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Nutraceuticals have potential for boosting the type 1 interferon response to RNA viruses including influenza and coronavirus
... In severe COVID-19 patients, the rise in the number of neutrophils is associated with the disease severity [6]. The production of high levels of proin ammatory cytokines leads to "cytokine storm" [2,7]. When the patient is admitted to the hospital, the disease is most likely to have advanced to the second or third stage, with respiratory problems and multiple organ failure. ...
... N-acetylcysteine (NAC) has been long employed to treat paracetamol (acetaminophen) poisoning caused [9] and as a mucolytic in chronic lung diseases. N-acetylcysteine is also an antioxidant and can reduce the oxidative stress [7] as a prodrug, acetylcysteine is transformed into L-cysteine [10], which is the precursor of the biological antioxidant, glutathione. Therefore, the administration of N-acetylcysteine renews glutathione sources. ...
This study aimed to compare the effects of N-acetylcysteine and Bromhexine on the recovery rate and prevention of hospitalization in outpatients with COVID-19. PCR-confirmed COVID-19 patients were divided into three groups: N-acetylcysteine group, Bromhexine group, and control group. Patients were followed up on the seventh and fourteenth days of the disease, and hospitalization and mortality rates were evaluated after one month. The study found that both N-acetylcysteine and Bromhexine can effectively reduce hospitalization rates and mortality and shorten the duration of hospitalization. The third visit of patients who received N-acetylcysteine showed an increase of 1.33% in oxygen saturation compared to their first visit, and in patients who received Bromhexine, this increase was 1.19%. The mortality rate was 9.33% in the control group and zero in both groups of patients who received medication. This study provides evidence for the early initiation of N-acetylcysteine and Bromhexine in outpatients with COVID-19. Clinical trial code: IRCT20220302054167N1, ethics code: IR.UMSHA.REC.1400.957.
... In severe COVID-19 patients, the rise in the number of neutrophils is associated with the disease severity [6]. The production of high levels of proin ammatory cytokines leads to "cytokine storm" [2,7]. When the patient is admitted to the hospital, the disease is most likely to have advanced to the second or third stage, with respiratory problems and multiple organ failure. ...
... N-acetylcysteine (NAC) has been long employed to treat paracetamol (acetaminophen) poisoning caused [9] and as a mucolytic in chronic lung diseases. N-acetylcysteine is also an antioxidant and can reduce the oxidative stress [7] as a prodrug, acetylcysteine is transformed into L-cysteine [10], which is the precursor of the biological antioxidant, glutathione. Therefore, the administration of N-acetylcysteine renews glutathione sources. ...
This study aimed to compare the effects of N-acetylcysteine and Bromhexine on the recovery rate and prevention of hospitalization in outpatients with COVID-19. PCR-confirmed COVID-19 patients were divided into three groups: N-acetylcysteine group, Bromhexine group, and control group. Patients were followed up on the seventh and fourteenth days of the disease, and hospitalization and mortality rates were evaluated after one month. The study found that both N-acetylcysteine and Bromhexine can effectively reduce hospitalization rates and mortality and shorten the duration of hospitalization. The third visit of patients who received N-acetylcysteine showed an increase of 1.33% in oxygen saturation compared to their first visit, and in patients who received Bromhexine, this increase was 1.19%. The mortality rate was 9.33% in the control group and zero in both groups of patients who received medication. This study provides evidence for the early initiation of N-acetylcysteine and Bromhexine in outpatients with COVID-19. Clinical trial code: IRCT20220302054167N1, ethics code: IR.UMSHA.REC.1400.957.
... In severe COVID-19 patients, the rise in the number of neutrophils is associated with the disease severity [6]. The production of high levels of proin ammatory cytokines leads to "cytokine storm" [2,7]. When the patient is admitted to the hospital, the disease is most likely to have advanced to the second or third stage, with respiratory problems and multiple organ failure. ...
... N-acetylcysteine (NAC) has been long employed to treat paracetamol (acetaminophen) poisoning caused [9] and as a mucolytic in chronic lung diseases. N-acetylcysteine is also an antioxidant and can reduce the oxidative stress [7] As a prodrug, acetylcysteine is transformed into L-cysteine [10], which is the precursor of the biological antioxidant, glutathione. Therefore, the administration of N-acetylcysteine renews glutathione sources. ...
