Exploring the Impact of Cyanidin-3-Glucoside on Inflammatory Bowel Diseases: Investigating New Mechanisms for Emerging Interventions



1. Introduction

2. Cyanidin-3-O-Glucoside

2.1. Chemical Structure

2.2. Dietary Sources

2.3. Bowel Metabolism

2.4. Health Effects

3. Inflammatory Bowel Disease (IBD)

3.1. Epidemiology

3.2. Pathogenesis

3.3. Therapeutic Options

3.4. Natural Products

4. Therapeutic Effects of C3G in IBD

4.1. C3G Inhibits NF-κB Pathway Activation

4.2. C3G Activates Nrf2 Pathway and Modulates Cytoprotective Enzymes Expression

4.3. C3G Modulates IFN Pathways

4.4. C3G Reduces Reactive Species and Pro-Inflammatory Cytokines

4.5. C3G Modulates Gut Microbiota

4.6. Clinical Aspects

5. Conclusions

Author Contributions


Institutional Review Board Statement

Informed Consent Statement

Data Availability Statement

Conflicts of Interest



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Year; Author Study Type Subjects (Animal/Cell Models/Individuals) Dose IBD Indicators Related Molecular Mechanisms in Regulation of IBD
[125] In vitro CM stimulated T84 cells 25, 50, 100 μM for 4 h NA ↓ IP-10 (CXCL10)
[115] In vitro Cytokine stimulated HT-29 cells 12.5 to 50 μM for 24 h NA ↓ NO,↓ PGE2, ↓ IL-8, ↓ iNOS

↓ COX-2↓ STAT1

[116] In vitro Cytokine stimulated HT-29 cells 25 μM, for 1 h ↑ Nrf2 pathway,

↑ HO-1,↑ GCLC and GCLM


↓ Reactive species
[114] In vitro Caco-2 cells + TNF-α 20–40 μM for24 h ↑ Nrf2 pathway,


↑ HO-1 and NQO-1 mRNA Levels

↓ TNF-α, ↓ IKKα/β

phosphorylation/activation and IκBα, ↓ NF-κB pathway

↓ Il-6 induced by TNF-α, COX-2, PGE2 and TXB2

[118] In vitro Caco-2 cells 0.25, 0.5 and 1 μM for 24 h ↑ FITC-dextran permeability ↓ IKKα, ↓ p65 phosphorylation, ↓ MLC, ↓ TNFα, ↓ NF-kB pathway,


[121] In vitro Caco-2-HUVECs 20 or 40 μM for 24 h NA ↓ NF-κB pathway, ↓ TNF-α, ↓ IL-8

↓ endothelial cells activation:

↓ E-selectin, ↓ VCAM-1 mRNA, ↓ leukocyte adhesion

[39] In vivo and in vitro BALB/c TNBS-induced colitic mice

Caco-2 cell monolayer model +LPS

200 μL for 12 h before TNBS injection

24.2–96.8 g/kgBW daily for 3 days

NA ↓ MPO, ↓ TEER, ↓ LY flux values.

↓ NO, ↓ TNF-α, ↓ IL-1b, ↓ IL-6, ↓ IFN-γ

↓ histological damage

[117] In vitro (Cell culture: RAW 264.7 cells+ IFNα+ IFNβ, 24 h)

Naïve mouse peritoneal macrophages, lymphocytes removed + 1 ug/mL LPS, 24 h

1 ug/mL for 24 h NA Direct inhibition of CD80 and


Inhibition of CD169 Expression induced by Type I IFN

↓ IL-1β, IL-18, IL-6, IL-17, and TNF-α

[36] In vitro Caco-2 cells + 100 μM PA

(basolateral side)

10 or 20 μM for 24 h ↑ Nrf2/EpRE pathway

↑ NQO-1

↓ NF-κB pathway

↓ IL-6 and IL-8 mRNA levels

↓ COX-2


[113] In vitro Caco-2 cells+ LPS ± HPP C3G-BP complexes (100–100 μg/mL) ↑ IL-10 ↓ depolarization of mitochondria,


↓ IL-1β, TNF-α, and IL-8

↓ iNOS, COX-2, Bcl-2 and cleaved caspase-3 levels

Inhibition of apoptosis

[119] In vitro Caco-2 cells +TNF- α 0.18, 0.37, 0.75, 1.5 μg C3G eq./mL for 24 h

(ACN-rich purified and standardized bilberry and blackcurrant extract (BBE))

Activation of Nrf2/ Keap1 pathway Inhibition of NF-κB pathway activated by TNF-α

↓ IL-8 and ↓ IL-6 mRNA levels

[124] In vivo DSS-induced colitic UC mice + HHP treatment HPP 200 mg/kg C3G+ blueberry pectin complex (Oral administration) ↑ protein levels of the ratio Bcl-2/Bax and caspase-3/cleaved caspase-3 genes

↑ Bacteroidetes, Verrucomicrobia Candidatus Saccharibacteria.

↓ mRNA expression of pro-inflammatory factors

↓ NF-κB P65, ↓ NF-κB pathway

↓ Firmicutes, Proteobacteria,

↓ Firmicutes to Bacteroidetes (F/B) ratio

[126] Cohort study 47 IBD patients

Administration of a purple corn supplement to IBD patients receiving infliximab

Purple corn supplement composed by 2 mg GAE/g DW (gallic acid equivalents per g of dry weight) and total anthocyanin content

of 0.5 mg cyanidin 3-glucoside (C3G)

NA CD group only, not UC:

↓ CRP, ↓ IFN-γ

↓ TNF-α, IL-5, IL-9, IL-10, IL-12p70, and IL-17A

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Frountzas, M.; Karanikki, E.; Toutouza, O.; Sotirakis, D.; Schizas, D.; Theofilis, P.; Tousoulis, D.; Toutouzas, K.G. Exploring the Impact of Cyanidin-3-Glucoside on Inflammatory Bowel Diseases: Investigating New Mechanisms for Emerging Interventions. Int. J. Mol. Sci. 2023, 24, 9399. https://doi.org/10.3390/ijms24119399

Frountzas M, Karanikki E, Toutouza O, Sotirakis D, Schizas D, Theofilis P, Tousoulis D, Toutouzas KG. Exploring the Impact of Cyanidin-3-Glucoside on Inflammatory Bowel Diseases: Investigating New Mechanisms for Emerging Interventions. International Journal of Molecular Sciences. 2023; 24(11):9399. https://doi.org/10.3390/ijms24119399

Chicago/Turabian Style

Frountzas, Maximos, Eva Karanikki, Orsalia Toutouza, Demosthenis Sotirakis, Dimitrios Schizas, Panagiotis Theofilis, Dimitris Tousoulis, and Konstantinos G. Toutouzas. 2023. “Exploring the Impact of Cyanidin-3-Glucoside on Inflammatory Bowel Diseases: Investigating New Mechanisms for Emerging Interventions” International Journal of Molecular Sciences 24, no. 11: 9399. https://doi.org/10.3390/ijms24119399

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