Nutraceutical Strategies for Suppressing NLRP3 Inflammasome Activation: Pertinence to the Management of COVID-19 and Beyond

The Coronavirus Disease 2019 (COVID-19) pandemic has become a global crisis and is more devastating than any other previous infectious disease. It has affected a significant proportion of the global population both physically and mentally, and destroyed businesses and societies. Current evidence suggested that immunopathology may be responsible for COVID-19 pathogenesis, including lymphopenia, neutrophilia, dysregulation of monocytes and macrophages, reduced or delayed type I interferon (IFN-I) response, antibody-dependent enhancement, and especially, cytokine storm (CS). The CS is characterized by hyperproduction of an array of pro-inflammatory cytokines and is closely associated with poor prognosis. These excessively secreted pro-inflammatory cytokines initiate different inflammatory signaling pathways via their receptors on immune and tissue cells, resulting in complicated medical symptoms including fever, capillary leak syndrome, disseminated intravascular coagulation, acute respiratory distress syndrome, and multiorgan failure, ultimately leading to death in the most severe cases. Therefore, it is clinically important to understand the initiation and signaling pathways of CS to develop more effective treatment strategies for COVID-19. Herein, we discuss the latest developments in the immunopathological characteristics of COVID-19 and focus on CS including the current research status of the different cytokines involved. We also discuss the induction, function, downstream signaling, and existing and potential interventions for targeting these cytokines or related signal pathways. We believe that a comprehensive understanding of CS in COVID-19 will help to develop better strategies to effectively control immunopathology in this disease and other infectious and inflammatory diseases.

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“…Several studies have shown that NLRP3 inflammasome is a potential therapeutic target for COVID-CS. 164 , 348 , 349 …”

Section: Blockade Of Signaling Pathwaysmentioning

confidence: 99%

The signal pathways and treatment of cytokine storm in COVID-19

Yang

Xie

et al. 2021

Sig Transduct Target Ther

466

413

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“…These include polyphenols, lipid extracts, and tomato-based nutraceuticals, all of which have been suggested for the potential prevention of cardiovascular complications of COVID-19, such as thrombosis (32,69). Melatonin is another supplement that has been identified as a potential antiviral agent against SARS-CoV-2 by computational methods (235), and it has also been highlighted as a potential therapeutic agent for COVID-19 due to its documented antioxidant, antiapoptotic, immunomodulatory, and anti-inflammatory effects (69,236,237). Notably, melatonin, vitamin D, and zinc have attracted public attention because they were included in the treatment plan of the former president of the United States upon his hospitalization due to COVID-19 (238).…”

Section: Discussionmentioning

confidence: 99%

Dietary Supplements and Nutraceuticals under Investigation for COVID-19 Prevention and Treatment

2021

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Coronavirus disease 2019 (COVID-19) has caused global disruption and a significant loss of life. Existing treatments that can be repurposed as prophylactic and therapeutic agents may reduce the pandemic’s devastation. Emerging evidence of potential applications in other therapeutic contexts has led to the investigation of dietary supplements and nutraceuticals for COVID-19. Such products include vitamin C, vitamin D, omega 3 polyunsaturated fatty acids, probiotics, and zinc, all of which are currently under clinical investigation. In this review, we critically appraise the evidence surrounding dietary supplements and nutraceuticals for the prophylaxis and treatment of COVID-19. Overall, further study is required before evidence-based recommendations can be formulated, but nutritional status plays a significant role in patient outcomes, and these products may help alleviate deficiencies. For example, evidence indicates that vitamin D deficiency may be associated with a greater incidence of infection and severity of COVID-19, suggesting that vitamin D supplementation may hold prophylactic or therapeutic value. A growing number of scientific organizations are now considering recommending vitamin D supplementation to those at high risk of COVID-19. Because research in vitamin D and other nutraceuticals and supplements is preliminary, here we evaluate the extent to which these nutraceutical and dietary supplements hold potential in the COVID-19 crisis. IMPORTANCE Sales of dietary supplements and nutraceuticals have increased during the pandemic due to their perceived “immune-boosting” effects. However, little is known about the efficacy of these dietary supplements and nutraceuticals against the novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) or the disease that it causes, CoV disease 2019 (COVID-19). This review provides a critical overview of the potential prophylactic and therapeutic value of various dietary supplements and nutraceuticals from the evidence available to date. These include vitamin C, vitamin D, and zinc, which are often perceived by the public as treating respiratory infections or supporting immune health. Consumers need to be aware of misinformation and false promises surrounding some supplements, which may be subject to limited regulation by authorities. However, considerably more research is required to determine whether dietary supplements and nutraceuticals exhibit prophylactic and therapeutic value against SARS-CoV-2 infection and COVID-19. This review provides perspective on which nutraceuticals and supplements are involved in biological processes that are relevant to recovery from or prevention of COVID-19.

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“…Several nutraceuticals may also suppress the contribution of NLRP3 inflammasomes to many inflammation-linked pathologies. Amongst them are lipoic acid, ferulic acid, melatonin, phycocyanobilin, berberine, N-acetylcysteine, glucosamine, taurine, folate, vitamin B12, and betaine [ 159 ]. There are also reports suggesting that some plant-derived compounds and Chinese herbal medicines have a neuroprotective effect in treating AD by attenuating the activation of the NLRP3 inflammasome pathway [ 160 ].…”

Section: Inflammasomes As a Possible Link Between Inflammation-associated Peripheral And Brain Insulin Resistance In Metabolic Disease Anmentioning

confidence: 99%

Inflammasome NLRP3 Potentially Links Obesity-Associated Low-Grade Systemic Inflammation and Insulin Resistance with Alzheimer’s Disease

Litwiniuk

Bik

Kalisz

et al. 2021

IJMS

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Alzheimer’s disease (AD) is the most common form of neurodegenerative dementia. Metabolic disorders including obesity and type 2 diabetes mellitus (T2DM) may stimulate amyloid β (Aβ) aggregate formation. AD, obesity, and T2DM share similar features such as chronic inflammation, increased oxidative stress, insulin resistance, and impaired energy metabolism. Adiposity is associated with the pro-inflammatory phenotype. Adiposity-related inflammatory factors lead to the formation of inflammasome complexes, which are responsible for the activation, maturation, and release of the pro-inflammatory cytokines including interleukin-1β (IL-1β) and interleukin-18 (IL-18). Activation of the inflammasome complex, particularly NLRP3, has a crucial role in obesity-induced inflammation, insulin resistance, and T2DM. The abnormal activation of the NLRP3 signaling pathway influences neuroinflammatory processes. NLRP3/IL-1β signaling could underlie the association between adiposity and cognitive impairment in humans. The review includes a broadened approach to the role of obesity-related diseases (obesity, low-grade chronic inflammation, type 2 diabetes, insulin resistance, and enhanced NLRP3 activity) in AD. Moreover, we also discuss the mechanisms by which the NLRP3 activation potentially links inflammation, peripheral and central insulin resistance, and metabolic changes with AD.

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Nutraceutical Strategies for Suppressing NLRP3 Inflammasome Activation: Pertinence to the Management of COVID-19 and Beyond

Cited by 39 publications

References 279 publications

The signal pathways and treatment of cytokine storm in COVID-19

The signal pathways and treatment of cytokine storm in COVID-19

Dietary Supplements and Nutraceuticals under Investigation for COVID-19 Prevention and Treatment

Inflammasome NLRP3 Potentially Links Obesity-Associated Low-Grade Systemic Inflammation and Insulin Resistance with Alzheimer’s Disease

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