Table 1.

Antioxidant and anti-inflammatory properties of in vitro and in vivo application of plant extracts containing ellagitannins or application of purified ellagitannins and downstream metabolites (ellagic acid or urolithins). ↑: increased; ↓: decreased; x: counteracted.

Compound Tested	Experimental System	Findings	References
pomegranate extract	human consumption of capsules	↑ antioxidant capacity of plasma (ORAC) within 30 min	[83]
	Alzheimer’s disease transgenic R1.40 mice model	non-significant ↓ TNFα, IL-1 and COX2	[84]
pomegranate flower extract	Zucker diabetic fatty rat	↓ interstitial and perivascular collagen accumulation in heart, expression of collagen I, collagen III, fibronectin, ET1, ETA, ETB, x NFκB activity	[85]
pomegranate juice	hyperoxia rat model	↓ neutrophil infiltration, albumin leak, ROS, apoptotic bodies in lungs, IL-1β, IL-6	[86]
pomegranate leaf ethanolic extract	intranasal application in asthma mouse model	↓ IL-1β, IL-5, inflammatory cell infiltration in lung, mucous glycoprotein secretion	[64]
pomegranate peel extract	neutrophil culture and LPS-stimulated mice	x MPO activity in neutrophils, ↓ lung invasion of inflammatory cells	[87]
	LPS-induced RAW264.7 macrophages	↓ TLR4 expression, ↓ IL-1β, IL-6, TNFα, NO, PGE2, ROS production, x nuclear translocation of NFκB nuclear translocation	[70]
walnut methanolic extract	human aorta endothelial cells (HAEC)	↓ TNFα-induced VCAM1 and ICAM1 expression	[80]
	KS483 osteoblastic cells line	nodule formation induced
corilagin	HSV-1 infected MV-2 microglia cells	↓ secretion of NO, TNFα, IL-1β, ↑ secretion of IL-10, cytochrome c, caspase-3, -8, -9 and -12	[65]
	HSV-1 infected mice	↓ numbers of inflammatory cells in the brain, ↓ neuronal degeneration and interstitial edema
punicalagin	acute respiratory distress mouse model	↓ inflammatory cell lung invasion, alveolar wall thickening, pulmonary congestion, ↓ TNFα, IL-1β, and IL-6 levels, MPO activity, TLR4 expression, x phosphorylation of IκBα and NFκB p65	[67]
	Jurkat cells	T cell activation by NFAT	[88]
	activated CD4+ murine splenic lymphocytes	↓ IL-2 mRNA and protein
	PMA-induced ear edema in mice	↓ hyperplasia and inflammatory cell infiltration
	LPS-induced RAW264.7 macrophages	↓ TLR4 expression, ↓ IL-1β, IL-6, TNFα, NO, PGE2, ROS production, x nuclear translocation of NFκB nuclear translocation	[70]
ellagic acid	human aorta endothelial cells (HAEC)	↓ TNFα-induced VCAM1 and ICAM1 expression	[80]
	KS483 osteoblastic cells line	nodule formation induced
	mice on high fat diet	↓ aortic lesions, plasma cholesterol and triglyceride, ↓sICAM1 and E-selectin expression, ↑ Nrf2, HO-1 protein and aortic NOS activity	[81]
	human umbilical vein endothelial cells (HUVEC)	Nrf2-mediated cytoprotection, ↑ HO-1 protein
	human Caco-2 intestinal cells	↓ NFκB activation after LPS stimulation, ↑ IκB-α phosphorylation and IL-8 secretion after IL-1β stimulation	[89]
	in combination with oseltamivir and isoprinosine in influenza A infected mice	↑ glutathione reductase activity, ↓ TBARS in blood plasma and lungs during infection	[21]
	LPS-induced RAW264.7 macrophages	↓ TLR4 expression, ↓ IL-1β, IL-6, TNFα, NO, PGE2, ROS production, x nuclear translocation of NFκB nuclear translocation	[70]
	Caco-2 and HT-29/B6 intestinal cells	↑ transepithelial resistance, ↓ caludin-4, -7, -15 expression	[90]
urolithin A	experimental autoimmune encephalomyelitis	↓ demyelination and inflammatory infiltrating cells, reduce severity of disease, ↓ activation of dendritic cells and CNS microglia	[68]
	bone marrow-derived dendritic cells and SIM-A9 microglia	↓ IL-1β, IL-6, TNFα, ↑ IL-10
	inflammatory bowel disease model LPS-stimulated BMDM	↓IκB-α phosphorylation, IL-1β, IL-2, IL-6, IL-12, TNFα, NOS2, double-stranded DNA breaks, superoxide production, MAPK and PI3K activation, proinflammatory miRNAs	[69]
	Caco-2 and HT-29/B6 intestinal cells	x TNF-α induced drop in transepithelial resistance	[31]
urolithins	LPS-stimulated BV2 microglia	↓ NO, TNFα and IL-6, improved SH-SY5Y neuronal cell viability in H2O2	[63]