Lactucopicrin: A Sesquiterpene Lactone with Anti-Inflammatory Activity Modulates the Crosstalk between NF-kB and AHR Pathways
Year: 2025
Type: article
Abstract: ABSTRACT 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 intybus L. (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 and opening new avenues for leveraging natural products in targeted anti-inflammatory strategies.
Source: Journal of Medicinal Chemistry
Institutions: Instituto de Biologia Experimental e Tecnológica, Universidade Nova de Lisboa, Universidade do Porto, i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Instituto de Biologia Molecular e Celular, University of Oxford, Ludwig Cancer Research, Leibniz-Forschungsinstitut für Molekulare Pharmakologie, NOVA Institute for Medical Systems Biology
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
Funders: International Business Machines Corporation, Ludwig Institute for Cancer Research, Cancer Research UK, University of Oxford, European Commission, Universidade Nova de Lisboa, Ministério da Ciência, Tecnologia e Ensino Superior, Universidade do Porto, Horizon 2020 Framework Programme, Fundação para a Ciência e a Tecnologia, European Regional Development Fund, Cancer Research UK Cambridge Institute, University of Cambridge
Awards: Parkinson’s disease bRain-on-ChIp Model to disclose polyphEnols potential (PRIME), G1684591577, Chicory as a multipurpose crop for dietary fibre and medicinal terpenes, G2913891876, The effect of gut-phenolic metabolites on the gut inflammatory response and the role of the AHR, G4214845467, G434337789, G4937468798, NOVA Institute for Medical Systems Biology, G6551555630, G6964253023, Improvement of the gut-brain axis imbalance in Parkinson’s disease through a (poly)phenol-enriched diet: mechanistic insights, G8394915505, G8535144208
OpenAlex ID: W4415869768