TY  - CONF
AU  - Koprivica, Ivan
AU  - Jonić, Natalija
AU  - Chatzigiannis, Christos
AU  - Tsiailanis, Antonis
AU  - Tzakos, Andreas G
AU  - Stojanović, Ivana D.
PY  - 2023
UR  - https://benbedphar.org/wp-content/uploads/2023/10/abstract_book_Graz_final.pdf
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6474
AB  - Aryl hydrocarbon receptor (AhR) and nuclear factor erythroid 2-related factor 2 (Nrf2) are
transcription factors involved in the regulation of drug-metabolizing enzymes. Moreover,
both of them can modulate the immune response. AhR activation can lead to the activation
or inhibition of specific immune cells, especially at barrier tissues such as skin, lungs, gutassociated lymphoid tissue, etc. Nrf2 was also shown to play a role in the anti-inflammatory
process by inhibiting the recruitment of inflammatory cells and regulating anti-inflammatory
gene expression. Nrf2 gene transcription can be directly modulated by AhR activation, as
the Nrf2 promoter possesses three xenobiotic response element-like elements that were
shown to be able to bind AhR in response to a known Ahr agonist TCDD.
In this study, we explored the effect of newly synthetized AhR agonists (indole-based
derivatives) termed C46 and B19 on mouse macrophage differentiation. Peritoneal cells
were incubated with 1.5 µM of AhR ligands for 24 h, after which the proinflammatory M1
(F4/80+CD40+) and anti-inflammatory M2 (F4/80+CD206+) macrophage phenotype was
determined by flow cytometry. The results indicate that both compounds push
macrophages towards a more inflammatory state, as C46 tripled the M1/M2 ratio in culture,
while B19 doubled it, compared to the DMSO (0.005% v/v) control. Additionally, both
mRNA and protein expression of cytochrome P450 1A1 (CYP1A1), commonly used as an
indicator of AhR activation, were also increased by C46 and B19. Finally, western blot
analysis showed that both of the tested AhR ligands downregulated the protein expression
of Nrf2 within the treated cells.
These results suggest that AhR activation and subsequent Nrf2 down-regulation by the
newly synthesized AhR agonists C46 and B19 boosted the proinflammatory phenotype of
mouse peritoneal macrophages.
PB  - BenBedPhar Consortium
C3  - 5th Scientific Meeting of the COST Action CA20121: Bench to Bedside Transition for Pharmacological Regulation of NRF2 in non-communicable diseases (BenBedPhar): Translating NRF2 Research into Clinical Practice; 2023 Oct 12-13; Graz, Austria
T1  - Nrf2 down-regulation mediates pro-inflammatory effects of novel synthetic AhR ligands
SP  - 38
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6474
ER  - 

@conference{
author = "Koprivica, Ivan and Jonić, Natalija and Chatzigiannis, Christos and Tsiailanis, Antonis and Tzakos, Andreas G and Stojanović, Ivana D.",
year = "2023",
abstract = "Aryl hydrocarbon receptor (AhR) and nuclear factor erythroid 2-related factor 2 (Nrf2) are
transcription factors involved in the regulation of drug-metabolizing enzymes. Moreover,
both of them can modulate the immune response. AhR activation can lead to the activation
or inhibition of specific immune cells, especially at barrier tissues such as skin, lungs, gutassociated lymphoid tissue, etc. Nrf2 was also shown to play a role in the anti-inflammatory
process by inhibiting the recruitment of inflammatory cells and regulating anti-inflammatory
gene expression. Nrf2 gene transcription can be directly modulated by AhR activation, as
the Nrf2 promoter possesses three xenobiotic response element-like elements that were
shown to be able to bind AhR in response to a known Ahr agonist TCDD.
In this study, we explored the effect of newly synthetized AhR agonists (indole-based
derivatives) termed C46 and B19 on mouse macrophage differentiation. Peritoneal cells
were incubated with 1.5 µM of AhR ligands for 24 h, after which the proinflammatory M1
(F4/80+CD40+) and anti-inflammatory M2 (F4/80+CD206+) macrophage phenotype was
determined by flow cytometry. The results indicate that both compounds push
macrophages towards a more inflammatory state, as C46 tripled the M1/M2 ratio in culture,
while B19 doubled it, compared to the DMSO (0.005% v/v) control. Additionally, both
mRNA and protein expression of cytochrome P450 1A1 (CYP1A1), commonly used as an
indicator of AhR activation, were also increased by C46 and B19. Finally, western blot
analysis showed that both of the tested AhR ligands downregulated the protein expression
of Nrf2 within the treated cells.
These results suggest that AhR activation and subsequent Nrf2 down-regulation by the
newly synthesized AhR agonists C46 and B19 boosted the proinflammatory phenotype of
mouse peritoneal macrophages.",
publisher = "BenBedPhar Consortium",
journal = "5th Scientific Meeting of the COST Action CA20121: Bench to Bedside Transition for Pharmacological Regulation of NRF2 in non-communicable diseases (BenBedPhar): Translating NRF2 Research into Clinical Practice; 2023 Oct 12-13; Graz, Austria",
title = "Nrf2 down-regulation mediates pro-inflammatory effects of novel synthetic AhR ligands",
pages = "38",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6474"
}

