Uticaj različitih ekstrakata krastavca (Cucumis sativus L. cv. Chinese long) na encefalitogeni potencijal T limfocita pacova u eksperimentalnom autoimunskom encefalomijelitisu
Effects of different Cucumber extracts (Cucumis sativus L. cv. Chinese long) on the encephalitogenic pontential of T lymphocytes in experimental autoimmune encephalomyelitis
Doctoral thesis (Published version)
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Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system (CNS). T lymphocytes, which produce interferon-γ (Th1) or interleukin-17 (Th17), and activated macrophages, that lead to CNS damage, are the major pathogenic cell populations in EAE. Having in mind that cucumber (Cucumis sativus) is a rich source of secondary metabolites such as polyphenols and cucurbitacins, in this study, for the first time, the effects of various cucumber extracts were investigated on encephalytogenic T lymphocytes, effector function of macrophages and antigen-presenting activities of dendritic cells (DC). The results show that cucumber leaf extract (CLE) expresses the most potent effect by inhibiting the production of IFN-γ and IL-17 in encephalytogenic T lymphocytes, through modulation of signaling pathways Nf-κB and p38 (MAPK). Additionally, CLE imposes an inhibitory effect on the effector functions of macrophages and antigen-presenting activity of DC in concentrations that do not show cytotoxicity in zebrafish (Danio rerio) in vivo. Also, CLE inhibits generation of encephalitogenic cells in vivo. Phytochemical analysis of CLE, characterized by mass spectrometry, confirmed the presence of 37 different compounds, among which cucurbitacins were the most abundant compounds. Hence, the immunomodulatory effects of cucurbitacin B and cucurbitacin E were also examined on the major immune cells involved in EAE pathogenesis. The obtained results confirm the effects of CLE, suggesting that cucurbitacins are, at least partially, responsible for its effects. The results of this doctoral dissertation indicate that the cucumber leaf extract and its major constituents cucurbitacins have anti-encephalitogenic effects in the EAE model, Moreover, they suggest the importance of additional research towards novel highly efficient CNS autoimmunity treatments.
Keywords:Experimental autoimmune encephalomyelitis; Encephalitogenic T cells; Cucumber leaf extract; Cucurbitacins
Source:University of Belgrade, Faculty of Biology, 2018, 1-141
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