Next Article in Journal
Protoflavone-Chalcone Hybrids Exhibit Enhanced Antitumor Action through Modulating Redox Balance, Depolarizing the Mitochondrial Membrane, and Inhibiting ATR-Dependent Signaling
Previous Article in Journal
Comparative Studies on Different Citrus Cultivars: A Revaluation of Waste Mandarin Components
Open AccessArticle

Nrf2 Activator PB125® as a Potential Therapeutic Agent against COVID-19

1
Pathways Bioscience, Aurora, CO 80045, USA
2
Department of Medicine, Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
*
Author to whom correspondence should be addressed.
Antioxidants 2020, 9(6), 518; https://doi.org/10.3390/antiox9060518
Received: 15 May 2020 / Revised: 4 June 2020 / Accepted: 10 June 2020 / Published: 12 June 2020
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
Nrf2 is a transcription factor that regulates cellular redox balance and the expression of a wide array of genes involved in immunity and inflammation, including antiviral actions. Nrf2 activity declines with age, making the elderly more susceptible to oxidative stress-mediated diseases, which include type 2 diabetes, chronic inflammation, and viral infections. Published evidence suggests that Nrf2 activity may regulate important mechanisms affecting viral susceptibility and replication. We examined gene expression levels by GeneChip microarray and by RNA-seq assays. We found that the potent Nrf2-activating composition PB125® downregulates ACE2 and TMPRSS2 mRNA expression in human liver-derived HepG2 cells. ACE2 is a surface receptor and TMPRSS2 activates the spike protein for SARS-CoV-2 entry into host cells. Furthermore, in endotoxin-stimulated primary human pulmonary artery endothelial cells, we report the marked downregulation by PB125 of 36 genes encoding cytokines. These include IL-1-beta, IL-6, TNF-α, the cell adhesion molecules ICAM-1, VCAM-1, and E-selectin, and a group of IFN-γ-induced genes. Many of these cytokines have been specifically identified in the “cytokine storm” observed in fatal cases of COVID-19, suggesting that Nrf2 activation may significantly decrease the intensity of the storm. View Full-Text
Keywords: Nrf2; SARS-CoV-2; coronavirus; COVID-19; ALI; cytokine storm; NFE2L2; TMPRSS2; HDAC5; LIF; CXCL10; ACE2 Nrf2; SARS-CoV-2; coronavirus; COVID-19; ALI; cytokine storm; NFE2L2; TMPRSS2; HDAC5; LIF; CXCL10; ACE2
Show Figures

Graphical abstract

MDPI and ACS Style

McCord, J.M.; Hybertson, B.M.; Cota-Gomez, A.; Geraci, K.P.; Gao, B. Nrf2 Activator PB125® as a Potential Therapeutic Agent against COVID-19. Antioxidants 2020, 9, 518.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop