2025/11/04 by María Ángeles Ávila‐Gálvez, María Ángeles Ávila-Gálvez, Catarina J G Pinto +12 · 3 citations
Biochemistry, Genetics and Molecular Biology · Medicine · #Crosstalk #Gene silencing #Herbal Medicine Research Studies #Inflammation #Plant Toxicity and Pharmacological Properties #Proinflammatory cytokine #Sesquiterpene #Sesquiterpene lactone #Sesquiterpenes and Asteraceae Studies #Signal transduction #Transcription factor
paper · doi:10.1021/acs.jmedchem.5c02294
published in Journal of Medicinal Chemistry 68(21), 23406-23420 (American Chemical Society)
openalex created_date 2025/11/04 · openalex publication_date 2025/11/04 · openalex updated_date 2026/07/29
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 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.