TY  - JOUR
AU  - Nikolić-Kokić, Aleksandra
AU  - Oreščanin Dušić, Zorana
AU  - Spasojevic, Ivan
AU  - Slavic, Marija
AU  - Mijuskovic, Ana
AU  - Paskulin, Roman
AU  - Miljevic, Cedo
AU  - Spasić, Mihajlo
AU  - Blagojević, Duško
PY  - 2015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1970
AB  - Ethnopharmacological relevance: Ibogaine is a naturally occurring
   alkaloid with psychotropic and metabotropic effects, derived from the
   bark of the root of the West African Tabernanthe iboga plant. The tribes
   of Kongo basin have been using iboga as a stimulant, for medicinal
   purposes, and in rite of passage ceremonies, for centuries. Besides, it
   has been found that this drug has anti-addictive effects.
   Aim of the study: Previous studies have demonstrated that ibogaine
   changed the quantity of ATP and energy related enzymes as well as the
   activity of antioxidant enzymes in cells thus altering redox equilibrium
   in a time manner. In this work, the mechanism of its action was further
   studied by measuring the effects of ibogaine in human erythrocytes in
   vitro on ATP liberation, membrane fluidity and antioxidant enzymes
   activity.
   Materials and methods: Heparinized human blood samples were incubated
   with ibogaine (10 and 20 mu M) at 37 degrees C for 1 h. Blood plasma was
   separated by centrifugation and the levels of ATP and uric acid were
   measured 10 mm after the addition of ibogaine using standard kits. The
   activity of copper zinc superoxide dismutase (SOD1), catalase (CAT),
   glutathione peroxidase (GSH-Px) and glutathione reductase (GR) were
   measured in erythrocytes after incubation period. The stability of SOD1
   activity was further tested through in vitro incubation with H2O2 and
   scanning of its electrophoretic profiles. Membrane fluidity was
   determined using an electron paramagnetic resonance spin-labelling
   method.
   Results: Results showed that ibogaine treatment of erythrocytes in vitro
   increased ATP concentration in the blood plasma without changes in
   neither erythrocytes membrane fluidity nor uric acid concentration.
   lbogaine also increased SOD1 activity in erythrocytes at both doses
   applied here. Treatment with 20 mu M also elevated GR activity after in
   vitro incubation at 37 degrees C. Electrophoretic profiles revealed that
   incubation with ibogaine mitigates H2O2 mediated suppression of SOD1
   activity.
   Conclusion: Some of the effects of ibogaine seem to be mediated through
   its influence on energy metabolism, redox active processes and the
   effects of discrete fluctuations of individual reactive oxygen species
   on different levels of enzyme activities. Overall, ibogaine acts as a
   pro-antioxidant by increasing activity of antioxidative enzymes and as
   an adaptagene in oxidative distress. (C) 2015 Published by Elsevier
   Ireland Ltd.
T2  - Journal of Ethnopharmacology
T1  - Ex vivo effects of ibogaine on the activity of antioxidative enzymes in
 human erythrocytes
VL  - 164
DO  - 10.1016/j.jep.2015.01.037
SP  - 64
EP  - 70
ER  - 

@article{
author = "Nikolić-Kokić, Aleksandra and Oreščanin Dušić, Zorana and Spasojevic, Ivan and Slavic, Marija and Mijuskovic, Ana and Paskulin, Roman and Miljevic, Cedo and Spasić, Mihajlo and Blagojević, Duško",
year = "2015",
abstract = "Ethnopharmacological relevance: Ibogaine is a naturally occurring
   alkaloid with psychotropic and metabotropic effects, derived from the
   bark of the root of the West African Tabernanthe iboga plant. The tribes
   of Kongo basin have been using iboga as a stimulant, for medicinal
   purposes, and in rite of passage ceremonies, for centuries. Besides, it
   has been found that this drug has anti-addictive effects.
   Aim of the study: Previous studies have demonstrated that ibogaine
   changed the quantity of ATP and energy related enzymes as well as the
   activity of antioxidant enzymes in cells thus altering redox equilibrium
   in a time manner. In this work, the mechanism of its action was further
   studied by measuring the effects of ibogaine in human erythrocytes in
   vitro on ATP liberation, membrane fluidity and antioxidant enzymes
   activity.
   Materials and methods: Heparinized human blood samples were incubated
   with ibogaine (10 and 20 mu M) at 37 degrees C for 1 h. Blood plasma was
   separated by centrifugation and the levels of ATP and uric acid were
   measured 10 mm after the addition of ibogaine using standard kits. The
   activity of copper zinc superoxide dismutase (SOD1), catalase (CAT),
   glutathione peroxidase (GSH-Px) and glutathione reductase (GR) were
   measured in erythrocytes after incubation period. The stability of SOD1
   activity was further tested through in vitro incubation with H2O2 and
   scanning of its electrophoretic profiles. Membrane fluidity was
   determined using an electron paramagnetic resonance spin-labelling
   method.
   Results: Results showed that ibogaine treatment of erythrocytes in vitro
   increased ATP concentration in the blood plasma without changes in
   neither erythrocytes membrane fluidity nor uric acid concentration.
   lbogaine also increased SOD1 activity in erythrocytes at both doses
   applied here. Treatment with 20 mu M also elevated GR activity after in
   vitro incubation at 37 degrees C. Electrophoretic profiles revealed that
   incubation with ibogaine mitigates H2O2 mediated suppression of SOD1
   activity.
   Conclusion: Some of the effects of ibogaine seem to be mediated through
   its influence on energy metabolism, redox active processes and the
   effects of discrete fluctuations of individual reactive oxygen species
   on different levels of enzyme activities. Overall, ibogaine acts as a
   pro-antioxidant by increasing activity of antioxidative enzymes and as
   an adaptagene in oxidative distress. (C) 2015 Published by Elsevier
   Ireland Ltd.",
journal = "Journal of Ethnopharmacology",
title = "Ex vivo effects of ibogaine on the activity of antioxidative enzymes in
 human erythrocytes",
volume = "164",
doi = "10.1016/j.jep.2015.01.037",
pages = "64-70"
}

