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Potential mGAT4 inhibitors derived from the lead substance (S)-SNAP-5114 have been synthesized and characterized for their inhibitory potency. Variations from the parent compound included the substitution of one of its aromatic 4-methoxy and 4-methoxyphenyl groups, respectively, with a more polar moiety, including a carboxylic acid, alcohol, nitrile, carboxamide, sulfonamide, aldehyde or ketone function, or amino acid partial structures. Furthermore, it was investigated how the substitution of more than one of the aromatic 4-methoxy groups affects the potency and selectivity of the resulting compounds. Among the synthesized test substances (S)-1-{2-[(4-formylphenyl)bis(4-methoxyphenyl)-methoxy]ethyl}piperidine-3-carboxylic acid, that features a carbaldehyde function in place of one of the aromatic 4-methoxy moieties of (S)-SNAP-5114, was found to have a pIC50 value of 5.89±0.07, hence constituting a slightly more potent mGAT4 inhibitor than the parent substance while showing comparable subtype selectivity. 相似文献
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Hadi Munarko Azis Boing Sitanggang Feri Kusnandar Slamet Budijanto 《International Journal of Food Science & Technology》2021,56(9):4540-4548
Germination of brown rice can be completed by full soaking and partial soaking methods. This study aimed to analyse the influence of germination methods on the bioactive accumulations in germinated brown rice (GBR). Germination was conducted in four treatments: (i) membrane reactor with full (RFS) and (ii) partial soaking method soaking (RAG), (iii) manual soaking for complete germination (MFS) and (iv) partial manual soaking in combination with atmospheric germination (MAG). The results showed that soaking BR in membrane reactor accelerated the shoots' growth and increased GABA (γ-aminobutyric acid) content compared with the manual soaking method. The RAG treatment achieved higher GABA content (up to 125 mg/100 g), total phenolic and flavonoid content, and antioxidant activity than other germination methods. The main finding of this research indicates that membrane reactor effectively enhances the growth of sprouts. The combination of partial soaking in membrane reactor and atmospheric germination (RAG) is a suited method to increase GABA accumulation in GBR. 相似文献
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Monitoring Technology for Gamma‐Aminobutyric acid Production in Polished Mochi Barley Grains using a Carbon Dioxide Sensor 下载免费PDF全文
Gamma‐aminobutyric acid (GABA) has many biological functions, including the inhibition of blood pressure increases and acceleration of growth hormone secretion. In this study, we discovered the utility of measuring the concentration of carbon dioxide (CO2) dissolved in the reaction solution, for development of a real‐time and convenient technique to estimate GABA production. In addition to mochi barley bran, we examined the polished grains of three species: mochi barley (a variant of hulless barley), barley, and Japanese millet, all soaked in l ‐glutamic acid (l ‐Glu) solution at pH 4.5. We found a positive correlation between GABA and CO2 concentrations, and the production of CO2 was suppressed in the absence of l ‐Glu at pH 4.5. These results suggest that GABA content can be easily predicted by measuring the aqueous CO2 content using a CO2 sensor, during the process of GABA production in polished mochi barley grains and bran. 相似文献
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Lucía Calatrava-Ferreras Rafael Gonzalo-Gobernado Diana Reimers Antonio S. Herranz Adriano Jiménez-Escrig Juan José Díaz-Gil María José Casarejos María Teresa Montero-Vega Eulalia Bazán 《International journal of molecular sciences》2014,15(10):19056-19073
Cerebellar ataxias (CA) comprise a heterogeneous group of neurodegenerative diseases characterized by a lack of motor coordination. They are caused by disturbances in the cerebellum and its associated circuitries, so the major therapeutic goal is to correct cerebellar dysfunction. Neurotrophic factors enhance the survival and differentiation of selected types of neurons. Liver growth factor (LGF) is a hepatic mitogen that shows biological activity in neuroregenerative therapies. We investigate the potential therapeutic activity of LGF in the 3-acetylpiridine (3-AP) rat model of CA. This model of CA consists in the lesion of the inferior olive-induced by 3-AP (40 mg/kg). Ataxic rats were treated with 5 