Pomegranate (Punica granatum L.) is a rich source of polyphenols, including ellagitannins and ellagic acid. The plant is used in traditional medicine, and its purified components can provide anti-inflammatory and antioxidant activity and support of host defenses during viral infection and recovery from disease. Pomegranate extracts, ellagitannins and ellagic acid are promising agents to target the SARS-CoV-2 virus and to restrict the host inflammatory response to viral infections, as well as to supplement the depleted host antioxidant levels during the stage of recovery from COVID-19.
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] | |||||
influenza B | synergistic effect on viral proliferation inhibition with oseltamivir | [ | 22] | pomegranate flower extract |
Zucker diabetic fatty rat | ||
pomegranate leaf ethanolic extract |
HSV-2 | ↓ interstitial and perivascular collagen accumulation in heart, expression of collagen I, collagen III, fibronectin, ET1, ETA, ETB, x NFκB activity |
Zika[85] | ||||
reduces viral proliferation in cells | [ | 24 | ] | pomegranate juice | hyperoxia rat model | ↓ neutrophil infiltration, albumin leak, ROS, apoptotic bodies in lungs, IL-1β, IL-6 | [86] |
pomegranate peel extract and fruit juice | HCV | inhibition of NS3/4A protease activity | [26] | pomegranate leaf ethanolic extract |
intranasal application in asthma mouse model | ||
pomegranate peel extract, punicalin | ↓ IL-1β, IL-5, inflammatory cell infiltration in lung, | mucous glycoprotein secretion |
SARS-CoV-2[64] | ||||
binds to SARS-CoV-2 S-glycoprotein and inhibits | binding to ACE2 | [91] | pomegranate peel extract | ||||
Rhodiola rosea | neutrophil culture and LPS-stimulated mice | extractx MPO activity in neutrophils, ↓ lung invasion of inflammatory cells |
[87] | ||||
Ebola | inhibits viral entry in cells | 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] | ||||
[ | 20 | ] | |||||
punicalagin and Zn(II) | SARS-CoV-2 | inhibition of 3CL protease, synergistic effect with Zn(II) | [92] | ||||
chebulagic acid, punicalagin |
SARS-CoV-2 | non-competitive inhibition of 3CL protease | [93] | ||||
HSV-1 | inhibits viral entry in cells and cell-to-cell spread via viral glycoprotein and host glucosaminoglycans interaction |
[25] | |||||
HCMV HCV DENV MV RSV |
inhibits viral attachment to cells | [94] | HSV-1 infected mice | ↓ numbers of inflammatory cells in the brain, ↓ neuronal degeneration and interstitial edema | |||
geraniin | SARS-CoV-2 | binds SARS-CoV-2 S-glycoprotein receptor binding domain |
[95] | 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] |
corilagin | SARS-CoV-2 | binds to SARS-CoV-2 S-glycoprotein and inhibits binding to ACE2 |
[96] | Jurkat cells | T cell activation by NFAT | ||
[ | 88 | ] | |||||
SARS-CoV-2 | inhibits activity of RNA-dependent RNA polymerase nsp12 | [ | 97] | activated CD4+ murine splenic lymphocytes | ↓ IL-2 mRNA and protein | ||
ellagic acid | Zika | hypothetical interaction with cell surface to prevent viral infection |
[24] | PMA-induced ear edema in mice | ↓ hyperplasia and inflammatory cell infiltration | ||
HIV-1 | blocks viral integrase but not protease | [98] | LPS-induced RAW264.7 macrophages | ↓ TLR4 expression, ↓ IL-1β, IL-6, TNFα, NO, PGE2, ROS production, x nuclear translocation of NFκB nuclear translocation |
[70] | ||
HRV2 HRV3 |
reduces viral proliferation in cells | [23] | ellagic acid | human aorta endothelial cells (HAEC) | ↓ TNFα-induced VCAM1 and ICAM1 expression | [80] | |
HBV | blocks HBeAg secretion from cells | [99] | KS483 osteoblastic cells line | nodule formation induced | |||
Ebola | inhibits viral entry in cells | 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] | |||
[ | 20 | ] | 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] |
Compound Tested | Viral Target | Molecular Mechanism | References |
---|---|---|---|
ellagic acid | influenza A | synergistic effect on antioxidant defenses with oseltamivir and isoprinosine |
[21] |
pomegranate polyphenol extract, punicalagin |
influenza A | ||