Nikolić-Kokić, A., Oreščanin Dušić, Z., Spasojevic, I., Slavic, M., Mijuskovic, A., Paskulin, R., Miljevic, C., Spasić, M.,& Blagojević, D.. (2015). Ex vivo effects of ibogaine on the activity of antioxidative enzymes in
 human erythrocytes. in Journal of Ethnopharmacology, 164, 64-70.
https://doi.org/10.1016/j.jep.2015.01.037

Nikolić-Kokić A, Oreščanin Dušić Z, Spasojevic I, Slavic M, Mijuskovic A, Paskulin R, Miljevic C, Spasić M, Blagojević D. Ex vivo effects of ibogaine on the activity of antioxidative enzymes in
 human erythrocytes. in Journal of Ethnopharmacology. 2015;164:64-70.
doi:10.1016/j.jep.2015.01.037 .

Nikolić-Kokić, Aleksandra, Oreščanin Dušić, Zorana, Spasojevic, Ivan, Slavic, Marija, Mijuskovic, Ana, Paskulin, Roman, Miljevic, Cedo, Spasić, Mihajlo, Blagojević, Duško, "Ex vivo effects of ibogaine on the activity of antioxidative enzymes in
 human erythrocytes" in Journal of Ethnopharmacology, 164 (2015):64-70,
https://doi.org/10.1016/j.jep.2015.01.037 . .

TY  - JOUR
AU  - Paskulin, Roman
AU  - Jamnik, Polona
AU  - Danevcić, Tjasa
AU  - Kozelj, Gordana
AU  - Krasovec, Rok
AU  - Krstić Milošević, Dijana
AU  - Blagojević, Duško
AU  - Strukelj, Borut
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1149
AB  - Ethnopharmacological relevance: The root bark of iboga plant-Tabernanthe iboga has been used traditionally in Central Africa as a psychoactive substance in religious rituals, while in smaller doses it is appreciated due to its stimulant properties. The iboga root bark, iboga extract or pure ibogaine are being recognized in the West as an anti-addiction remedy and their use is increasing. Aim of the study: Our previous studies have demonstrated a transient ATP pool reduction under ibogaine accompanied by the induction of energy metabolism related enzymes. The present study aimed to find the cause of this energy deprivation and to foresee its immediate and long-term impact on metabolism. The overall project is designed to disclose the common mechanism of action at these seemingly diverse indications for iboga use, to predict eventual adverse effects and to build the grounds for its safe and beneficial utilization. Materials and methods: The rate of carbon dioxide (CO2) as a marker of energy metabolism in stationary yeast model under aerobic conditions in the presence of ibogaine at concentration of 1, 4 and 20 mg/l was measured for 5 h by gas chromatography. The overall oxidative load was determined fluorimetrically by 2',7'-dichlorofluorescein diacetate (H(2)DCFDA) and in vitro antioxidant properties of ibogaine were defined by 1,1-diphenyl-2-picrylhydrazyl (DPPH) test. Results: The CO2 production under ibogaine was temporarily increased in a dose dependent manner. The increased energy consumption as an early effect of ibogaine was proven by the fact that in spite of energy mobilization, the ATP pool has been simultaneously decreased. Although increased cellular respiration co-produces reactive oxygen species (ROS), the overall oxidative load was significantly lowered by ibogaine. Since ibogaine does not show any significant in vitro antioxidant properties, the results indicate its stimulating influence on physiological oxidative stress defence system. Conclusion: Ibogaine triggers remodeling of the housekeeping metabolism. Under the initial energy cost it results in increased efficacy of physiological antioxidative systems, which reduce oxidative damage and lowers basal metabolic needs. Together with induced catabolic enzymes they set a new metabolic equilibrium that saves energy and makes it easily available in case of extra needs. While healthy organism profits from improved fitness and mental performance and can withstand higher stress without risking a disease, due to the same principle ibogaine provides beneficial support at the recovery after diseases including addiction syndrome. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
T2  - Journal of Ethnopharmacology
T1  - Metabolic plasticity and the energy economizing effect of ibogaine, the principal alkaloid of Tabernanthe iboga
IS  - 1
VL  - 143
SP  - 1035
EP  - 324
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1149
ER  - 

