct4 expressing cells, disappeared following TX-402 treatment. In conclusion, hypoxia promoted the expansion of CSCs expressing CD133 and CD44 accompanied by an increase of stem cell factors. Its

  13. The Inhibitory Effects of RFamide-Related Peptide 3 on Luteinizing Hormone Release Involves an Estradiol-Dependent Manner in Prepubertal but Not in Adult Female Mice.

    PubMed

    Xiang, Wei; Zhang, Baoyun; Lv, Fenglin; Ma, Yunxia; Chen, Hang; Chen, Long; Yang, Fang; Wang, Pingqing; Chu, Mingxing

    2015-08-01

    The mammalian gonadotropin-inhibitory hormone (GnIH) ortholog, RFamide-related peptide (RFRP), is considered to act on gonadotropin-releasing hormone (GnRH) neurons and the pituitary to inhibit gonadotropin synthesis and release. However, there is little evidence documenting whether RFamide-related peptide 3 (RFRP-3) plays a primary role in inhibition of the hypothalamo-pituitary-gonadal (HPG) axis prior to the onset of puberty. The present study aimed to understand the functional significance of the neuropeptide on pubertal development. The developmental changes in reproductive-related gene expression at the mRNA level were investigated in the hypothalamus of female mice. The results indicated that RFRP-3 may be an endogenous inhibitory factor for the activation of the HPG axis prior to the onset of puberty. In addition, centrally administered RFRP-3 significantly suppressed plasma luteinizing hormone (LH) levels in prepubertal female mice. Surprisingly, centrally administered RFRP-3 had no effects on plasma LH levels in ovariectomized (OVX) prepubescent female mice. In contrast, RFRP-3 also inhibited plasma LH levels in OVX prepubescent female mice that were treated with 17beta-estradiol replacement. Our study also examined the effects of RFRP-3 on plasma LH release in adult female mice that were ovariectomized at dioestrus, with or without estradiol (E2). Our results showed that the inhibitory effects of RFRP-3 were independent of E2 status. Quantitative real-time PCR and immunohistochemistry analyses showed that RFRP-3 inhibited GnRH expression at both the mRNA and protein levels in the hypothalamus. These data demonstrated that RFRP-3 could effectively suppress pituitary LH release, via the inhibition of GnRH transcription and translation in prepubescent female mice, which is associated with estrogen signaling pathway and developmental stages.

  14. Contribution of anterior cingulate cortex and descending pain inhibitory system to analgesic effect of lemon odor in mice

    PubMed Central

    2014-01-01

    Background Affections are thought to regulate pain perception through the descending pain inhibitory system in the central nervous system. In this study, we examined in mice the affective change by inhalation of the lemon oil, which is well used for aromatherapy, and the effect of lemon odor on pain sensation. We also examined the anterior cingulate cortex (ACC) and descending pain inhibitory system to such regulation of pain. Results In the elevated plus maze, the time spent in the open arms was increased by inhalation of lemon oil. The pain behavior induced by injection of formalin into the hind paw was decreased. By inhalation of lemon oil, the number of c-Fos expression by formalin injection was significantly increased in the ACC, periaqueductal grey (PAG), nucleu raphe magnus (NRM) and locus ceruleus, and decreased in the spinal dorsal horn (SDH). The destruction of the ACC with ibotenic acid led to prevent the decrease of formalin-evoked nocifensive behavior in mice exposed to lemon oil. In these mice, the change of formalin-induced c-Fos expression in the ACC, lateral PAG, NRM and SDH by lemon odor was also prevented. Antagonize of dopamine D1 receptor in the ACC prevented to the analgesic effect of lemon oil. Conclusions These results suggest that the analgesic effect of lemon oil is induced by dopamine-related activation of ACC and the descending pain inhibitory system. PMID:24555533

  15. Zeaxanthin and α-tocopherol reduce the inhibitory effects of photodynamic stress on phagocytosis by ARPE-19 cells.

    PubMed

    Olchawa, Magdalena M; Herrnreiter, Anja M; Pilat, Anna K; Skumatz, Christine M B; Niziolek-Kierecka, Magdalena; Burke, Janice M; Sarna, Tadeusz J

    2015-12-01

    Zeaxanthin and α-tocopherol have been previously shown to efficiently protect liposomal membrane lipids against photosensitized peroxidation, and to protect cultured RPE cells against photodynamic killing. Here the protective action of combined zeaxanthin and α-tocopherol was analyzed in ARPE-19 cells subjected to photodynamic (PD) stress mediated by rose Bengal (RB) or merocyanine-540 (MC-540) at sub-lethal levels. Stress-induced cytotoxicity was analyzed by the MTT assay. The peroxidation of membrane lipids was determined by HPLC-EC (Hg) measurements of cholesterol hydroperoxides using cholesterol as a mechanistic reporter molecule. The specific phagocytosis of FITC-labeled photoreceptor outer segments (POS) isolated from bovine retinas was measured by flow cytometry, and the levels of phagocytosis receptor proteins αv integrin subunit, β5 integrin subunit and MerTK were quantified by Western blot analysis. Cytotoxicity measures confirmed that PD stress levels used for phagocytosis analysis were sub-lethal and that antioxidant supplementation protected against higher, lethal PD doses. Sub-lethal PD stress mediated by both photosensitizers induced the accumulation of 5α-OOH and 7α/β-OOH cholesterol hydroperoxides and the addition of the antioxidants substantially inhibited their accumulation. Antioxidant delivery prior to PD stress also reduced the inhibitory effect of stress on POS phagocytosis and partially reduced the stress-induced diminution of phagocytosis receptor proteins. The use of a novel model system where oxidative stress was induced at sub-lethal levels enable observations that would not be detectable using lethal stress models. Moreover, novel observations about the protective effects of zeaxanthin and α-tocopherol on photodynamic damage to ARPE-19 cell membranes and against reductions in the abundance of receptor proteins involved in POS phagocytosis, a process essential for photoreceptor survival, supports the importance of the

  16. Inhibitory effect of hydroxypropyl methylcellulose acetate succinate on drug recrystallization from a supersaturated solution assessed using nuclear magnetic resonance measurements.

    PubMed

    Ueda, Keisuke; Higashi, Kenjirou; Yamamoto, Keiji; Moribe, Kunikazu

    2013-10-01

    We examined the inhibitory effect of hydroxypropyl methylcellulose acetate succinate (HPMC-AS) on drug recrystallization from a supersaturated solution using carbamazepine (CBZ) and phenytoin (PHT) as model drugs. HPMC-AS HF grade (HF) inhibited the recrystallization of CBZ more strongly than that by HPMC-AS LF grade (LF). 1D-1H NMR measurements showed that the molecular mobility of CBZ was clearly suppressed in the HF solution compared to that in the LF solution. Interaction between CBZ and HF in a supersaturated solution was directly detected using nuclear Overhauser effect spectroscopy (NOESY). The cross-peak intensity obtained using NOESY of HF protons with CBZ aromatic protons was greater than that with the amide proton, which indicated that CBZ had hydrophobic interactions with HF in a supersaturated solution. In contrast, no interaction was observed between CBZ and LF in the LF solution. Saturation transfer difference NMR measurement was used to determine the interaction sites between CBZ and HF. Strong interaction with CBZ was observed with the acetyl substituent of HPMC-AS although the interaction with the succinoyl substituent was quite small. The acetyl groups played an important role in the hydrophobic interaction between HF and CBZ. In addition, HF appeared to be more hydrophobic than LF because of the smaller ratio of the succinoyl substituent. This might be responsible for the strong hydrophobic interaction between HF and CBZ. The intermolecular interactions between CBZ and HPMC-AS shown by using NMR spectroscopy clearly explained the strength of inhibition of HPMC-AS on drug recrystallization.

  17. Zeaxanthin and α-tocopherol reduce the inhibitory effects of photodynamic stress on phagocytosis by ARPE-19 cells

    PubMed Central

    Olchawa, Magdalena M.; Herrnreiter, Anja M.; Pilat, Anna K.; Skumatz, Christine M. B.; Niziolek-Kierecka, Magdalena; Burke, Janice M.; Sarna, Tadeusz J.

    2016-01-01

    Zeaxanthin and α-tocopherol have been previously shown to efficiently protect liposomal membrane lipids against photosensitized peroxidation, and to protect cultured RPE cells against photodynamic killing. Here the protective action of combined zeaxanthin and α-tocopherol was analyzed in ARPE-19 cells subjected to photodynamic (PD) stress mediated by rose Bengal (RB) or merocyanine-540 (MC-540) at sub-lethal levels. Stress-induced cytotoxicity was analyzed by the MTT assay. The peroxidation of membrane lipids was determined by HPLC-EC(Hg) measurements of cholesterol hydroperoxides using cholesterol as a mechanistic reporter molecule. The specific phagocytosis of FITC-labeled photoreceptor outer segments (POS) isolated from bovine retinas was measured by flow cytometry, and the levels of phagocytosis receptor proteins αv integrin subunit, β5 integrin subunit and MerTK were quantified by Western blot analysis. Cytotoxicity measures confirmed that PD stress levels used for phagocytosis analysis were sub-lethal and that antioxidant supplementation protected against higher, lethal PD doses. Sub-lethal PD stress mediated by both photosensitizers induced the accumulation of 5α-OOH and 7α/β-OOH cholesterol hydroperoxides and the addition of the antioxidants substantially inhibited their accumulation. Antioxidant delivery prior to PD stress also reduced the inhibitory effect of stress on POS phagocytosis and partially reduced the stress-induced diminution of phagocytosis receptor proteins. The use of a novel model system where oxidative stress was induced at sub-lethal levels enable observations that would not be detectable using lethal stress models. Moreover, novel observations about the protective effects of zeaxanthin and α-tocopherol on photodynamic damage to ARPE-19 cell membranes and against reductions in the abundance of receptor proteins involved in POS phagocytosis, a process essential for photoreceptor survival, supports the importance of the antioxidants

  18. The inhibitory effects of Geranium thunbergii on interferon-γ- and LPS-induced inflammatory responses are mediated by Nrf2 activation.

