Ferulaldehyde Improves the Effect of Methotrexate in Experimental Arthritis

Methotrexate (MTX) is still the gold standard for treatment of rheumatoid arthritis (RA). The therapeutic efficacy of low-dose of MTX can be increased by its combination with a natural substance, ferulaldehyde (FRA). The aim of this study was to evaluate the effect FRA and MTX administered alone or...

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Main Authors: Lukáš Slovák, Karol Švík, Danica Mihalová, Jaroslav Tóth, Szilvia Czigle, Ľudmila Pašková, František Bilka, Katarína Bauerová
Format: Article
Language:English
Published: MDPI AG 2017-11-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/22/11/1911
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author Lukáš Slovák
Karol Švík
Danica Mihalová
Jaroslav Tóth
Szilvia Czigle
Ľudmila Pašková
František Bilka
Katarína Bauerová
author_facet Lukáš Slovák
Karol Švík
Danica Mihalová
Jaroslav Tóth
Szilvia Czigle
Ľudmila Pašková
František Bilka
Katarína Bauerová
author_sort Lukáš Slovák
collection DOAJ
description Methotrexate (MTX) is still the gold standard for treatment of rheumatoid arthritis (RA). The therapeutic efficacy of low-dose of MTX can be increased by its combination with a natural substance, ferulaldehyde (FRA). The aim of this study was to evaluate the effect FRA and MTX administered alone or in combination in adjuvant arthritis. The disease was induced to Lewis male rats by intradermal injection, which contains a suspension of heat-inactivated Mycobacterium butyricum in incomplete Freund’s adjuvant. The experiment of 28 days included: healthy animals, arthritic animals, arthritic animals with administration of FRA at the oral daily dose of 15 mg/kg, arthritic animals with administration of MTX at the oral dose of 0.3 mg/kg twice a week, and arthritic animals administered with FRA and MTX. FRA in monotherapy decreased significantly only the level of interleukin-1β (IL-1β) and matrix metalloproteinase-9 in plasma. Combination of FRA and low-dose MTX was more effective than MTX alone when comparing body weight, hind paw volume, arthritic score, plasmatic levels of IL-1β, activity of γ-glutamyl transferase, and relative mRNA expression of IL-1β in the spleen. Therefore, the combination treatment was the most effective. The obtained results are interesting for future possible innovative therapy of patients with RA.
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spelling doaj.art-074fbcbbb4ee41be9046476c5454f0472022-12-21T20:36:25ZengMDPI AGMolecules1420-30492017-11-012211191110.3390/molecules22111911molecules22111911Ferulaldehyde Improves the Effect of Methotrexate in Experimental ArthritisLukáš Slovák0Karol Švík1Danica Mihalová2Jaroslav Tóth3Szilvia Czigle4Ľudmila Pašková5František Bilka6Katarína Bauerová7Institute of Experimental Pharmacology & Toxicology, Slovak Academy of Sciences, Dúbravská Cesta 9, 841 04 Bratislava, SlovakiaInstitute of Experimental Pharmacology & Toxicology, Slovak Academy of Sciences, Dúbravská Cesta 9, 841 04 Bratislava, SlovakiaInstitute of Experimental Pharmacology & Toxicology, Slovak Academy of Sciences, Dúbravská Cesta 9, 841 04 Bratislava, SlovakiaFaculty of Pharmacy, Comenius University in Bratislava, Odbojárov 10, 832 32 Bratislava, SlovakiaFaculty of Pharmacy, Comenius University in Bratislava, Odbojárov 10, 832 32 Bratislava, SlovakiaFaculty of Pharmacy, Comenius University in Bratislava, Odbojárov 10, 832 32 Bratislava, SlovakiaFaculty of Pharmacy, Comenius University in Bratislava, Odbojárov 10, 832 32 Bratislava, SlovakiaInstitute of Experimental Pharmacology & Toxicology, Slovak Academy of Sciences, Dúbravská Cesta 9, 841 04 Bratislava, SlovakiaMethotrexate (MTX) is still the gold standard for treatment of rheumatoid arthritis (RA). The therapeutic efficacy of low-dose of MTX can be increased by its combination with a natural substance, ferulaldehyde (FRA). The aim of this study was to evaluate the effect FRA and MTX administered alone or in combination in adjuvant arthritis. The disease was induced to Lewis male rats by intradermal injection, which contains a suspension of heat-inactivated Mycobacterium butyricum in incomplete Freund’s adjuvant. The experiment of 28 days included: healthy animals, arthritic animals, arthritic animals with administration of FRA at the oral daily dose of 15 mg/kg, arthritic animals with administration of MTX at the oral dose of 0.3 mg/kg twice a week, and arthritic animals administered with FRA and MTX. FRA in monotherapy decreased significantly only the level of interleukin-1β (IL-1β) and matrix metalloproteinase-9 in plasma. Combination of FRA and low-dose MTX was more effective than MTX alone when comparing body weight, hind paw volume, arthritic score, plasmatic levels of IL-1β, activity of γ-glutamyl transferase, and relative mRNA expression of IL-1β in the spleen. Therefore, the combination treatment was the most effective. The obtained results are interesting for future possible innovative therapy of patients with RA.https://www.mdpi.com/1420-3049/22/11/1911ferulaldehydemethotrexateadjuvant arthritiscombination treatmentrheumatoid arthritis
spellingShingle Lukáš Slovák
Karol Švík
Danica Mihalová
Jaroslav Tóth
Szilvia Czigle
Ľudmila Pašková
František Bilka
Katarína Bauerová
Ferulaldehyde Improves the Effect of Methotrexate in Experimental Arthritis
Molecules
ferulaldehyde
methotrexate
adjuvant arthritis
combination treatment
rheumatoid arthritis
title Ferulaldehyde Improves the Effect of Methotrexate in Experimental Arthritis
title_full Ferulaldehyde Improves the Effect of Methotrexate in Experimental Arthritis
title_fullStr Ferulaldehyde Improves the Effect of Methotrexate in Experimental Arthritis
title_full_unstemmed Ferulaldehyde Improves the Effect of Methotrexate in Experimental Arthritis
title_short Ferulaldehyde Improves the Effect of Methotrexate in Experimental Arthritis
title_sort ferulaldehyde improves the effect of methotrexate in experimental arthritis
topic ferulaldehyde
methotrexate
adjuvant arthritis
combination treatment
rheumatoid arthritis
url https://www.mdpi.com/1420-3049/22/11/1911
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AT jaroslavtoth ferulaldehydeimprovestheeffectofmethotrexateinexperimentalarthritis
AT szilviaczigle ferulaldehydeimprovestheeffectofmethotrexateinexperimentalarthritis
AT ludmilapaskova ferulaldehydeimprovestheeffectofmethotrexateinexperimentalarthritis
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