@article{
author = "Paskulin, Roman and Jamnik, Polona and Danevcić, Tjasa and Kozelj, Gordana and Krasovec, Rok and Krstić Milošević, Dijana and Blagojević, Duško and Strukelj, Borut",
year = "2012",
abstract = "Ethnopharmacological relevance: The root bark of iboga plant-Tabernanthe iboga has been used traditionally in Central Africa as a psychoactive substance in religious rituals, while in smaller doses it is appreciated due to its stimulant properties. The iboga root bark, iboga extract or pure ibogaine are being recognized in the West as an anti-addiction remedy and their use is increasing. Aim of the study: Our previous studies have demonstrated a transient ATP pool reduction under ibogaine accompanied by the induction of energy metabolism related enzymes. The present study aimed to find the cause of this energy deprivation and to foresee its immediate and long-term impact on metabolism. The overall project is designed to disclose the common mechanism of action at these seemingly diverse indications for iboga use, to predict eventual adverse effects and to build the grounds for its safe and beneficial utilization. Materials and methods: The rate of carbon dioxide (CO2) as a marker of energy metabolism in stationary yeast model under aerobic conditions in the presence of ibogaine at concentration of 1, 4 and 20 mg/l was measured for 5 h by gas chromatography. The overall oxidative load was determined fluorimetrically by 2',7'-dichlorofluorescein diacetate (H(2)DCFDA) and in vitro antioxidant properties of ibogaine were defined by 1,1-diphenyl-2-picrylhydrazyl (DPPH) test. Results: The CO2 production under ibogaine was temporarily increased in a dose dependent manner. The increased energy consumption as an early effect of ibogaine was proven by the fact that in spite of energy mobilization, the ATP pool has been simultaneously decreased. Although increased cellular respiration co-produces reactive oxygen species (ROS), the overall oxidative load was significantly lowered by ibogaine. Since ibogaine does not show any significant in vitro antioxidant properties, the results indicate its stimulating influence on physiological oxidative stress defence system. Conclusion: Ibogaine triggers remodeling of the housekeeping metabolism. Under the initial energy cost it results in increased efficacy of physiological antioxidative systems, which reduce oxidative damage and lowers basal metabolic needs. Together with induced catabolic enzymes they set a new metabolic equilibrium that saves energy and makes it easily available in case of extra needs. While healthy organism profits from improved fitness and mental performance and can withstand higher stress without risking a disease, due to the same principle ibogaine provides beneficial support at the recovery after diseases including addiction syndrome. (C) 2012 Elsevier Ireland Ltd. All rights reserved.",
journal = "Journal of Ethnopharmacology",
title = "Metabolic plasticity and the energy economizing effect of ibogaine, the principal alkaloid of Tabernanthe iboga",
number = "1",
volume = "143",
pages = "1035-324",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1149"
}

Paskulin, R., Jamnik, P., Danevcić, T., Kozelj, G., Krasovec, R., Krstić Milošević, D., Blagojević, D.,& Strukelj, B.. (2012). Metabolic plasticity and the energy economizing effect of ibogaine, the principal alkaloid of Tabernanthe iboga. in Journal of Ethnopharmacology, 143(1), 1035-324.
https://hdl.handle.net/21.15107/rcub_ibiss_1149

Paskulin R, Jamnik P, Danevcić T, Kozelj G, Krasovec R, Krstić Milošević D, Blagojević D, Strukelj B. Metabolic plasticity and the energy economizing effect of ibogaine, the principal alkaloid of Tabernanthe iboga. in Journal of Ethnopharmacology. 2012;143(1):1035-324.
https://hdl.handle.net/21.15107/rcub_ibiss_1149 .

