TY  - CONF
AU  - Jonić, Natalija
AU  - Chatzigiannis, Christos M.
AU  - Koprivica, Ivan
AU  - Marinho, Sergio
AU  - Moura-Alves, Pedro
AU  - Pavić, Aleksandar
AU  - Otašević, Vesna
AU  - Pejnović, Nada
AU  - Tzakos, Andreas
AU  - Stojanović, Ivana D.
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6295
AB  - Introduction: The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor which is highly expressed in mucosal tissues - by epithelial cells and immune cells such as Th17 CD4+ and T regulatory cells (Treg). Besides its function of clearing environmental pollutants from the body, it was also revealed that AhR has immunoregulatory effects, thus becoming a potential therapeutic target for modulating the immune response. For that purpose we tested a novel synthetic AhR modulator under the code name C43.
Methods: CYP1A1 (downstream effector of AhR) activation was tested by the EROD assay. Sort-purified CD4+ cells from mesenteric lymph nodes (MLN) were treated with C43 for 24 h. Zebrafish embryos were used to test the toxicity of C43. Male C57BL/6 mice orally received C43 (10 mg/kg) for 5 consecutive days, after which MLN were harvested. Phenotype and function of the cells were analyzed by flow cytometry.
Results: C43 showed mild AhR agonistic activity. After treating the sort-purified CD4+ cells with C43, there was a shift in the Th17/Treg ratio in favour of the latter. C43 showed no signs of toxicity when tested on zebrafish embryos. MLN cells from mice that received C43 revealed a shift in the Th1/Treg ratio in favour of Tregs, with a documented rise of the portion of Tregs that expressed CYP1A1 in comparison with the control group of mice. 
Conclusion: C43 can modulate the immune response through the intestine by promoting the immunosuppressive Treg population.
PB  - Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade
C3  - Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia
T1  - Novel aryl hydrocarbon receptor modulator promotes immunosupressive immune response by stimulating T regulatory cells in the gut
SP  - 38
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6295
ER  - 

@conference{
author = "Jonić, Natalija and Chatzigiannis, Christos M. and Koprivica, Ivan and Marinho, Sergio and Moura-Alves, Pedro and Pavić, Aleksandar and Otašević, Vesna and Pejnović, Nada and Tzakos, Andreas and Stojanović, Ivana D.",
year = "2023",
abstract = "Introduction: The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor which is highly expressed in mucosal tissues - by epithelial cells and immune cells such as Th17 CD4+ and T regulatory cells (Treg). Besides its function of clearing environmental pollutants from the body, it was also revealed that AhR has immunoregulatory effects, thus becoming a potential therapeutic target for modulating the immune response. For that purpose we tested a novel synthetic AhR modulator under the code name C43.
Methods: CYP1A1 (downstream effector of AhR) activation was tested by the EROD assay. Sort-purified CD4+ cells from mesenteric lymph nodes (MLN) were treated with C43 for 24 h. Zebrafish embryos were used to test the toxicity of C43. Male C57BL/6 mice orally received C43 (10 mg/kg) for 5 consecutive days, after which MLN were harvested. Phenotype and function of the cells were analyzed by flow cytometry.
Results: C43 showed mild AhR agonistic activity. After treating the sort-purified CD4+ cells with C43, there was a shift in the Th17/Treg ratio in favour of the latter. C43 showed no signs of toxicity when tested on zebrafish embryos. MLN cells from mice that received C43 revealed a shift in the Th1/Treg ratio in favour of Tregs, with a documented rise of the portion of Tregs that expressed CYP1A1 in comparison with the control group of mice. 
Conclusion: C43 can modulate the immune response through the intestine by promoting the immunosuppressive Treg population.",
publisher = "Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade",
journal = "Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia",
title = "Novel aryl hydrocarbon receptor modulator promotes immunosupressive immune response by stimulating T regulatory cells in the gut",
pages = "38",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6295"
}

Jonić, N., Chatzigiannis, C. M., Koprivica, I., Marinho, S., Moura-Alves, P., Pavić, A., Otašević, V., Pejnović, N., Tzakos, A.,& Stojanović, I. D.. (2023). Novel aryl hydrocarbon receptor modulator promotes immunosupressive immune response by stimulating T regulatory cells in the gut. in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia
Belgrade: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade., 38.
https://hdl.handle.net/21.15107/rcub_ibiss_6295

Jonić N, Chatzigiannis CM, Koprivica I, Marinho S, Moura-Alves P, Pavić A, Otašević V, Pejnović N, Tzakos A, Stojanović ID. Novel aryl hydrocarbon receptor modulator promotes immunosupressive immune response by stimulating T regulatory cells in the gut. in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia. 2023;:38.
https://hdl.handle.net/21.15107/rcub_ibiss_6295 .

Jonić, Natalija, Chatzigiannis, Christos M., Koprivica, Ivan, Marinho, Sergio, Moura-Alves, Pedro, Pavić, Aleksandar, Otašević, Vesna, Pejnović, Nada, Tzakos, Andreas, Stojanović, Ivana D., "Novel aryl hydrocarbon receptor modulator promotes immunosupressive immune response by stimulating T regulatory cells in the gut" in Abstract Book: CoMBoS2 - the Second Congress of Molecular Biologists of Serbia; 2023 Oct 6-8; Belgrade, Serbia (2023):38,
https://hdl.handle.net/21.15107/rcub_ibiss_6295 .