µg/rat LGF or vehicle during 3 weeks, analyzing: (a) motor coordination by using the rota-rod test; and (b) the immunohistochemical and biochemical evolution of several parameters related with the olivo-cerebellar function. Motor coordination improved in 3-AP-lesioned rats that received LGF treatment. LGF up-regulated NeuN and Bcl-2 protein levels in the brainstem, and increased calbindin expression and the number of neurons receiving calbindin-positive projections in the cerebellum. LGF also reduced extracellular glutamate and GABA concentrations and microglia activation in the cerebellum. In view of these results, we propose LGF as a potential therapeutic agent in cerebellar ataxias. 相似文献
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Wirtshafter David; Davis John D.; Stratford Thomas R. 《Canadian Metallurgical Quarterly》2011,125(4):529
Previous studies have shown that microinjections of the GABA-A agonist muscimol into the median raphe nucleus (MR) result in large increases in the intake of solid foods. In the current study, we used microstructural techniques to characterize the effects of intra-MR muscimol injections on the consumption of either a 0.05 M or a 0.29 M sucrose solution. After injections of either saline or muscimol, animals consumed more of the 0.29 M than the 0.05 M solution, an effect which resulted primarily from increases in the initial rate of consumption with no change in the rate at which licking decayed across the test session. In contrast, intra-MR muscimol injections had little effect on the initial licking rate, but greatly increased meal duration, indicating that this treatment affected ingestion in a different way than did altering the sucrose concentration. Muscimol injections produced a significantly larger increase in the intake of the 0.29 M than of the 0.05 M solution. Intra-MR muscimol injections did not alter the within burst rate of licking, suggesting that they did not affect the functioning of the licking pattern generator. In contrast, these injections did increase the number of licks contained within “clusters,” that is groups of licks separated from each other by intervals of more than 0.5 sec. These findings show that inactivation of the MR produces a powerful effect on the intake of liquid diets, and that the nature of this effect is different from that produced here by changes in sucrose concentration and from those reported after pharmacological manipulations of a number of other brain systems. We additionally discuss several theoretical issues arising in the interpretation of microstructural data. (PsycINFO Database Record (c) 2011 APA, all rights reserved) 相似文献
8.
Hyejin Yang Young-Chul Lee Kyoung-Sik Han Harjinder Singh Minseok Yoon Ji-Hae Park Chang-Won Cho Suengmok Cho 《Food chemistry》2013
Kiwifruit is one of the most popular fruits worldwide, and it has various biological properties, including antioxidant, anti-allergic, and cardiovascular protective effects. The peel of kiwifruit, which is a by-product of processing, is a good source of flavonoids; however, its bioactivity has not been widely investigated. In this study, we evaluated the hypnotic effects of green (GRPE, Actinidia deliciosa) and gold (GOPE, Actinidia chinensis) kiwifruit peel ethanol extracts and their solvent fractions, and the possible underlying mechanisms. Oral GRPE and GOPE administration (125–1000 mg/kg) produced a dose-dependent decrease in sleep latency and an increase in sleep duration in pentobarbital-treated mice. Among three different solvent fractions of GRPE and GOPE, ethyl acetate (EA) fractions had the greatest effect on sleep duration at 250 mg/kg. The total flavonoid contents of solvent fractions were proportional to sleep duration. Like diazepam (a GABAA–benzodiazepine (BZD) receptor agonist), the hypnotic effects of GRPE, GOPE, and their EA fractions were fully inhibited by flumazenil (a GABAA–BZD receptor antagonist). These results suggest that potentiation effects of GRPE and GOPE on pentobarbital-induced sleep in mice may be modulated by a GABAergic mechanism. 相似文献
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选择全国不同地区生产的61种传统发酵豆制品(包括豆豉、腐乳、豆酱和酱油),使用高效液相色谱法(HPLC)柱前衍生测定其γ-氨基丁酸(GABA)含量。研究表明,中国传统发酵豆制品富含GABA,从所试样品来看,腐乳样品GABA平均含量最高,为277.26mg/100g干重,含量最高的样品达1 159.46 mg/100g干重。所试豆豉、豆酱和酱油中平均GABA含量分别为116.81 mg/100g干重、68.81mg/100g干重和141.51mg/100mL。同一种类不同品牌发酵豆制品中GABA含量存在较大差异,这与发酵豆制品的不同生产工艺相关。通过工艺改进,可望富集GABA,生产富含GABA的功能性发酵豆制品。 相似文献
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