Koprivica, I., Jonić, N., Chatzigiannis, C., Tsiailanis, A., Tzakos, A. G.,& Stojanović, I. D.. (2023). Nrf2 down-regulation mediates pro-inflammatory effects of novel synthetic AhR ligands. in 5th Scientific Meeting of the COST Action CA20121: Bench to Bedside Transition for Pharmacological Regulation of NRF2 in non-communicable diseases (BenBedPhar): Translating NRF2 Research into Clinical Practice; 2023 Oct 12-13; Graz, Austria
BenBedPhar Consortium., 38.
https://hdl.handle.net/21.15107/rcub_ibiss_6474

Koprivica I, Jonić N, Chatzigiannis C, Tsiailanis A, Tzakos AG, Stojanović ID. Nrf2 down-regulation mediates pro-inflammatory effects of novel synthetic AhR ligands. in 5th Scientific Meeting of the COST Action CA20121: Bench to Bedside Transition for Pharmacological Regulation of NRF2 in non-communicable diseases (BenBedPhar): Translating NRF2 Research into Clinical Practice; 2023 Oct 12-13; Graz, Austria. 2023;:38.
https://hdl.handle.net/21.15107/rcub_ibiss_6474 .

Koprivica, Ivan, Jonić, Natalija, Chatzigiannis, Christos, Tsiailanis, Antonis, Tzakos, Andreas G, Stojanović, Ivana D., "Nrf2 down-regulation mediates pro-inflammatory effects of novel synthetic AhR ligands" in 5th Scientific Meeting of the COST Action CA20121: Bench to Bedside Transition for Pharmacological Regulation of NRF2 in non-communicable diseases (BenBedPhar): Translating NRF2 Research into Clinical Practice; 2023 Oct 12-13; Graz, Austria (2023):38,
https://hdl.handle.net/21.15107/rcub_ibiss_6474 .

TY  - CONF
AU  - Stegnjaić, Goran
AU  - Lazarević, Milica
AU  - Tsiailanis, Antonios D
AU  - Antoniou, Thomas
AU  - Gkalpinos, Vasileios K
AU  - Nikolovski, Neda
AU  - Stanisavljević, Suzana
AU  - Dimitrijević, Mirjana
AU  - Momčilović, Miljana
AU  - Miljković, Đorđe
AU  - Tzakos, Andreas G
AU  - Jevtić, Bojan
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6299
AB  - This study aimed to evaluate the effects of a synthetic gallic acid (GA) derivative in the
central nervous system (CNS) autoimmunity, i.e. in experimental autoimmune
encephalomyelitis (EAE), an animal model of multiple sclerosis. EAE was induced in DA
rats by injection of autologous spinal cord homogenate, with a gallic acid derivative being
applied subcutaneously (20 mg/kg, day 7-22 post-immunization). GA derivative
ameliorated EAE. Cells from lymph nodes draining the site of immunization (DLNC),
isolated in the inductive phase of the disease, and spinal cord immune cells (SCIC),
isolated at the peak of disease, were exposed to GA derivative in vitro. Encephalitogenic
cytokines, interferon (IFN)-γ and interleukin (IL)-17, were decreased in SCIC and DLNC
under the influence of GA derivative. The proportion of IL-17-producing CD4+ T cells was
reduced in SCIC (flow cytometry). Treatment of microglial BV2 cells with GA derivative
led to inhibition of NO, IL-6, and tumor necrosis factor release. These results imply that
the synthesized GA derivative is a potent immunomodulator, able to ameliorate EAE. Its
effects on the CNS autoimmunity are related to the inhibition of encephalitogenic T cells
and macrophage/microglia activity in our study.
PB  - Belgrade: Faculty of Chemistry
C3  - Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia
T1  - The effect of a gallic acid derivative on encephalitogenic cells
SP  - 140
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6299
ER  - 

@conference{
author = "Stegnjaić, Goran and Lazarević, Milica and Tsiailanis, Antonios D and Antoniou, Thomas and Gkalpinos, Vasileios K and Nikolovski, Neda and Stanisavljević, Suzana and Dimitrijević, Mirjana and Momčilović, Miljana and Miljković, Đorđe and Tzakos, Andreas G and Jevtić, Bojan",
year = "2022",
abstract = "This study aimed to evaluate the effects of a synthetic gallic acid (GA) derivative in the
central nervous system (CNS) autoimmunity, i.e. in experimental autoimmune
encephalomyelitis (EAE), an animal model of multiple sclerosis. EAE was induced in DA
rats by injection of autologous spinal cord homogenate, with a gallic acid derivative being
applied subcutaneously (20 mg/kg, day 7-22 post-immunization). GA derivative
ameliorated EAE. Cells from lymph nodes draining the site of immunization (DLNC),
isolated in the inductive phase of the disease, and spinal cord immune cells (SCIC),
isolated at the peak of disease, were exposed to GA derivative in vitro. Encephalitogenic
cytokines, interferon (IFN)-γ and interleukin (IL)-17, were decreased in SCIC and DLNC
under the influence of GA derivative. The proportion of IL-17-producing CD4+ T cells was
reduced in SCIC (flow cytometry). Treatment of microglial BV2 cells with GA derivative
led to inhibition of NO, IL-6, and tumor necrosis factor release. These results imply that
the synthesized GA derivative is a potent immunomodulator, able to ameliorate EAE. Its
effects on the CNS autoimmunity are related to the inhibition of encephalitogenic T cells
and macrophage/microglia activity in our study.",
publisher = "Belgrade: Faculty of Chemistry",
journal = "Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia",
title = "The effect of a gallic acid derivative on encephalitogenic cells",
pages = "140",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6299"
}