TY  - CONF
AU  - Jonić, Natalija
AU  - Chatzigiannis, Christos M.
AU  - Koprivica, Ivan
AU  - Marinho, Sergio
AU  - Moura-Alves, Pedro
AU  - Pavić, Aleksandar
AU  - Otašević, Vesna
AU  - Pejnović, Nada
AU  - Tzakos, Andreas
AU  - Stojanović, Ivana D.
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6296
AB  - The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that has an important role in regulating the immune system, with high expression in Th17 CD4+ T cells and T regulatory cells (Treg). The expression of AhR is especially important at mucosal surfaces where it is involved in balancing the immune response towards external factors. The aim of our research was to evaluate the effect on the gut immune system of a novel fluorescent indole-containing compound that was designed as a putative AhR ligand (encoded C43). By using the EROD assay, we determined that C43 has mild AhR agonistic activity. Sort-purified mesenteric lymph node (MLN) CD4+ cells were treated with C43 for 24 h and flow cytometry analysis (FCM) showed that the Treg/Th17 ratio shifted in favour of Tregs. Zebrafish embryos were used for the evaluation of potential C43 toxicity. No nephrotoxicity, hepatotoxicity or cardiotoxicity was detected, even at the highest concentrations. Next, C43 was orally administered to healthy male C57BL/6 mice for 5 consecutive days, and later its effects on the gut immune system were recorded by analyzing the MLNs. FCM unveiled a higher proportion of Treg cells that expressed CYP1A1 (downstream effector of AhR) and the ratio of Treg/Th1 shifted towards Tregs. The presence of C43 was also visualized by confocal microscopy in the small intestine lamina propria of treated animals. With such results obtained from healthy animals, C43 presents a promising compound for the treatment of inflammatory diseases that generally involve activation of the gut immune system.
PB  - European Federation of Immunological Societies (EFIS)
C3  - Program and Abstracts: 12th EFIS-EJI South Eastern European Immunology School (SEEIS2023); 2023 Oct 20-23; Trogir, Croatia
T1  - Development of a novel compound that upregulates Treg in the gut by modulating aryl hydrocarbon receptor's activity
SP  - 17
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6296
ER  - 

@conference{
author = "Jonić, Natalija and Chatzigiannis, Christos M. and Koprivica, Ivan and Marinho, Sergio and Moura-Alves, Pedro and Pavić, Aleksandar and Otašević, Vesna and Pejnović, Nada and Tzakos, Andreas and Stojanović, Ivana D.",
year = "2023",
abstract = "The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that has an important role in regulating the immune system, with high expression in Th17 CD4+ T cells and T regulatory cells (Treg). The expression of AhR is especially important at mucosal surfaces where it is involved in balancing the immune response towards external factors. The aim of our research was to evaluate the effect on the gut immune system of a novel fluorescent indole-containing compound that was designed as a putative AhR ligand (encoded C43). By using the EROD assay, we determined that C43 has mild AhR agonistic activity. Sort-purified mesenteric lymph node (MLN) CD4+ cells were treated with C43 for 24 h and flow cytometry analysis (FCM) showed that the Treg/Th17 ratio shifted in favour of Tregs. Zebrafish embryos were used for the evaluation of potential C43 toxicity. No nephrotoxicity, hepatotoxicity or cardiotoxicity was detected, even at the highest concentrations. Next, C43 was orally administered to healthy male C57BL/6 mice for 5 consecutive days, and later its effects on the gut immune system were recorded by analyzing the MLNs. FCM unveiled a higher proportion of Treg cells that expressed CYP1A1 (downstream effector of AhR) and the ratio of Treg/Th1 shifted towards Tregs. The presence of C43 was also visualized by confocal microscopy in the small intestine lamina propria of treated animals. With such results obtained from healthy animals, C43 presents a promising compound for the treatment of inflammatory diseases that generally involve activation of the gut immune system.",
publisher = "European Federation of Immunological Societies (EFIS)",
journal = "Program and Abstracts: 12th EFIS-EJI South Eastern European Immunology School (SEEIS2023); 2023 Oct 20-23; Trogir, Croatia",
title = "Development of a novel compound that upregulates Treg in the gut by modulating aryl hydrocarbon receptor's activity",
pages = "17",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6296"
}

Jonić, N., Chatzigiannis, C. M., Koprivica, I., Marinho, S., Moura-Alves, P., Pavić, A., Otašević, V., Pejnović, N., Tzakos, A.,& Stojanović, I. D.. (2023). Development of a novel compound that upregulates Treg in the gut by modulating aryl hydrocarbon receptor's activity. in Program and Abstracts: 12th EFIS-EJI South Eastern European Immunology School (SEEIS2023); 2023 Oct 20-23; Trogir, Croatia
European Federation of Immunological Societies (EFIS)., 17.
https://hdl.handle.net/21.15107/rcub_ibiss_6296

Jonić N, Chatzigiannis CM, Koprivica I, Marinho S, Moura-Alves P, Pavić A, Otašević V, Pejnović N, Tzakos A, Stojanović ID. Development of a novel compound that upregulates Treg in the gut by modulating aryl hydrocarbon receptor's activity. in Program and Abstracts: 12th EFIS-EJI South Eastern European Immunology School (SEEIS2023); 2023 Oct 20-23; Trogir, Croatia. 2023;:17.
https://hdl.handle.net/21.15107/rcub_ibiss_6296 .

Jonić, Natalija, Chatzigiannis, Christos M., Koprivica, Ivan, Marinho, Sergio, Moura-Alves, Pedro, Pavić, Aleksandar, Otašević, Vesna, Pejnović, Nada, Tzakos, Andreas, Stojanović, Ivana D., "Development of a novel compound that upregulates Treg in the gut by modulating aryl hydrocarbon receptor's activity" in Program and Abstracts: 12th EFIS-EJI South Eastern European Immunology School (SEEIS2023); 2023 Oct 20-23; Trogir, Croatia (2023):17,
https://hdl.handle.net/21.15107/rcub_ibiss_6296 .