    PubMed

    Choi, Hee-Jin; Choi, Hee-Jung; Park, Mi-Ju; Lee, Ji-Yeon; Jeong, Seung-Il; Lee, Seongoo; Kim, Kyun Ha; Joo, Myungsoo; Jeong, Han-Sol; Kim, Jai-Eun; Ha, Ki-Tae

    2015-05-01

    Geranium thunbergii Sieb. et Zucc. (GT; which belongs to the Geraniaceae family) has been used as a traditional medicine in East Asia for the treatment of inflammatory diseases, including arthritis and diarrhea. However, the underlying mechanisms of the anti-inflammatory effects of GT remain poorly understood. In the present study, we examined the mechanisms responsible for the anti-inflammatory activity of GT in macrophages. The results revealed that GT significantly inhibited the lipopolysaccharide (LPS)- and interferon-γ (IFN-γ)-induced expression of pro-inflammatory genes, such as inducible nitric oxide synthase, tumor necrosis factor-α and interleukin-1β, as shown by RT-PCR. However, the inhibitory effects of GT on LPS- and IFN-γ-induced inflammation were associated with an enhanced nuclear factor erythroid 2-related factor 2 (Nrf2) activity, but not with the suppression of nuclear factor (NF)-κB activity, as shown by western blot analysis. In addition, in bone marrow-derived macrophages (BMDM) isolated from Nrf2 knockout mice, GT did not exert any inhibitory effect on the LPS- and IFN-γ-induced inflammation. Taken together, our findings indicate that the anti-inflammatory effects of GT may be associated with the activation of Nrf2, an anti-inflammatory transcription factor.

  19. Cooperative inhibitory effects of antisense oligonucleotide of cell adhesion molecules and cimetidine on cancer cell adhesion

    PubMed Central

    Tang, Nan-Hong; Chen, Yan-Ling; Wang, Xiao-Qian; Li, Xiu-Jin; Yin, Feng-Zhi; Wang, Xiao-Zhong

    2004-01-01

    AIM: To explore the cooperative effects of antisense oligonucleotide (ASON) of cell adhesion molecules and cimetidine on the expression of E-selectin and ICAM-1 in endothelial cells and their adhesion to tumor cells. METHODS: After treatment of endothelial cells with ASON and/or cimetidine and induction with TNF-α, the protein and mRNA changes of E-selectin and ICAM-1 in endothelial cells were examined by flow cytometry and RT-PCR, respectively. The adhesion rates of endothelial cells to tumor cells were measured by cell adhesion experiment. RESULTS: In comparison with TNF-α inducing group, lipo-ASON and lipo-ASON/cimetidine could significantly decrease the protein and mRNA levels of E-selectin and ICAM-1 in endothelial cells, and lipo-ASON/cimetidine had most significant inhibitory effect on E-selectin expression (from 36.37 ± 1.56% to 14.23 ± 1.07%, P < 0.001). Meanwhile, cimetidine alone could inhibit the expression of E-selectin (36.37 ± 1.56% vs 27.2 ± 1.31%, P < 0.001), but not ICAM-1 (69.34 ± 2.50% vs 68.07 ± 2.10%, P > 0.05)and the two kinds of mRNA, either. Compared with TNF-α inducing group, the rate of adhesion was markedly decreased in lipo-E-selectin ASON and lipo-E-selectin ASON/cimetidine treated groups(P < 0.05), and lipo-E-selectin ASON/cimetidine worked better than lipo-E-selectin ASON alone except for HepG2/ECV304 group (P < 0.05). However, the decrease of adhesion was not significant in lipo-ICAM-1 ASON and lipo-ICAM-1 ASON/cimetidine treated groups except for HepG2/ECV304 group (P > 0.05). CONCLUSION: These data demonstrate that ASON in combination with cimetidine in vitro can significantly reduce the adhesion between endothelial cells and hepatic or colorectal cancer cells, which is stronger than ASON or cimetidine alone. This study provides some useful proofs for gene therapy of antiadhesion. PMID:14695770

  20. The effect of chemical additives on the synthesis of ethanol

    SciTech Connect

    Chuang, S.S.C.

    1988-11-14

    The objective of this research is to elucidate the role of various chemical additives on ethanol synthesis over Rh- and Ni-based catalysts. Chemical additives used for this study will include S, P, Ag, Cu, Mn, and Na which have different electronegativities. The effect of additives on the surface state of the catalysts, heat of adsorption of reactant molecules, reaction intermediates, reaction pathways, reaction kinetics, and product distributions is/will be investigated by a series of experimental studies including temperature programmed desorption, infrared study of NO adsorption, reactive probing, steady state rate measurement, and transient kinetic study. A better understanding of the role of additive on the synthesis reaction may allow us to use chemical additives to manipulate the catalytic properties of Rh- and Ni-based catalysts for producing high yields of ethanol from syngas.

  1. The effect of chemical additives on the synthesis of ethanol

    SciTech Connect

    Chuang, S.S.C.

    1990-07-01

    The objective of this research is to elucidate the role of various chemical additives on ethanol synthesis over Rh- and Ni-based catalysts. Chemical additives used for this study will include S, P, Ag, Cu, Mn, and Na which have different electronegativities. The effect of additives on the surface state of the catalysts, heat of adsorption of reactant molecules, reaction intermediates, reaction pathways, reaction kinetics, and product distributions is/will be investigated by a series of experimental studies of NO adsorption, reaction probing, study state rate measurement, and transient kinetic study. A better understanding of the role of additive on the synthesis reaction may allow us to sue chemical additives to manipulate the catalytic properties of Rh- and Ni-based catalysts for producing high yields of ethanol from syngas. (VC)

  2. The effect of chemical additives on the synthesis of ethanol

    SciTech Connect

    Chuang, S.S.C.

    1990-11-01

    The objective of this research is to elucidate the role of additives on the ethanol synthesis over Rh- and Ni-based catalysts. Chemical additives used for this study will include S, P, Ag, Cu, Mn, and Na which have different electronegativities. The effect of additives on the surface state of the catalysts, heat of adsorption of reactant molecules, reaction intermediates, reaction pathways, reaction kinetics, and product distributions is/will be investigated by a series of experimental studies of NO adsorption, reaction probing, study state rate measurement, and transient kinetic study. A better understanding of the role of additive on the synthesis reaction may allow them to use chemical additives to manipulate the catalytic properties of Rh- and Ni-based catalysts for producing high yields of ethanol from syngas. 49 refs., 6 figs., 3 tabs.

  3. Effects of additives on alum hematoxylin staining solutions.

    PubMed

    Clark, G

    1975-03-01

    All additives tested (ethyl alcohol, glycerine, chloral hydrate, ethylene and propylene glycol, and citric, malonic and maleic acids) in varying degrees limited the conversion of hematein to insoluble compounds. Peak absorbances increased slightly in hematoxylin solutions containing citric, malonic and maleic acids, but decreased with other additives, and in controls. After four months storage the absorbance in all solutions increased about 50%, acidity increased and staining effectiveness increased.

  4. Cuminaldehyde as the Major Component of Cuminum cyminum, a Natural Aldehyde with Inhibitory Effect on Alpha-Synuclein Fibrillation and Cytotoxicity.

    PubMed

    Morshedi, Dina; Aliakbari, Farhang; Tayaranian-Marvian, Amir; Fassihi, Afshin; Pan-Montojo, Francisco; Pérez-Sánchez, Horacio

    2015-10-01

    Fibrillation of alpha-synuclein (α-SN) is a critical process in the pathophysiology of several neurodegenerative diseases, especially Parkinson's disease. Application of bioactive inhibitory compounds from herbal extracts is a potential therapeutic approach for this cytotoxic process. Here, we investigated the inhibitory effects of the Iranian Cuminum cyminum essential oil on the fibrillation of α-SN. Analysis of different fractions from the total extract identified cuminaldehyde as the active compound involved in the antifibrillation activity. In comparison with baicalein, a well-known inhibitor of α-SN fibrillation, cuminaldehyde showed the same activity in some aspects and a different activity on other parameters influencing α-SN fibrillation. The presence of spermidine, an α-SN fibrillation inducer, dominantly enforced the inhibitory effects of cuminaldehyde even more intensively than baicalein. Furthermore, the results from experiments using preformed fibrils and monobromobimane-labeled monomeric protein also suggest that cuminaldehyde prevents α-SN fibrillation even in the presence of seeds, having no disaggregating impact on the preformed fibrils. Structural studies showed that cuminaldehyde stalls protein assembly into β-structural fibrils, which might be achieved by the interaction with amine groups through its aldehyde group as a Schiff base reaction. This assumption was supported by FITC labeling efficiency assay. In addition, cytotoxicity assays on PC12 cells showed that cuminaldehyde is a nontoxic compound, treatment with cuminaldehyde throughout α-SN fibrillation showed no toxic effects on the cells. Taken together, these results show for the first time that the small abundant natural compound, cuminaldehyde, can modulate α-SN fibrillation. Hence, suggesting that such natural active aldehyde could have potential therapeutic applications.

