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Effects of vitamin C on protein expression of NF-κB p65 in CORT-treated A549 cells. NF-κB p65 levels in A549 cells were determined by western blotting and normalized by β-actin. Significant difference from the normal group at P # # < 0.01 and from the CORT group at P * * < 0.01 .
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It is well known that vitamin C could protect against influenza infection, but little is known about the mechanisms. This study aimed to investigate the influence and possible mechanisms of vitamin C on pneumonia induced by influenza virus in stressed mice. Results showed that restraint stress significantly increased the mortality and the severity...
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Citations
... In vitro studies on different inflammatory environments have shown that vitamin C acts against pro-inflammatory cytokines in two different ways. In its reduced form as an ascorbate, it can directly scavenge ROS inhibiting ROS-mediated NF-κB signaling [205,206], while in its oxidized form as a dehydroascorbate produced following the ROS scavenging mechanism, it inhibits the kinase activity involved in the NF-κB pathway, such as that of IκBα and β, and in the MAPK cascade, such as that of P38 kinase [207][208][209][210]. However, it has been shown that the effect of vitamin C as an antiinflammatory molecule is dependent on the cell type and organ involved, interfering with different molecular pathways in various health conditions. ...
Respiratory viral diseases are among the most important causes of disability, morbidity, and death worldwide. Due to the limited efficacy or side effects of many current therapies and the increase in antiviral-resistant viral strains, the need to find new compounds to counteract these infections is growing. Since the development of new drugs is a time-consuming and expensive process, numerous studies have focused on the reuse of commercially available compounds, such as natural molecules with therapeutic properties. This phenomenon is generally called drug repurposing or repositioning and represents a valid emerging strategy in the drug discovery field. Unfortunately, the use of natural compounds in therapy has some limitations, due to their poor kinetic performance and consequently reduced therapeutic effect. The advent of nanotechnology in biomedicine has allowed this limitation to be overcome, showing that natural compounds in nanoform may represent a promising strategy against respiratory viral infections. In this narrative review, the beneficial effects of some promising natural molecules, curcumin, resveratrol, quercetin, and vitamin C, which have been already studied both in native form and in nanoform, against respiratory viral infections are presented and discussed. The review focuses on the ability of these natural compounds, analyzed in in vitro and in vivo studies, to counteract inflammation and cellular damage induced by viral infection and provide scientific evidence of the benefits of nanoformulations in increasing the therapeutic potential of these molecules.
... Intravenous AA administration has been successfully used (complete clinical recovery) in the treatment of viral encephalitis (Klenner, 1949;Klenner, 1951, Klenner 1953), viral pneumonia and bronchitis (Dalton 1962), measles (Joffe, 1983), mumps (Karam, 1953), Herpes (Zureick, 1950), influenza (Cai, 2015) and rabies in guinea pigs (Banic,1975). Human case reports have also supported that the intravenous administration of AA is useful in the treatment of influenza (Vilchèze et al., 2018) mononucleosis (Mikir ova, 2014), chikungunya (Marcial-Vega, 2015, Adrover, 2015, Zika (Gonzalez, 2016), and SARS COV-2 (Gonzalez, 2020). ...
Vitamin C, Ascorbic acid (AA) is an essential water-soluble nutrient involved in many physiologic functions such as energy metabolism, neurotransmitter synthesis, tissue repair, immune function, and the regeneration and the recycling of many molecules. The physiological need for this nutrient can vary widely and is increased in the presence of physiological stress such as trauma, infection, inflammation, increased toxin load, chemotherapy, radiotherapy, and diseases such as diabetes and cancer. It has been found that low plasma levels of ascorbate often correlate with increased severity of disease and symptoms. In addition, it has been reported that when ascorbic acid is given at supraphysiologic levels, a variety of pharmacologic effects can be observed. In-vitro and in-vivo clinical research has allowed us to understand some of the mechanisms involved and even correlate concentrations to effect. Recent reports suggest that, even in high-income countries like the United States, a considerable proportion of the population have inadequate levels. Given the prevalence of ascorbate insufficiency and its role in maintaining homeosta-sis and tissue repair, it is important to evaluate plasma levels to properly assess the patient's health. This assessment could be useful to optimize outcomes by providing the nutritional and pharmacologic benefits of AA as needed. We present a guide to the interpretation of plasma ascorbate. This guide includes seven levels with the corresponding descriptor, intake levels, and plasma concentrations to facilitate clinical decisions pertaining to intravenous Ascorbic Acid therapy.