This study aimed to compare the effects of N-acetylcysteine and Bromhexine on the recovery rate and prevention of hospitalization in outpatients with COVID-19. PCR-confirmed COVID-19 patients were divided into three groups: N-acetylcysteine group, Bromhexine group, and control group. Patients were followed up on the seventh and fourteenth days of the disease, and hospitalization and mortality rates were evaluated after one month. The study found that both N-acetylcysteine and Bromhexine can effectively reduce hospitalization rates and mortality and shorten the duration of hospitalization. The third visit of patients who received N-acetylcysteine showed an increase of 1.33% in oxygen saturation compared to their first visit, and in patients who received Bromhexine, this increase was 1.19%. The mortality rate was 9.33% in the control group and zero in both groups of patients who received medication. This study provides evidence for the early initiation of N-acetylcysteine and Bromhexine in outpatients with COVID-19. Clinical trial code: IRCT20220302054167N1, ethics code: IR.UMSHA.REC.1400.957.
... In severe COVID-19 patients, the rise in the number of neutrophils is associated with the disease severity [6]. The production of high levels of proin ammatory cytokines leads to "cytokine storm" [2,7]. When the patient is admitted to the hospital, the disease is most likely to have advanced to the second or third stage, with respiratory problems and multiple organ failure. ...
... N-acetylcysteine (NAC) has been long employed to treat paracetamol (acetaminophen) poisoning caused [9] and as a mucolytic in chronic lung diseases. N-acetylcysteine is also an antioxidant and can reduce the oxidative stress [7] As a prodrug, acetylcysteine is transformed into L-cysteine [10], which is the precursor of the biological antioxidant, glutathione. Therefore, the administration of N-acetylcysteine renews glutathione sources. ...
Objectives: Due to the referral of COVID-19 patients to outpatient centers in the early stages, the aim of the present study is to compare the effect of N-acetylcysteine and Bromhexine on the recovery rate and prevention of hospitalization in outpatients with COVID-19
Methodology: This study was conducted from April 2022 to September 2022. First, PCR-confirmed COVID-19 patients were divided into tree groups, one of these groups received N-acetylcysteine while the other received bromhexine and One of these groups did not receive any medication. The patients were followed up on the seventh and fourteenth days of the disease in terms of the duration of changes in oxygen saturation and recovery. The hospitalization and death of the patients were also evaluated after one month.
Results: Out of 225 studied patients, oxygen saturation was increased by 1.33% in the third visit of the patients who received N-acetylcysteine compared to their first visit. This percentage was 1.19% in the patients who received bromhexine.29.77% of the patients were admitted to the hospital and 70.23% of them had no history of hospitalization within 14 day and their mortality rate was 9.33% in control group and it was zero in both groups of patients who received drug.
Conclusions: The results of this study showed that early initiation of Bromhexine and N-acetylcysteine can effectively reduce the hospitalization rate and mortality and shorten the duration of hospitalization.
Clinical trial code: IRCT20220302054167N1 and ethics code: IR.UMSHA.REC.1400.957
... szükségesek kontrollált beavatkozásos tanulmányok a bél mikroflórájának összetételével és aktivitásával kapcsolatban. [7,9] év; 172 400 ...
... [8] A közelmúltban egy tanulmányban arról olvashattunk, hogy a β-glükán potenciális szerepet tölt be, mint természetes táplálék, az 1-es típusú interferon válasz (olyan citokinek, melyek aktiválják az immunrendszert és a környező sejtek védekező mechanizmusait) fokozásában az olyan RNS-vírusok ellen, mint az influenza vagy a koronavírus. [9] Számos tisztítási és roncsolási eljárást fejlesztettek ki e molekulák elkülönítésére és egyedi bioaktivitásuk tesztelésére. többek között a fagyasztásos-olvasztásos elválasztást, az oldószeres kezelést, a dialízist, az ultraszűrést vagy az oszlopos frakcionálást alkalmazták általában, mivel egyszerű módszerekről van szó. ...