  5. Time-dependent inhibitory effects of cGMP-analogues on thrombin-induced platelet-derived microparticles formation, platelet aggregation, and P-selectin expression.

    PubMed

    Nygaard, Gyrid; Herfindal, Lars; Kopperud, Reidun; Aragay, Anna M; Holmsen, Holm; Døskeland, Stein Ove; Kleppe, Rune; Selheim, Frode

    2014-07-01

    In platelets, nitric oxide (NO) activates cGMP/PKG signalling, whereas prostaglandins and adenosine signal through cAMP/PKA. Cyclic nucleotide signalling has been considered to play an inhibitory role in platelets. However, an early stimulatory effect of NO and cGMP-PKG signalling in low dose agonist-induced platelet activation have recently been suggested. Here, we investigated whether different experimental conditions could explain some of the discrepancy reported for platelet cGMP-PKG-signalling. We treated gel-filtered human platelets with cGMP and cAMP analogues, and used flow cytometric assays to detect low dose thrombin-induced formation of small platelet aggregates, single platelet disappearance (SPD), platelet-derived microparticles (PMP) and thrombin receptor agonist peptide (TRAP)-induced P-selectin expression. All four agonist-induced platelet activation phases were blocked when platelets were costimulated with the PKG activators 8-Br-PET-cGMP or 8-pCPT-cGMP and low-doses of thrombin or TRAP. However, extended incubation with 8-Br-PET-cGMP decreased its inhibition of TRAP-induced P-selectin expression in a time-dependent manner. This effect did not involve desensitisation of PKG or PKA activity, measured as site-specific VASP phosphorylation. Moreover, PKG activators in combination with the PKA activator Sp-5,6-DCL-cBIMPS revealed additive inhibitory effect on TRAP-induced P-selectin expression. Taken together, we found no evidence for a stimulatory role of cGMP/PKG in platelets activation and conclude rather that cGMP/PKG signalling has an important inhibitory function in human platelet activation.

  6. Cuminaldehyde as the Major Component of Cuminum cyminum, a Natural Aldehyde with Inhibitory Effect on Alpha-Synuclein Fibrillation and Cytotoxicity.

    PubMed

    Morshedi, Dina; Aliakbari, Farhang; Tayaranian-Marvian, Amir; Fassihi, Afshin; Pan-Montojo, Francisco; Pérez-Sánchez, Horacio

    2015-10-01

    Fibrillation of alpha-synuclein (α-SN) is a critical process in the pathophysiology of several neurodegenerative diseases, especially Parkinson's disease. Application of bioactive inhibitory compounds from herbal extracts is a potential therapeutic approach for this cytotoxic process. Here, we investigated the inhibitory effects of the Iranian Cuminum cyminum essential oil on the fibrillation of α-SN. Analysis of different fractions from the total extract identified cuminaldehyde as the active compound involved in the antifibrillation activity. In comparison with baicalein, a well-known inhibitor of α-SN fibrillation, cuminaldehyde showed the same activity in some aspects and a different activity on other parameters influencing α-SN fibrillation. The presence of spermidine, an α-SN fibrillation inducer, dominantly enforced the inhibitory effects of cuminaldehyde even more intensively than baicalein. Furthermore, the results from experiments using preformed fibrils and monobromobimane-labeled monomeric protein also suggest that cuminaldehyde prevents α-SN fibrillation even in the presence of seeds, having no disaggregating impact on the preformed fibrils. Structural studies showed that cuminaldehyde stalls protein assembly into β-structural fibrils, which might be achieved by the interaction with amine groups through its aldehyde group as a Schiff base reaction. This assumption was supported by FITC labeling efficiency assay. In addition, cytotoxicity assays on PC12 cells showed that cuminaldehyde is a nontoxic compound, treatment with cuminaldehyde throughout α-SN fibrillation showed no toxic effects on the cells. Taken together, these results show for the first time that the small abundant natural compound, cuminaldehyde, can modulate α-SN fibrillation. Hence, suggesting that such natural active aldehyde could have potential therapeutic applications. PMID:26351865

  7. Phytochemical screening of Nepeta cataria extracts and their in vitro inhibitory effects on free radicals and carbohydrate-metabolising enzymes.

    PubMed

    Naguib, Abdel Moneam Mohamed; Ebrahim, Mohamed Elsayed; Aly, Hanan Farouk; Metawaa, Hemaia Mohamed; Mahmoud, Ahlam Hosni; Mahmoud, Ebtissam A; Ebrahim, Faten Mohamed

    2012-01-01

    This research was performed to investigate in vitro the biological activities of successive as well as 70% ethanol extracts of Nepeta cataria on some biochemical parameters including oxidative markers and carbohydrate-hydrolysing enzyme activities (α-amylase, β-galactosidase and α-glucosidase). Powdered N. cataria and its successive extracts were screened for their phytochemical constituents. Tests for tannins, carbohydrates, glycosides and flavonoids were positive in ethanolic extract, but those for steroids and terpenoids were positive in petroleum ether and chloroform extracts. Also, different extracts were chromatographically investigated. The results obtained demonstrated that different successive extracts of N. cataria exhibited an inhibitory effect on oxidative stress indices and carbohydrate-hydrolysing enzymes. It is observed that 70% ethanol, petroleum ether and chloroform extracts showed, respectively, the most potent inhibitory activities, while ethyl acetate and ethanol successive extracts appeared with moderate or low reducing activities.

  8. Phytochemical screening of Nepeta cataria extracts and their in vitro inhibitory effects on free radicals and carbohydrate-metabolising enzymes.

    PubMed

    Naguib, Abdel Moneam Mohamed; Ebrahim, Mohamed Elsayed; Aly, Hanan Farouk; Metawaa, Hemaia Mohamed; Mahmoud, Ahlam Hosni; Mahmoud, Ebtissam A; Ebrahim, Faten Mohamed

    2012-01-01

    This research was performed to investigate in vitro the biological activities of successive as well as 70% ethanol extracts of Nepeta cataria on some biochemical parameters including oxidative markers and carbohydrate-hydrolysing enzyme activities (α-amylase, β-galactosidase and α-glucosidase). Powdered N. cataria and its successive extracts were screened for their phytochemical constituents. Tests for tannins, carbohydrates, glycosides and flavonoids were positive in ethanolic extract, but those for steroids and terpenoids were positive in petroleum ether and chloroform extracts. Also, different extracts were chromatographically investigated. The results obtained demonstrated that different successive extracts of N. cataria exhibited an inhibitory effect on oxidative stress indices and carbohydrate-hydrolysing enzymes. It is observed that 70% ethanol, petroleum ether and chloroform extracts showed, respectively, the most potent inhibitory activities, while ethyl acetate and ethanol successive extracts appeared with moderate or low reducing activities. PMID:22103287

  9. Empirical prediction and validation of antibacterial inhibitory effects of various plant essential oils on common pathogenic bacteria.

    PubMed

    Akdemir Evrendilek, Gulsun

    2015-06-01

    In this study, fractional compound composition, antioxidant capacity, and phenolic substance content of 14 plant essential oils-anise (Pimpinella anisum), bay leaves (Laurus nobilis), cinnamon bark (Cinnamomum verum), clove (Eugenia caryophyllata), fennel (Foeniculum vulgare), hop (Humulus lupulus), Istanbul oregano (Origanum vulgare subsp. hirtum), Izmir oregano (Origanum onites), mint (Mentha piperita), myrtus (Myrtus communis), orange peel (Citrus sinensis), sage (Salvia officinalis), thyme (Thymbra spicata), and Turkish oregano (Origanum minutiflorum)--were related to inhibition of 10 bacteria through multiple linear or non-linear (M(N)LR) models-four Gram-positive bacteria of Listeria innocua, coagulase-negative staphylococci, Staphylococcus aureus, and Bacillus subtilis, and six Gram-negative bacteria of Yersinia enterocolitica, Salmonella Enteritidis, Salmonella Typhimurium, Proteus mirabilis, Escherichia coli O157:H7, and Klebsiella oxytoca. A total of 65 compounds with different antioxidant capacity, phenolic substance content and antibacterial properties were detected with 14 plant essential oils. The best-fit M(N)LR models indicated that relative to anise essential oil, the essential oils of oreganos, cinnamon, and thyme had consistently high inhibitory effects, while orange peel essential oil had consistently a low inhibitory effect. Regression analysis indicated that beta-bisabolene (Turkish and Istanbul oreganos), and terpinolene (thyme) were found to be the most inhibitory compounds regardless of the bacteria type tested. PMID:25764982

  10. Inhibitory effects of catechin gallates on o-methyltranslation of protocatechuic acid in rat liver cytosolic preparations and cultured hepatocytes.

