Eveline Dischkaln Stolz

Universidade Federal do Rio Grande do Sul, Pôrto de São Francisco dos Casaes, Rio Grande do Sul, Brazil

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Publications (12)29.08 Total impact

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    ABSTRACT: Combinations of different classes of antidepressants (including herbal adjuvants) have been used as an alternative means of achieving better results in the treatment of depressed patients. However, studies characterizing the interactions between herbal adjuvants and antidepressants are lacking. This study is the first to investigate the interaction between diene valepotriates (VAL) from Valeriana glechomifolia, a species with antidepressant-like effects, and imipramine (IMI), desipramine (DESI) and bupropion (BUP). The interactions were assessed via isobolographic analyses, which represent a tool for evaluating interactions between drugs. The interaction between VAL and each antidepressant was evaluated in mice given concurrent oral administration of each drug with fixed ED50 ratios and subjected to a forced swimming test (FST). Spontaneous locomotion was measured in the open field test. The drug combinations produced a dose-dependent anti-immobility effect in the FST without altering mouse locomotor activity. Isobolographic analysis revealed that VAL resulted in synergistic interactions in combination with each of the antidepressants tested. The synergistic interactions between VAL and IMI, DESI and BUP highlight the potential for VAL to serve as adjuvants to antidepressant drugs and suggest that VAL does not directly target the same sites on neuronal transporters as the antidepressants. © 2015 Royal Pharmaceutical Society.
    04/2015; DOI:10.1111/jphp.12396
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    ABSTRACT: Uliginosin B is a natural phloroglucinol derivative, obtained from Hypericum species native to South America. Previous studies have shown that uliginosin B presents antidepressant-like and antinociceptive effects. Although its mechanism of action is still not completely elucidated, it is known that it involves the activation of monoaminergic neurotransmission. The aim of the current study was to further investigate the antinociceptive mechanism of action of uliginosin B by combining it with different drugs used for treating pain in clinical practice. The intraperitoneal administration of uliginosin B, morphine, amitriptyline and clonidine, alone or in mixture, produced a dose-dependent antinociceptive effect in the hot-plate assay in mice. The effect of the mixtures of drugs was studied using an adapted isobologram analysis at the effect level of 50% of the maximal effect observed. The analysis showed that the interactions between uliginosin B and morphine was synergistic, while the interactions between uliginosin B and amitriptyline or clonidine were additive. These findings point to uliginosin B as a potential adjuvant for pain pharmacotherapy, especially for opioid analgesia. Copyright © 2014 Elsevier GmbH. All rights reserved.
    Phytomedicine 10/2014; 21(12):1684–1688. DOI:10.1016/j.phymed.2014.08.009 · 2.88 Impact Factor
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    ABSTRACT: A new dimeric acylphloroglucinol derivative, andinin A (1), was isolated from the underground plant parts of Hypericum andinum, along with three known dimeric acylphloroglucinols, uliginosin A (2), uliginosin B (3), and isouliginosin B (4). The structure of 1 was elucidated using 1D and 2D NMR and MS experiments and by comparison with previously reported data for Hypericum dimeric acylphloroglucinols. Andinin A (1) displayed antidepressant-like activity in a mouse forced-swimming test when administered orally at doses of 3, 10, and 30 mg/kg.
    Journal of Natural Products 09/2014; 77(10). DOI:10.1021/np500426m · 3.95 Impact Factor
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    ABSTRACT: Objective Investigate the involvement of monoaminergic and glutamatergic systems on the antinociceptive and ataxic effects of uliginosin B, which we have already demonstrated to be a promising molecular scaffold to develop new analgesic drugs.Methods Uliginosin B was obtained from hexane extract of aerial parts of Hypericum polyanthemum by chromatographic methods. Uliginosin B antinociceptive and motor coordination effects were evaluated in mice by using hot-plate (15 and 90 mg/kg, i.p.) and rotarod (90 mg/kg, i.p.) tests, respectively. The mechanism of action was investigated through pretreatments with prazosin 1 mg/kg intraperitoneal (α1 receptor antagonist), yohimbine 5 mg/kg intraperitoneal (α2 receptor antagonist), pCPA 300 mg/kg intraperitoneal (serotonin synthesis inhibitor) and MK-801 0.25 mg/kg intraperitoneal (N-methyl-D-aspartic acid receptor antagonist).Key findingsThe antinociceptive effect of uliginosin B (15 and 90 mg/kg, i.p.) was reduced significantly by pCPA and MK-801. Prazosin and yohimbine improved the antinociceptive effect of the highest dose (90 mg/kg, i.p.) of uliginosin B only. The ataxic effect of uliginosin B (90 mg/kg, i.p.) was completely prevented by pretreatment with pCPA or MK-801, but it was unaffected by pretreatment with prazosin or yohimbine.Conclusion These data confirm the contribution of monoaminergic neurotransmission as well as provide the first evidence of glutamatergic neurotransmission contribution to the uliginosin B effects.
