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Depression is one of the most common affective disorders. According to the World Health Organization (WHO), it is currently the fourth major global health problem (Kessler et al. 2003). The growing number of people suffering from depression has motivated the scientists to search for new antidepressant drugs. Since numerous studies revealed that NMDA receptor may be involved in the mechanism of action of the antidepressant agents, modulation of the NMDA receptor function by different ligands has been taken into consideration. There are some promising results demonstrating the antidepressant activity of the antagonists binding to the polyamine site of the NMDA receptor complex. Ifenprodil belongs to a family of the selective, atypical non-competitive antagonists of the NMDA receptors. It acts via inhibition of the polyamine binding site of the NR2B subunit (Williams 1993). An antidepressantlike effect of ifenprodil was observed in several behavioral studies, for example in the forced swimming test (Carter et al. 1990, Williams 1993, Layer et al. 1995, Scolnik 1999, Paoletti and Neyton 2007). It was shown that its antidepressant-like activity is increased by other antidepressant drugs (imipramine and fluoxetine). The aim of our work was to evaluate the antidepressant activity of the joint administration of ifenprodil and NMDA ligands in the mouse forced swimming test (FST). The experiments were carried out on male Albino Swiss mice. In order to avoid the risk of obtaining the false positive/negative effects in the FST test caused by a possible influence of the tested substances on the locomotor activity, the spontaneous locomotor activity was measured. The obtained results demonstrated that ifenprodil at the dose of 10 mg/ kg enhances the antidepressant-like effect of the following NMDA receptor ligands: a competitive NMDA receptor antagonist – CGP 37849 (0.312 mg/kg), an antagonist at glycine site – L-701,324 (1 mg/kg) and a non-competitive antagonist at phencyclidyne – MK801 (0.05 mg/kg). However, it did not potentiate the antidepressant activity of the inorganic modulators of the NMDA receptor complex, such as Zn2+ (2.5 mg/kg) and Mg2+ (10 mg/kg). Treatment with the tested agents did not influence the locomotor activity. In conclusion, our findings indicated that antidepressant-like activity of ifenprodil is connected with serotoninergic and glutamatergic system.
Depression is one of the most frequent chronic and life-debilitating health problems in the world. Though its epidemiology, risk factors and development have been continuously studied for decades, the optimal treatment of the depressed patients still remains an important clinical dilemma. The conventional antidepressant therapy is not sufficient due to the common ineffectiveness and adverse reactions. The search for better alternatives seems to be crucial. Recently, much consideration has been given to both totally novel chemical compounds as well as to the unique combinations of the well-known drugs. The use of the NMDA receptor ligands, particularly in co-administration with other agents exerting the antidepressant activity, emerged amongst the new ideas. The main objective of our study was to evaluate the influence of caffeine on the antidepressant-like activity of various NMDA receptor modulators. The antidepressant-like effect was assessed by the forced swim test in mice. The obtained results demonstrated the significant interaction between caffeine (5 mg/kg) and the following NMDA receptor ligands: CGP 37849 (0.312 mg/kg), L-701,324 (1 mg/kg) and D-cycloserine (2.5 mg/ kg). Interaction between caffeine and the inorganic modulators, i.e. Zn2+ (2.5 mg/kg) and Mg2+ (10 mg/kg), was not considered as significant. The antidepressant-like potential of the NMDA receptor ligands (except for Zn2+ and Mg2+) given concomitantly with caffeine was reinforced. The possible mechanism of the observed interaction may involve the influence of caffeine on the glutamatergic system.
In vitro cultures of Cistus ×incanus (pink rock-rose) were maintained on two vari­ants of Murashige and Skoog (MS) medium differing in terms of composition of plant growth regulators (PGRs): 6-benzyladenine (BA) and 1-naphthaleneacetic acid (NAA) at the following concentrations: 3 mg/L and 0, 3 mg/L and 1 mg/L, respectively, and on a variant without PGRs – a control. Cultures were maintained in a form of agar and agitated shoot cultures. The qualitative and quantitative analyzes of three groups of phenolic compounds (catechins, flavonoids, and free phenolic acids) were performed by using the HPLC-DAD technique in methanolic extracts of in vitro biomasses and of commercial plant raw material. In analyzed extracts from in vitro cultures, the presence of catechin [max. 197.80 mg / 100 g dry weight (DW)], epicatechin gallate (max. 30.74 mg / 100 g DW), gallic acid (max. 83.23 mg / 100 g DW), quercetin (max. 10.15 mg / 100 g DW), and quercitrin (max. 72.89 mg / 100 g DW) was confirmed. The quantities of accumulated compounds varied and depended on the type of in vitro culture and the concentration of PGRs in media. The highest amounts of all estimated compounds were obtained in biomasses from agar cultures cultivated on medium without PGRs in vitro. In extracts obtained from commercial raw material, gallic acid (max. 261.80 mg / 100 g DW) and quercetin (max. 255.96 mg / 100 g DW) were detected as being the dominant compounds.
Optimization of the process of biotransformation of hydroquinone into its β-D-glucoside – arbutin, was performed in agitated shoot cultures of Schisandra chinensis. The optimisation involved testing various concentrations of the precursor and different ways of administering it. Arbutin was accumulated mainly in the in vitro cultured biomass (85.2–98.6%). By optimizing the process, a 2.26-fold increase in the overall product content was obtained. The highest amount (17.8 mg·g–1 DW) was found after administering 384 mg·l–1 hydroquinone in a dose divided into two portions. An experiment with the biotransformation of 4-hydro- xybenzoic acid did not produce arbutin but a mixture of two products of glucosylation of the precursor – hydroxybenzoic acid 4-O-β-glucopyranoside and 4-hydroxybenzoic acid β-glucopyranosyl ester. The identity of all biotransformation products was confirmed by 1H-NMR analysis. The results for the production of arbutin by the biotransformation of hydroquinone are of potential practical importance. On the other hand, the fact of confirming the presence of two glucosylation products has a great cognitive value.