    PubMed

    Kadowaki, Masaaki; Ootani, Emi; Sugihara, Narumi; Furuno, Koji

    2005-08-01

    Flavonoids including tea catechins and gallic acid esters were characterized for their ability to inhibit o-methyltranslation of protocatechuic acid (PCA) to form vanillic acid (VA) in rat liver cytosolic preparations and cultured hepatocytes. Flavonols and flavones exhibited different behaviors in inhibiting the formation of VA between the cell-free enzymatic preparations and the intact cells. The underlying mechanism of the inhibitory effects of flavonols and flavones on PCA o-methylation in cultured hepatocytes may not be due to the inhibition of the enzyme activity of catechol o-methyl transferase (COMT). Catechin gallates inhibited PCA o-methylation in liver cytosolic preparations with markedly higher potency than other flavonoids. As compared with catechin gallates, ungallated catechins had two to three orders of magnitude lower efficiency in inhibiting cytosolic PCA o-methylation. Gallic acid esters inhibited cytosolic PCA o-methylation with strong potency almost equal to that of catechin gallates. These results suggest that the COMT-inhibitory activity of catechin gallates is derived from the presence of the galloyl moiety at the C3 position in the C-ring. Catechin gallates and gallic acid esters inhibited PCA o-methylation in cultured hepatocytes with two orders of magnitude lower efficacy than that in cytosolic preparations. The inhibitory effects of catechin gallates and gallic acid esters on cellular PCA o-methylation appear to be due to the direct inhibition of COMT activity.

  11. Empirical prediction and validation of antibacterial inhibitory effects of various plant essential oils on common pathogenic bacteria.

    PubMed

    Akdemir Evrendilek, Gulsun

    2015-06-01

    In this study, fractional compound composition, antioxidant capacity, and phenolic substance content of 14 plant essential oils-anise (Pimpinella anisum), bay leaves (Laurus nobilis), cinnamon bark (Cinnamomum verum), clove (Eugenia caryophyllata), fennel (Foeniculum vulgare), hop (Humulus lupulus), Istanbul oregano (Origanum vulgare subsp. hirtum), Izmir oregano (Origanum onites), mint (Mentha piperita), myrtus (Myrtus communis), orange peel (Citrus sinensis), sage (Salvia officinalis), thyme (Thymbra spicata), and Turkish oregano (Origanum minutiflorum)--were related to inhibition of 10 bacteria through multiple linear or non-linear (M(N)LR) models-four Gram-positive bacteria of Listeria innocua, coagulase-negative staphylococci, Staphylococcus aureus, and Bacillus subtilis, and six Gram-negative bacteria of Yersinia enterocolitica, Salmonella Enteritidis, Salmonella Typhimurium, Proteus mirabilis, Escherichia coli O157:H7, and Klebsiella oxytoca. A total of 65 compounds with different antioxidant capacity, phenolic substance content and antibacterial properties were detected with 14 plant essential oils. The best-fit M(N)LR models indicated that relative to anise essential oil, the essential oils of oreganos, cinnamon, and thyme had consistently high inhibitory effects, while orange peel essential oil had consistently a low inhibitory effect. Regression analysis indicated that beta-bisabolene (Turkish and Istanbul oreganos), and terpinolene (thyme) were found to be the most inhibitory compounds regardless of the bacteria type tested.

  12. Inhibitory Effects of Highly Oxygenated Lanostane Derivatives from the Fungus Ganoderma lucidum on P-Glycoprotein and α-Glucosidase.

    PubMed

    Zhao, Xi-Run; Huo, Xiao-Kui; Dong, Pei-Pei; Wang, Chao; Huang, Shan-Shan; Zhang, Bao-Jing; Zhang, Hou-Li; Deng, Sa; Liu, Ke-Xin; Ma, Xiao-Chi

    2015-08-28

    Twelve new highly oxygenated lanostane triterpenoids and nine known ganoderic acids were isolated from the fruiting body of Ganoderma lucidum. The new compounds were lanostane nortriterpenoids with 27 carbons (1-5 and 8), lanostane nor-triterpenoids with 25 carbons (6 and 7), and lanostane triterpenoids (9-12) based on multiple spectroscopic data analysis, including HRESIMS, 1D-NMR, 2D-NMR, and CD. Compounds 1-5 were identified as rare nor-lanostanoids that contain a 17β-pentatomic lactone ring. Compound 13, possessing a lactone ring, had been isolated previously. The P-glycoprotein (P-gp) inhibitory effects of compounds 1-21 were evaluated at a concentration of 20 μM using an adriamycin (ADM)-resistant human breast adenocarcinoma cell line (MCF-7/ADR). Compounds 1, 5, 18, and 20 and verapamil increased the accumulation of ADM in MCF-7/ADR cells approximately 3-fold when compared with the negative control. These data support the significant P-glycoprotein inhibitory activities of compounds 1, 5, 18, and 20. In silico docking analysis suggested these compounds had similar P-gp recognition mechanisms compared with those of verapamil (a classical inhibitor). Furthermore, in an in vitro bioassay, compounds 2, 4, 5, 6, and 18 showed moderate inhibitory effects against α-glucosidase compared with those of the positive control acarbose.

  13. Inhibitory Effects of Physalis alkekengi L., Alcea rosea L., Bunium persicum B. Fedtsch. and Marrubium vulgare L. on Mushroom Tyrosinase

    PubMed Central

    Namjoyan, Foroogh; Jahangiri, Alireza; Azemi, Mohammad Ebrahim; Arkian, Elaheh; Mousavi, Hamideh

    2015-01-01

    Background: The key enzyme in the process of melanin biosynthesis is tyrosinase. Skin hyperpigmentation and browning of foods are undesirable phenomena which tyrosinase represents. Therefore, tyrosinase inhibitors have been used increasingly for medicinal and cosmetic products. Objectives: In this study, inhibitory effects of four plants including: physalis alkekengi L., Alcea rosea L., Bunium persicum B. Fedtsch. and Marrubium vulgare L. on diphenolase activity of mushroom tyrosinase were evaluated. Materials and Methods: The inhibitory activities of hydroalcoholic extracts of plants against oxidation of L-Dopa (as a substrate) by mushroom tyrosinase were investigated. Results: The hydroalcoholic extract of P. alkekengi showed the most tyrosinase inhibitory effect with IC50 of 0.09 mg/mL vs. 0.38, 0.38 and 2.82 mg/mL of B. persicum, A. rosea and M. vulgare, respectively. M. vulgare exhibited uncompetitive inhibition and other plants showed mixed type inhibition on mushroom tyrosinase. Conclusions: All plants could inhibit mushroom tyrosinase, but more investigations on human tyrosinase and clinical studies are needed. PMID:25866725

  14. Lysophospholipid receptors LPA1–3 are not required for the inhibitory effects of LPA on mouse retinal growth cones

    PubMed Central

    Birgbauer, Eric; Chun, Jerold

    2016-01-01

    One of the major requirements in the development of the visual system is axonal guidance of retinal ganglion cells toward correct targets in the brain. A novel class of extracellular lipid signaling molecules, lysophospholipids, may serve as potential axon guidance cues. They signal through cognate G protein-coupled receptors, at least some of which are expressed in the visual system. Here we show that in the mouse visual system, a lysophospholipid known as lysophosphatidic acid (LPA) is inhibitory to retinal neurites in vitro when delivered extracellularly, causing growth cone collapse and neurite retraction. This inhibitory effect of LPA is both active in the nanomolar range and specific compared to the related lysophospholipid, sphingosine 1-phosphate (S1P). Knockout mice lacking three of the five known LPA receptors, LPA1–3, continue to display retinal growth cone collapse and neurite retraction in response to LPA, demonstrating that these three receptors are not required for these inhibitory effects and indicating the existence of one or more functional LPA receptors expressed on mouse retinal neurites that can mediate neurite retraction. PMID:26966392

  15. Inhibitory Effect of Crocin(s) on Lens α-Crystallin Glycation and Aggregation, Results in the Decrease of the Risk of Diabetic Cataract.