    09/2014; 66(12). DOI:10.1111/jphp.12307
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    ABSTRACT: The antidepressant-like effects of phloroglucinol and seven synthetic related derivatives were investigated using the tail suspension test (TST) in mice. Compounds 2-methyl-1-[2,4,6-trihydroxy-3-(2-methylpropanoyl)phenyl] propan-l-one (5), 1-(2,4,6-trihydroxyphenyl)ethan-l-one (6), 1-(3-acetyl-2,4,6-trihydroxyphenyl)ethan-l-one (7), 2-methyl-1 -[2,4,6-trihydroxy-3-(2-methylpropanoyl)-5-{ [2,4,6-trihydroxy-3,5-bis(2-methylpropanoyl)phenyl]methyl phenyl] propan-1-one (9) and 1-{3-acetyl-5-[(3,5-diacetyl-2,4,6-trihydroxyphenyl)methyl]-2,4,6-trihydroxyphenyl}ethan-1-one (10), containing acyl groups, decreased the immobile behavior of mice treated orally with equimolar doses of imipramine 20 mg/kg, with no alterations in locomotor activity as assessed by the open-field test. These results suggest that these phloroglucinol derivatives could represent a new molecular model in the search for antidepressant drugs.
    Natural product communications 05/2014; 9(5):671-4. · 0.92 Impact Factor
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    ABSTRACT: Ethnobotanical data can be an important tool in the search for new drugs. The Brazilian Health Surveillance Agency accepts the registration of herbal medicines based on ethnopharmacological and ethnobotanical studies. With the purpose of increasing the knowledge of potentially useful plants for the treatment of painful conditions, we analyzed the ethnobotanical studies carried out in Rio Grande do Sul state (RS-Southern Brazil); we had access to nineteen studies. To our knowledge, this is the first compilation of ethnobotanical studies that focus on pain relief carried out in RS. The species native to RS cited in at least nine (about 50%) of these studies were selected. The search retrieved 28 native species cited as used to alleviate painful conditions, which are distributed in eighteen botanical families, being Asteraceae the most mentioned. The species more frequently cited for pain relief were Achyrocline satureioides, Baccharis articulata, Baccharis crispa, Lepidium didymum, Eugenia uniflora and Maytenus ilicifolia. The only species not reported in any pre-clinical study associated with pain relief was B. articulata. Among the six species cited, no studies on clinical efficacy were found. In conclusion, the folk use of native plants with therapeutic purposes is widespread in RS State (Brazil), being pain relief an important property.
    Revista Brasileira de Farmacognosia 04/2014; 24(2):185–196. DOI:10.1016/j.bjp.2014.03.007 · 0.80 Impact Factor
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    ABSTRACT: Herein, a new continuous preparation method for inclusion compound based on cyclodextrin supramolecular system was developed using spray drying process (SD-LT) as alternative of freeze drying (FD) with less energy consuming. In order to improve conventional spray drying methods to obtain this inclusion compounds, isothermal titration calorimetry (ITC) and nuclear magnetic resonance (2D ROESY) were used to get insights on the guest insertion into β-cyclodextrin (βCD) cavity. Sertraline hydrochloride (SRT) was used as a low water solubility drug molecule. The results demonstrated that SRT presents a preferred inclusion into βCD cavity when lower temperatures are used in the SD-LT preparation process. The physical-chemical results obtained from this new method is comparable with those obtained using the FD process, one of the most used method. In addition, inclusion compounds were tested in mice by tail suspension and open field tests and the results shown that the antidepressant-like effect for the SD-LT inclusion compounds was similar to that obtained by FD, contrary to that obtained by conventional SD method.
    Chemical Engineering Journal 07/2013; 228:345-351. DOI:10.1016/j.cej.2013.04.074 · 4.06 Impact Factor
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    ABSTRACT: ETHNOPHARMACOLOGICAL RELEVANCE: Passiflora alata is a Southern American species that constitutes many traditional remedies as well as phytomedicines used for sedative and anxiolytic purposes in Brazil. However studies on repeated treatment effects are scarce. AIM OF THE STUDY: To evaluate behavioral, physiological and biochemical effects of the repeated treatment with an aqueous spray-dried extract of P. alata leaves containing 2.5% (w/v) of flavonoids (PA) in mice. MATERIAL AND METHODS: Male adult CF1 mice were treated (p.o.) for 14 days with PA (2.5; 25 or 250mg/kg). The feeding behavior was evaluated at the beginning (one hour after the first adminsitration) and at the end of the treatment (15(th) day). The body weight gain and food consumption were monitored along the days. On day 15 mice were evaluated on plus maze, spontaneous locomotor activity, catalepsy and barbiturate sleeping time tests. Serum glucose, lipids, ALT and AST enzymes were determined. Liver, kidney, perirenal fat, epididymal and peritoneal fat were analyzed. RESULTS: The repeated treatment with the highest dose tested (250mg/kg) did not alter the mice behavior on open field, elevated plus maze, catalepsy and barbiturate sleeping time tests. Repeated administration of PA 250 decreased mice feeding behavior and weight gain. PA 25 and PA 250 reduced mice relative liver weight and caused mild hepatic hydropic degeneration as well as a decrease in alanine aminotransferase (ALT) serum level. CONCLUSIONS: These results indicate that P.alata does not present central cumulative effects and point to the needs of further studies searching for its hepatotoxicity as well as potential anorexigenic.
    Journal of ethnopharmacology 10/2012; 145(1). DOI:10.1016/j.jep.2012.10.034 · 2.94 Impact Factor
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    ABSTRACT: The aim of the present work was to evaluate the antidepressant like-effect and plasma concentration of Sertraline (SRT) using an inclusion complex (IC) with β-cyclodextrin (βCD) in mice. This supramolecular system was prepared using two different molar ratios at 1:1 and 1:2 SRT:βCD and both were characterized to assess the drug inclusion into the host cavity. Based on the X-ray powder diffraction, Fourier transform infrared spectroscopy and thermal analysis the interaction between host and guest molecules could be suggested. This result indicates that the freeze drying process was efficient to prepare the ICs, when these are compared with the physical mixtures. By comparing the solid state results of 1:1 and 1:2 ICs no significant chemical or structural changes were identified between these systems. However, in vivo experiments indicated that the host-guest ratio was able to modify the SRT activity. Mice treated with both ICs (20 mg kg(-1), p.o.) have shown lower immobility time in the tail suspension test in comparison with mice treated with free SRT (20 mg kg(-1), p.o.). Mice spontaneous locomotor activity was not affected by any treatment. Higher SRT plasma concentration was determined after 30 min of treatment with 1:1 IC in comparison with free SRT, demonstrating the IC greater drug transport efficacy.
    International Journal of Pharmaceutics 07/2012; 436(1-2):478-85. DOI:10.1016/j.ijpharm.2012.06.061 · 3.79 Impact Factor
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    ABSTRACT: Previous studies have shown that uliginosin B inhibits dopamine reuptake in rat brain. This compound occurs in Hypericum polyanthemum and H. caprifoliatum for which was reported to have antinociceptive effect sensitive to naloxone. The aim of this study was to assess the antinociceptive effect of uliginosin B and to evaluate the involvement of opioid and dopaminergic receptors activation. Uliginosin B presented antinociceptive effect in hot-plate and abdominal writhing tests, in mice, at doses that did not impair the motor coordination (15 mg/kg, i.p.). Uliginosin B in high dose (90 mg/kg, i.p.) presented ataxic effect in the rotarod apparatus. These effects seem to be mediated by distinct receptors since the effect on the hot-plate was completely abolished by naloxone and sulpiride, but it was unaffected by SCH 23390. On the other hand, the motor impairment induced by uliginosin B was completely prevented by naloxone and partially prevented by sulpiride and SCH 23390. However, the receptors' activation appears to be indirect since uliginosin B did not bind to opioid and dopaminergic receptors. Thus, uliginosin B effects probably are due to its ability to inhibit monoamine reuptake with consequent activation of dopamine receptors and indirect stimulation of opioid system.
