Lactucopicrin: A sesquiterpene lactone with anti-inflammatory activity modulates the crosstalk between NF-kB and AHR pathways

Avila Galvez, M. A.; Pinto, C.; Pita, C. R.; Silva, I. P.; Janowska, A. T.; Marinho, S.; Saitch, R.; Lian, Y.; Louphrasitthiphol, P.; Protze, J.; Krause, G.; Moura-Alves, P.; dos Santos, C. N.

doi:10.1101/2025.08.02.667913

bioRxiv · 10.1101/2025.08.02.667913

Lactucopicrin: A sesquiterpene lactone with anti-inflammatory activity modulates the crosstalk between NF-kB and AHR pathways

Avila Galvez, M. A.·Pinto, C.·Pita, C. R.·Silva, I. P.·Janowska, A. T.·Marinho, S.·Saitch, R.·Lian, Y.·Louphrasitthiphol, P.·Protze, J.·Krause, G.·Moura-Alves, P.·dos Santos, C. N.

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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 TNF-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.

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Avila Galvez, M. A., Pinto, C., Pita, C. R., Silva, I. P., Janowska, A. T., Marinho, S., Saitch, R., Lian, Y., Louphrasitthiphol, P., Protze, J., Krause, G., Moura-Alves, P., dos Santos, C. N.. 2025-08-04. Lactucopicrin: A sesquiterpene lactone with anti-inflammatory activity modulates the crosstalk between NF-kB and AHR pathways. https://doi.org/10.1101/2025.08.02.667913

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