    PubMed

    Bahmani, Fereshteh; Bathaie, Seyedeh Zahra; Aldavood, Seyed Javid; Ghahghaei, Arezou

    2016-01-01

    The current study investigates the inhibitory effect of crocin(s), also known as saffron apocarotenoids, on protein glycation and aggregation in diabetic rats, and α-crystallin glycation. Thus, crocin(s) were administered by intraperitoneal injection to normal and streptozotocin-induced diabetic rats. The cataract progression was recorded regularly every two weeks and was classified into four stages. After eight weeks, the animals were sacrificed and the parameters involved in the cataract formation were measured in the animal lenses. Some parameters were also determined in the serum and blood of the rats. In addition, the effect of crocin(s) on the structure and chaperone activity of α-crystallin in the presence of glucose was studied by different methods. Crocin(s) lowered serum glucose levels of diabetic rats and effectively maintained plasma total antioxidants, glutathione levels and catalase activity in the lens of the animals. In the in vitro study, crocin(s) inhibited α-crystallin glycation and aggregation. Advanced glycation end products fluorescence, hydrophobicity and protein cross-links were also decreased in the presence of crocin(s). In addition, the decreased chaperone activity of α-crystallin in the presence of glucose changed and became close to the native value by the addition of crocin(s) in the medium. Crocin(s) thus showed a powerful inhibitory effect on α-crystallin glycation and preserved the structure-function of this protein. Crocin(s) also showed the beneficial effects on prevention of diabetic cataract. PMID:26821002

  16. Study on thermal effects & sulfurized additives, in lubricating greases

    NASA Astrophysics Data System (ADS)

    Shah, Ami Atul

    Lithium Base grease constitutes about 50% of market. The greases are developed to be able to work in multiple working conditions and have longer working life. Greases with extreme pressure additives and anti-wear additives have been developed as a solution to many of the applications. These developed greases are tested under ASTM D2266 testing conditions to meet the requirements. The actual working conditions, although, differ than the real testing conditions. The loading, speed and temperature conditions can be more harsh, or fluctuating in nature. The cyclic nature of the parameters cannot be directly related to the test performance. For this purpose studies on the performance under spectrum loading, variable speed and fluctuating temperature must be performed. This study includes tests to understand the effect of thermal variation on some of the most commonly used grease additives that perform well under ASTM D2266 testing conditions. The studied additives include most widely used industrial extreme pressure additive MoS2. Performance of ZDDP which is trying to replace MoS2 in its industrial applications has also been studied. The tests cover study of extreme pressure, anti-wear and friction modifier additives to get a general idea on the effects of thermal variation in three areas. Sulphur is the most common extreme pressure additive. Sulphur based MoS 2 is extensively used grease additive. Study to understand the tribological performance of this additive through wear testing and SEM/EDX studies has been done. This performance is also studied for other metallic sulfides like WS2 and sulphur based organic compound. The aim is to study the importance of the type of bond that sulphur shares in its additive's structure on its performance. The MoS2 film formation is found to be on the basis of the FeS formation on the substrate and protection through sacrificial monolayer deposition of the MoS2 sheared structure. The free Mo then tends to oxidise. An attempt to

  17. Interaction of some limbic structures which exert inhibitory effect on corticosterone secretion.

    PubMed

    Suárez, M; Perassi, N I

    1990-12-01

    The interaction between limbic structures which exert inhibitory influence on corticosterone secretion was investigated in the rat. The following experiments were performed: 1) electrical stimulation at mammillary medial nucleus (MMN) in rats with lesioned anterodrosal thalami nucleus (ADTN) or intermediate tegmental area; 2) electrical stimulation at ADTN in rats with lesioned retrosplenial cortex (RC). Bilateral stimulation at MMN in ADTN or RC-lesioned rats produces an increase in plasma corticosterone concentration. In animals with lesioned RC, values of plasma corticosterone after stimulation at ADTN were higher than before stimulation. Taking into consideration that electrical stimulation of MMN or ADTN in intact rats produces a decrease in plasma corticosterone concentration, these studies demonstrate that MMN and ADTN exert inhibitory influence on corticoadrenal activity only when their projection areas remain intact.

  18. Facilitatory effect of substance P on learning and memory in the inhibitory avoidance test for goldfish.

    PubMed

    Santangelo, E M; Morato, S; Mattioli, R

    2001-05-01

    The aim of this study was to investigate if substance P (SP) can improve learning and memory processes in goldfish, using an inhibitory avoidance test. A two-compartment aquarium with a central sliding door was used. The animals were placed in the white compartment, and after 20 s the door was opened. As they entered the dark compartment, a weight was dropped in front of them. This procedure was repeated three times. After training, the animals were injected intraperitoneally with SP or vehicle. Twenty-four hours after training, the animals were tested and their latency was recorded. The group injected with SP showed an increase in the latency on the test day as compared with the vehicle group. These results suggest SP can facilitate memory in goldfish in an inhibitory avoidance test.

  19. Inhibitory effects of flavonoids on phosphodiesterase isozymes from guinea pig and their structure-activity relationships.

    PubMed

    Ko, Wun-Chang; Shih, Chwen-Ming; Lai, Ya-Hsin; Chen, Jun-Hao; Huang, Hui-Lin

    2004-11-15

    The structure-activity relationships of flavonoids with regard to their inhibitory effects on phosphodiesterase (PDE) isozymes are little known. The activities of PDE1-5 were measured by a two-step procedure using cAMP with [(3)H]-cAMP or cGMP with [(3)H]-cGMP as substrates. In the present results, PDE1, 5, 2, and 4 isozymes were partially purified from guinea pig lungs in that order, and PDE3 was from the heart. The IC(50) values of PDE1-5 were greater than those reported previously for the reference drugs, vinpocetin, EHNA, milrinone, Ro 20-1724, and zaprinast, by 5-, 5-, 7-, 5-, and 3-fold, respectively. As shown in Table 2, luteolin revealed non-selective inhibition of PDE1-5 with IC(50) values in a range of 10-20 microM, as did genistein except with a low potency on PDE5. Daidzein, an inactive analogue of genistein in tyrosine kinase inhibition, showed selective inhibition of PDE3 with an IC(50) value of around 30 microM, as did eriodictyol with an IC(50) value of around 50 microM. Hesperetin and prunetin exhibited more-selective inhibition of PDE4 with IC(50) values of around 30 and 60 microM, respectively. Luteolin-7-glucoside exhibited dual inhibition of PDE2/PDE4 with an IC(50) value of around 40 microM. Diosmetin more-selectively inhibited PDE2 (IC(50) of 4.8 microM) than PDE1, PDE4, or PDE5. However, biochanin A more-selectively inhibited PDE4 (IC(50) of 8.5 microM) than PDE1 or PDE2. Apigenin inhibited PDE1-3 with IC(50) values of around 10-25 microM. Myricetin inhibited PDE1-4 with IC(50) values of around 10-40 microM. The same was true for quercetin, but we rather consider that it more-selectively inhibited PDE3 and PDE4 (IC(50) of < 10 microM). In conclusion, it is possible to synthesize useful drugs through elucidating the structure-activity relationships of flavonoids with respect to inhibition of PDE isozymes at concentrations used in this in vitro study.

  20. Inhibitory effects of flavonoids on phosphodiesterase isozymes from guinea pig and their structure-activity relationships.

    PubMed

    Ko, Wun-Chang; Shih, Chwen-Ming; Lai, Ya-Hsin; Chen, Jun-Hao; Huang, Hui-Lin

    2004-11-15

    The structure-activity relationships of flavonoids with regard to their inhibitory effects on phosphodiesterase (PDE) isozymes are little known. The activities of PDE1-5 were measured by a two-step procedure using cAMP with [(3)H]-cAMP or cGMP with [(3)H]-cGMP as substrates. In the present results, PDE1, 5, 2, and 4 isozymes were partially purified from guinea pig lungs in that order, and PDE3 was from the heart. The IC(50) values of PDE1-5 were greater than those reported previously for the reference drugs, vinpocetin, EHNA, milrinone, Ro 20-1724, and zaprinast, by 5-, 5-, 7-, 5-, and 3-fold, respectively. As shown in Table 2, luteolin revealed non-selective inhibition of PDE1-5 with IC(50) values in a range of 10-20 microM, as did genistein except with a low potency on PDE5. Daidzein, an inactive analogue of genistein in tyrosine kinase inhibition, showed selective inhibition of PDE3 with an IC(50) value of around 30 microM, as did eriodictyol with an IC(50) value of around 50 microM. Hesperetin and prunetin exhibited more-selective inhibition of PDE4 with IC(50) values of around 30 and 60 microM, respectively. Luteolin-7-glucoside exhibited dual inhibition of PDE2/PDE4 with an IC(50) value of around 40 microM. Diosmetin more-selectively inhibited PDE2 (IC(50) of 4.8 microM) than PDE1, PDE4, or PDE5. However, biochanin A more-selectively inhibited PDE4 (IC(50) of 8.5 microM) than PDE1 or PDE2. Apigenin inhibited PDE1-3 with IC(50) values of around 10-25 microM. Myricetin inhibited PDE1-4 with IC(50) values of around 10-40 microM. The same was true for quercetin, but we rather consider that it more-selectively inhibited PDE3 and PDE4 (IC(50) of < 10 microM). In conclusion, it is possible to synthesize useful drugs through elucidating the structure-activity relationships of flavonoids with respect to inhibition of PDE isozymes at concentrations used in this in vitro study. PMID:15476679

  1. Inhibitory effect of isoprenoid-substituted flavonoids isolated from Artocarpus heterophyllus on melanin biosynthesis.

    PubMed

    Arung, Enos Tangke; Shimizu, Kuniyoshi; Kondo, Ryuichiro

    2006-07-01

    Isoprenoid-substituted flavonoids were isolated from the wood of Artocarpus heterophyllus by means of activity-guided fractionation. Artocarpin (1), cudraflavone C (2), 6-prenylapigenin (3), kuwanon C (4), norartocarpin (5) and albanin A (6) inhibited melanin biosynthesis in B16 melanoma cells without inhibiting tyrosinase. A structure-activity investigation indicated that the presence of the isoprenoid-substituted moiety enhanced the inhibitory activity on melanin production in B16 melanoma cells.

