Autor(es): Ávila-Gálvez, María Ángeles ; J G Pinto, Catarina ; Rafael-Pita, Carlos ; P. Silva, Inês ; Janowska, Aleksandra T. ; Marinho, Sérgio ; Saitch, Rory ; Lian, Yilong ; Louphrasitthiphol, Pakavarin ; Protze, Jonas ; Krause, Gerd ; Moura-Alves, Pedro ; Nunes dos Santos, Cláudia
Data: 2025
Identificador Persistente: http://hdl.handle.net/10362/191559
Origem: Repositório Institucional da UNL
Assunto(s): Molecular Medicine; Drug Discovery; SDG 3 - Good Health and Well-being
Funding Information: This work was supported by EU Horizon 2020 Research & Innovation programme (H2020-NMBP-BIO-2017) (grant number 760891), European Commission program Teaming for Excellence, Grant No. 101060346, the European Union\u2019s Horizon 2020 research and innovation programme under grant agreement No. 951921, NORTE2030-FEDER-01777300 - SCALE-ImmunoHUB2030 supported by Norte Portugal Regional Operational Programme (NORTE 2030), under the PORTUGAL 2030 Partnership Agreement, through the European Regional Development Fund (FEDER); Ludwig Institute for Cancer Research Core Award; COMPETE2030-FEDER-00693400, supported by FEDER and national Funds (Fundac\u0327a\u0303o para a Cie\u0302ncia e Tecnologia, FCT), operation number 15824 relative to applications to MPr-2023-12. iNOVA4Health (LISBOA-01-0145-FEDER-007344; UIDB/04462/2020), cofunded by FCT/Ministe\u0301rio da Cie\u0302ncia e do Ensino Superior (MCTES) through national funds and by FEDER under the PT2020 Partnership Agreement, and also LS4FUTURE Associated Laboratory (LA/P/0087/2020) are acknowledged. C.J.G.P. (grant No. 2022.11465.BD), C.R.P. (grant No. 2023.00453.BD), and I.P.S. (grant No. 2023.02417.BD) are recipients of PhD fellowships from FCT. P.M.-A., A.T.J., R.S., Y.L., and P.L. acknowledge support from the Ludwig Institute for Cancer Research Core Award. P.M.-A. and S.M. thank funding from the European Union\u2019s Horizon 2020 research and innovation programme under grant agreement No. 951921, NORTE2030-FEDER-01777300 - SCALE-ImmunoHUB2030, and COMPETE2030-FEDER-00693400. C.N.S acknowledges European Research Council (ERC) under the European Union\u2019s Horizon 2020 research and innovation program under grant agreement No 804229. Publisher Copyright: © 2025 American Chemical Society
Chronic inflammatory diseases, including inflammatory bowel diseases and cardiovascular diseases, share inflammation as a central pathological feature. The transcription factors NF-kB and AHR are key regulators of inflammatory responses, yet their interplay remains underexplored in the context of natural anti-inflammatory compounds. This study investigates the anti-inflammatory properties of sesquiterpene lactones derived from Cichorium intybusL. (chicory), focusing on their modulation of NF-kB and AHR signaling pathways. Using a TNFα-induced inflammation model in macrophages, endothelial, and intestinal epithelial cells, we identified lactucopicrin as a potent NF-kB antagonist. Notably, in silico docking and functional assays revealed lactucopicrin as a novel AHR modulator. Crucially, silencing AHR expression attenuated lactucopicrin-mediated NF-kB inhibition, uncovering a previously unrecognized AHR-NF-kB crosstalk mechanism. These findings not only position lactucopicrin as a dual-pathway modulator but also highlight the therapeutic potential of chicory-derived sesquiterpene lactones in treating inflammation-driven diseases, opening new avenues for leveraging natural products in targeted anti-inflammatory strategies.