... La administración intravenosa de AA se ha utilizado con éxito (recuperación clínica completa) en el tratamiento de la encefalitis viral (Klenner, 1949;Klenner, 1951, Klenner 1953, neumonía y bronquitis virales (Dalton 1962), sarampión (Joffe, 1983 , paperas (Karam, 1953), Herpes (Zureick, 1950), influenza (Cai, 2015) y rabia en cobayas (Banic, 1975). Reportes de casos humanos también han apoyado que la administración intravenosa de AA es útil en el tratamiento de influenza (Vilchèze et al., 2018) mononucleosis (Mikirova, 2014), chikungunya (Marcial Vega, 2015, Adrover, 2015, Zika ( González, 2016), y SARS COV-2 (González, 2020). ...
La investigación clínica in vitro e in vivo nos ha permitido comprender algunos de los mecanismos involucrados e incluso correlacionar las concentraciones con el efecto. Informes recientes sugieren que, incluso en países de altos ingresos como losEstados Unidos, una proporción considerable dela población tiene niveles inadecuados. Dada laprevalencia de la insuficiencia de ascorbato y su papel en el mantenimiento de la homeostasis y la reparación tisular, es importante evaluar los niveles plasmáticos para evaluar adecuadamente la salud del paciente. Esta evaluación podría ser útil para optimizar los resultados al proporcionar los beneficios nutricionales y farmacológicos de AA segúnsea necesario. Presentamos una guía para la interpretación del ascorbato plasmático. Esta guía incluye siete niveles con el correspondiente descriptor, niveles de ingesta y concentraciones plasmáticaspara facilitar las decisiones clínicas relacionadascon la terapia con ácido ascórbico intravenoso.
... According to clinical trials 1 g/day of VitC increases PMBC secretion of IL-10 to control inflammatory (Shakoor et al. 2020). VitC also has a mechanism of action against influenza caused by the H1N1 virus; administration of 125-250 mg/kg decreased the lethality of the virus in animals and upregulates the mitochondrial antiviral response (Cai et al. 2015). The intravenous administration of VitC alone or in combination with other drugs has also been promoted for the therapeutic management of different types of cancer (Boretti and Banik 2020). ...
The immune system is a complex assembly of coordinated cells to maintain human health. Nowadays, there is a growing interest in maintaining the immune system in proper conditions to counteract noncommunicable chronic diseases, harmful entities (toxic xenobiotics, allergens, and microbial pathogens), cancer, and emerging infectious and autoimmune diseases that currently affect health systems worldwide. Adequate human nutrition is essential for the maintenance and modulation of the immune system. This is due to the different functional ingredients that can be found in food matrices such as fruits, vegetables, dairy products, meat, cereals, and oils. Among these, polyphenolic antioxidants, vitamins, probiotics, prebiotics, and peptides can be highlighted. All the above dietary functional ingredients act as immunomodulators since they have a direct or indirect immunostimulatory response by interacting with immune cells and triggering stimulating responses for antibodies and anti-inflammatory cytokine and chemokine secretions but also for suppressing pro-inflammatory cytokines. Therefore, these immunomodulator compounds have been considered as adjuvants in the prevention and treatment of some infectious diseases and some others related to autoimmunity.
... On the other hand, vitamin C has been demonstrated to enhance the expression of several ISG, including MDA-5 and RIG-I, which are involved in the viral dsRNA recognition; and Mx1, a protein that interferes with the viral polymerase activity of the influenza virus [137][138][139]. However, the antiviral response influenced by this vitamin could be an indirect effect since it has been reported that it preserves mitochondrial functions [140,141] and prevent the decrease of the mitochondrial antiviral signal-protein (MAVS) induced by influenza virus infection in mice [142]. MAVS is an outer mitochondrial membrane protein necessary to anchor MDA-5 and RIG-I during their activation for IFN-I production [143]. ...
Viral respiratory infections could range from a common cold to severe pneumonia, and their resolution mainly relies on appropriate immune system function. The widespread popular knowledge that nutritional habits influence immune system function has been demonstrated over the past decades in which increasing scientific evidence unveils certain nutrients as critical drivers of immunity. Micronutrients encompass minerals and vitamins necessary for a broad range of biological processes; since their deficiency could cause several clinical manifestations, such as weakness, growth retardation, and susceptibility to infections; hence, micronutrients represent one of the multiple factors that modulate immune function. Among micronutrients are those that act mainly as antioxidants, regulating gene expression and as a structural part of proteins for their proper function. Here, we review how some of the most recognized micronutrients are participating at the molecular level in each step of the innate and adaptive immune response against viruses focusing on viral respiratory tract infections, such as those caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).