... Although the purpose of recommending antioxidant therapy is not new, the recent pandemic brought antioxidant therapy to the frontline, as COVID-19 lacks specific antiviral drugs. N-acetyl cysteine (NAC) is considered to be the best-known antioxidant for alleviating SARS-CoV-2 infection [65]. There are Figure 4. Changes in the redox landscape (thiol-based redox mechanisms) facilitate viral fusion and replication. ...
... Although the purpose of recommending antioxidant therapy is not new, the recent pandemic brought antioxidant therapy to the frontline, as COVID-19 lacks specific antiviral drugs. N-acetyl cysteine (NAC) is considered to be the best-known antioxidant for alleviating SARS-CoV-2 infection [65]. There are some possible mechanisms proposed thus far, such as interfering with angiotensin II cleavage to angiotensin 1-7 via ACE2 and attenuating oxidative damage by increasing TLR-7, restoring type-IFN production [66], and antagonizing proteasome inhibitors to reduce the accumulation of the viral proteins [66,67]. ...
Over hundreds of years, humans have faced multiple pandemics and have overcome many of them with scientific advancements. However, the recent coronavirus disease (COVID-19) has challenged the physical, mental, and socioeconomic aspects of human life, which has introduced a general sense of uncertainty among everyone. Although several risk profiles, such as the severity of the disease, infection rate, and treatment strategy, have been investigated, new variants from different parts of the world put humans at risk and require multiple strategies simultaneously to control the spread. Understanding the entire system with respect to the commonly involved or essential
mechanisms may be an effective strategy for successful treatment, particularly for COVID-19. Any treatment for COVID-19 may alter the redox profile, which can be an effective complementary method for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry and further replication. Indeed, redox profiles are one of the main barriers that suddenly shift the immune response in favor of COVID-19. Fortunately, several redox components exhibit antiviral and anti-inflammatory activities. However, access to these components as support elements against COVID-19 is limited. Therefore,
understanding redox-derived species and their nodes as a common interactome in the system will facilitate the treatment of COVID-19. This review discusses the redox-based perspectives of the entire system during COVID-19 infection, including how redox-based molecules impact the accessibility of SARS-CoV-2 to the host and further replication. Additionally, to demonstrate its feasibility as a viable approach, we discuss the current challenges in redox-based treatment options for COVID-19.
... Different classes of nutraceuticals have been evaluated for coping with RNA virus infection, like phycocyanobilin from spirulina, ferulic acid, zinc, lipoic acid, selenium, epigallocatechin, theaflavin gallate, and curcumin (Chen, Chang, et al., 2016;McCarty & DiNicolantonio, 2020). These nutraceuticals could reduce viral response both by suppressing viral spread, and by attenuating pro-inflammatory signaling in endothelial cells that promotes influx of inflammatory cells (McCarty & DiNicolantonio, 2020). ...
... Different classes of nutraceuticals have been evaluated for coping with RNA virus infection, like phycocyanobilin from spirulina, ferulic acid, zinc, lipoic acid, selenium, epigallocatechin, theaflavin gallate, and curcumin (Chen, Chang, et al., 2016;McCarty & DiNicolantonio, 2020). These nutraceuticals could reduce viral response both by suppressing viral spread, and by attenuating pro-inflammatory signaling in endothelial cells that promotes influx of inflammatory cells (McCarty & DiNicolantonio, 2020). ...
Nowadays, the pharma and food industries have been gearing up to meet the urgent need for anti-infective and anti-inflammatory nutritional formulations. In this way, several nutraceutical compounds are being re–evaluated due to their established bioactivities. Few compounds have been or may be efficiently targeted against infections, inflammatory conditions and for immune modulation. However, for successful management of these metabolic conditions, the nutraceuticals need to be designed into effective nutritional formulations. Over recent years there have been tremendous progress in the re-engineering of structurally delivery vehicles which provide stability, enhance bioaccessibility and bioavailability of these compounds. In this perspective, this review focuses on the structural and functional aspects of several such bio-based delivery vehicles like the micro and nano particles, nano-emulsions and liposome-based models. The aim is to bring forth recent information on the efficacious nutraceuticals and the suitable delivery vehicles which would be useful against infections and inflammatory conditions.
