The effect of the phenethyl esters of rosmarinic and gallic acid on the course of the disease and the characteristics of immune cells involved in the etiopathogenesis of experimental autoimmune encephalomyelitis

[G. Stegnjaić]

104 str.

Biologija - Imunobiologija / Biology - Immunobiology

Ruzmarinska kiselina i galna kiselina su fenolna jedinjenja koja se nalaze u različitim vrstama biljaka i koja su poznata po svojim antioksidativnim i antiinflamacijskim svojstvima. U ovoj studiji su ispitivani fenetil estarski derivati ovih jedinjenja zbog prethodno zapažene povećane biodostupnosti i efikasnosti u odnosu na prekursorne supstance. Istraživanja su vršena in vitro i in vivo na modelu autoimunosti centralnog nervnog sistema (CNS), eksperimentalnom autoimunskom encefalomijelitisu (EAE). Fenetil estri ruzmarinske (PERA) i galne kiseline (PEGA) su smanjili produkciju encefalitogenih citokina, uključujući interferon (IFN)-γ i interleukin (IL)-17, u imunskim ćelijama i prečišćenim CD4+ ćelijama poplitealnih limfnih čvorova (PLČ) i imunskim ćelijama koje infiltriraju kičmenu moždinu (SCIC). Pored toga, oba derivata su pokazala sposobnost da suprimiraju produkciju NO od strane SCIC i BV2 ćelija mikroglije, dok su stimulisali produkciju NO u ćelijama PLČ. Takođe, ova jedinjenja su smanjila količinu proinflamacijskih citokina koje proizvode BV2 ćelije. PERA nije ostvario efekat na udeo regulatornih T-ćelija (Treg), pomoćničkih T (“T helper” - Th)1 ćelija i Th17 ćelija među SCIC. PEGA je smanjio procenat Th17 ćelija, ali ne i Treg i Th1. Oba jedinjenja su značajno smanjila udeo aktivisanih Th ćelija (CD25+) među CD4+ ćelijama SCIC. Konačno, primena bilo kog od derivata u EAE je dovela do ograničavanja neuroloških znakova bolesti, smanjenja broja infiltrata na preseku kičmene moždine, broja ćelija po infiltratu i područja demijelinizacije u kičmenoj moždini. Ovi rezultati ukazuju na potencijalna imunomodulacijska svojstva PERA i PEGA u kontekstu autoimunosti CNS, te ih preporučuju za dalja istraživanja u cilju terapijske primene.

Rosmarinic acid and gallic acid are phenolic compounds found in various plants and are known for their antioxidant and anti-inflammatory properties. Due to the enhanced bioavailability and efficacy of ester compounds, phenethyl ester derivatives of rosmarinic and gallic acid were investigated in vitro and in vivo using an animal model of the central nervous system (CNS) autoimmunity - experimental autoimmune encephalomyelitis (EAE). Phenethyl ester of rosmarinic acid (PERA) and phenethyl ester of gallic acid (PEGA) showed a remarkable ability to reduce the production of encephalitogenic cytokines, including interferon (IFN)-γ and interleukin (IL)-17, in immune cells from popliteal lymph nodes (PLN), CD4+ T cells from PLN, and spinal cord immune cells (SCIC). In addition, both derivatives showed the ability to suppress NO production by SCIC and microglial BV2 cells, while increasing its production in PLN. Also, PERA and PEGA decreased the amount of proinflammatory cytokines produced by BV2 cells. PERA had no effect on the proportion of regulatory T cells (Treg), helper T (Th) 1 cells, and Th17 cells among SCIC. PEGA decreased the percentage of Th17 cells, whereas proportion of Treg and Th1 cells was unaffected. Both PERA and PEGA significantly decreased proportion of CD25+ cells among CD4+ cells, i.e. activated Th cells in SCIC. Administration of PERA and PEGA significantly improved EAE symptoms, and decreased the number of infiltrates on spinal cord sections, the number of cells per infiltrate, and the demyelination area in the spinal cord. These results highlight the promising immunomodulatory properties of PERA and PEGA in the context of CNS autoimmunity, and position them as potential therapeutic candidates.

ruzmarinska kiselina, galna kiselina, fenetil-estarski derivati, eksperimentalni autoimunski encefalomijelits, encefalitogeni citokini, imunske ćelije, NO, BV2 ćelije, T-ćelije, imunomodulacijska svojstva

osmarinic acid, gallic acid, phenethyl ester derivatives, experimental autoimmune encephalomyelitis, encephalitogenic cytokines, immune cells, NO, BV2 cells, T-cells, immunomodulatory properties

577.27:616-097(043.3)

Tekst