... The effect of ascorbic acid was confirmed in an ex vivo model by an independent interaction with protein complexes in the electron transport chain to stabilize the function of the isolated lung by preserving mitochondrial activity [62]. Furthermore, ascorbic acid was found to reduce capillary-alveolar damage and mortality in restraint-stressed mice with H1N1 viral-induced pneumonia [63]. This explains the possibility of ascorbic acid in improving the clinical status of COVID-19 patients. ...
Current evidence suggests that ascorbic acid improves the host’s immune system and, therefore, may play a role in reducing the severity of infectious diseases. Coronavirus disease 2019 (COVID-19) is a potentially life-threatening viral infection that mainly infects the lungs. The objective of this review was to synthesize the existing findings from studies related to the effect of intravenous ascorbic acid on lung function in COVID-19 patients. For this review, PubMed, Cochrane, SCOPUS, EMBASE, Clinical Trial Registry, and Google Scholar databases were searched from December 2019 to May 2022. There was a total of six studies that investigated the large dose of ascorbic acid infusion intravenously on lung function in severely ill subjects with COVID-19. Out of six, three studies found that high-dose intravenous ascorbic acid improved lung function markers, and three studies found null results. Infusions of 12 g/d and 24 g/d of intravenous ascorbic acid had shown a significant improvement in lung function markers in two clinical trials. Studies that administered 8 g/d, 2 g/d, and 50 mg/kg/d of intravenous ascorbic acid found no influence on mechanical ventilation need and other lung function markers in critically ill subjects with COVID-19. Overall, the effect of intravenous ascorbic acid on the lung function of subjects with COVID yielded equivocal findings. More double-blinded, randomized, clinical studies with a larger sample size are required to confirm the effect of ascorbic acid in ameliorating the lung pathologies associated with COVID infection.
... These changes can lead to antiviral effects. NF-κB is a member of transcription factors that participate in inflammasome regulation, differentiation of innate immune cells, and induces the expression of different pro-inflammatory genes [99]. Based on the evidence from the mentioned clinical studies, it can be concluded that vitamin C can be helpful in the treatment of respiratory and other viral infections. ...
COVID-19 is a rapidly spreading disease, which has caught the world by surprise. Millions of people suffer from illness, and the mortality rates are dramatically high. Currently, there is no specific and immediate treatment for this disease. Remedies are limited to supportive regiments and few antiviral and anti-inflammatory drugs. The lack of a definite cure for COVID-19 is the reason behind its high mortality and global prevalence. COVID-19 can lead to a critical illness with severe respiratory distress and cytokine release. Increased oxidative stress and excessive production of inflammatory cytokines are vital components of severe COVID-19. Micronutrients, metalloids, and vitamins such as iron, manganese, selenium, Zinc, Copper, vitamin A, B family, and C are among the essential and trace elements that play a pivotal role in human nutrition and health. They participate in metabolic processes that lead to energy production. In addition, they support immune functions and act as antioxidants. Therefore, maintaining an optimal level of micronutrients intake, particularly those with antioxidant activities, is essential to fight against oxidative stress, modulate inflammation, and boost the immune system. Therefore, these factors could play a crucial role in COVID-19 prevention and treatment. In this review, we aimed to summarize antiviral properties of different vitamins and minerals. Moreover, we will investigate the correlation between them and their effects in COVID-19 patients.
... The VC-mediated reduction of ROS prevents ROS-induced lung damage in the course of viral infections [125,145]. Increased survival associated with AA treatment was observed by Valero et al. [146] in mice infected with the Venezuelan equine encephalitis virus and by Cai et al. [147] in restraint-stressed mice infected with the H1N1 virus. ...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still spreading worldwide. For this reason, new treatment methods are constantly being researched. Consequently, new and already-known preparations are being investigated to potentially reduce the severe course of coronavirus disease 2019 (COVID-19). SARS-CoV-2 infection induces the production of pro-inflammatory cytokines and acute serum biomarkers in the host organism. In addition to antiviral drugs, there are other substances being used in the treatment of COVID-19, e.g., those with antioxidant properties, such as vitamin C (VC). Exciting aspects of the use of VC in antiviral therapy are its antioxidant and pro-oxidative abilities. In this review, we summarized both the positive effects of using VC in treating infections caused by SARS-CoV-2 in the light of the available research. We have tried to answer the question as to whether the use of high doses of VC brings the expected benefits in the treatment of COVID-19 and whether such treatment is the correct therapeutic choice. Each case requires individual assessment to determine whether the positives outweigh the negatives, especially in the light of populational studies concerning the genetic differentiation of genes encoding the solute carriers responsible forVC adsorption. Few data are available on the influence of VC on the course of SARS-CoV-2 infection. Deducing from already-published data, high-dose intravenous vitamin C (HDIVC) does not significantly lower the mortality or length of hospitalization. However, some data prove, among other things, its impact on the serum levels of inflammatory markers. Finally, the non-positive effect of VC administration is mainly neutral, but the negative effect is that it can result in urinary stones or nephropathies.