    Progress in Neuro-Psychopharmacology and Biological Psychiatry 05/2012; 39(1):80-7. DOI:10.1016/j.pnpbp.2012.05.012 · 4.03 Impact Factor
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    ABSTRACT: In this study we have demonstrated that cyclohexane extract of Hypericum polyanthemum (POL) and its main phloroglucinol derivative uliginosin B (ULI) present antidepressant-like activity in rodent forced swimming test (FST). The involvement of monoaminergic neurotransmission on the antidepressant-like activity of ULI was evaluated in vivo and in vitro. POL 90 mg/kg (p.o.) and ULI 10 mg/kg (p.o.) reduced the immobility time in the mice FST without altering locomotion activity in the open-field test. The combination of sub-effective doses of POL (45 mg/kg, p.o.) and ULI (5 mg/kg, p.o.) with sub-effective doses of imipramine (10 mg/kg, p.o.), bupropion (3 mg/kg, p.o.) and fluoxetine (15 mg/kg, p.o.) induced a significant reduction on immobility time in FST. The pretreatment with SCH 23390 (15 μg/kg, s.c., dopamine D1 receptor antagonist), sulpiride (50 mg/kg, i.p., dopamine D2 receptor antagonist), prazosin (1mg/kg, i.p., α1-adrenoceptor antagonist), yohimbine (1mg/kg, i.p., α2-adrenoceptor antagonist) and pCPA (100 mg/kg/day, i.p., p-chlorophenilalanine methyl ester, inhibitor of serotonin synthesis, for four consecutive days) before ULI administration (10 mg/kg, p.o.) significantly prevented the anti-immobility effect in FST. ULI was able to inhibit synaptosomal uptake of dopamine (IC50 = 90 ± 38 nM), serotonin (IC50 = 252 ± 13 nM) and noradrenaline (280 ± 48 nM), but it did not bind to any of the monoamine transporters. These data firstly demonstrated the antidepressant-like effect of POL and ULI, which depends on the activation of the monoaminergic neurotransmission in a different manner from the most antidepressants.
    Behavioural brain research 12/2011; 228(1):66-73. DOI:10.1016/j.bbr.2011.11.031 · 3.39 Impact Factor
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    ABSTRACT: The crude extracts of HYPERICUM species native to South Brazil showed analgesic and antidepressant-like effects in rodents. The chemical characterization of these species revealed that they are rich in flavonoids and phloroglucinol derivatives. In the present study a detailed investigation was performed on the activities of hyperoside (HYP), a common flavonoid in the genus HYPERICUM. Hyperoside was obtained from the aerial parts of H. CAPRIFOLIATUM by chromatographic procedures. Mice treated with single doses (10, 20 and 40 mg/kg i.p.) did not present signs of toxicity or weight loss. At 20 and 40 mg/kg i.p. the mice exploratory behavior in the open field test was reduced. At 20 mg/kg i. p. the pentobarbital sleeping time increased, but not the sleeping latency. No activity was found on the hot-plate (10 and 20 mg/kg i.p.) or in the acetic acid-induced writhing test (20 and 40 mg/kg p.o.). Nevertheless, an antidepressant-like effect in the forced swimming test in mice and rats was observed (HYP 10 and 20 mg/kg i.p. in mice; HYP 1.8 mg/kg/day p.o. in rats). The antidepressant-like effect in rats was prevented by the administration of sulpiride (50 mg/kg i.p.) a D2 antagonist. In conclusion, hyperoside was found to present a depressor effect on the central nervous system as well as an antidepressant-like effect in rodents which is, at least in part, mediated by the dopaminergic system.
    Planta Medica 10/2010; 77(4):334-9. DOI:10.1055/s-0030-1250386 · 2.34 Impact Factor

Publication Stats

40 Citations
29.08 Total Impact Points


  • 2010–2014
    • Universidade Federal do Rio Grande do Sul
      • Faculty of Pharmacy
      Pôrto de São Francisco dos Casaes, Rio Grande do Sul, Brazil