Paskulin, Roman, Jamnik, Polona, Danevcić, Tjasa, Kozelj, Gordana, Krasovec, Rok, Krstić Milošević, Dijana, Blagojević, Duško, Strukelj, Borut, "Metabolic plasticity and the energy economizing effect of ibogaine, the principal alkaloid of Tabernanthe iboga" in Journal of Ethnopharmacology, 143, no. 1 (2012):1035-324,
https://hdl.handle.net/21.15107/rcub_ibiss_1149 .

TY  - JOUR
AU  - Jamnik, Polona
AU  - Paskulin, Roman
AU  - Obermajer, Natasa
AU  - Slavić, Marija
AU  - Strukelj, Borut
PY  - 2010
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1401
AB  - Ibogaine has been extensively studied in the last decades in relation to its anti-addictive properties that have been repeatedly reported as being addiction interruptive and craving eliminative. In our previous study we have already demonstrated induction of energy related enzymes in rat brains treated with ibogaine at a dose of 20 mg/kg i.p. 24 and 72 h prior to proteomic analysis. In this study a model organism yeast Saccharomyces cerevisiae was cultivated with ibogaine in a concentration of 1 mg/l. Energy metabolism cluster enzymes glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase, enolase and alcohol dehydrogenase were induced after 5 h of exposure. This is a compensation of demonstrated ATP pool decrease after ibogaine. Yeast in a stationary growth phase is an accepted model for studies of housekeeping metabolism of eukaryotes, including humans. Study showed that ibogaine's influence on metabolism is neither species nor tissue specific. Effect is not mediated by binding of ibogaine to receptors, as previously described in literature since they are lacking in this model. (C) 2009 Elsevier B.V. All rights reserved.
T2  - European Journal of Pharmacology
T1  - Induction of energy metabolism related enzymes in yeast Saccharomyces cerevisiae exposed to ibogaine is adaptation to acute decrease in ATP energy pool
IS  - 1-3
VL  - 627
EP  - 135
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1401
ER  - 

@article{
author = "Jamnik, Polona and Paskulin, Roman and Obermajer, Natasa and Slavić, Marija and Strukelj, Borut",
year = "2010",
abstract = "Ibogaine has been extensively studied in the last decades in relation to its anti-addictive properties that have been repeatedly reported as being addiction interruptive and craving eliminative. In our previous study we have already demonstrated induction of energy related enzymes in rat brains treated with ibogaine at a dose of 20 mg/kg i.p. 24 and 72 h prior to proteomic analysis. In this study a model organism yeast Saccharomyces cerevisiae was cultivated with ibogaine in a concentration of 1 mg/l. Energy metabolism cluster enzymes glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase, enolase and alcohol dehydrogenase were induced after 5 h of exposure. This is a compensation of demonstrated ATP pool decrease after ibogaine. Yeast in a stationary growth phase is an accepted model for studies of housekeeping metabolism of eukaryotes, including humans. Study showed that ibogaine's influence on metabolism is neither species nor tissue specific. Effect is not mediated by binding of ibogaine to receptors, as previously described in literature since they are lacking in this model. (C) 2009 Elsevier B.V. All rights reserved.",
journal = "European Journal of Pharmacology",
title = "Induction of energy metabolism related enzymes in yeast Saccharomyces cerevisiae exposed to ibogaine is adaptation to acute decrease in ATP energy pool",
number = "1-3",
volume = "627",
pages = "135",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1401"
}

Jamnik, P., Paskulin, R., Obermajer, N., Slavić, M.,& Strukelj, B.. (2010). Induction of energy metabolism related enzymes in yeast Saccharomyces cerevisiae exposed to ibogaine is adaptation to acute decrease in ATP energy pool. in European Journal of Pharmacology, 627(1-3).
https://hdl.handle.net/21.15107/rcub_ibiss_1401

Jamnik P, Paskulin R, Obermajer N, Slavić M, Strukelj B. Induction of energy metabolism related enzymes in yeast Saccharomyces cerevisiae exposed to ibogaine is adaptation to acute decrease in ATP energy pool. in European Journal of Pharmacology. 2010;627(1-3):null-135.
https://hdl.handle.net/21.15107/rcub_ibiss_1401 .

Jamnik, Polona, Paskulin, Roman, Obermajer, Natasa, Slavić, Marija, Strukelj, Borut, "Induction of energy metabolism related enzymes in yeast Saccharomyces cerevisiae exposed to ibogaine is adaptation to acute decrease in ATP energy pool" in European Journal of Pharmacology, 627, no. 1-3 (2010),
https://hdl.handle.net/21.15107/rcub_ibiss_1401 .