Ferulaldehyde Improves the Effect of Methotrexate in Experimental Arthritis

Abstract

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.

Protective Effects of Gynostemma pentaphyllum (var. Ginpent) against Lipopolysaccharide-Induced Inflammation and Motor Alteration in Mice

“…In addition, anthocyanins prevent the action of reactive oxygen species (ROS) generated by the administration of LPS, as observed by some authors [ 48 , 51 ]. Another polyphenol identified and worthy of interest is ferulaldehyde, a hydroxycinnamaldehyde found to be able to reduce the inflammatory response by reducing the release of cytokines, such as interleukin-1β and TNF-α, and by inhibiting the LPS-induced activation of the nuclear factor kappaB pathway in mice models [ 52 ]. Interestingly, some authors reported a synergistic effect of ferulaldehyde with Methotrexate in the therapy of inflammatory arthritis [ 52 ].…”

“…Another polyphenol identified and worthy of interest is ferulaldehyde, a hydroxycinnamaldehyde found to be able to reduce the inflammatory response by reducing the release of cytokines, such as interleukin-1β and TNF-α, and by inhibiting the LPS-induced activation of the nuclear factor kappaB pathway in mice models [ 52 ]. Interestingly, some authors reported a synergistic effect of ferulaldehyde with Methotrexate in the therapy of inflammatory arthritis [ 52 ]. Among other molecules, sinapine is one of the most representative phenolic acids in our samples, followed by m -coumaric acid and 2-hydroxybenzoic acid.…”

The possible role of heat shock protein-70 induction in collagen-induced arthritis in rats

“…Therefore, the role of 17-AAG was suggested not only to be preventive but also therapeutic. Some previous studies started the treatments of RA during induction of arthritis (45,55). Therefore, it is a limitation in this study that it could have been supplemented with experimental groups in which treatment would have been started after the onset of arthritis.…”

The Role of Endogenous Antioxidants in the Treatment of Experimental Arthritis

“…Adjuvant arthritis (AA) was induced by intradermal injection of Mycobacterium butyricum in incomplete Freund's adjuvant to male Lewis rats [36,37]. The experiment included healthy control animals (HC), arthritic animals (AA), and arthritic animals with administration of CoQ 10 (liquid liposomal CoQ 10 -LiQSorb ® ) in the oral daily dose of 100 mg/kg b.w.…”

“…(1) Not treated control groups (HC) (2) Arthritic animals not treated with HA (AA) Adjuvant arthritis was induced by a single intradermal injection of heat-inactivated Mycobacterium butyricum [36,37]. Blood was collected to obtain plasma and erythrocytes.…”