Arbutin (hydroquinone β-D-glucoside) is a compound of plant origin possessing valuable therapeutic (urinary tract disinfection) and cosmetic (skin whitening) properties, which can be obtained from in vitro cultures of plants belonging to different taxa via biotransformation of exogenously supplemented hydroquinone. Agitating cultures of Aronia melanocarpa were maintained on the Murashige and Skoog medium containing growth regulators: the cytokinin - BAP (6-benzylaminopurine), 2 mg/l and the auxin NAA (α-naphthaleneacetic acid), 2 mg/l. The biomass was cultured for 2 weeks and then hydroquinone was supplemented at the following doses: 96, 144, 192, 288 and 384 mg/l either undivided or divided into two or three portions added at 24-hour intervals. The content of the reaction product - arbutin, was determined using an HPLC method in methanolic extracts from biomass and lyophilized medium samples collected 24 hours after the addition of the last precursor dose. The total amounts of arbutin were very diverse, from 2.71 to 8.27 g/100g d.w. The production of arbutin rose with increasing hydroquinone concentration. The maximum content of the product was observed after hydroquinone addition at 384 mg/l divided into two portions. Biotransformation efficiency also varied widely, ranging from 37.04% do 73.80%. The identity of the product - arbutin, after its isolation and purification was confirmed by spectral analysis (1H-NMR spectrum). The maximum amount of arbutin obtained was higher than that required by the latest 9th Edition of the Polish Pharmacopoeia and by the newest 8th Edithion of European Pharmacopoeia for Uvae ursi folium (7.0 g/100g d.w.), and is interesting from practical point of view.
Argireline® is well know, innovative anti-aging product used in the cosmetic market. This short chain peptide is used as active ingredient in dermal ointment and creams. Argireline® prevents formation of skin lines and wrinkles in a very similar way to the botulinum toxin (Botox), inhibiting neurotransmitter release at the neuromuscular junction. Argireline® does not require under skin muscle injections and it is believed to be relatively safe. However, despite the fact that some toxicity data has been provided by the product manufacturer, there is an evident lack of reliable information about cytotoxicity of argireline® in the literature. The aim of the presented study was to estimate the antiproliferation effect of argireline® solution in several concentrations. The influence of argireline® on cellular proliferation was examined against: human embryonic kidney HEK-293 cell line, human neuroblastoma IMR-32 cell line, and human primary skin fibroblasts. Tests were performed using formazan-based cell proliferation assay: EZ4U, which allows to measure the efficiency of mitochondrial oxidative activity in living cells. The argireline® inhibitory concentration, IC50 values were calculated and the results were compared to the IC50 value of the reference compound: doxorubicin. In conclusion, the considered method resulted in dose-dependent argireline® anti-proliferation effects. However, the significant cytotoxicity of argireline® solution was observed under 18 to 10 000 fold higher concentrations (depending on cells that were examined) in comparison to doxorubicin.
The flower (inflorescence, basket-type inflorescence) of marigold (Calendulae officinalis flos) is a wellknown plant raw material in traditional phytomedicine. It has a complex chemical composition, dominated by flavonoids and terpenoids. Terpenoids are mainly represented by oleanolic acid derivatives specific for this species: triterpenoid saponins – calendulosides A–H and triterpenoid glycosides, so-called calendulaglycosides A and B. Biological activity profiles of the raw material, such as anti-inflammatory, antimicrobial, immunostimulatory and antioxidant properties, determine its use especially in the treatment of dermatological diseases. In addition to spasmolitic, hypolipemic and antidiabetic properties of this flower, scientific studies also demonstrated its cardioprotective, hepatoregenerative, pancreas-regenerating, neuroprotective and even anticancer health-promoting effects. Moreover, C. officinalis is used in the cosmetology and food industry.
BACKGROUND AND AIMS: Though depression is known as one of the most frequent chronic health problems in the world, the optimal treatment of the depressed patients remains an important challenge. Due to serious adverse reactions and common ineffectiveness, the conventional antidepressant therapy is usually not sufficient. The identification of the best treatment strategies and development of new, safer, and more effective ones are crucial. Literature data confirm participation of adenosine neurotransmission in the development of depression. Adenosine, which is responsible for the suppressed release of serotonin, noradrenalin, and dopamine, contributes to a decrease of neuronal excitability. The main objective of our study was to investigate an antidepressant activity of a joint administration of adenosine A2A receptor antagonist DMPX (3,7-dimethyl-1-propargylxanthine) and the common antidepressant drugs: imipramine, reboxetine, escitalopram, tianeptine, venlafaxine, moclobemide, and agomelatine. METHODS: The experiments were carried out on male Albino Swiss mice. The antidepressant-like effect was assessed by the forced swim test. In order to avoid the risk of obtaining the false positive/negative effects, the spontaneous locomotor activity was measured as well. RESULTS: The obtained results demonstrated that DMPX at the dose of 3 mg/kg significantly enhanced the antidepressant-like effect of imipramine (15 mg/kg), reboxetine (2.5 mg/kg), escitalpram (2 mg/kg), tianeptine (15 mg/kg), venlafaxine (1 mg/kg), moclobemide (1.5 mg/kg), and agomelatine (20 mg/kg). None of the used combinations changed the overall spontaneous locomotor activity of the animals. CONCLUSION: Forced swim test outcomes indicated a synergistic action of adenosine A2A receptor antagonist in combination with the tested antidepressants.
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