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Updated: May 28, 2026

Investigating Intestinal Inflammation in DSS-induced Model of IBD
Published on: February 1, 2012
Anti-Inflammatory Activity of In Vitro Digested Manna in a Caco-2 and RAW264.7 Cells Co-Culture Model of Inflammatory
Ilenia Concetta Giardina1, Mussa Makran2, Ignazio Restivo1
1Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo, Via Archirafi 28, 90123 Palermo, Italy.
Abstract:
Inflammatory bowel disease (IBD) involves intestinal barrier dysfunction and chronic inflammation. Manna, derived from the solidified phloem sap of Fraxinus species, is rich in mannitol and polyphenols and valued for its laxative, antioxidant, and anti-inflammatory properties. In this study, manna was digested in vitro to obtain its bioaccessible fraction (BFM), whose anti-inflammatory activity was tested in a Caco-2/RAW264.7 co-culture model. Caco-2 cells were pretreated with BFM (1/20 v/v, 6 mg/mL) 90 min before LPS stimulation (1 µg/mL, 24 h) of macrophages, using budesonide (1 μM) as reference. BFM pretreatment significantly reduced IL-8 secretion (70.8%) in Caco-2 cells, and IL-6 (43.1%) and TNF-α (83.1%) in RAW264.7 macrophages. It also improved redox balance in Caco-2 cells by decreasing iNOS (48.2%), NOx (33.2%), and ROS (26.4%), while stabilizing tight junctions through occludin upregulation (18.3%). Mechanistically, BFM downregulated NF-κB-COX-2-PGE2 signaling in macrophages, reducing NF-κB p65 nuclear translocation (65.6%), COX-2 levels (79.3%), and PGE2 production (50.8%). Co-treatment with budesonide showed antagonism for most markers (Combination Index (CI), 0.41-0.76), but additive/synergistic effects on ROS (CI, 1.06 ± 0.06) and NOx (CI, 1.10 ± 0.04). These findings highlight manna's strong anti-inflammatory activity at a low, non-laxative dose (3.8 g/day), supporting its nutraceutical potential in IBD management.
Insights
Manna
Area of Science:
- Gastroenterology
- Pharmacology
- Cell Biology
Background:
- Inflammatory bowel disease (IBD) is characterized by intestinal barrier dysfunction and chronic inflammation.
- Manna, from *Fraxinus* species, contains mannitol and polyphenols with known antioxidant and anti-inflammatory properties.
- Its potential therapeutic applications in IBD require further investigation.
Purpose of the Study:
- To evaluate the anti-inflammatory effects of a bioaccessible fraction of manna (BFM).
- To investigate the mechanisms underlying BFM's anti-inflammatory activity in an in vitro IBD model.
- To assess the potential synergistic or antagonistic effects of BFM with budesonide.
Main Methods:
- An in vitro Caco-2/RAW264.7 co-culture model was used to simulate IBD conditions.
- Caco-2 cells and RAW264.7 macrophages were pretreated with BFM before lipopolysaccharide (LPS) stimulation.
- Key inflammatory markers, redox balance indicators, tight junction proteins, and signaling pathways (NF-κB) were analyzed.
Main Results:
- BFM significantly reduced pro-inflammatory cytokines (IL-8, IL-6, TNF-α) in both cell types.
- BFM improved redox balance by decreasing iNOS, NOx, and ROS, and upregulated occludin, stabilizing tight junctions.
- BFM inhibited NF-κB signaling, reducing NF-κB p65 translocation, COX-2, and PGE2 production.
Conclusions:
- Manna's bioaccessible fraction exhibits potent anti-inflammatory and intestinal barrier-protective effects.
- BFM demonstrates therapeutic potential for managing inflammatory bowel disease at a non-laxative dose.
- Further research into manna as a nutraceutical for IBD is warranted.
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