... Being a potent antioxidant biomolecule, NAC may combat against the production of ROS and most importantly the cytokine storm creating the emergence of oxidative stress (OS) [29,30]. It is supposed that the immunopathology of SARS-CoV and SARS-CoV-2 is similar and triggers an immunological response incorporating various types of pro-inflammatory cytokines like IL-1, IL-2, IL-4, TNF, and IFNs. ...
... During SARS-CoV-2 infection, the above process leads to delayed IFN response by cytokine storm syndrome. NAC may lead to amplification of signal cascades triggered by toll-like receptor 7 and mitochondrial antiviral signal protein in restoration of SARS-CoV-2-mediated type-I IFN production [29]. NF-κB has been reported to cause the cytokine storm by accelerating the synthesis of several pro-inflammatory cytokines and acts as a mediator of SARS-CoV-2 pathology. ...
Background
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), causing the coronavirus disease 2019 (COVID-19), has shown its persistent pandemic strength. This viral infectivity, kinetics, and the mechanisms of its actions in human body are still not completely understood. In addition, the infectivity and COVID-19 severity reportedly differ with patient’s gender with men being more susceptible to the disease. Thus, different studies have also suggested the adverse impact of COVID-19 on male reproductive functions, mainly emphasizing on high expressions of angiotensin-converting enzyme 2 (ACE2) in the testes that allows the viral entry into the cells.
Main body
The N-acetylcysteine (NAC), a potent therapeutic agent of COVID-19, may be effective in reducing the impairing impacts of this disease on male reproductive functions. NAC acts as mucolytic agent by reducing sulfide bonds in the cross-linked glycoprotein matrix in mucus owing to its free sulfhydryl group. Since NAC also breaks the viral disulfide bonds required for the host cell invasion, it may help to prevent direct SARS-CoV-2 invasion into the testicular cells as well. NAC also acts as a potent anti-inflammatory and antioxidant, directly scavenging reactive oxygen species (ROS) and regulating the redox state by maintaining the thiol pool being a precursor of cysteine (an essential substrate for glutathione synthesis). Since it is suggested that male reproductive impairment in COVID-19 patient may be caused by secondary immune responses owing to systemic inflammation and OS, the anti-inflammatory and antioxidant properties of NAC explained above may attribute in protecting the male reproduction functions from these COVID-19-mediated damages.
Conclusion
This article explains the mechanisms how NAC treatment for COVID-19 may prevent the infection-mediated disruptions in male reproduction.
... In addition, Zn supplementation (50 mg/day) for three months prevents COVID-19 complications in cancer patients [76]. Zn at doses of 30-50 mg/d may aid in the protection of humans against RNA viruses [77]. ...
There is currently no particular cure for coronavirus disease-19 (COVID-19). However, studies suggest that certain medicinal plants, fruits, and vegetables possess bioactive substances capable of ameliorating the disease. This review aims to articulate fruits, vegetables, and medicinal plants that have anti-coronavirus properties. Relevant articles were collected from reputable academic repositories, namely SpringerLink, PubMed, Google Scholar, and Scopus. Available information shows that alkaline-rich fruits and vegetables, such as mango, cabbage, lemon, onion, okra, carrot, cucumber, pepper, spinach, and avocado, have anti-coronavirus properties. The mentioned fruits and vegetables stimulate an unfavorable pH for the replication of the virus and normalize the acid-base imbalance induced in the lungs and kidneys of the infected. Fruits and vegetables also contain health-boosting substances such as proteins, amino acids, glycosides, vitamins, and minerals. Medicinal plants, including Clitoria ternatea L., Vitex trifolia L., Sphaeranthus indicus L., Clerodendrum inerme L. Gaertn., Glycyrrhiza glabra L., Strobilanthes cusia (Nees) Kuntze, Vitis vinifera var. aestivalis (Michx.) Kuntze, Hyoscyamus niger L., and Cedrela Sinensis Juss., also possess anti-coronavirus properties. Clitoria ternatea and Cedrela sinensis reduce the virus’s replication by shredding its receptor, called the angiotensin-converting enzyme 2 (ACE2). Vitex trifolia and Sphaeranthus indicus prevent hyper-inflammatory responses and cytokine storms. Glycyrrhiza glabra induces nitrous oxide synthase and blocks the virus’s replication. Clerodendrum inerme and Strobilanthes cusia inhibit the virus’s ribosome and protein translation. Vitis vinifera represses nucleocapsid protein and lowers apoptosis. Hyoscyamus niger inhibits Ca2+ channels and lessens breathing difficulties induced by the coronavirus. Thus, dietary supplements and drugs formulated with these medicinal plants, fruits, and vegetables may lessen the effects of COVID-19.