TY  - CONF
AU  - Jonić, Natalija
AU  - Chatzigiannis, Christos M
AU  - Koprivica, Ivan
AU  - Marinho, Sérgio
AU  - Moura-Alves, Pedro
AU  - Pavić, Aleksandar
AU  - Dimitrijević, Mirjana
AU  - Jovanović, Anđelina
AU  - Jovanović, Milan B
AU  - Otašević, Vesna
AU  - Pejnović, Nada
AU  - Tzakos, Andreas
AU  - Stojanović, Ivana D.
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5731
AB  - Aril ugljovodonični receptor (AhR) je transkripcioni faktor aktiviran ligandom i prevashodno je eksprimiran u imunskom tkivu creva. Kako istraživanja ukazuju na povezanost mukoznog imuniteta i različitih inflamatornih i autoimunskih oboljenja, ispitivali smo modulaciju imunskih ćelija creva pomoću novosintetisanog liganda AhR (šifra C43). Primenjen u kulturi mišjih CD4+ ćelija izolovanih iz mezenteričnih limfnih čvorova (MLČ), kao i na humanim ćelijama izolovanih iz tonzila, C43 je značajno uvećao udeo Treg nakon 24h. Nakon što je pokazano da C43 ne ostvaruje toksičnost (ni pri najvećim koncentracijama) pri razviću embriona zebrica (lat. Danio rerio), gavažom je 5 dana davan zdravim C57BL/6 mužjacima. U odnosu zastupljenosti Th1/Treg u MLČ, uočeno je pomeranje balansa ka Treg, kao i povećanje udela Treg koje eksprimiraju Cyp1a1 (nishodni signalni molekul od AhR) kod tretiranih miševa. Kada je C43 gavažom davan C57BL/6 mužjacima kojima je dijabetes tipa 1 (DT1) indukovan streptozotocinom, glikemijski indeksi su bili niži, a histološka analiza pankreasa je pokazala bolje očuvanje β ćelija i pankreasnih ostrvaca. Analiza lamine proprije tankog creva je pokazala povećanje udela tolerogenih dendritskih ćelija (tolDC), dok je udeo CD11b+MHCII+ ćelija bio snižen. Udeo Treg je takođe bio veći, kao i Cyp1a1+ Treg i IL-10+ Treg. Analizom pankreasnog limfnog čvora uočeno je sniženje udela Th1 i CD8+ ćelija, uz povećanje udela tolDC koje eksprimiraju indolamin 2,3-dioksigenazu, što je zabeleženo i u inflitratima pankreasa. Na osnovu dobijenih rezultata može se zaključiti da C43 ostvaruje antiinflamatorni efekat u DT1 i da pristup stimulacije AhR u mukozi creva može imati povoljan efekat u modulaciji autoimunosti i/ili inflamatornih oboljenja.
PB  - Belgrade: Serbian Academy of Sciences and Arts
C3  - Naučni skup Svetski dan imunologije 2023; 2023 Apr 27; Belgrade, Serbia
T1  - Novosintetisani fluorescentni AhR ligand podstiče povećanje udela T regulatornih ćelija i ublažava kliničku sliku dijabetesa tipa 1 kod C57BL/6 miševa
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5731
ER  - 

@conference{
author = "Jonić, Natalija and Chatzigiannis, Christos M and Koprivica, Ivan and Marinho, Sérgio and Moura-Alves, Pedro and Pavić, Aleksandar and Dimitrijević, Mirjana and Jovanović, Anđelina and Jovanović, Milan B and Otašević, Vesna and Pejnović, Nada and Tzakos, Andreas and Stojanović, Ivana D.",
year = "2023",
abstract = "Aril ugljovodonični receptor (AhR) je transkripcioni faktor aktiviran ligandom i prevashodno je eksprimiran u imunskom tkivu creva. Kako istraživanja ukazuju na povezanost mukoznog imuniteta i različitih inflamatornih i autoimunskih oboljenja, ispitivali smo modulaciju imunskih ćelija creva pomoću novosintetisanog liganda AhR (šifra C43). Primenjen u kulturi mišjih CD4+ ćelija izolovanih iz mezenteričnih limfnih čvorova (MLČ), kao i na humanim ćelijama izolovanih iz tonzila, C43 je značajno uvećao udeo Treg nakon 24h. Nakon što je pokazano da C43 ne ostvaruje toksičnost (ni pri najvećim koncentracijama) pri razviću embriona zebrica (lat. Danio rerio), gavažom je 5 dana davan zdravim C57BL/6 mužjacima. U odnosu zastupljenosti Th1/Treg u MLČ, uočeno je pomeranje balansa ka Treg, kao i povećanje udela Treg koje eksprimiraju Cyp1a1 (nishodni signalni molekul od AhR) kod tretiranih miševa. Kada je C43 gavažom davan C57BL/6 mužjacima kojima je dijabetes tipa 1 (DT1) indukovan streptozotocinom, glikemijski indeksi su bili niži, a histološka analiza pankreasa je pokazala bolje očuvanje β ćelija i pankreasnih ostrvaca. Analiza lamine proprije tankog creva je pokazala povećanje udela tolerogenih dendritskih ćelija (tolDC), dok je udeo CD11b+MHCII+ ćelija bio snižen. Udeo Treg je takođe bio veći, kao i Cyp1a1+ Treg i IL-10+ Treg. Analizom pankreasnog limfnog čvora uočeno je sniženje udela Th1 i CD8+ ćelija, uz povećanje udela tolDC koje eksprimiraju indolamin 2,3-dioksigenazu, što je zabeleženo i u inflitratima pankreasa. Na osnovu dobijenih rezultata može se zaključiti da C43 ostvaruje antiinflamatorni efekat u DT1 i da pristup stimulacije AhR u mukozi creva može imati povoljan efekat u modulaciji autoimunosti i/ili inflamatornih oboljenja.",
publisher = "Belgrade: Serbian Academy of Sciences and Arts",
journal = "Naučni skup Svetski dan imunologije 2023; 2023 Apr 27; Belgrade, Serbia",
title = "Novosintetisani fluorescentni AhR ligand podstiče povećanje udela T regulatornih ćelija i ublažava kliničku sliku dijabetesa tipa 1 kod C57BL/6 miševa",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5731"
}

