Table 2.
Anti-inflammatory activity of urolithin A relevant to the intestine
| Cell line/model | Mechanism | Ref. |
| CCD18-Co/cytokine-induced inflammation IL-1β or TNF-α | ↓IL-1β-induced PGE2 level | Giménez-Bastida et al[41] |
| ↓IL-1β or TNF-α -stimulated migration | ||
| ↓non-stimulated migration | ||
| ↓IL-1β-stimulated adhesion | ||
| ↑TNF-α -decreased cell viability | ||
| ↓IL-1β or TNF-α -induced expression of members of the EGF, PGF, PDGF, VEGF, M-CSF, and IGF families | ||
| ↓IL-1β -induced PAI-1 and TNF-α -induced IL-8 levels | ||
| Fischer rats/DSS-induced colitis | ↑HCT, RBCs | Larrosa et al[42] |
| ↓Loss of epithelium, total histological scores | ||
| ↑Bifidobacteria | ||
| ↓E. coli, enterobacteria, and total aerobic bacteria CAT activity | ||
| ↓NO, iNOS | ||
| ↓PGE2, COX-2, PTGES | ||
| ↑Rb1, p53 ↓CD40, IL-1β and IL-4 | ||
| C57BL/6 x FVB F1/BRB intervention | ↑Shannon diversity index | Gu et al[44] |
| ↑Bacteroidetes, Barnesiella | ||
| ↓Firmicutes, Clostridium, Turicibacter, Lactobacillus | ||
| BMDMs/LPS | ↓IL-6, TNF-α level | Singh et al[45] |
| C57BL/6 mice | ↓LPS-induced serum level of IL-6, TNF-α | Singh et al[45] |
| ↑Colonic and hepatic Cyp1A1 activity in WT not in AhR−/− mice | ||
| ↑Colonic Cldn4, Nrf2, and NQO1 in WT not in AhR−/− and Nrf2−/− mice | ||
| ↑Colonic Cldn4, Nrf2, and NQO1 in WT not in AhR−/− and Nrf2−/− mice | ||
| HT-29, Caco-2 | ↑Cldn4, Ocln, and ZO1 | Singh et al[45] |
| ↑Cldn4, Ocln, and ZO1 | ||
| ↓LPS-induced leakage of FITC-dextran | ||
| ↑Cyp1A1, Cyp1A1 protein expression, and activity | ||
| ↑AhR-reporter, nuclear translocation of AhR | ||
| Cldn4 expression not affected in Ahr SiRNA and CYP1A1 SiRNA cells | ||
| ↑Nrf2 levels, nuclear translocation of Nrf2 | ||
| C57BL/6 mice/TNBS | ↓Weight loss, diseases activity index, intestinal permeability | Singh et al[45] |
| ↓Colonic MPO level | ||
| ↓Serum IL-6, TNF-α, CXCL1, and IL-1β levels | ||
| ↑Colon length, Cldn4 | ||
| ↓Tissue damage and inflammation scores | ||
| AhR-knockdown caco-2 cells/TCDD/IL-1β /TMF | ↓IL-6, CYP1A1, PTGS2 in siControl | Muku et al[47] |
| NS IL-6, CYP1A1, PTGS2 in siAhR |
AhR: Aryl hydrocarbon receptor; BMDMs: Mouse bone marrow derived macrophages, BRB: Black raspberries; CAT: Catalase; Cldn4: Claudin 4; COX-2: Cyclooxygenase 2; CXCL1: Chemokine (C-X-C motif) ligand 1; CYP: Cytochrome; EGF: Epidermal growth factor; HCT: Haematocrit; IGF: Insulin-like growth factor; IL: Interleukin; iNOS: Inducible nitric oxide synthase; LPS: Lipopolysaccharide; M-CSF: Macrophage colony-stimulating factor; MPO: Myeloperoxidase; ns: non significant change; NO: Nitric oxide; Nrf2: Nuclear factor erythroid 2-related factor 2 ; NQO1: NAD(P)H dehydrogenase [quinone] 1; Ocln: Occludin; siAhR: AhR knockdown by siRNA Caco-2 cells; siControl: Caco-2 cells transfected with siControl; PAI-1: Plasminogen activator inhibitor-1; PDGF: Platelet-derived growth factor; PGE2: Prostaglandin E2; PTGES: Prostaglandin E synthase; PGF: Placental growth factor; PTGS2: Prostaglandin-endoperoxide synthase; RBCs: Red blood cells; TCDD: 2,3,7,8-tetrachlorodibenzo-p-dioxin (agonist of AhR); TMF: 6,2',4'-trimethoxyflavone (AhR antagonist); TNBS: 2,4,6-Trinitrobenzenesulfonic acid; TNF-α: Tumor necrosis factor α; WT: Wild type; VEGF: Vascular endothelial growth factor; ZO-1: Zonula occludens-1.