... It is not only used as an ingredient of nutrient and natural dyes for food and cosmetics, but it is also used as potent therapeutic agent and fluorescent markers (de Morais et al., 2018). Phycocyanin has garnered attention in biomedical research due to its antiviral (McCarty and DiNicolantonio, 2020;Raj et al., 2020), anti-tumoral (Cotas et al., 2020;Dev et al., 2020;Pagels et al., 2021), and anti-inflammatory properties (Guo et al., 2022;Liu et al., 2022). However, it is important to note that the phycocyanin extraction process from S. platensis results in a significant amount of by-products. ...
This study was designed to investigate the efficacy of alternative prebiotic supplements derived from phycocyanin extraction by-product in enhancing the growth of probiotic. These alternative prebiotic supplements included Spirulina platensis, the by-product of phycocyanin extraction, and inulin. The efficacy of alternative prebiotics was assessed using beneficial bacteria (Lactobacillus johnsonii ck-3 and ck-8), pathogenic bacteria (Staphylococcus aureus and Escherichia coli), and yeast (Saccharomyces cerevisiae). The alternative prebiotics source was used to analyse the chemical composition, prebiotic activity, and bacteria growth. It was demonstrated that the phycocyanin extraction by-product included a high concentration of crude protein (67.74% DM), carbohydrates (31.29% DM). The phycocyanin extraction by-product has a high content of glucose, fructose, and sucrose (63.55, 68.00, and 0.24 µg/ml, respectively). The phycocyanin extraction by-product has presented hydrolysis ability (in vitro) at 2.51% while S. platensis showed at 1.81 %. The composition of the phycocyanin extraction by-product showed similar activation of probiotic bacteria to inulin. Especially, Lactobacillus strain showed the best growth was achieved with the phycocyanin extraction by-product with decrease the final pH and high microbial colony number at 48 hours in 7.5–9.5 log10 colony-forming unit per milliliter (CFU/ml) when compared with the glucose group. The study results revealed that the phycocyanin extraction by-product with the prebiotic potential are effective at increasing numbers of Lactobacillus strain. Consequently, the study reveals that phycocyanin extraction by-product are effective as alternative prebiotic supplement, significantly enhancing beneficial probiotic bacteria. These findings suggest the potential use of phycocyanin extraction by-products in creating new prebiotic formulations for gut microbiota modulation through dietary
... The hyperactivated Nf-kB signal in the CNS induces reactive changes in microglia and astrocytes, further amplifying the neuroinflammatory response [15,224]. Another noteworthy aspect of NAC is its potential contribution to preventing and controlling infections caused by RNA viruses [225] by enhancing the signalling functions of TLR7 and the mitochondrial antiviral signalling protein, resulting in increased production of IFN-1 [226]. Moreover, ALC and NAC mitigate Nf-kB overactivated signal, attenuating NLRP3 inflammasome pathway (IL1β and IL18) and decreasing serum TNF-alpha, IL-1, IL-6 levels, and PCR [161,202,217], thereby their immunomodulatory activities [161,227,228], and protecting against cytokine storms [82,135,218]. ...
