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  - 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 . .