title: Effect of N-Feruloylserotonin and Methotrexate on Severity of Experimental Arthritis and on Messenger RNA Expression of Key Proinflammatory Markers in Liver.
abstract: Rheumatoid arthritis (RA) is a chronic inflammatory disease, leading to progressive destruction of joints and extra-articular tissues, including organs such as liver and spleen. The purpose of this study was to compare the effects of a potential immunomodulator, natural polyphenol N-feruloylserotonin (N-f-5HT), with methotrexate (MTX), the standard in RA therapy, in the chronic phase of adjuvant-induced arthritis (AA) in male Lewis rats. The experiment included healthy controls (CO), arthritic animals (AA), AA given N-f-5HT (AA-N-f-5HT), and AA given MTX (AA-MTX). N-f-5HT did not affect the body weight change and clinical parameters until the 14th experimental day. Its positive effect was rising during the 28-day experiment, indicating a delayed onset of N-f-5HT action. Administration of either N-f-5HT or MTX caused reduction of inflammation measured as the level of CRP in plasma and the activity of LOX in the liver. mRNA transcription of TNF-α and iNOS in the liver was significantly attenuated in both MTX and N-f-5HT treated groups of arthritic rats. Interestingly, in contrast to MTX, N-f-5HT significantly lowered the level of IL-1β in plasma and IL-1β mRNA expression in the liver and spleen of arthritic rats. This speaks for future investigations of N-f-5HT as an agent in the treatment of RA in combination therapy with MTX.
authors.affiliation: Department of Cell and Molecular Biology of Drugs, Faculty of Pharmacy, Comenius University, 832 32 Bratislava, Slovakia.
authors.forename: Ľudmila
authors.identifier: 0000-0001-8732-7054
authors.initials: Ľ
authors.lastname: Pašková
authors.affiliation: Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, 841 04 Bratislava, Slovakia.
authors.forename: Viera
authors.identifier: 0000-0002-6205-5619
authors.initials: V
authors.lastname: Kuncírová
authors.affiliation: Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, 841 04 Bratislava, Slovakia.
authors.forename: Silvester
authors.initials: S
authors.lastname: Poništ
authors.affiliation: Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, 841 04 Bratislava, Slovakia.
authors.forename: Danica
authors.initials: D
authors.lastname: Mihálová
authors.affiliation: Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, 841 04 Bratislava, Slovakia.
authors.forename: Radomír
authors.initials: R
authors.lastname: Nosáľ
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 166 10 Prague, Czech Republic.
authors.forename: Juraj
authors.initials: J
authors.lastname: Harmatha
authors.affiliation: Faculty of Food and Biochemical Technology, University of Chemistry and Technology, 166 28 Prague, Czech Republic.
authors.forename: Iveta
authors.initials: I
authors.lastname: Hrádková
authors.affiliation: Department of Cell and Molecular Biology of Drugs, Faculty of Pharmacy, Comenius University, 832 32 Bratislava, Slovakia.
authors.forename: Tomáš
authors.identifier: 0000-0001-6822-4498
authors.initials: T
authors.lastname: Čavojský
authors.affiliation: Department of Cell and Molecular Biology of Drugs, Faculty of Pharmacy, Comenius University, 832 32 Bratislava, Slovakia.
authors.forename: František
authors.identifier: 0000-0003-0357-4088
authors.initials: F
authors.lastname: Bilka
authors.affiliation: Department of Cell and Molecular Biology of Drugs, Faculty of Pharmacy, Comenius University, 832 32 Bratislava, Slovakia.
authors.forename: Katarína
authors.initials: K
authors.lastname: Šišková
authors.affiliation: Department of Cell and Molecular Biology of Drugs, Faculty of Pharmacy, Comenius University, 832 32 Bratislava, Slovakia.
authors.forename: Ingrid
authors.identifier: 0000-0002-6284-6701
authors.initials: I
authors.lastname: Paulíková
authors.affiliation: Department of Cell and Molecular Biology of Drugs, Faculty of Pharmacy, Comenius University, 832 32 Bratislava, Slovakia.
authors.forename: Lýdia
authors.initials: L
authors.lastname: Bezáková
authors.affiliation: Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, 841 04 Bratislava, Slovakia; Department of Galenic Pharmacy, Faculty of Pharmacy, Comenius University, 832 32 Bratislava, Slovakia.
authors.forename: Katarína
authors.identifier: 0000-0002-7863-2142
authors.initials: K
authors.lastname: Bauerová
mesh_terms: D000818:Animals; D001091:Arachidonate Lipoxygenases / Q000235:genetics / Q000378:metabolism; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D015415:Biomarkers; D002097:C-Reactive Protein; D016207:Cytokines / Q000097:blood / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D018836:Inflammation Mediators; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008727:Methotrexate / Q000494:pharmacology*; D009928:Organ Specificity; D051381:Rats; D012701:Serotonin / Q000031:analogs & derivatives* / Q000494:pharmacology; D012720:Severity of Illness Index; D013997:Time Factors; D059467:Transcriptome
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; C512561:N-feruloylserotonin; D012701:Serotonin; D002097:C-Reactive Protein; D001091:Arachidonate Lipoxygenases; D008727:Methotrexate