Jonić, N., Chatzigiannis, C. M., Koprivica, I., Marinho, S., Moura-Alves, P., Pavić, A., Dimitrijević, M., Jovanović, A., Jovanović, M. B., Otašević, V., Pejnović, N., Tzakos, A.,& Stojanović, I. D.. (2023). Novosintetisani fluorescentni AhR ligand podstiče povećanje udela T regulatornih ćelija i ublažava kliničku sliku dijabetesa tipa 1 kod C57BL/6 miševa. in Naučni skup Svetski dan imunologije 2023; 2023 Apr 27; Belgrade, Serbia
Belgrade: Serbian Academy of Sciences and Arts..
https://hdl.handle.net/21.15107/rcub_ibiss_5731

Jonić N, Chatzigiannis CM, Koprivica I, Marinho S, Moura-Alves P, Pavić A, Dimitrijević M, Jovanović A, Jovanović MB, Otašević V, Pejnović N, Tzakos A, Stojanović ID. Novosintetisani fluorescentni AhR ligand podstiče povećanje udela T regulatornih ćelija i ublažava kliničku sliku dijabetesa tipa 1 kod C57BL/6 miševa. in Naučni skup Svetski dan imunologije 2023; 2023 Apr 27; Belgrade, Serbia. 2023;.
https://hdl.handle.net/21.15107/rcub_ibiss_5731 .

Jonić, Natalija, Chatzigiannis, Christos M, Koprivica, Ivan, Marinho, Sérgio, Moura-Alves, Pedro, Pavić, Aleksandar, Dimitrijević, Mirjana, Jovanović, Anđelina, Jovanović, Milan B, Otašević, Vesna, Pejnović, Nada, Tzakos, Andreas, Stojanović, Ivana D., "Novosintetisani fluorescentni AhR ligand podstiče povećanje udela T regulatornih ćelija i ublažava kliničku sliku dijabetesa tipa 1 kod C57BL/6 miševa" in Naučni skup Svetski dan imunologije 2023; 2023 Apr 27; Belgrade, Serbia (2023),
https://hdl.handle.net/21.15107/rcub_ibiss_5731 .

TY  - JOUR
AU  - Stegnjaić, Goran
AU  - Tsiailanis, Antonios D.
AU  - Lazarević, Milica
AU  - Gkalpinos, Vasileios K.
AU  - Nikolovski, Neda
AU  - Antoniou, Thomas
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/123456789/5305
AB  - Gallic acid is a phenolic acid present in various plants, nuts, and fruits. It is well known for
its anti-oxidative and anti-inflammatory properties. The phenethyl ester of gallic acid (PEGA) was
synthesized with the aim of increasing the bioavailability of gallic acid, and thus its pharmacological
potential. Here, the effects of PEGA on encephalitogenic cells were examined, and PEGA was
found to modulate the inflammatory activities of T cells and macrophages/microglia. Specifically,
PEGA reduced the release of interleukin (IL)-17 and interferon (IFN)-γ from T cells, as well as NO,
and IL-6 from macrophages/microglia. Importantly, PEGA ameliorated experimental autoimmune
encephalomyelitis, an animal model of chronic inflammatory disease of the central nervous system
(CNS)—multiple sclerosis. Thus, PEGA is a potent anti-inflammatory compound with a perspective
to be further explored in the context of CNS autoimmunity and other chronic inflammatory disorders.
PB  - Basel: MDPI
T2  - Molecules
T1  - Phenethyl Ester of Gallic Acid Ameliorates Experimental Autoimmune Encephalomyelitis
IS  - 24
VL  - 27
DO  - 10.3390/molecules27248770
SP  - 8770
ER  - 

@article{
author = "Stegnjaić, Goran and Tsiailanis, Antonios D. and Lazarević, Milica and Gkalpinos, Vasileios K. and Nikolovski, Neda and Antoniou, Thomas and Stanisavljević, Suzana and Dimitrijević, Mirjana and Momčilović, Miljana and Miljković, Đorđe and Tzakos, Andreas G. and Jevtić, Bojan",
year = "2022",
abstract = "Gallic acid is a phenolic acid present in various plants, nuts, and fruits. It is well known for
its anti-oxidative and anti-inflammatory properties. The phenethyl ester of gallic acid (PEGA) was
synthesized with the aim of increasing the bioavailability of gallic acid, and thus its pharmacological
potential. Here, the effects of PEGA on encephalitogenic cells were examined, and PEGA was
found to modulate the inflammatory activities of T cells and macrophages/microglia. Specifically,
PEGA reduced the release of interleukin (IL)-17 and interferon (IFN)-γ from T cells, as well as NO,
and IL-6 from macrophages/microglia. Importantly, PEGA ameliorated experimental autoimmune
encephalomyelitis, an animal model of chronic inflammatory disease of the central nervous system
(CNS)—multiple sclerosis. Thus, PEGA is a potent anti-inflammatory compound with a perspective
to be further explored in the context of CNS autoimmunity and other chronic inflammatory disorders.",
publisher = "Basel: MDPI",
journal = "Molecules",
title = "Phenethyl Ester of Gallic Acid Ameliorates Experimental Autoimmune Encephalomyelitis",
number = "24",
volume = "27",
doi = "10.3390/molecules27248770",
pages = "8770"
}

