# Lactucopicrin: A Sesquiterpene Lactone with Anti-Inflammatory Activity Modulates the Crosstalk between NF-kB and AHR Pathways

## TL;DR

This paper explores how lactucopicrin, a compound from chicory, reduces inflammation by affecting two key pathways, suggesting potential for treating inflammatory diseases.

## Contribution

The study reveals lactucopicrin as a novel dual modulator of NF-kB and AHR pathways, uncovering a new crosstalk mechanism.

## Key findings

- Lactucopicrin inhibits NF-kB signaling in inflammation models.
- Lactucopicrin modulates the Aryl Hydrocarbon Receptor (AHR) pathway.
- AHR silencing reduces lactucopicrin's anti-inflammatory effects, indicating pathway crosstalk.

## 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.