  2. Inhibitory effects of α-Na8SiW11CoO40 on tyrosinase and its application in controlling browning of fresh-cut apples.

    PubMed

    Chen, Bing-Nian; Xing, Rui; Wang, Fang; Zheng, A-Ping; Wang, Li

    2015-12-01

    α-Na8SiW11CoO40 was synthesized and characterized. The inhibitory effects of α-Na8SiW11CoO40 on the activity of mushroom tyrosinase and the effects of α-Na8SiW11CoO40 on the browning of fresh-cut apples were studied. The Native-PAGE result showed that α-Na8SiW11CoO40 had a significant inhibitory effect on tyrosinase. Kinetic analyses showed that α-Na8SiW11CoO40 was an irreversible and competitive inhibitor. The inhibitor concentration leading to a 50% reduction in activity (IC50) was estimated to be 0.239 mM. Additionally, the results also showed that α-Na8SiW11CoO40 treatment could significantly decrease the browning process of apple slices and inhibit the polyphenol oxidase (PPO) activity. Moreover, application of α-Na8SiW11CoO40 resulted in higher peroxidase activity and promoted high amounts of phenolic compounds and ascorbic acid. This study may provide a promising method for the use of polyoxometalates to inhibit tyrosinase activity and control the browning of fresh-cut apples.

  3. Inhibitory effects of α-Na8SiW11CoO40 on tyrosinase and its application in controlling browning of fresh-cut apples.

    PubMed

    Chen, Bing-Nian; Xing, Rui; Wang, Fang; Zheng, A-Ping; Wang, Li

    2015-12-01

    α-Na8SiW11CoO40 was synthesized and characterized. The inhibitory effects of α-Na8SiW11CoO40 on the activity of mushroom tyrosinase and the effects of α-Na8SiW11CoO40 on the browning of fresh-cut apples were studied. The Native-PAGE result showed that α-Na8SiW11CoO40 had a significant inhibitory effect on tyrosinase. Kinetic analyses showed that α-Na8SiW11CoO40 was an irreversible and competitive inhibitor. The inhibitor concentration leading to a 50% reduction in activity (IC50) was estimated to be 0.239 mM. Additionally, the results also showed that α-Na8SiW11CoO40 treatment could significantly decrease the browning process of apple slices and inhibit the polyphenol oxidase (PPO) activity. Moreover, application of α-Na8SiW11CoO40 resulted in higher peroxidase activity and promoted high amounts of phenolic compounds and ascorbic acid. This study may provide a promising method for the use of polyoxometalates to inhibit tyrosinase activity and control the browning of fresh-cut apples. PMID:26041180

  4. Effect of subinihibitory and inhibitory concentrations of Plectranthus amboinicus (Lour.) Spreng essential oil on Klebsiella pneumoniae.

    PubMed

    Gonçalves, Thially Braga; Braga, Milena Aguiar; de Oliveira, Francisco F M; Santiago, Gilvandete M P; Carvalho, Cibele B M; Brito e Cabral, Paula; de Melo Santiago, Thiago; Sousa, Jeanlex S; Barros, Eduardo Bedê; do Nascimento, Ronaldo Ferreira; Nagao-Dias, Aparecida T

    2012-08-15

    We evaluated the antimicrobial activity and some mechanisms used by subinhibitory and inhibitory concentrations of the essential oil, obtained from leaves of Plectranthus amboinicus, against a standard strain of Klebsiella pneumoniae and 5 multiresistant clinical isolates of the bacteria. The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC), the rate of kill and the pH sensitivity of the essential oil were determined by microdilution tests performed in 96-well plates. Subinhibitory and inhibitory concentrations of the essential oil were tested in order to check its action on K. pneumoniae membrane permeability, capsule expression, urease activity and cell morphology. The MIC and MBC of the essential oil were 0.09±0.01%. A complete inhibition of the bacterial growth was observed after 2 h of incubation with twice the MIC of the essential oil. A better MIC was found when neutral or alkaline pH broth was used. Alteration in membrane permeability was found by the increase of crystal violet uptake when the bacteria were incubated with twice the MIC levels of the essential oil. The urease activity could be prevented when all the subinhibitory concentrations were tested in comparison to the untreated group (p<0.001). Alteration of the bacterial morphology besides inhibition of the capsule expression was verified by atomic force microscopy, and Anthony's stain method, respectively. Our data allow us to conclude that the essential oil of P. amboinicus can be a good candidate for future research. PMID:22776104

  5. The Inhibitory Effect of Botulinum Toxin Type A on Rat Pyloric Smooth Muscle Contractile Response to Substance P In Vitro

    PubMed Central

    Shao, Yu-Feng; Xie, Jun-Fan; Ren, Yin-Xiang; Wang, Can; Kong, Xiang-Pan; Zong, Xiao-Jian; Fan, Lin-Lan; Hou, Yi-Ping

    2015-01-01

    A decrease in pyloric myoelectrical activity and pyloric substance P (SP) content following intrasphincteric injection of botulinum toxin type A (BTX-A) in free move rats have been demonstrated in our previous studies. The aim of the present study was to investigate the inhibitory effect of BTX-A on rat pyloric muscle contractile response to SP in vitro and the distributions of SP and neurokinin 1 receptor (NK1R) immunoreactive (IR) cells and fibers within pylorus. After treatment with atropine, BTX-A (10 U/mL), similar to [D-Arg1, D-Phe5, D-Trp7,9, Leu11]-SP (APTL-SP, 1 μmol/L) which is an NK1R antagonist, decreased electric field stimulation (EFS)-induced contractile tension and frequency, whereas, subsequent administration of APTL-SP did not act on contractility. Incubation with BTX-A at 4 and 10 U/mL for 4 h respectively decreased SP (1 μmol/L)-induced contractions by 26.64% ± 5.12% and 74.92% ± 3.62%. SP-IR fibers and NK1R-IR cells both located within pylorus including mucosa and circular muscle layer. However, fewer SP-fibers were observed in pylorus treated with BTX-A (10 U/mL). In conclusion, BTX-A inhibits SP release from enteric terminals in pylorus and EFS-induced contractile responses when muscarinic cholinergic receptors are blocked by atropine. In addition, BTX-A concentration- and time-dependently directly inhibits SP-induced pyloric smooth muscle contractility. PMID:26501321

  6. Ascorbic Acid Offsets the Inhibitory Effect of Bioactive Dietary Polyphenolic Compounds on Transepithelial Iron Transport in Caco-2 Intestinal Cells12

    PubMed Central

    Kim, Eun-Young; Ham, Soo-Kyung; Bradke, Daniel; Ma, Qianyi; Han, Okhee

    2011-01-01

    We previously reported that (-)-epigallocatechin-3-gallate (EGCG) and grape seed extract (GSE) at high concentration nearly blocked intestinal iron transport across the enterocyte. In this study, we aimed to determine whether small amounts of EGCG, GSE, and green tea extract (GT) are capable of inhibiting iron absorption, to examine if ascorbic acid counteracts the inhibitory action of polyphenols on iron absorption, and to explore the mechanisms of polyphenol-mediated apical iron uptake and basolateral iron release. An55Fe absorption study was conducted by adding various concentrations of EGCG, GSE, and GT using Caco-2 intestinal cells. Polyphenols were found to inhibit the transepithelial 55Fe transport in a dose-dependent manner. The addition of ascorbic acid offset the inhibitory effects of polyphenols on iron transport. Ascorbic acid modulated the transepithelial iron transport without changing the apical iron uptake and the expression of ferroportin-1 protein in the presence of EGCG. The polyphenol-mediated apical iron uptake was inhibited by membrane impermeable Fe2+ chelators (P < 0.001), but at a low temperature (4°C), the apical iron uptake was still higher than the control values at 37°C (P < 0.001). These results suggest that polyphenols enhance the apical iron uptake partially by reducing the conversion of ferric to ferrous ions and possibly by increasing the uptake of polyphenol-iron complexes via the energy-independent pathway. The present results indicate that the inhibitory effects of dietary polyphenols on iron absorption can be offset by ascorbic acid. Further studies are needed to confirm the current findings in vivo. PMID:21430251

  7. Effect of GdL Addition on Physico-chemical Properties of Fermented Sausages during Ripening

    PubMed Central

    Yim, Dong-Gyun

    2015-01-01

    This study investigated the effects of glucono-δ-lactone (GdL) addition on physicochemical and microbiological characteristics of fermented sausages during ripening and drying. Five batches of sausages were produced under ripening conditions: without GdL and with 0, 0.1, 0.25, 0.5 and 0.75% of GdL addition. Samples from each treatment were taken for physicochemical and microbiological analyses on the 0, 1, 3, 5, 7, 10, 15, 20 and 25th day of ripening. Chemical analysis showed a significant decrease in moisture content of sausages with increasing amounts of GdL added (p<0.05). The moisture contents decreased, whereas the fat, protein and ash contents increased throughout ripening (p<0.05). Increasing levels of GdL caused a decrease in the pH values (p<0.05), which can have an inhibitory effect against microflora. Water holding capacity content of samples decreased with increasing GdL concentration (p<0.05). The shear force values of fermented sausages showed the highest in T4 (p<0.05). During ripening, the shear force values of sausages were increased on the 25th day compared to day 0 (p<0.05). The higher GdL level produced lighter and more yellow sausages. The addition of 0.75% GdL was effective in controlling bacteria counts. Addition of GdL in sausages resulted in the physicochemical and microbiological attributes equal to or better than no addition of GdL without any harmful effect. PMID:26761846

  8. Inhibitory effect of natural organic matter or other background constituents on photocatalytic advanced oxidation processes: Mechanistic model development and validation.

