PMID- 36986641
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230331
IS  - 1999-4923 (Print)
IS  - 1999-4923 (Electronic)
IS  - 1999-4923 (Linking)
VI  - 15
IP  - 3
DP  - 2023 Feb 26
TI  - 2-Styrylchromones Prevent IL-1beta-Induced Pro-Inflammatory Activation of 
      Fibroblast-like Synoviocytes while Increasing COX-2 Expression.
LID - 10.3390/pharmaceutics15030780 [doi]
LID - 780
AB  - Rheumatoid arthritis (RA) is characterized by systemic immune and chronic 
      inflammatory features, leading to the destruction of the joints. Presently, there 
      are no effective drugs able to control synovitis and catabolism in the process of 
      RA. 2-Styrylchromones (2-SC) are a small group of compounds characterized by the 
      attachment of a styryl group to the chromone core that have already been 
      associated to a wide range of biological activities, including antioxidant and 
      anti-inflammatory activities. The present study investigated the effect of a set 
      of six 2-SC on the interleukin-1beta (IL-1beta)-induced increase of nitric oxide 
      ((*)NO), inducible form of nitric oxide synthase (iNOS), cyclooxygenase-2 
      (COX-2), and matrix metalloproteinase-3 (MMP-3) expression levels in human 
      fibroblast-like synoviocytes (HFLS), pointing to the role of nuclear factor 
      kappa-light-chain-enhancer of activated B cells (NF-kappaB) activation in the 
      process. From a set of six 2-SC, presenting hydroxy and methoxy substituents, the 
      one presenting two methoxy substituents at C-5 and C-7 of A ring and a catechol 
      group on B ring, significantly reduced (*)NO production and the expression of its 
      inducible synthase (iNOS). It also significantly reduced the catabolic MMP-3 
      protein expression. This 2-SC inhibited the NF-kappaB pathway by reversing the IL-1beta 
      - induced levels of cytoplasmatic NF-kB inhibitor alpha (IkappaBalpha), and decreasing 
      the p65 nuclear levels, suggesting the involvement of these pathways in the 
      observed effects. The same 2-SC significantly increased the COX-2 expression, 
      which may indicate a negative feedback loop mechanism of action. The properties 
      of 2-SC may be of great value in the development of new therapies with improved 
      efficacy and selectivity towards RA, and thus deserve further exploitation and 
      evaluation to disclose the full potential of 2-SC.
FAU - Rufino, Ana Teresa
AU  - Rufino AT
AUID- ORCID: 0000-0002-8800-9020
AD  - LAQV, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, 
      Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira No. 228, 
      4050-313 Porto, Portugal.
FAU - Lucas, Mariana
AU  - Lucas M
AUID- ORCID: 0000-0001-8976-0708
AD  - LAQV, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, 
      Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira No. 228, 
      4050-313 Porto, Portugal.
FAU - Silva, Artur M S
AU  - Silva AMS
AUID- ORCID: 0000-0003-2861-8286
AD  - LAQV, REQUIMTE, Department of Chemistry, University of Aveiro, Campus 
      Universitario de Santiago, 3810-193 Aveiro, Portugal.
FAU - Ribeiro, Daniela
AU  - Ribeiro D
AUID- ORCID: 0000-0001-9733-7934
AD  - LAQV, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, 
      Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira No. 228, 
      4050-313 Porto, Portugal.
AD  - Faculty of Agrarian Sciences and Environment, University of the Azores, Rua 
      Capitao Joao d'Avila-Pico da Urze, 9700-042 Angra do Heroismo, Portugal.
FAU - Fernandes, Eduarda
AU  - Fernandes E
AUID- ORCID: 0000-0001-6424-0976
AD  - LAQV, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, 
      Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira No. 228, 
      4050-313 Porto, Portugal.
LA  - eng
GR  - UIDB/50006/2020/Fundacao para a Ciencia e Tecnologia/
GR  - POCI-01-0145- FEDER-029253-Project PTDC/MED-382 QUI/29253/2017/European Union/
PT  - Journal Article
DEP - 20230226
PL  - Switzerland
TA  - Pharmaceutics
JT  - Pharmaceutics
JID - 101534003
PMC - PMC10053337
OTO - NOTNLM
OT  - 2-Styrylchromones
OT  - COX-2
OT  - NF-kB
OT  - fibroblast-like synoviocytes
OT  - inflammation
OT  - rheumatoid arthritis
COIS- The authors declare no conflict of interest.
EDAT- 2023/03/30 06:00
MHDA- 2023/03/30 06:01
PMCR- 2023/02/26
CRDT- 2023/03/29 02:02
PHST- 2023/02/01 00:00 [received]
PHST- 2023/02/14 00:00 [revised]
PHST- 2023/02/21 00:00 [accepted]
PHST- 2023/03/30 06:01 [medline]
PHST- 2023/03/29 02:02 [entrez]
PHST- 2023/03/30 06:00 [pubmed]
PHST- 2023/02/26 00:00 [pmc-release]
AID - pharmaceutics15030780 [pii]
AID - pharmaceutics-15-00780 [pii]
AID - 10.3390/pharmaceutics15030780 [doi]
PST - epublish
SO  - Pharmaceutics. 2023 Feb 26;15(3):780. doi: 10.3390/pharmaceutics15030780.