Stegnjaić, G., Tsiailanis, A. D., Lazarević, M., Gkalpinos, V. K., Nikolovski, N., Antoniou, T., Stanisavljević, S., Dimitrijević, M., Momčilović, M., Miljković, Đ., Tzakos, A. G.,& Jevtić, B.. (2022). Phenethyl Ester of Gallic Acid Ameliorates Experimental Autoimmune Encephalomyelitis. in Molecules
Basel: MDPI., 27(24), 8770.
https://doi.org/10.3390/molecules27248770

Stegnjaić G, Tsiailanis AD, Lazarević M, Gkalpinos VK, Nikolovski N, Antoniou T, Stanisavljević S, Dimitrijević M, Momčilović M, Miljković Đ, Tzakos AG, Jevtić B. Phenethyl Ester of Gallic Acid Ameliorates Experimental Autoimmune Encephalomyelitis. in Molecules. 2022;27(24):8770.
doi:10.3390/molecules27248770 .

Stegnjaić, Goran, Tsiailanis, Antonios D., Lazarević, Milica, Gkalpinos, Vasileios K., Nikolovski, Neda, Antoniou, Thomas, Stanisavljević, Suzana, Dimitrijević, Mirjana, Momčilović, Miljana, Miljković, Đorđe, Tzakos, Andreas G., Jevtić, Bojan, "Phenethyl Ester of Gallic Acid Ameliorates Experimental Autoimmune Encephalomyelitis" in Molecules, 27, no. 24 (2022):8770,
https://doi.org/10.3390/molecules27248770 . .

TY  - JOUR
AU  - Koprivica, Ivan
AU  - Jonić, Natalija
AU  - Diamantis, Dimitris
AU  - Mićanović, Dragica
AU  - Saksida, Tamara
AU  - Pejnović, Nada
AU  - Tzakos, Andreas G.
AU  - Stojanović, Ivana D.
PY  - 2022
UR  - https://linkinghub.elsevier.com/retrieve/pii/S0024320521011711
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4700
AB  - Aims: Rosmarinic acid (RA) is a polyphenol that occurs in plants of the Lamiaceae family. Phenethyl ester of RA (PERA), a novel RA derivative, has been developed and evaluated in vivo in an animal model of type 1 diabetes (T1D). Methods: T1D was induced in male C57BL/6 mice using multiple low doses of streptozotocin (STZ) administered intraperitoneally for 5 consecutive days. Intraperitoneal administration of PERA (2.5 mg/kg bw) began from the first STZ injection and continued for 20 days. Key findings: PERA-treated mice exhibited lower incidence of T1D (monitored up to 38 days from the disease induction), and fluorescent histochemical analysis showed that their pancreatic islets expressed more insulin. PERA treatment significantly down-regulated the proportions of CD11b+ and CD11c+ myeloid cells in the immune cell infiltrates in the pancreatic islets early during T1D pathogenesis (on day 9 after T1D induction), while on day 15, PERA significantly reduced the proportions of CD11c+, CD8+, Th1 and Th17 cells. Simultaneously, it was found that the cells from the pancreatic infiltrates of PERA-treated mice produced significantly less reactive oxygen species than cells from the control group. Significance: These findings suggest that PERA efficiently prevented T1D development in mice. Interestingly, PERA attenuated the inflammatory process in the islets through temporally specific interference with the innate and adaptive immune response and therefore shows great promise for further clinical evaluation as a novel T1D therapeutic.
T2  - Life Sciences
T1  - Phenethyl ester of rosmarinic acid attenuates autoimmune responses during type 1 diabetes development in mice
VL  - 288
DO  - 10.1016/j.lfs.2021.120184
SP  - 120184
ER  - 

@article{
author = "Koprivica, Ivan and Jonić, Natalija and Diamantis, Dimitris and Mićanović, Dragica and Saksida, Tamara and Pejnović, Nada and Tzakos, Andreas G. and Stojanović, Ivana D.",
year = "2022",
abstract = "Aims: Rosmarinic acid (RA) is a polyphenol that occurs in plants of the Lamiaceae family. Phenethyl ester of RA (PERA), a novel RA derivative, has been developed and evaluated in vivo in an animal model of type 1 diabetes (T1D). Methods: T1D was induced in male C57BL/6 mice using multiple low doses of streptozotocin (STZ) administered intraperitoneally for 5 consecutive days. Intraperitoneal administration of PERA (2.5 mg/kg bw) began from the first STZ injection and continued for 20 days. Key findings: PERA-treated mice exhibited lower incidence of T1D (monitored up to 38 days from the disease induction), and fluorescent histochemical analysis showed that their pancreatic islets expressed more insulin. PERA treatment significantly down-regulated the proportions of CD11b+ and CD11c+ myeloid cells in the immune cell infiltrates in the pancreatic islets early during T1D pathogenesis (on day 9 after T1D induction), while on day 15, PERA significantly reduced the proportions of CD11c+, CD8+, Th1 and Th17 cells. Simultaneously, it was found that the cells from the pancreatic infiltrates of PERA-treated mice produced significantly less reactive oxygen species than cells from the control group. Significance: These findings suggest that PERA efficiently prevented T1D development in mice. Interestingly, PERA attenuated the inflammatory process in the islets through temporally specific interference with the innate and adaptive immune response and therefore shows great promise for further clinical evaluation as a novel T1D therapeutic.",
journal = "Life Sciences",
title = "Phenethyl ester of rosmarinic acid attenuates autoimmune responses during type 1 diabetes development in mice",
volume = "288",
doi = "10.1016/j.lfs.2021.120184",
pages = "120184"
}

Koprivica, I., Jonić, N., Diamantis, D., Mićanović, D., Saksida, T., Pejnović, N., Tzakos, A. G.,& Stojanović, I. D.. (2022). Phenethyl ester of rosmarinic acid attenuates autoimmune responses during type 1 diabetes development in mice. in Life Sciences, 288, 120184.
https://doi.org/10.1016/j.lfs.2021.120184

Koprivica I, Jonić N, Diamantis D, Mićanović D, Saksida T, Pejnović N, Tzakos AG, Stojanović ID. Phenethyl ester of rosmarinic acid attenuates autoimmune responses during type 1 diabetes development in mice. in Life Sciences. 2022;288:120184.
doi:10.1016/j.lfs.2021.120184 .

