NLRP3 inflammasome activation and oxidative stress status in the mild and moderate SARS-CoV-2 infected patients: impact of melatonin as a medicinal supplement

Abstract

The inflammasome as a multiprotein complex has a role in activating ASC and caspase-1 resulting in activating IL-1β in various infections and diseases like corona virus infection in various tissues. It was shown that these tissues are affected by COVID-19 patients. According to the current evidence, melatonin is not veridical while possessing a high safety profile, however, it possesses indirect anti-viral actions owing to its anti-oxidation, anti-inflammation, and immune improving properties. This study aims to assess the impacts of melatonin as the complementary treatments on oxidative stress agents and inflammasome activation in patients with COVID-19. Melatonin supplement (9 mg daily, orally) was provided for the patients hospitalized with a COVID-19 analysis for 14 days. For measuring IL-10, IL-1β, and TNF-α cytokines and malondialdehyde (MDA), nitric oxide (NO), and superoxide dismutase (SOD) level and the expression of CASP1 and ASC genes, blood samples were gathered from the individuals at the start and termination of the therapy. Our findings indicated that melatonin is used as a complementary treatment to reduce the levels of TNF-α and IL-1β cytokines, MDA, and NO levels in COVID-19 patients and significantly increase SOD level, however, the levels of IL-10 cytokine possesses no considerable changes. The findings revealed that genes of CASP1 and ASC were dysregulated by melatonin regulating the inflammasome complex. Based on the findings of the current study, it is found that melatonin can be effective as a medicinal supplement in decreasing the inflammasome multiprotein complex and oxidative stress along with beneficial impacts on lung cytokine storm of COVID-19 patients.

Differential Co-Expression Network Analysis Reveals Key Hub-High Traffic Genes as Potential Therapeutic Targets for COVID-19 Pandemic

“…Besides, activation of CASP1 promotes pyroptosis (a highly inflammatory and Caspase-1-dependent form of programmed cell death), which can lead to secretion of a wide range of inflammatory mediators ( 241 , 242 ). Melatonin suppressed the lung cytokine storm in COVID-19 patients by reducing CASP1 expression ( 243 ).…”

Melatonin: highlighting its use as a potential treatment for SARS-CoV-2 infection

“…Since the classification of SARS-CoV-2 infection as a pandemic, in excess of 140 publications have urged consideration of melatonin as a safe and potentially effective treatment for this worldwide disease [1][2][3][4][5][6][7][8][9][10][11][12][13]. The rationale for its use not only stems from its high safety profile [14][15][16] but also from its multiple beneficial actions in experimental and clinical studies related to the pandemic.…”

Potential benefits of ginseng against COVID-19 by targeting inflammasomes

“…The effect of SARS-CoV-2 infection has also been demonstrated in blood cells and circulating monocytes of COVID-19 patients. The NLRP3 inflammasome is triggered in blood cells of COVID-19 patients, leading to elevated levels of proinflammatory cytokines in serum [ 37 ]. SARS-CoV-2 also initiates the NLRP3 inflammasome in circulating monocytes of COVID-19 patients, resulting in pyroptotic death of circulating monocytes and secretion of pro-inflammatory cytokines from the cells [ 38 , 39 ].…”

“… Types Roles Activators/inhibitors Models Ref. NLRP3 Activation SARS-CoV-2 spike protein Caco-2 [ 24 ] SARS-CoV-2 viroporin HEK293 & A549 [ 25 ] SARS-CoV-2 single-stranded RNA Macrophages [ 26 ] SARS-CoV-2 envelope protein BMDMs [ 27 ] SARS-CoV-2 nucleocapsid protein BMDMs & THP-1 [ 28 ] SARS-CoV-2 spike protein PBMCs [ 30 ] SARS-CoV-2 spike protein HSPCs & EPCs [ 31 ] SARS-CoV-2 spike protein HSPCs & EPCs [ 34 ] SARS-CoV-2 NSP6 Lung epithelial cells of COVID-19 patients [ 35 ] SARS-CoV-2 Blood cells of COVID-19 patients [ 37 ] SARS-CoV-2 Circulating monocytes of COVID-19 patients [ 38 ] SARS-CoV-2 Circulating monocytes of COVID-19 patients [ 39 ] SARS-CoV-2 spike protein BV-2 [ 42 ] SARS-CoV-2 Cerebral cortical tissues of COVID-19 patients [ 43 ] SARS-CoV-2 Aged COVID-19 patients [ 46 ] Inhibition SARS-CoV-2 NSP1 and NSP13 HEK293 & THP-1 [ 29 ] …”