What question did this study set out to answer?

This study aims to investigate the effects of the dietary flavonoid apigenin on human intestinal inflammation in the context of inflammatory bowel diseases (IBD).

January 23, 2026

P0116The dietary flavonoid apigenin modulates human intestinal inflammation: A Multi-Platform Ex-Vivo Study in IBD

Key Points

This study aims to investigate the effects of the dietary flavonoid apigenin on human intestinal inflammation in the context of inflammatory bowel diseases (IBD).
Colonic and small bowel mucosal explants from patients with Crohn's disease and controls were treated with apigenin.
Differential gene expression was assessed using RNA-sequencing and pathway enrichment analyses.
Cytokine levels in explant supernatants were measured by ELISA after treatment with apigenin.
Peripheral blood mononuclear cells were stimulated and analyzed for cytokine production in the presence of apigenin.
Human intestinal organoids were utilized to study inflammatory responses to apigenin.
Apigenin treatment significantly altered the expression of 2708 genes in mucosal explants.
Treatment led to reduced levels of cytokines IL6, IL8, IL1β, and CXCL1 in ileal mucosal explants, with statistical significance.
Colonic explants showed a significant decrease in IL6 but not other cytokines under treatment.
Cytokine secretion inhibition rates varied significantly across individuals, ranging from 0% to 79%.
Apigenin also notably decreased cytokine production in stimulated PBMCs.

Abstract

Abstract Background Inflammatory bowel diseases (IBD) are chronic inflammatory disorders shaped by environmental factors, including diet. The Mediterranean diet, beneficial for IBD, is rich in flavonoids. Apigenin, a dietary flavonoid with suggested anti-inflammatory effects in experimental IBD models, was thus selected as a prototype flavonoid for testing its effects on the human intestinal mucosa, and the underlying mechanisms. Methods Colonic and small bowel mucosal explants were obtained from patients with Crohn’s disease (CD) and non-IBD controls (NC). Explants were incubated overnight with/without 50 µM apigenin. Explants’ differential gene expression was assessed by RNA-sequencing followed by DESeq2 and pathway enrichment analyses. Supernatants from the same explant cultures were analyzed for IL6, IL8, IL1β, and CXCL1 (ELISA). Peripheral blood mononuclear cells (PBMCs) from patients with IBD and NC were stimulated with IFNγ and heat-killed E. coli with/without 5–50 µM apigenin; supernatants were analyzed for IL6 and IL8 (ELISA). To simulate inflammatory conditions NC human intestinal organoids (HIOs) were stimulated with IFNγ or heat-killed E. coli with/without 50 µM apigenin, and supernatants were analyzed for CXCL1and IL8 (ELISA). Results Mucosal explants, HIO and PBMCs used for ex-vivo assessments were obtained from 30 patients with IBD and 12 NC. Apigenin-treated CD mucosal explants (n = 6) had 2708 differentially expressed genes identified (RNA-seq) compared to untreated controls. Downregulated pathways included innate immunity (TLR2, IL24, IL1b), epithelial functions, i.e. redox regulation (DUOX2, DUOXA2, NOS2) and mucin expression (MUC1, MUC4, MUC17). Upregulated pathways included extracellular matrix organization (FMOD, ECM2 and several COL genes), antigen presentation (HLA-DQA1, HLA-DQA2, HLA-DRB1) and cell growth (IGF1, NGF, GDF9). Cytokine secretion of ileal mucosal explants was significantly reduced by apigenin, specifically IL6, IL8 IL1β and CXCL1 levels (p 0.01, p 0.05, p 0.05, and p 0.05, respectively) while in colonic explants only IL6 secretion was significantly (p 0.05) reduced. Apigenin reduced CXCL1secretion in stimulated HIOs and significantly decreased IL6 and IL8 production by stimulated PBMCs (p 0.01). Inhibition rates of cytokine secretion from colonic and ileal mucosal explants as well as PBMCs ranged from 0% to 79%, reflecting marked inter-individual variability. Conclusion Apigenin exerts anti-inflammatory effects in human intestinal mucosa, modifying both immune and epithelial pathways. Ex-vivo testing of dietary metabolites like apigenin may provide a functional framework for predicting individual responses and advancing mechanism-based nutritional therapy in IBD. Conflict of interest: Dr. Rabinowitz, Keren Masha: No conflict of interest Abu-Taha, Hanan: No conflict of interest Shafran, Yana: No conflict of interest Grunwald, Assaf: No conflict of interest Arruas, Jessica: No conflict of interest Avraham, Sharon: No conflict of interest Kaboub, Kawsar: No conflict of interest Cohen Kedar, Sarit: No conflict of interest White, Ian: No conflict of interest Wasserberg, Nir: No conflict of interest Brook, Elena: No conflict of interest Levy Barda, Adva: No conflict of interest Yanai, Henit: Grant: Pfizer, ISF Personal Fees: AbbVie, Janssen, Pfizer, Takeda, Bristol Myers Squibb, and Elly Lilli. Godny, Lihi: Grant: Helmsley Charitable Trust Dotan, Iris: Grant: The Leona M. and Harry B. Helmsley Charitable Trust, Altman Research, Pfizer, BMS Personal Fees: Pfizer, Falk, Ferring, Abbvie, Janssen, Celltrion, Takeda, Celgene/BMS, Gilead, Galapagos, Materia Prima, Sandoz, Sublimity, Sangamo, Spyre, Eli-Lilly, Harp Diagnostics, Gutreat, Astra Zeneca

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P0116The dietary flavonoid apigenin modulates human intestinal inflammation: A Multi-Platform Ex-Vivo Study in IBD

Key Points

Abstract

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