Koprivica, Ivan, Jonić, Natalija, Diamantis, Dimitris, Mićanović, Dragica, Saksida, Tamara, Pejnović, Nada, Tzakos, Andreas G., Stojanović, Ivana D., "Phenethyl ester of rosmarinic acid attenuates autoimmune responses during type 1 diabetes development in mice" in Life Sciences, 288 (2022):120184,
https://doi.org/10.1016/j.lfs.2021.120184 . .

TY  - JOUR
AU  - Stegnjaić, Goran
AU  - Lazarević, Milica
AU  - Diamantis, Dimitrois A
AU  - Nikolovski, Neda
AU  - Jevtić, Bojan
AU  - Stanisavljević, Suzana
AU  - Dimitrijević, Mirjana
AU  - Momčilović, Miljana
AU  - Tzakos, Andreas G
AU  - Miljković, Đorđe
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5085
AB  - Rosmarinic acid is a polyphenolic compound, abundantly present in herbs of the Lamiaceae family. The aim of
the study was to evaluate the immunomodulatory properties of a recently developed phenethyl ester derivative
of rosmarinic acid (PERA), with enhanced ability of diffusion through biological membranes, in an animal model
of the central nervous system (CNS) autoimmunity. To this end, experimental autoimmune encephalomyelitis
(EAE), an animal model of multiple sclerosis was used. Daily subcutaneous administration of PERA (30 mg/kg)
from day 7 to day 22 after immunization successfully ameliorated EAE induced in Dark Agouti rats, shortening
the disease duration and reducing maximal, cumulative and mean clinical score. PERA efficiently reduced
production of major encephalitogenic cytokines, interferon (IFN)-γ and interleukin (IL)-17, in immune cells from
the CNS or the lymph nodes draining the site of immunization of EAE rats, as well as in CD4+ T cells purified
from the lymph nodes. Also, PERA inhibited NO production in the CNS and the lymph nodes, as well as in
macrophages and microglial cells. Finally, microglial ability to produce pro-inflammatory cytokines IL-6, and
tumor necrosis factor (TNF) were also reduced by PERA. Our results clearly imply that PERA possesses antiencephalitogenic properties. Thus, further studies on the relevance of the observed effects for the therapy of
multiple sclerosis are warranted.
PB  - Amsterdam : Elsevier
T2  - Immunology Letters
T1  - Phenethyl ester of rosmarinic acid ameliorates experimental autoimmune encephalomyelitis
VL  - 251-252
DO  - 10.1016/j.imlet.2022.09.006
SP  - 9
EP  - 19
ER  - 

@article{
author = "Stegnjaić, Goran and Lazarević, Milica and Diamantis, Dimitrois A and Nikolovski, Neda and Jevtić, Bojan and Stanisavljević, Suzana and Dimitrijević, Mirjana and Momčilović, Miljana and Tzakos, Andreas G and Miljković, Đorđe",
year = "2022",
abstract = "Rosmarinic acid is a polyphenolic compound, abundantly present in herbs of the Lamiaceae family. The aim of
the study was to evaluate the immunomodulatory properties of a recently developed phenethyl ester derivative
of rosmarinic acid (PERA), with enhanced ability of diffusion through biological membranes, in an animal model
of the central nervous system (CNS) autoimmunity. To this end, experimental autoimmune encephalomyelitis
(EAE), an animal model of multiple sclerosis was used. Daily subcutaneous administration of PERA (30 mg/kg)
from day 7 to day 22 after immunization successfully ameliorated EAE induced in Dark Agouti rats, shortening
the disease duration and reducing maximal, cumulative and mean clinical score. PERA efficiently reduced
production of major encephalitogenic cytokines, interferon (IFN)-γ and interleukin (IL)-17, in immune cells from
the CNS or the lymph nodes draining the site of immunization of EAE rats, as well as in CD4+ T cells purified
from the lymph nodes. Also, PERA inhibited NO production in the CNS and the lymph nodes, as well as in
macrophages and microglial cells. Finally, microglial ability to produce pro-inflammatory cytokines IL-6, and
tumor necrosis factor (TNF) were also reduced by PERA. Our results clearly imply that PERA possesses antiencephalitogenic properties. Thus, further studies on the relevance of the observed effects for the therapy of
multiple sclerosis are warranted.",
publisher = "Amsterdam : Elsevier",
journal = "Immunology Letters",
title = "Phenethyl ester of rosmarinic acid ameliorates experimental autoimmune encephalomyelitis",
volume = "251-252",
doi = "10.1016/j.imlet.2022.09.006",
pages = "9-19"
}

Stegnjaić, G., Lazarević, M., Diamantis, D. A., Nikolovski, N., Jevtić, B., Stanisavljević, S., Dimitrijević, M., Momčilović, M., Tzakos, A. G.,& Miljković, Đ.. (2022). Phenethyl ester of rosmarinic acid ameliorates experimental autoimmune encephalomyelitis. in Immunology Letters
Amsterdam : Elsevier., 251-252, 9-19.
https://doi.org/10.1016/j.imlet.2022.09.006

Stegnjaić G, Lazarević M, Diamantis DA, Nikolovski N, Jevtić B, Stanisavljević S, Dimitrijević M, Momčilović M, Tzakos AG, Miljković Đ. Phenethyl ester of rosmarinic acid ameliorates experimental autoimmune encephalomyelitis. in Immunology Letters. 2022;251-252:9-19.
doi:10.1016/j.imlet.2022.09.006 .