Stegnjaić, G., Lazarević, M., Tsiailanis, A. D., Antoniou, T., Gkalpinos, V. K., Nikolovski, N., Stanisavljević, S., Dimitrijević, M., Momčilović, M., Miljković, Đ., Tzakos, A. G.,& Jevtić, B.. (2022). The effect of a gallic acid derivative on encephalitogenic cells. in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia
Belgrade: Faculty of Chemistry., 140.
https://hdl.handle.net/21.15107/rcub_ibiss_6299

Stegnjaić G, Lazarević M, Tsiailanis AD, Antoniou T, Gkalpinos VK, Nikolovski N, Stanisavljević S, Dimitrijević M, Momčilović M, Miljković Đ, Tzakos AG, Jevtić B. The effect of a gallic acid derivative on encephalitogenic cells. in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia. 2022;:140.
https://hdl.handle.net/21.15107/rcub_ibiss_6299 .

Stegnjaić, Goran, Lazarević, Milica, Tsiailanis, Antonios D, Antoniou, Thomas, Gkalpinos, Vasileios K, Nikolovski, Neda, Stanisavljević, Suzana, Dimitrijević, Mirjana, Momčilović, Miljana, Miljković, Đorđe, Tzakos, Andreas G, Jevtić, Bojan, "The effect of a gallic acid derivative on encephalitogenic cells" in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia (2022):140,
https://hdl.handle.net/21.15107/rcub_ibiss_6299 .

TY  - CONF
AU  - Lazarević, Milica
AU  - Stegnjaić, Goran
AU  - Diamantis, Dimitris
AU  - Papaemmanouil, Christina
AU  - Nikolovski, Neda
AU  - Jevtić, Bojan
AU  - Tzakos, Andreas G
AU  - Miljković, Đorđe
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6297
AB  - Rosmarinic acid is a polyphenolic compound, abundantly presentin herbs of the Lamiaceae
family. The aim of the study was to evaluate a recently developed rosmarinic acid
derivative (RAd), with an enhanced ability of diffusion through biological membranes 1, in
preclinical settingsof the central nervous system autoimmunity. To this extent,
experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis
was used. EAE was induced in DA rats by subcutaneous injection of autologous spinal
cord homogenate 2, while treatment with RAd (30 mg/kg) started at 7 day post
immunization and lasted for 15 days. Subcutaneous RAd administration successfully
ameliorated EAE, leading to abbreviation of the disease duration and reducement of
maximal, cumulative and meanclinical score. Also, RAd effects on draining lymph node
cells (DLNC) isolated in the inductive phase of EAE and spinal cord immune cells (SCIC)
obtained at the peak of the diseasewere evaluated. In vitro treatment with RAd (5 μM)
reduced production of major encephalitogenic cytokines, i.e.interferon (IFN)-γ and
interleukin (IL)-17, both in DLNC and SCIC. The reduction of IFN-γ and IL-17
production under the influence of RAd was also detected in the CD4+ T cells purified
fromDLNC, thus suggesting that RAd had a direct effect on CD4+ T cells. Additionally,
the effects of in vitro treatment with RAd were examinedon macrophages (Mf), immune
cells with important role in EAE pathogenesis. Treatment of peritoneal Mf,obtained from
non-immunized DA rats, with RAd (25 μM) led to reduction of NO and IL-6 production,
exterted no effect on IL-1beta production, and elevated tumor necrosis factor production in
Mf. Expression of MHC II and co-stimulatory molecule CD80, the phagocytic ability and
the production of reactive oxygen species in RAd-treated Mf were also downregulated.
Our results imply that RAd possesses anti-inflammatory and antiencephalitogenicproperties. Thus, further studies on the mechanisms behind the observed
effects and their relevance for the therapy of multiple sclerosis are warranted.
PB  - Belgrade: Faculty of Chemistry
C3  - Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia
T1  - The effect of novel rosmarinic acid derivative on the pathogenesis of experimental autoimmune encephalomyelitis in rats
SP  - 79
EP  - 80
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6297
ER  - 

@conference{
author = "Lazarević, Milica and Stegnjaić, Goran and Diamantis, Dimitris and Papaemmanouil, Christina and Nikolovski, Neda and Jevtić, Bojan and Tzakos, Andreas G and Miljković, Đorđe",
year = "2021",
abstract = "Rosmarinic acid is a polyphenolic compound, abundantly presentin herbs of the Lamiaceae
family. The aim of the study was to evaluate a recently developed rosmarinic acid
derivative (RAd), with an enhanced ability of diffusion through biological membranes 1, in
preclinical settingsof the central nervous system autoimmunity. To this extent,
experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis
was used. EAE was induced in DA rats by subcutaneous injection of autologous spinal
cord homogenate 2, while treatment with RAd (30 mg/kg) started at 7 day post
immunization and lasted for 15 days. Subcutaneous RAd administration successfully
ameliorated EAE, leading to abbreviation of the disease duration and reducement of
maximal, cumulative and meanclinical score. Also, RAd effects on draining lymph node
cells (DLNC) isolated in the inductive phase of EAE and spinal cord immune cells (SCIC)
obtained at the peak of the diseasewere evaluated. In vitro treatment with RAd (5 μM)
reduced production of major encephalitogenic cytokines, i.e.interferon (IFN)-γ and
interleukin (IL)-17, both in DLNC and SCIC. The reduction of IFN-γ and IL-17
production under the influence of RAd was also detected in the CD4+ T cells purified
fromDLNC, thus suggesting that RAd had a direct effect on CD4+ T cells. Additionally,
the effects of in vitro treatment with RAd were examinedon macrophages (Mf), immune
cells with important role in EAE pathogenesis. Treatment of peritoneal Mf,obtained from
non-immunized DA rats, with RAd (25 μM) led to reduction of NO and IL-6 production,
exterted no effect on IL-1beta production, and elevated tumor necrosis factor production in
Mf. Expression of MHC II and co-stimulatory molecule CD80, the phagocytic ability and
the production of reactive oxygen species in RAd-treated Mf were also downregulated.
Our results imply that RAd possesses anti-inflammatory and antiencephalitogenicproperties. Thus, further studies on the mechanisms behind the observed
effects and their relevance for the therapy of multiple sclerosis are warranted.",
publisher = "Belgrade: Faculty of Chemistry",
journal = "Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia",
title = "The effect of novel rosmarinic acid derivative on the pathogenesis of experimental autoimmune encephalomyelitis in rats",
pages = "79-80",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6297"
}

Lazarević, M., Stegnjaić, G., Diamantis, D., Papaemmanouil, C., Nikolovski, N., Jevtić, B., Tzakos, A. G.,& Miljković, Đ.. (2021). The effect of novel rosmarinic acid derivative on the pathogenesis of experimental autoimmune encephalomyelitis in rats. in Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia
Belgrade: Faculty of Chemistry., 79-80.
https://hdl.handle.net/21.15107/rcub_ibiss_6297

Lazarević M, Stegnjaić G, Diamantis D, Papaemmanouil C, Nikolovski N, Jevtić B, Tzakos AG, Miljković Đ. The effect of novel rosmarinic acid derivative on the pathogenesis of experimental autoimmune encephalomyelitis in rats. in Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia. 2021;:79-80.
https://hdl.handle.net/21.15107/rcub_ibiss_6297 .

Lazarević, Milica, Stegnjaić, Goran, Diamantis, Dimitris, Papaemmanouil, Christina, Nikolovski, Neda, Jevtić, Bojan, Tzakos, Andreas G, Miljković, Đorđe, "The effect of novel rosmarinic acid derivative on the pathogenesis of experimental autoimmune encephalomyelitis in rats" in Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia (2021):79-80,
https://hdl.handle.net/21.15107/rcub_ibiss_6297 .

TY  - CONF
AU  - Jonić, Natalija
AU  - Chatzigiannis, Christos M.
AU  - Koprivica, Ivan
AU  - Savic, Anisia
AU  - Mićanović, Dragica
AU  - Saksida, Tamara
AU  - Pejnović, Nada
AU  - Tzakos, Andreas
AU  - Stojanović, Ivana D.
PY  - 2021
UR  - https://onlinelibrary.wiley.com/toc/15214141/2021/51/S1
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4883
AB  - Aryl hydrocarbon receptor (AhR) is a ligand‐activated transcription factor that responds to various aromatic compounds, both endogenous such as kynurenine and exogenous such as natural plant flavonoids, polyphenolics and indoles. AhR has been recently identified as the regulator of immune cells function. The activation of AhR generally leads to the attenuation of the immune response, while its inhibition promotes the opposite effects. In this study we have selected several plant‐derived indol derivatives and tested them for their AhR ligand activity. A potent AhR antagonist was identified (code C46) and further evaluated on mouse peritoneal macrophages for its ability to modulate macrophage function. Macrophages were exposed in vitro to compound C46 in concentrations ranging from 250 ng/ml to 1000 ng/ml for 48 h. Flow cytometry analysis showed that C46 significantly and dose‐dependently up‐regulated the proportion of M1 macrophages (F4/80+CD40+). Interestingly, C46 influenced only M1 macrophages, as the proportion of M2 (F4/80+CD206+) remained stable upon the exposure to C46. In addition, C46 increased the cytocidal function of macrophages by increasing the content of nitric oxide as determined by DAF‐FM staining. Similarly to in vitro effects, intraperitoneal C46 administration up‐regulated the proportion of M1 macrophages in the peritoneum, 72 h after the treatment. In conclusion, blocking of AhR pathway by C46 potentiates pro‐inflammatory function of macrophages and it may represent a promising approach for future testing in animal models of cancer.
PB  - Wiley‐VCH GmbH
C3  - 6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting
T1  - Novel aryl hydrocarbon receptor antagonist promotes macrophage pro-inflammatory phenotype
DO  - 10.1002/eji.202170200
SP  - 207
ER  - 