    PubMed

    Brame, Jonathon; Long, Mingce; Li, Qilin; Alvarez, Pedro

    2015-11-01

    The ability of reactive oxygen species (ROS) to interact with priority pollutants is crucial for efficient water treatment by photocatalytic advanced oxidation processes (AOPs). However, background compounds in water such as natural organic matter (NOM) can significantly hinder targeted reactions and removal efficiency. This inhibition can be complex, interfering with degradation in solution and at the photocatalyst surface as well as hindering illumination efficiency and ROS production. We developed an analytical model to account for various inhibition mechanisms in catalytic AOPs, including competitive adsorption of inhibitors, scavenging of produced ROS at the surface and in solution, and the inner filtering of the excitation illumination, which combine to decrease ROS-mediated degradation. This model was validated with batch experiments using a variety of ROS producing systems (OH-generating TiO2 photocatalyst and H2O2-UV; (1)O2-generating photosensitive functionalized fullerenes and rose bengal) and inhibitory compounds (NOM, tert-butyl alcohol). Competitive adsorption by NOM and ROS scavenging were the most influential inhibitory mechanisms. Overall, this model enables accurate simulation of photocatalytic AOP performance when one or more inhibitory mechanisms are at work in a wide variety of application scenarios, and underscores the need to consider the effects of background constituents on degradation efficiency.

  9. Effect of inhibitory avoidance training on [3H]-glutamate binding in the hippocampus and parietal cortex of rats.

    PubMed

    Schröder, N; De-Paris, F; Roesler, R; Medina, J H; Souza, D O; Izquierdo, I

    2000-02-01

    Glutamate receptors have been implicated in memory formation. The aim of the present study was to determine the effect of inhibitory avoidance training on specific [3H]-glutamate binding to membranes obtained from the hippocampus or parietal cortex of rats. Adult male Wistar rats were trained (0.5-mA footshock) in a step-down inhibitory avoidance task and were sacrificed 0, 5, 15 or 60 min after training. Hippocampus and parietal cortex were dissected and membranes were prepared and incubated with 350 nM [3H]-glutamate (N = 4-6 per group). Inhibitory avoidance training induced a 29% increase in glutamate binding in hippocampal membranes obtained from rats sacrificed at 5 min (P<0.01), but not at 0, 15, or 60 min after training, and did not affect glutamate binding in membranes obtained from the parietal cortex. These results are consistent with previous evidence for the involvement of glutamatergic synaptic modification in the hippocampus in the early steps of memory formation.

  10. Inhibitory effects of superoxide dismutase and cyclic guanosine 3',5'-monophosphate on estrogen production in cultured rat granulosa cells.

    PubMed

    LaPolt, P S; Hong, L S

    1995-12-01

    Superoxide dismutases (SOD) modulate oxygen free radical metabolism and influence second messenger signaling in a variety of cell types. We have investigated the influence and possible mechanisms of action of SOD on aromatase activity in cultured rat granulosa cells. Although treatment of granulosa cells with FSH (0.3-30 ng/ml) resulted in a dose-dependent stimulation of estrogen levels, cotreatment of cells with SOD (10(-6) M) significantly attenuated estrogen production at the highest doses of FSH. The effects of SOD were dose dependent between 10(-7)-10(-5) M, with increasing amounts of SOD causing decreasing concentrations of estrogen. Cotreatment of cells with catalase (1500 U/ml) failed to prevent the inhibitory influence of SOD on estrogen production, indicating that the effects of SOD were not due to accumulation of hydrogen peroxide. Although incubation with either forskolin or (Bu)2cAMP alone stimulated estrogen production from granulosa cells, cotreatment with SOD significantly attenuated estrogen levels, indicating that SOD can inhibit aromatase activity at one or more post-FSH receptor sites. Treatment of cells with SOD, FSH, or forskolin resulted in small, but significant, increase in cGMP concentrations. In contrast, cotreatment of cells with FSH plus SOD as well as forskolin plus SOD had a marked synergistic effect on cGMP content, increasing cGMP levels over 100-fold. Incubation of granulosa cells with (Bu)2cGMP (2 mM) significantly decreased FSH-induced estrogen levels in a dose-dependent manner (0.25-2 mM). In addition, (Bu)2cGMP attenuated both forskolin- and (Bu)2cAMP-induced estrogen production. In contrast to the effects of (Bu)2cGMP and SOD on estradiol levels, these agents had no significant effect on progesterone production by cultured granulosa cells. These results demonstrate attenuated induction of aromatase activity by FSH in cultured rat granulosa cells cotreated with SOD, suggesting a potential modulatory role of this antioxidant on

  11. In vitro and in silico studies of the inhibitory effects of some novel kojic acid derivatives on tyrosinase enzyme

    PubMed Central

    Asadzadeh, Azizeh; Sirous, Hajar; Pourfarzam, Morteza; Yaghmaei, Parichehreh; Afshin, Fassihi

    2016-01-01

    Objective(s): Tyrosinase is a key enzyme in pigment synthesis. Overproduction of melanin in parts of the skin results in hyperpigmentation diseases. This enzyme is also responsible for the enzymatic browning in fruits and vegetables. Thus, its inhibitors are of great importance in the medical, cosmetic and agricultural fields. Materials and Methods: A series of twelve kojic acid derivatives were designed to be evaluated as tyrosinase activity inhibitors. The potential inhibitory activity of these compounds was investigated in silico using molecular docking simulation method. Four compounds with a range of predicted tyrosinase inhibitory activities were prepared and their inhibitory effect on tyrosinase activity was evaluated. The antioxidant properties of these compounds were also investigated by in vitro DPPH (2,2-diphenyl-1-picrylhydrazyl) and hydrogen peroxide scavenging assays. Results: Compound IIId exhibited the highest tyrosinase inhibitory activity with an IC50 value of 0.216 ± 0.009 mM which was in accordance with the in silico ΔGbind results (-13.24 Kcal/mol). Conclusion: Based on the docking studies, from the twelve compounds studied, one (IIId) appeared to have the highest inhibition on tyrosinase activity. This was confirmed by enzyme activity measurements. Compound IIId has an NO2 group which binds to both of Cu2+ ions located inside the active site of the enzyme. This compound appeared to be even stronger than kojic acid in inhibiting tyrosinase activity. The DPPH free radical scavenging ability of all the studied compounds was more than that of BHT. However, they were not as strong as BHT or gallic acid in scavenging hydrogen peroxide. PMID:27081457

  12. microRNA-145 Mediates the Inhibitory Effect of Adipose Tissue-Derived Stromal Cells on Prostate Cancer.

    PubMed

    Takahara, Kiyoshi; Ii, Masaaki; Inamoto, Teruo; Nakagawa, Takatoshi; Ibuki, Naokazu; Yoshikawa, Yuki; Tsujino, Takuya; Uchimoto, Taizo; Saito, Kenkichi; Takai, Tomoaki; Tanda, Naoki; Minami, Koichiro; Uehara, Hirofumi; Komura, Kazumasa; Hirano, Hajime; Nomi, Hayahito; Kiyama, Satoshi; Asahi, Michio; Azuma, Haruhito

    2016-09-01

    Adipose-derived stromal cell (ASC), known as one of the mesenchymal stem cells (MSCs), is a promising tool for regenerative medicine; however, the effect of ASCs on tumor growth has not been studied sufficiently. We investigated the hypothesis that ASCs have an inhibitory effect on metastatic tumor progression. To evaluate the in vitro inhibitory effect of ASCs on metastatic prostate cancer (PCa), direct coculture and indirect separate culture experiments with PC3M-luc2 cells and human ASCs were performed, and ASCs were administered to PC3M-luc2 cell-derived tumor-bearing nude mice for in vivo experiment. We also performed exosome microRNA (miRNA) array analysis to explore a mechanistic insight into the effect of ASCs on PCa cell proliferation/apoptosis. Both in vitro and in vivo experiments exhibited the inhibitory effect of ASCs on PC3M-luc2 cell proliferation, inducing apoptosis and PCa growth, respectively. Among upregulated miRNAs in ASCs compared with fibroblasts, we focused on miR-145, which was known as a tumor suppressor. ASC-derived conditioned medium (CM) significantly inhibited PC3M-luc2 cell proliferation, inducing apoptosis, but the effect was canceled by miR-145 knockdown in ASCs. ASC miR-145 knockdown CM also reduced the expression of Caspase 3/7 with increased antiapoptotic protein, BclxL, expression in PC3M-luc2 cells. This study provides preclinical data that ASCs inhibit PCa growth, inducing PCa cell apoptosis with reduced activity of BclxL, at least in part, by miR-145, including exosomes released from ASCs, suggesting that ASC administration could be a novel and promising therapeutic strategy in patients with PCa. PMID:27465939

  13. Concentration-dependent inhibitory effects of apolipoprotein E on Alzheimer's beta-amyloid fibril formation in vitro.