Stegnjaić, Goran, Lazarević, Milica, Diamantis, Dimitrois A, Nikolovski, Neda, Jevtić, Bojan, Stanisavljević, Suzana, Dimitrijević, Mirjana, Momčilović, Miljana, Tzakos, Andreas G, Miljković, Đorđe, "Phenethyl ester of rosmarinic acid ameliorates experimental autoimmune encephalomyelitis" in Immunology Letters, 251-252 (2022):9-19,
https://doi.org/10.1016/j.imlet.2022.09.006 . .

TY  - CONF
AU  - Jonić, Natalija
AU  - Chatzigiannis, Christos M.
AU  - Koprivica, Ivan
AU  - Savić, Anisia
AU  - Mićanović, Dragica
AU  - Saksida, Tamara
AU  - Pejnović, Nada
AU  - Tzakos, Andreas
AU  - Stojanović, Ivana D.
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5605
AB  - A novel way of regulating the function of immune cells has been discovered and is done by targeting the activation of the aryl hydrocarbon receptor (AhR)1. It is found that AhR is a ligand-activated transcription factor that responds to various aromatic compounds - exogenous such as plant flavonoids, polyphenolics and indoles and endogenous such as kynurenine2. By inhibiting its activation a pro-inflammatory immune response is promoted, whereas its activation gives an opposite effect1. Therefore, a selection of plant-derived indol derivatives was tested as an AhR ligand to establish their effects on the receptor’s activity. The one that was found to be a potent AhR antagonist was an indol derivative under the code C46 and was further tested on mouse peritoneal macrophages for its ability to modulate macrophage function. Macrophages were exposed to the compound C46 in vitro in concentrations ranging from 250 ng/ml to 1000 ng/ml for 48 h. By using flow cytometry we established that C46 significantly and dose-dependently up-regulated the proportion of M1 macrophages (F4/80+CD40+) and not only that, but it affected only M1 macrophages, while the proportion of M2 (F4/80+CD206+) remained stable throughout the exposure to different concentrations of C46. In further analysis with DAF-FM staining, it was found that C46 increased the cytocidal function of macrophages, since their content of nitric oxide was increased. With intraperitoneal administration of C46 the results were similar - the proportion of M1 macrophages in the peritoneum was up-regulated, 72 h after the treatment. In conclusion, by blocking the AhR signal pathway with C46, a pro-inflammatory immune response could be achieved by promoting the M1 macrophage phenotype and it may as well be a a promising approach for future testing in animal models of cancer.
PB  - Belgrade: Faculty of Chemistry: Serbian Biochemical Society
C3  - Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia
T1  - Promoting the pro-inflammatory phenotype in macrophages by blocking the aryl hydrocarbon receptor
SP  - 69
EP  - 70
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5605
ER  - 

@conference{
author = "Jonić, Natalija and Chatzigiannis, Christos M. and Koprivica, Ivan and Savić, Anisia and Mićanović, Dragica and Saksida, Tamara and Pejnović, Nada and Tzakos, Andreas and Stojanović, Ivana D.",
year = "2021",
abstract = "A novel way of regulating the function of immune cells has been discovered and is done by targeting the activation of the aryl hydrocarbon receptor (AhR)1. It is found that AhR is a ligand-activated transcription factor that responds to various aromatic compounds - exogenous such as plant flavonoids, polyphenolics and indoles and endogenous such as kynurenine2. By inhibiting its activation a pro-inflammatory immune response is promoted, whereas its activation gives an opposite effect1. Therefore, a selection of plant-derived indol derivatives was tested as an AhR ligand to establish their effects on the receptor’s activity. The one that was found to be a potent AhR antagonist was an indol derivative under the code C46 and was further tested on mouse peritoneal macrophages for its ability to modulate macrophage function. Macrophages were exposed to the compound C46 in vitro in concentrations ranging from 250 ng/ml to 1000 ng/ml for 48 h. By using flow cytometry we established that C46 significantly and dose-dependently up-regulated the proportion of M1 macrophages (F4/80+CD40+) and not only that, but it affected only M1 macrophages, while the proportion of M2 (F4/80+CD206+) remained stable throughout the exposure to different concentrations of C46. In further analysis with DAF-FM staining, it was found that C46 increased the cytocidal function of macrophages, since their content of nitric oxide was increased. With intraperitoneal administration of C46 the results were similar - the proportion of M1 macrophages in the peritoneum was up-regulated, 72 h after the treatment. In conclusion, by blocking the AhR signal pathway with C46, a pro-inflammatory immune response could be achieved by promoting the M1 macrophage phenotype and it may as well be a a promising approach for future testing in animal models of cancer.",
publisher = "Belgrade: Faculty of Chemistry: Serbian Biochemical Society",
journal = "Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia",
title = "Promoting the pro-inflammatory phenotype in macrophages by blocking the aryl hydrocarbon receptor",
pages = "69-70",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5605"
}

Jonić, N., Chatzigiannis, C. M., Koprivica, I., Savić, A., Mićanović, D., Saksida, T., Pejnović, N., Tzakos, A.,& Stojanović, I. D.. (2021). Promoting the pro-inflammatory phenotype in macrophages by blocking the aryl hydrocarbon receptor. in Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia
Belgrade: Faculty of Chemistry: Serbian Biochemical Society., 69-70.
https://hdl.handle.net/21.15107/rcub_ibiss_5605

Jonić N, Chatzigiannis CM, Koprivica I, Savić A, Mićanović D, Saksida T, Pejnović N, Tzakos A, Stojanović ID. Promoting the pro-inflammatory phenotype in macrophages by blocking the aryl hydrocarbon receptor. in Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia. 2021;:69-70.
https://hdl.handle.net/21.15107/rcub_ibiss_5605 .