@conference{
author = "Jonić, Natalija and Chatzigiannis, Christos M. and Koprivica, Ivan and Savic, Anisia and Mićanović, Dragica and Saksida, Tamara and Pejnović, Nada and Tzakos, Andreas and Stojanović, Ivana D.",
year = "2021",
abstract = "Aryl hydrocarbon receptor (AhR) is a ligand‐activated transcription factor that responds to various aromatic compounds, both endogenous such as kynurenine and exogenous such as natural plant flavonoids, polyphenolics and indoles. AhR has been recently identified as the regulator of immune cells function. The activation of AhR generally leads to the attenuation of the immune response, while its inhibition promotes the opposite effects. In this study we have selected several plant‐derived indol derivatives and tested them for their AhR ligand activity. A potent AhR antagonist was identified (code C46) and further evaluated on mouse peritoneal macrophages for its ability to modulate macrophage function. Macrophages were exposed in vitro to compound C46 in concentrations ranging from 250 ng/ml to 1000 ng/ml for 48 h. Flow cytometry analysis showed that C46 significantly and dose‐dependently up‐regulated the proportion of M1 macrophages (F4/80+CD40+). Interestingly, C46 influenced only M1 macrophages, as the proportion of M2 (F4/80+CD206+) remained stable upon the exposure to C46. In addition, C46 increased the cytocidal function of macrophages by increasing the content of nitric oxide as determined by DAF‐FM staining. Similarly to in vitro effects, intraperitoneal C46 administration up‐regulated the proportion of M1 macrophages in the peritoneum, 72 h after the treatment. In conclusion, blocking of AhR pathway by C46 potentiates pro‐inflammatory function of macrophages and it may represent a promising approach for future testing in animal models of cancer.",
publisher = "Wiley‐VCH GmbH",
journal = "6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting",
title = "Novel aryl hydrocarbon receptor antagonist promotes macrophage pro-inflammatory phenotype",
doi = "10.1002/eji.202170200",
pages = "207"
}

Jonić, N., Chatzigiannis, C. M., Koprivica, I., Savic, A., Mićanović, D., Saksida, T., Pejnović, N., Tzakos, A.,& Stojanović, I. D.. (2021). Novel aryl hydrocarbon receptor antagonist promotes macrophage pro-inflammatory phenotype. in 6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting
Wiley‐VCH GmbH., 207.
https://doi.org/10.1002/eji.202170200

Jonić N, Chatzigiannis CM, Koprivica I, Savic A, Mićanović D, Saksida T, Pejnović N, Tzakos A, Stojanović ID. Novel aryl hydrocarbon receptor antagonist promotes macrophage pro-inflammatory phenotype. in 6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting. 2021;:207.
doi:10.1002/eji.202170200 .

Jonić, Natalija, Chatzigiannis, Christos M., Koprivica, Ivan, Savic, Anisia, Mićanović, Dragica, Saksida, Tamara, Pejnović, Nada, Tzakos, Andreas, Stojanović, Ivana D., "Novel aryl hydrocarbon receptor antagonist promotes macrophage pro-inflammatory phenotype" in 6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting (2021):207,
https://doi.org/10.1002/eji.202170200 . .

TY  - CONF
AU  - Koprivica, Ivan
AU  - Jonić, Natalija
AU  - Diamantis, Dimitris
AU  - Papaemmanouil, Christina
AU  - Mićanović, Dragica
AU  - Stegnjaić, Goran
AU  - Jevtić, Bojan
AU  - Saksida, Tamara
AU  - Miljković, Đorđe
AU  - Tzakos, Andreas
AU  - Stojanović, Ivana D.
PY  - 2021
UR  - https://onlinelibrary.wiley.com/toc/15214141/2021/51/S1
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4877
AB  - Rosmarinic acid (RA) is a polyphenol compound that naturally occurs in plants of the Lamiaceae family. A novel rosmarinic acid derivative (RAd) has been developed and tested in the animal model of type 1 diabetes (T1D) and the animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). T1D was induced in male C57BL/6 mice using streptozotocin that was applied intraperitoneally for five consecutive days. EAE was induced in Dark Agouti (DA) rats by subcutaneous injection of autologous spinal cord homogenate. For T1D, intraperitoneal administration of RAd (10 mg/kg bw) began from the first streptozotocin injection and continued for 20 days, while for EAE, subcutaneous administration of RAd (28 mg/kg bw) started with the first clinical signs of the disease and continued for 15 days. RAd‐treated mice exhibited lower incidence of T1D (monitored up to 45 days from the disease induction), and fluorescent histochemical analysis showed that their pancreatic islets expressed more insulin. Additionally, RAd ameliorated EAE in DA rats. In T1D, RAd treatment significantly down‐regulated the proportions of CD11b⁺ and CD11c⁺ myeloid cells in the immune cell infiltrates in the pancreas, detected on day 10 after T1D induction. However, the proportions of cells of adaptive immunity (CD4⁺, CD8⁺, Th1, Th17) were comparable between the groups. These results suggest that chemically modified RA shows great promise for anti‐inflammatory approaches in autoimmune and inflammatory diseases, while our previous research illustrated that unmodified RA exerted no effect on T1D pathogenesis.
PB  - Wiley‐VCH GmbH
C3  - 6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting
T1  - Preclinical evaluation of a novel rosmarinic acid derivative on the pathogenesis of type 1 diabetes in a mouse model
DO  - 10.1002/eji.202170200
SP  - 399
ER  - 

