Abstract
2-Styrylchromones (2-SC) are heterocyclic compounds with a structure of at least 17 carbons and a styryl group attached to a benzoannelated γ-pyrone ring. Although the anti-inflammatory potential of 2-SC has become a subject of interest, their effects in inflammatory pathways are still unexplored. Therefore, to better understand the mechanisms of anti-inflammatory action of 2-SC, this study investigated the influence of 10 hydroxylated and methoxylated 2-SC on the inhibitory activity of cyclooxygenase (COX-2), through an in vitro non-cellular assay and an ex vivo assay in human whole blood, which were based on the fluorometric detection of prostaglandin (PG) G2 and colorimetric detection of PGE2, respectively. A 2-SC hydroxylated at C-7 and C-8 on the A-ring and C-3′ and C-4′ on the B-ring was the most active in the direct inhibition of COX-2 activity, whereas a 2-SC methoxylated at C-4′ on the B-ring was the most active in the ex vivo inhibition of PGE2 production. The obtained results suggest that the presence of OH groups, especially at C-8 on the A-ring, favor the direct inhibition of COX-2. Conversely, for inhibition of PGE2 production in a more complex matrix, human blood, it is the presence of an OCH3 at C-4′ on the B-ring that seems to be important.
Supplementary Materials
The following are available online at https://www.mdpi.com/article/10.3390/ECMC2022-13232/s1.
Author Contributions
Conceptualization, E.F. and D.R.; methodology, M.L.; validation, E.F. and D.R.; formal analysis, M.L.; investigation, M.L.; writing—original draft preparation, M.L.; writing—review and editing, M.L., M.F., A.M.S.S., E.F. and D.R.; supervision, A.M.S.S., E.F. and D.R.; project administration, E.F. and D.R.; funding acquisition, E.F. and D.R. 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 the European Union [FEDER funds through the Operational Competitiveness Program (COMPETE2020) PO-CI-01-0145-FEDER-029253-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). MF acknowledges her contract under the CEEC Individual (2020.04126.CEECIND/CP1596/CT0006) and also thanks LAQV/REQUIMTE for her contract under the reference LA/P/0008/2020.
Institutional Review Board Statement
The study was conducted in accordance with the Declaration of Helsinki, and approved by the Ethics Committee of Centro Hospitalar Univesitário do Porto/Instituto de Ciências Biomédicas Abel Salazar, Oporto, Portugal.
Informed Consent Statement
Informed consent was obtained from all subjects involved in the study.
Data Availability Statement
Not applicable.
Conflicts of Interest
The authors declare no conflict of interest.
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