Graphical abstract Highlights • CS triggered by excessive inflammatory response drives the pathogenesis of COVID-19. • ASX inhibits TNFα, IL1β, IL6 via regulation of NF-kB & JAK/STAT; prevents CS & ALI/ARDS. • ASX suppresses plasma CRP, iNOS, COX2, PGE2 & ICAM-1; prevents oxidative damages. • ASX inhibits NLRP3, HIF1α, activates Nrf2, Sirtuin pathways; exerts antioxidant effect. • ASX enhances immune responses, NK cell activity, T- & B- cell population. Host excessive inflammatory immune response to SARS-CoV-2 infection is thought to underpin the pathogenesis of COVID-19 associated severe pneumonitis and acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Once an immunological complication like cytokine storm occurs, anti-viral based monotherapy alone is not enough. Additional anti-inflammatory treatment is recommended. It must be noted that anti-inflammatory drugs such as JAK inhibitors, IL-6 inhibitors, TNF-α inhibitors, colchicine, etc., have been either suggested or are under trials for managing cytokine storm in COVID-19 infections. Natural astaxanthin (ASX) has a clinically proven safety profile and has antioxidant, anti-inflammatory, and immunomodulatory properties. There is evidence from preclinical studies that supports its preventive actions against ALI/ARDS. Moreover, ASX has a potent PPARs activity. Therefore, it is plausible to speculate that ASX could be considered as a potential adjunctive supplement. Here, we summarize the mounting evidence where ASX is shown to exert protective effect by regulating the expression of pro-inflammatory factors IL-1β, IL-6, IL-8 and TNF-α. We present reports where ASX is shown to prevent against oxidative damage and attenuate exacerbation of the inflammatory responses by regulating signaling pathways like NF-ĸB, NLRP3 and JAK/STAT. These evidences provide a rationale for considering natural astaxanthin as a therapeutic agent against inflammatory cytokine storm and associated risks in COVID-19 infection and this suggestion requires further validation with clinical studies.
【저자키워드】 COVID-19, Cytokine storm, acute respiratory distress syndrome, Anti-inflammatory, antioxidant, GM-CSF, granulocyte-macrophage colony-stimulating factor, MCP, monocyte chemoattractant protein, MIP, macrophage inflammatory protein, CRP, C-reactive protein, TNF, Tumor Necrosis Factor, MSCs, mesenchymal stem cells, NO, Nitric Oxide, TGF, Transforming growth factor, LDH, lactate dehydrogenase, VEGF, Vascular endothelial growth factor, HGF, Hepatocyte Growth Factor, MAPK, Mitogen-activated protein kinase, astaxanthin, G-CSF, granulocyte colony-stimulating factor, COX-2, cyclooxygenase-2, LPS, lipopolysaccharide, MMPs, matrix metalloproteinases, PDGF, platelet-derived growth factor, GSH, glutathione, IL-1RA, interleukin-1 receptor antagonist, MPO, myeloperoxidase, SOD, Superoxide dismutase, ICAM-1, Intercellular Adhesion Molecule-1, ALT, alanine transaminase, AST, aminotransferase, CCL-3, chemokine (C-C motif) ligand 3, dsRNA, double stranded ribonucleic acid, FOXO3, forkhead box O3 gene, HCFs, human cardiac fibroblasts, HDAC4, histone deacetylase 4, HIF-1α, hypoxia inducible factor 1α, IkB, inhibitor nuclear factor-kappa B, LFA-1, leukocyte function antigen 1, M-CSF, macrophage colony-stimulating factor, MDA, malondialdehyde, NT, nitrotyrosine, PGE2, prostaglandin E2, PPARs, peroxisome proliferator-activated receptors,