@conference{
author = "Koprivica, Ivan and Jonić, Natalija and Diamantis, Dimitris and Papaemmanouil, Christina and Mićanović, Dragica and Stegnjaić, Goran and Jevtić, Bojan and Saksida, Tamara and Miljković, Đorđe and Tzakos, Andreas and Stojanović, Ivana D.",
year = "2021",
abstract = "Rosmarinic acid (RA) is a polyphenol compound that naturally occurs in plants of the Lamiaceae family. A novel rosmarinic acid derivative (RAd) has been developed and tested in the animal model of type 1 diabetes (T1D) and the animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). T1D was induced in male C57BL/6 mice using streptozotocin that was applied intraperitoneally for five consecutive days. EAE was induced in Dark Agouti (DA) rats by subcutaneous injection of autologous spinal cord homogenate. For T1D, intraperitoneal administration of RAd (10 mg/kg bw) began from the first streptozotocin injection and continued for 20 days, while for EAE, subcutaneous administration of RAd (28 mg/kg bw) started with the first clinical signs of the disease and continued for 15 days. RAd‐treated mice exhibited lower incidence of T1D (monitored up to 45 days from the disease induction), and fluorescent histochemical analysis showed that their pancreatic islets expressed more insulin. Additionally, RAd ameliorated EAE in DA rats. In T1D, RAd treatment significantly down‐regulated the proportions of CD11b⁺ and CD11c⁺ myeloid cells in the immune cell infiltrates in the pancreas, detected on day 10 after T1D induction. However, the proportions of cells of adaptive immunity (CD4⁺, CD8⁺, Th1, Th17) were comparable between the groups. These results suggest that chemically modified RA shows great promise for anti‐inflammatory approaches in autoimmune and inflammatory diseases, while our previous research illustrated that unmodified RA exerted no effect on T1D pathogenesis.",
publisher = "Wiley‐VCH GmbH",
journal = "6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting",
title = "Preclinical evaluation of a novel rosmarinic acid derivative on the pathogenesis of type 1 diabetes in a mouse model",
doi = "10.1002/eji.202170200",
pages = "399"
}

Koprivica, I., Jonić, N., Diamantis, D., Papaemmanouil, C., Mićanović, D., Stegnjaić, G., Jevtić, B., Saksida, T., Miljković, Đ., Tzakos, A.,& Stojanović, I. D.. (2021). Preclinical evaluation of a novel rosmarinic acid derivative on the pathogenesis of type 1 diabetes in a mouse model. in 6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting
Wiley‐VCH GmbH., 399.
https://doi.org/10.1002/eji.202170200

Koprivica I, Jonić N, Diamantis D, Papaemmanouil C, Mićanović D, Stegnjaić G, Jevtić B, Saksida T, Miljković Đ, Tzakos A, Stojanović ID. Preclinical evaluation of a novel rosmarinic acid derivative on the pathogenesis of type 1 diabetes in a mouse model. in 6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting. 2021;:399.
doi:10.1002/eji.202170200 .

Koprivica, Ivan, Jonić, Natalija, Diamantis, Dimitris, Papaemmanouil, Christina, Mićanović, Dragica, Stegnjaić, Goran, Jevtić, Bojan, Saksida, Tamara, Miljković, Đorđe, Tzakos, Andreas, Stojanović, Ivana D., "Preclinical evaluation of a novel rosmarinic acid derivative on the pathogenesis of type 1 diabetes in a mouse model" in 6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting (2021):399,
https://doi.org/10.1002/eji.202170200 . .

TY  - JOUR
AU  - Vujičić, Milica
AU  - Nikolić, Ivana
AU  - Kontogianni, Vassiliki G.
AU  - Saksida, Tamara
AU  - Charisiadis, Pantelis
AU  - Vasić, Bobana
AU  - Stošić-Grujičić, Stanislava
AU  - Gerothanassis, Ioannis P.
AU  - Tzakos, Andreas G.
AU  - Stojanović, Ivana D.
PY  - 2016
UR  - http://doi.wiley.com/10.1111/1750-3841.13333
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2979
AB  - Type 1 diabetes (T1D) is an autoimmune disease that develops as a consequence of pancreatic β-cell death induced by proinflammatory mediators. Because Origanum vulgare L. ssp. hirtum (Greek oregano) contains antiinflammatory molecules, we hypothesized that it might be beneficial for the treatment of T1D. An ethyl acetate extract of oregano (EAO) was prepared from the leaves by a polar extraction method. Phytochemical composition was determined by liquid chromatography-UV diode array coupled to ion-trap mass spectrometry with electrospray ionization interface (LC/DAD/ESI-MSn). In vitro immunomodulatory effect of EAO was estimated by measuring proliferation (MTT) or cytokine secretion (ELISA) from immune cells. Diabetes was induced by multiple low doses of streptozotocin (MLDS) in male C57BL/6 mice and EAO was administered intraperitoneally for 10 d. Determination of cellular composition (flow cytometry) and cytokine production (ELISA) was performed on 12th d after diabetes induction. EAO suppressed the function of both macrophages and lymphocytes in vitro. In vivo, EAO treatment significantly preserved pancreatic islets and reduced diabetes incidence in MLDS-challenged mice. Besides down-modulatory effect on macrophages, EAO reduced the number of total CD4+ and activated CD4+CD25+ T cells. Furthermore, EAO affected the number of T helper 1 (Th1) and T helper 17 (Th17) cells through downregulation of their key transcription factors T-bet and RORγT. Because EAO treatment protects mice from development of hyperglycemia by reducing proinflammatory macrophage/Th1/Th17 response, this plant extract could represent a basis for future diabetes therapy.
PB  - Blackwell Publishing Inc.
T2  - Journal of Food Science
T1  - Ethyl Acetate Extract of Origanum vulgare L. ssp. hirtum Prevents Streptozotocin-Induced Diabetes in C57BL/6 Mice
IS  - 7
VL  - 81
DO  - 10.1111/1750-3841.13333
SP  - H1846
EP  - H1853
ER  - 

@article{
author = "Vujičić, Milica and Nikolić, Ivana and Kontogianni, Vassiliki G. and Saksida, Tamara and Charisiadis, Pantelis and Vasić, Bobana and Stošić-Grujičić, Stanislava and Gerothanassis, Ioannis P. and Tzakos, Andreas G. and Stojanović, Ivana D.",
year = "2016",
abstract = "Type 1 diabetes (T1D) is an autoimmune disease that develops as a consequence of pancreatic β-cell death induced by proinflammatory mediators. Because Origanum vulgare L. ssp. hirtum (Greek oregano) contains antiinflammatory molecules, we hypothesized that it might be beneficial for the treatment of T1D. An ethyl acetate extract of oregano (EAO) was prepared from the leaves by a polar extraction method. Phytochemical composition was determined by liquid chromatography-UV diode array coupled to ion-trap mass spectrometry with electrospray ionization interface (LC/DAD/ESI-MSn). In vitro immunomodulatory effect of EAO was estimated by measuring proliferation (MTT) or cytokine secretion (ELISA) from immune cells. Diabetes was induced by multiple low doses of streptozotocin (MLDS) in male C57BL/6 mice and EAO was administered intraperitoneally for 10 d. Determination of cellular composition (flow cytometry) and cytokine production (ELISA) was performed on 12th d after diabetes induction. EAO suppressed the function of both macrophages and lymphocytes in vitro. In vivo, EAO treatment significantly preserved pancreatic islets and reduced diabetes incidence in MLDS-challenged mice. Besides down-modulatory effect on macrophages, EAO reduced the number of total CD4+ and activated CD4+CD25+ T cells. Furthermore, EAO affected the number of T helper 1 (Th1) and T helper 17 (Th17) cells through downregulation of their key transcription factors T-bet and RORγT. Because EAO treatment protects mice from development of hyperglycemia by reducing proinflammatory macrophage/Th1/Th17 response, this plant extract could represent a basis for future diabetes therapy.",
publisher = "Blackwell Publishing Inc.",
journal = "Journal of Food Science",
title = "Ethyl Acetate Extract of Origanum vulgare L. ssp. hirtum Prevents Streptozotocin-Induced Diabetes in C57BL/6 Mice",
number = "7",
volume = "81",
doi = "10.1111/1750-3841.13333",
pages = "H1846-H1853"
}

Vujičić, M., Nikolić, I., Kontogianni, V. G., Saksida, T., Charisiadis, P., Vasić, B., Stošić-Grujičić, S., Gerothanassis, I. P., Tzakos, A. G.,& Stojanović, I. D.. (2016). Ethyl Acetate Extract of Origanum vulgare L. ssp. hirtum Prevents Streptozotocin-Induced Diabetes in C57BL/6 Mice. in Journal of Food Science
Blackwell Publishing Inc.., 81(7), H1846-H1853.
https://doi.org/10.1111/1750-3841.13333

Vujičić M, Nikolić I, Kontogianni VG, Saksida T, Charisiadis P, Vasić B, Stošić-Grujičić S, Gerothanassis IP, Tzakos AG, Stojanović ID. Ethyl Acetate Extract of Origanum vulgare L. ssp. hirtum Prevents Streptozotocin-Induced Diabetes in C57BL/6 Mice. in Journal of Food Science. 2016;81(7):H1846-H1853.
doi:10.1111/1750-3841.13333 .

Vujičić, Milica, Nikolić, Ivana, Kontogianni, Vassiliki G., Saksida, Tamara, Charisiadis, Pantelis, Vasić, Bobana, Stošić-Grujičić, Stanislava, Gerothanassis, Ioannis P., Tzakos, Andreas G., Stojanović, Ivana D., "Ethyl Acetate Extract of Origanum vulgare L. ssp. hirtum Prevents Streptozotocin-Induced Diabetes in C57BL/6 Mice" in Journal of Food Science, 81, no. 7 (2016):H1846-H1853,
https://doi.org/10.1111/1750-3841.13333 . .