Jonić, Natalija, Chatzigiannis, Christos M., Koprivica, Ivan, Savić, Anisia, Mićanović, Dragica, Saksida, Tamara, Pejnović, Nada, Tzakos, Andreas, Stojanović, Ivana D., "Promoting the pro-inflammatory phenotype in macrophages by blocking the aryl hydrocarbon receptor" in Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia (2021):69-70,
https://hdl.handle.net/21.15107/rcub_ibiss_5605 .

TY  - JOUR
AU  - Kontogianni, Vassiliki G
AU  - Tomić, Goran
AU  - Nikolić, Ivana
AU  - Nerantzaki, Alexandra A
AU  - Sayyad, Nisar
AU  - Stošić-Grujičić, Stanislava
AU  - Stojanović, Ivana D.
AU  - Gerothanassis, Ioannis P
AU  - Tzakos, Andreas G
PY  - 2013
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1068
AB  - The goal of this study was to monitor the anti-proliferative activity of Rosmarinus officinalis and Salvia officinalis extracts against cancer cells and to correlate this activity with their phytochemical profiles using liquid chromatography/diode array detection/electrospray ion trap tandem mass spectrometry (LC/DAD/ESI-MSn). For the quantitative estimation of triterpenic acids in the crude extracts an NMR based methodology was used and compared with the HPLC measurements, both applied for the first time, for the case of betulinic acid. Both extracts exerted cytotoxic activity through dose-dependent impairment of viability and mitochondrial activity of rat insulinoma m5F (RINm5F) cells. Decrease of RINm5F viability was mediated by nitric oxide (NO)-induced apoptosis. Importantly, these extracts potentiated NO and TNF-alpha release from macrophages therefore enhancing their cytocidal action. The rosemary extract developed more pronounced antioxidant, cytotoxic and immunomodifying activities, probably due to the presence of betulinic acid and a higher concentration of carnosic acid in its phytochemical profile. (C) 2012 Elsevier Ltd. All rights reserved.
T2  - Food Chemistry
T1  - Phytochemical profile of Rosmarinus officinalis and Salvia officinalis extracts and correlation to their antioxidant and anti-proliferative activity
IS  - 1
VL  - 136
DO  - 10.1016/j.foodchem.2012.07.091
SP  - 385
EP  - 129
ER  - 

@article{
author = "Kontogianni, Vassiliki G and Tomić, Goran and Nikolić, Ivana and Nerantzaki, Alexandra A and Sayyad, Nisar and Stošić-Grujičić, Stanislava and Stojanović, Ivana D. and Gerothanassis, Ioannis P and Tzakos, Andreas G",
year = "2013",
abstract = "The goal of this study was to monitor the anti-proliferative activity of Rosmarinus officinalis and Salvia officinalis extracts against cancer cells and to correlate this activity with their phytochemical profiles using liquid chromatography/diode array detection/electrospray ion trap tandem mass spectrometry (LC/DAD/ESI-MSn). For the quantitative estimation of triterpenic acids in the crude extracts an NMR based methodology was used and compared with the HPLC measurements, both applied for the first time, for the case of betulinic acid. Both extracts exerted cytotoxic activity through dose-dependent impairment of viability and mitochondrial activity of rat insulinoma m5F (RINm5F) cells. Decrease of RINm5F viability was mediated by nitric oxide (NO)-induced apoptosis. Importantly, these extracts potentiated NO and TNF-alpha release from macrophages therefore enhancing their cytocidal action. The rosemary extract developed more pronounced antioxidant, cytotoxic and immunomodifying activities, probably due to the presence of betulinic acid and a higher concentration of carnosic acid in its phytochemical profile. (C) 2012 Elsevier Ltd. All rights reserved.",
journal = "Food Chemistry",
title = "Phytochemical profile of Rosmarinus officinalis and Salvia officinalis extracts and correlation to their antioxidant and anti-proliferative activity",
number = "1",
volume = "136",
doi = "10.1016/j.foodchem.2012.07.091",
pages = "385-129"
}

Kontogianni, V. G., Tomić, G., Nikolić, I., Nerantzaki, A. A., Sayyad, N., Stošić-Grujičić, S., Stojanović, I. D., Gerothanassis, I. P.,& Tzakos, A. G.. (2013). Phytochemical profile of Rosmarinus officinalis and Salvia officinalis extracts and correlation to their antioxidant and anti-proliferative activity. in Food Chemistry, 136(1), 385-129.
https://doi.org/10.1016/j.foodchem.2012.07.091

Kontogianni VG, Tomić G, Nikolić I, Nerantzaki AA, Sayyad N, Stošić-Grujičić S, Stojanović ID, Gerothanassis IP, Tzakos AG. Phytochemical profile of Rosmarinus officinalis and Salvia officinalis extracts and correlation to their antioxidant and anti-proliferative activity. in Food Chemistry. 2013;136(1):385-129.
doi:10.1016/j.foodchem.2012.07.091 .

Kontogianni, Vassiliki G, Tomić, Goran, Nikolić, Ivana, Nerantzaki, Alexandra A, Sayyad, Nisar, Stošić-Grujičić, Stanislava, Stojanović, Ivana D., Gerothanassis, Ioannis P, Tzakos, Andreas G, "Phytochemical profile of Rosmarinus officinalis and Salvia officinalis extracts and correlation to their antioxidant and anti-proliferative activity" in Food Chemistry, 136, no. 1 (2013):385-129,
https://doi.org/10.1016/j.foodchem.2012.07.091 . .