... Previously, a new function for the effects of vitamin C on influenza virus-induced pneumonia was shown in restraint-stressed mice. The results showed that restraint stress considerably enhanced the mortality and severity of respiratory illness in mice infected with A/FM/1/47(H1N1) and manifestation of the disease was attenuated by oral administration of vitamin C (125 and 250 mg/kg) [49]. Available studies on the beneficial effects of using ascorbic acid (vitamin C) during the course of IAV infection are based on the retrospective observational studies, which have shown that vitamin C reduces morbidity during influenza pandemics and it can decrease seasonal influenza outbreaks [50]. ...
Background
Influenza A virus (IAV) infection remains a serious public health threat. Due to drug resistance and side effects of the conventional antiviral drugs, repurposing the available natural compounds with high tolerability and fewer side effects has attracted researchers’ attention. The aim of this study was to screen in vitro anti-influenza activity of three anionic compounds ascorbate, acetate, and citrate.
Methods
The non-cytotoxic concentration of the compounds was determined by MTT assay and examined for the activity against IAV in simultaneous, pre-, and post-penetration combination treatments over 1 h incubation on Madin-Darby Canine Kidney (MDCK) cell line. The virus titer and viral load were determined using hemagglutination assay (HA) and qPCR, respectively. Few pro-inflammatory and anti-inflammatory cytokines were evaluated at RNA and protein levels by qPCR and ELISA, respectively.
Results
The non-cytotoxic concentrations of the ascorbate (200 mg/ml), acetate and citrate (both 3 mg/ml) reduced the viral titer by 6.5, 4.5, and 1.5 logs in the simultaneous combination treatment. The M protein gene copy number decreased significantly in simultaneous treatment ( P < 0.01). The expression of cytokines was also affected by the treatment of these compounds.
Conclusions
These anionic compounds could affect the influenza virus load, thereby reducing pro-inflammatory cytokines and increasing anti-inflammatory cytokines levels.
... Aside from that, ascorbic acid influences the differentiation and growth of both natural killer and T-cells [67,68]. Previous studies revealed that the administration of vitamin C (125 and 250 mg/kg) to mice is connected with enhanced survival rates as well as a prolongation of the time surviavl. ...
... Aside from that, vitamin C has been shown to lower the levels of proinflammatory cytokines four days following an infection. They reached the conclusion that vitamin C could prevent influenza virus infection and subsequent pneumonia in a restraint-stressed mouse model by acting as an antiviral [68]. It has been demonstrated that vitamin C can lessen the likelihood of the formation of a cytokine storm during the late stage of COVID-19 in some patients [69,70].Patients with moderate (10 g daily) and severe (20 g daily) COVID-19 may also benefit from high doses of intravenous vitamin C, which may help them improve their clinical outcomes. ...
Vitamin C stands as an essential water-soluble vitamin, antioxidant and has been shown to enhance immunity. SARS-CoV-2 has been spreading rapidly across the worldwide, several cellular processes of innate and adaptive immunity are aided by vitamin C, which strengthens the immune system overall. Multiple lines of evidence in the literature associate vitamin C with antioxidant, anti-inflammatory, anticoagulant and immunomodulatory actions. Pneumonia and sepsis patients had poor ascorbic acid status and high oxidative stress, according to many studies. Pneumonia patients who get vitamin C may have less severe symptoms and a longer course of the illness if they do. To standardize plasma levels in sepsis patients, gram measurements of the vitamin must be administered intravenously (IV). This intervention has been shown in a few trials to reduce mortality. COVID-19 management in China and the United States has exhibited remarkable results when using a high percentage of intravenous vitamins C. It's acceptable to include vitamin C in the COVID-19 treatment protocol as a secondary measure based on the current active clinical studies looking at the impact of vitamin C on the management of COVID-19. Patients with hypovitaminosis C or severe respiratory illnesses, such as COVID-19, may benefit from taking vitamin C, due to its good safety profile, simplicity of use, and potential for rapid production scaling. The study's goal was to see whether high dosage intravenous vitamin C had any impact on individuals with severe COVID-19 (HDIVC). Finally we discuss recent research that has been published on the efficacy of vitamin C administration in the treatment of viral infection and life-threatening conditions. The purpose of this manuscript is to summarise existing research on the efficacy of vitamin C as a treatment for COVID-19 and to discuss possible explanations for why it may work in some individuals but not in others.
