title: N-feruloylserotonin in preventive combination therapy with methotrexate reduced inflammation in adjuvant arthritis.
abstract: Many of disease-modifying anti-rheumatic drugs often have side effects at high doses and/or during long-term administration. Increased efficacy without increased toxicity is expected for combination therapy of rheumatoid arthritis (RA). The aim of the study was to examine the effect of N-feruloylserotonin (N-f-5HT) and methotrexate (MTX) in monotherapy and in combination therapy on disease progression and inflammation in arthritic rats. Adjuvant arthritis was induced by intradermal injection of Mycobacterium butyricum in incomplete Freund's adjuvant in Lewis rats. The experiment included healthy animals, arthritic animals without any drug administration, arthritic animals with administration of N-f-5HT in the oral daily dose of 15 mg/kg b.w., arthritic animals with administration of MTX in the oral dose of 0.3 mg/kg b.w. twice a week and arthritic animals treated with the combination of N-f-5HT and MTX. N-f-5HT in monotherapy reduced only activation of NF-κB and did not have any significant effect on other parameters monitored. Low-dose treatment of MTX decreased the level of IL-1β and MCP-1 on day 14 and activation of NF-κB in liver without significant effect on other parameters. N-f-5HT and MTX combination showed both the anti-arthritic (hind paw volume and arthritic score) and anti-inflammatory effect (plasmatic levels of IL-1β, IL-17, MCP-1, CRP, and activation of NF-κB in liver). In combination with MTX, N-f-5HT markedly potentiated the therapeutic effect of MTX low dose, which resulted in significant improvement of all parameters measured. The findings showed that the combination therapy simultaneously decreased multiple markers of inflammation, a result crucial for future therapy of RA.
authors.affiliation: Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Dubravska cesta 9, SK-841 04, Bratislava, Slovak Republic.
authors.forename: Viera
authors.initials: V
authors.lastname: Kuncirova
authors.forename: Silvester
authors.initials: S
authors.lastname: Ponist
authors.forename: Danica
authors.initials: D
authors.lastname: Mihalova
authors.forename: Frantisek
authors.initials: F
authors.lastname: Drafi
authors.forename: Radomir
authors.initials: R
authors.lastname: Nosal
authors.forename: Alessandra
authors.initials: A
authors.lastname: Acquaviva
authors.forename: Concetta
authors.initials: C
authors.lastname: Gardi
authors.forename: Juraj
authors.initials: J
authors.lastname: Harmatha
authors.forename: Iveta
authors.initials: I
authors.lastname: Hradkova
authors.forename: Katarina
authors.initials: K
authors.lastname: Bauerova
mesh_terms: D000818:Animals; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000494:pharmacology; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005620:Freund's Adjuvant / Q000008:administration & dosage; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D012701:Serotonin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D018501:Antirheumatic Agents; D016328:NF-kappa B; C512561:N-feruloylserotonin; D012701:Serotonin; D005620:Freund's Adjuvant; D008727:Methotrexate
keywords: N-feruloylserotonin; arthritis; combination therapy; inflammation; methotrexate; oxidative stress