TY  - JOUR
AU  - Vujičić, Milica
AU  - Nikolić, Ivana
AU  - Kontogianni, Vassiliki G.
AU  - Saksida, Tamara
AU  - Charisiadis, Pantelis
AU  - Oreščanin Dušić, Zorana
AU  - Blagojević, Duško
AU  - Stošić-Grujičić, Stanislava
AU  - Tzakos, Andreas G.
AU  - Stojanović, Ivana D.
PY  - 2015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1988
AB  - Type 1 diabetes (T1D), an autoimmune inflammatory disorder, develops as
   a consequence of pancreatic beta-cell destruction and results in
   hyperglycaemia. Since current T1D therapy mainly involves insulin
   replacement, the aim of the present study was to evaluate the
   therapeutic potential of Origanum vulgare L. ssp. hirtum (Greek oregano)
   leaf extract rich in biophenols for the treatment of T1D. The
   phytochemical profile of methanolic oregano extract (MOE) and aqueous
   oregano extract (AOE) was determined by liquid
   chromatography/electrospray ion-trap tandem MS (LC/DAD/ESI-MSn), while
   their main compounds were quantified by HPLC with diode array detection.
   After establishing their potent in vitro antioxidant activity, the
   extracts were administered to C57BL/6 mice treated with multiple low
   doses of streptozotocin for diabetes induction. While prophylactic AOE
   therapy had no impact on diabetes induction, MOE reduced diabetes
   incidence and preserved normal insulin secretion. In addition, MOE
   scavenged reactive oxygen and nitrogen species and, therefore,
   alleviated the need for the up-regulation of antioxidant enzymes. MOE
   treatment specifically attenuated the pro-inflammatory response mediated
   by T helper 17 cells and enhanced anti-inflammatory T helper 2 and T
   regulatory cells through the impact on specific signalling pathways and
   transcription factors. Importantly, MOE preserved beta-cells from in
   vitro apoptosis via blockade of caspase 3. Finally, rosmarinic acid, a
   predominant compound in MOE, exhibited only partial protection from
   diabetes induction. In conclusion, acting as an antioxidant,
   immunomodulator and in an anti-apoptotic manner, MOE protected mice from
   diabetes development. Seemingly, there is more than one compound
   responsible for the beneficial effect of MOE.
T2  - British Journal of Nutrition
T1  - Methanolic extract of Origanum vulgare ameliorates type 1 diabetes
 through antioxidant, anti-inflammatory and anti-apoptotic activity
IS  - 5
VL  - 113
DO  - 10.1017/S0007114514004048
SP  - 770
EP  - 782
ER  - 

@article{
author = "Vujičić, Milica and Nikolić, Ivana and Kontogianni, Vassiliki G. and Saksida, Tamara and Charisiadis, Pantelis and Oreščanin Dušić, Zorana and Blagojević, Duško and Stošić-Grujičić, Stanislava and Tzakos, Andreas G. and Stojanović, Ivana D.",
year = "2015",
abstract = "Type 1 diabetes (T1D), an autoimmune inflammatory disorder, develops as
   a consequence of pancreatic beta-cell destruction and results in
   hyperglycaemia. Since current T1D therapy mainly involves insulin
   replacement, the aim of the present study was to evaluate the
   therapeutic potential of Origanum vulgare L. ssp. hirtum (Greek oregano)
   leaf extract rich in biophenols for the treatment of T1D. The
   phytochemical profile of methanolic oregano extract (MOE) and aqueous
   oregano extract (AOE) was determined by liquid
   chromatography/electrospray ion-trap tandem MS (LC/DAD/ESI-MSn), while
   their main compounds were quantified by HPLC with diode array detection.
   After establishing their potent in vitro antioxidant activity, the
   extracts were administered to C57BL/6 mice treated with multiple low
   doses of streptozotocin for diabetes induction. While prophylactic AOE
   therapy had no impact on diabetes induction, MOE reduced diabetes
   incidence and preserved normal insulin secretion. In addition, MOE
   scavenged reactive oxygen and nitrogen species and, therefore,
   alleviated the need for the up-regulation of antioxidant enzymes. MOE
   treatment specifically attenuated the pro-inflammatory response mediated
   by T helper 17 cells and enhanced anti-inflammatory T helper 2 and T
   regulatory cells through the impact on specific signalling pathways and
   transcription factors. Importantly, MOE preserved beta-cells from in
   vitro apoptosis via blockade of caspase 3. Finally, rosmarinic acid, a
   predominant compound in MOE, exhibited only partial protection from
   diabetes induction. In conclusion, acting as an antioxidant,
   immunomodulator and in an anti-apoptotic manner, MOE protected mice from
   diabetes development. Seemingly, there is more than one compound
   responsible for the beneficial effect of MOE.",
journal = "British Journal of Nutrition",
title = "Methanolic extract of Origanum vulgare ameliorates type 1 diabetes
 through antioxidant, anti-inflammatory and anti-apoptotic activity",
number = "5",
volume = "113",
doi = "10.1017/S0007114514004048",
pages = "770-782"
}

Vujičić, M., Nikolić, I., Kontogianni, V. G., Saksida, T., Charisiadis, P., Oreščanin Dušić, Z., Blagojević, D., Stošić-Grujičić, S., Tzakos, A. G.,& Stojanović, I. D.. (2015). Methanolic extract of Origanum vulgare ameliorates type 1 diabetes
 through antioxidant, anti-inflammatory and anti-apoptotic activity. in British Journal of Nutrition, 113(5), 770-782.
https://doi.org/10.1017/S0007114514004048

Vujičić M, Nikolić I, Kontogianni VG, Saksida T, Charisiadis P, Oreščanin Dušić Z, Blagojević D, Stošić-Grujičić S, Tzakos AG, Stojanović ID. Methanolic extract of Origanum vulgare ameliorates type 1 diabetes
 through antioxidant, anti-inflammatory and anti-apoptotic activity. in British Journal of Nutrition. 2015;113(5):770-782.
doi:10.1017/S0007114514004048 .

Vujičić, Milica, Nikolić, Ivana, Kontogianni, Vassiliki G., Saksida, Tamara, Charisiadis, Pantelis, Oreščanin Dušić, Zorana, Blagojević, Duško, Stošić-Grujičić, Stanislava, Tzakos, Andreas G., Stojanović, Ivana D., "Methanolic extract of Origanum vulgare ameliorates type 1 diabetes
 through antioxidant, anti-inflammatory and anti-apoptotic activity" in British Journal of Nutrition, 113, no. 5 (2015):770-782,
https://doi.org/10.1017/S0007114514004048 . .