Abstract
Rheumatoid arthritis (RA) is a progressive and chronic autoimmune disease that is characterized by persistent synovial inflammation and irreversible cartilage and bone damage that affects the synovial joints and adjacent tissues. Presently, effective drugs that can control RA process remain an unmet need. The role of fibroblast-like synoviocytes (FLS) on synovial inflammation initiation and progression makes these cells natural targets for the search for new effective molecules to stop disease progression. 2-Styrylchromones (2-SC) feature a wide range of biological properties, including antioxidant and anti-inflammatory activities. The present study investigates the effect of six hydroxylated and methoxylated 2-SC on the IL-1β-induced increase of •NO and iNOS levels in human FLS, pointing the role of NF-κB activation in the process. From the tested 2-SC, the one presenting two OCH3 at C-5 and C-7 on A-ring and a catechol group on B-ring, significantly reduced iNOS expression and •NO production. These effects seemed to be partially mediated by the reversion of IL-1β-induced cytoplasmic IkBα disappearance and nuclear p65 increase. These findings may be of great value in the development of new 2-SC which should be further explored and carefully evaluated to reveal their full potential on the treatment of RA.
Supplementary Materials
The poster can be downloaded at: https://www.mdpi.com/article/10.3390/ECMC2022-13183/s1.
Author Contributions
Conceptualization, A.T.R. and D.R.; methodology, A.T.R. and M.L.; validation, D.R. and E.F.; formal analysis, A.T.R. and D.R.; investigation, A.T.R. and M.L.; writing—original draft preparation, A.T.R.; writing—review and editing, D.R., M.L., A.M.S.S., and E.F.; supervision, D.R. and E.F.; project administration, D.R.; funding acquisition, D.R., A.M.S.S. and E.F. All authors have read and agreed to the published version of the manuscript.
Funding
This work received support from PT national funds (FCT/MCTES, Fundação para a Ciência e Tecnologia and Ministério da Ciência, Tecnologia e Ensino Superior) through the projects UIDB/50006/2020 and UIDP/50006/2020. Authors acknowledge FCT/MCTES (Fundação para a Ciência e Tecnologia and Ministério da Ciência, Tecnologia e Ensino Superior) for the national funds received through the project PTDC/MED-QUI/29253/2017). ML thanks FCT/MCTES and ESF (European Social Fund) through NORTE 2020 (Programa Operacional Região Norte) for her PhD grant (ref. 2021.06746.BD). ATR acknowledges her research contract to FCT under the Project PTDC/MED-QUI/29243/2017.
Institutional Review Board Statement
Not applicable.
Informed Consent Statement
Not applicable.
Data Availability Statement
Not applicable.
Conflicts of Interest
The authors declare no conflict of interest.
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