    PubMed

    Naiki, H; Gejyo, F; Nakakuki, K

    1997-05-20

    Recently, many research groups have examined the effect of apolipoprotein E (apoE) on beta-amyloid fibril (betaAf) formation in vitro. However, their data were somewhat controversial and no exact kinetic assessment of the role of apoE has thus far been available. We examined the effect of human apoE on betaAf formation in vitro, starting with various concentrations of freshly prepared beta-amyloid(1-40) (beta1-40) and using fluorescence spectroscopy with thioflavine T. When 50 microM of beta1-40 was incubated with a 1:1000 to 1:100 molar ratio of apoE, a dose-dependent inhibitory effect of apoE was observed. Both the nucleation and extension phases of betaAf formation in vitro were inhibited by apoE. On the other hand, when 300 microM of beta1-40 was incubated with a 1:100 molar ratio of apoE, the inhibitory effect of apoE was completely abolished. We then focused our study on the kinetics of the inhibitory effect of apoE on the extension phase of betaAf formation in vitro, utilizing the recently established first-order kinetic model of betaAf extension in vitro [Naiki, H., & Nakakuki, K. (1996) Lab. Invest. 74, 374-383]. The mathematical treatment of the data suggests that apoE inhibits the extension of betaAf in vitro, by making a complex with beta1-40, thus eliminating free beta1-40 from the reaction mixture. The equilibrium association constant with beta1-40 was practically the same among the three major recombinant apoE isoforms. These results indicate that the effects of apoE on betaAf formation in vitro is differential and could settle some of the controversy about beta-amyloid-apoE interaction in vitro.

  14. Structure-dependent inhibitory effects of green tea catechins on insulin secretion from pancreatic β-cells.

    PubMed

    Kaneko, Yukiko K; Takii, Miki; Kojima, Yumiko; Yokosawa, Hiroko; Ishikawa, Tomohisa

    2015-01-01

    The effects of green tea catechins on glucose-stimulated insulin secretion (GSIS) were investigated in the β-cell line INS-1D. Epigallocatechin gallate (EGCG) at 10 µM or gallocatechin gallate (GCG) at 30 µM caused significant inhibitory effects on GSIS, and each of these at 100 µM almost abolished it. In contrast, epicatechin (EC) or catechin (CA) had no effect on GSIS at concentrations up to 100 µM. We thus investigated the structure-activity relationship by using epigallocatechin (EGC) and gallocatechin (GC) containing a trihydroxyl group in the B-ring, and epicatechin gallate (ECG) and catechin gallate (CG) containing the gallate moiety. EGC, GC, and ECG caused an inhibition of GSIS, although significant effects were obtained only at 100 µM. At this concentration, EGC almost abolished GSIS, whereas GC and ECG partially inhibited it. In contrast, CG did not affect GSIS at concentrations up to 100 µM. EGCG also abolished the insulin secretion induced by tolbutamide, an ATP-sensitive K(+) channel blocker, and partially inhibited that induced by 30 mM K(+). Moreover, EGCG, but not EC, inhibited the oscillation of intracellular Ca(2+) concentration induced by 11.1 mM glucose. These results suggest that some catechins at supraphysiological concentrations have inhibitory effects on GSIS, the potency of which depends on their structure; the order of potency was EGCG>GCG>EGC>GC≈ECG. The inhibitory effects seem to be mediated by the inhibition of voltage-dependent Ca(2+) channels, which is caused, at least in part, by membrane hyperpolarization resulting from the activation of K(+) channels.

  15. Multitrophic effects of nutrient addition in upland grassland.

    PubMed

    Fountain, M T; Brown, V K; Gange, A C; Symondson, W O C; Murray, P J

    2008-06-01

    Although the effects of nutrient enhancement on aquatic systems are well documented, the consequences of nutritional supplements on soil food webs are poorly understood, and results of past research examining bottom-up effects are often conflicting. In addition, many studies have failed to separate the effects of nutrient enrichment and the physical effects of adding organic matter. In this field study, we hypothesised that the addition of nitrogen to soil would result in a trophic cascade, through detritivores (Collembola) to predators (spiders), increasing invertebrate numbers and diversity. Nitrogen and lime were added to plots in an upland grassland in a randomised block design. Populations of Collembola and spiders were sampled by means of pitfall traps and identified to species. Seventeen species of Collembola were identified from the nitrogen plus lime (N+L) and control plots. Species assemblage, diversity, richness, evenness and total number were not affected by nutrient additions. However, there was an increase in the number of Isotomidae juveniles and Parisotoma anglicana trapped in the N+L plots. Of the 44 spider species identified, over 80% were Linyphiidae. An effect on species assemblage from the addition of N+L to the plots was observed on two of the four sampling dates (July 2002 and June 2003). The linyphiid, Oedothorax retusus, was the only species significantly affected by the treatments and was more likely to be trapped in the control plots.The increased number of juvenile Collembola, and change in community composition of spiders, were consequences of the bottom-up effect caused by nutrient inputs. However, despite efforts to eliminate the indirect effects of nutrient inputs, a reduction in soil moisture in the N+L plots cannot be eliminated as a cause of the invertebrate population changes observed. Even so, this experiment was not confounded by the physical effects of habitat structure reported in most previous studies. It provides evidence

  16. Inhibitory Effect of Curcumin-Cu(II) and Curcumin-Zn(II) Complexes on Amyloid-Beta Peptide Fibrillation

    PubMed Central

    2014-01-01

    Mononuclear complexes of Curcumin with Cu(II) and Zn(II) have been synthesized and, characterized and their effects on the fibrillization and aggregation of amyloid-beta (Aβ) peptide have been studied. FTIR spectroscopy and atomic force microscopy (AFM) observations demonstrate that the complexes can inhibit the transition from less structured oligomers to β-sheet rich protofibrils which act as seeding factors for further fibrillization. The metal complexes also impart more improved inhibitory effects than Curcumin on peptide fibrillization. PMID:25147492

  17. Inhibitory effects of wild bitter melon leaf extract on Propionibacterium acnes-induced skin inflammation in mice and cytokine production in vitro.

    PubMed

    Huang, Wen-Cheng; Tsai, Tsung-Hsien; Huang, Ching-Jang; Li, You-Yi; Chyuan, Jong-Ho; Chuang, Lu-Te; Tsai, Po-Jung

    2015-08-01

    Propionibacterium acnes is a key pathogen involved in acne inflammation. Wild bitter melon (WBM, Momordica charantia L. var. abbreviate Seringe) is consumed as both a vegetable and as folk medicine in Taiwan. We examined the inhibitory activity of the total phenolic extract (TPE) of WBM leaf on P. acnes-induced inflammatory responses in vivo and in vitro. Our data showed that TPE significantly attenuated P. acnes-induced ear swelling in mice along with microabscess. Flow cytometry analysis revealed that TPE treatment significantly decreased the migration of neutrophils and interleukin (IL)-1β(+) populations in vivo. In P. acnes-stimulated human monocytic THP-1 cells, TPE suppressed the mRNA levels and production of IL-8, IL-1β, and tumor necrosis factor (TNF)-αin vitro. In addition, TPE suppressed P. acnes-induced matrix metalloproteinase-9 levels. TPE blocked nuclear factor-κB (NF-κB) activation and inactivated mitogen-activated protein kinases (MAPK); these actions may partially account for its inhibitory effect on cytokine production. The quantitative HPLC analysis revealed gallic, chlorogenic, caffeic, ferulic, and cinnamic acids, myricetin, quercetin, luteolin, apigenin, and thymol in TPE. All these phenolics significantly suppressed P. acnes-induced IL-8 production in vitro. Our results suggest that WBM leaf extract effectively inhibits P. acnes-induced inflammatory responses and may be useful to relieve the inflammation of acne. PMID:26098998

  18. Mitigation of the inhibitory effect of soap by magnesium salt treatment of crude glycerol--a novel approach for enhanced biohydrogen production from the biodiesel industry waste.

    PubMed

    Sarma, Saurabh Jyoti; Brar, Satinder Kaur; Le Bihan, Yann; Buelna, Gerardo; Soccol, Carlos Ricardo

    2014-01-01

    Owing to its inhibitory effect on microbial growth, soap present in crude glycerol (CG) is a concern in biological valorization of the biodiesel manufacturing waste. By salting out strategy, up to 42% of the soap has been removed and the approach has beneficial effect on H2 production; however, removal of more than 7% of the soap was found to be inhibitory. Actually, soap is utilized as a co-substrate and due to removal; the carbon-nitrogen ratio of the medium might have decreased to reduce the production. Alternatively, without changing the carbon-nitrogen ratio of CG, MgSO4 treatment can convert the soap to its inactive form (scum). The approach was found to increase the H2 production rate (33.82%), cumulative H2 production (34.70%) as well as glycerol utilization (nearly 2.5-folds). Additionally, the treatment can increase the Mg (a nutrient) content of the medium from 0.57 ppm to 201.92 ppm.