COVID-19 is associated with neuropsychiatric symptoms, such as anosmia, anxiety, depression, stress-related reactions, and psychoses. The illness can cause persistent cognitive impairment and "brain fog", suggesting chronic brain involvement. Clinical entities of ongoing symptomatic COVID-19 and Post COVID Syndrome (PCS) mainly present neuropsychiatric symptoms such as dysgeusia, headache, fatigue, anxiety, depression, sleep disturbances, and post-traumatic stress disorder. The pathophysiology of COVID-19-related brain damage is unclear, but it is linked to various mechanisms such as inflammation, oxidative stress, immune dysregulation, impaired glutamate homeostasis, glial and glymphatic damage, and hippocampal degeneration. Noteworthy is that the metabotropic receptor mGluR2 was discovered as a mechanism of internalisation of SARS-CoV-2 in Central Nervous System (CNS) cells. N-acetylcysteine (NAC) and acetyl-L-carnitine (ALC) are two supplements that have already been found effective in treating psychiatric conditions. Furthermore, NAC showed evidence in relieving cognitive symptomatology in PCS, and ALC was found effective in treating depressive symptomatology of PCS. The overlapping effects on the glutamatergic system of ALC and NAC could help treat COVID-19 psychiatric symptoms and PCS, acting through different mechanisms on the xc-mGluR2 network, with potentially synergistic effects on chronic pain and neuro-astrocyte protection. This paper aims to summarise the current evidence on the potential therapeutic role of NAC and ALC, providing an overview of the underlying molecular mechanisms and pathophysiology. It proposes a pathophysiological model explaining the effectiveness of NAC and ALC in treating COVID-19-related neuropsychiatric symptoms.
... The daily requirement for zinc is 8-11 mg/day, with an upper limit of 40 mg/day. Zinc intake as many as 30-50 mg/day during infection is recommended to control RNA virus, such as influenza and coronavirus (Institute of Medicine, 2001;McCarty & DiNicolantonio, 2020). If zinc deficiency occurs, then there will be an increase in the risks of viral infection, thymic atrophy, lymphopenia, and decreased lymphocyte responses. ...
COVID-19 has become a pandemic in the last 3 years worldwide and cases cause high mortality and morbidity. To reduce COVID-19 infection, we need to keep our immune system healthy. Several nutrients have been shown to have specific abilities to increase the power of the immune system, but their use in the treatment of COVID-19 is still being debated. This review aims to determine the role of minerals and synbiotics in increasing immunity during the COVID-19 pandemic. Specific minerals such as zinc, selenium, iron and copper have promising potential to treat COVID-19 by reducing clinical impact, markers of inflammation, and improving immunological biomarkers. In addition to increasing mineral intake, maintaining a healthy immune system can also be done by improving the health of the gut microbiota. One of the therapies that is considered to have a positive impact on handling COVID-19 is using synbiotics (a combination of prebiotics and probiotics). However, the safety and efficacy of mineral and synbiotic supplementation in COVID-19 patients as adjunctive therapy still requires further research. Minerals and synbiotics can help boost the immune system and reduce symptoms during a COVID-19 infection.
... The accepted RDA of zinc is 8-11 mg/day for adults, but it has been proposed that a zinc intake of 30-50 mg/day may help fight against viral infection [96]. However, according to Walsh [97], high-dose zinc supplementation can decrease immune function and should be avoided. ...
It is well known that during prolonged, high-intensity physical training, athletes experience a state of immunosuppression and that balanced nutrition can help maintain immunity. This review summarizes the effects (amplified by virus infection) of high-intensity, long-term exercise on immunity, critically presenting key micronutrients and supplementation strategies that can influence athletes’ performance and their immune system. The main conclusion is that micronutrient supplementation with diet could help to protect the immune system from the stress effects induced by intense physical activities. The importance of personalized supplementation has been also recommended.
... Zinc is one of the micronutrients known for its effectiveness in combating various viral infections and has been suggested to be useful against COVID-19. It is important for developing and functioning components of innate and adaptive immunity [38]. It is found in the structure of every metalloenzyme in the body and involved in more than 300 reactions. ...
Introduction: Although few studies have emphasized the preventive and therapeutic efficacy of dietary supplements in COVID-19, their efficacy in the postinfection period has not been focused. The aim of the current study was to examine the effects of therapeutic use of dietary supplements during COVID-19 treatment on post-COVID academic motivation in college students Methodology: The study was conducted with 1584 college students studying at Karamanoğlu Mehmetbey University. Three-day food consumption was recorded and anthropometric measurements (height and body weight) were taken to assess nutritional status. The Academic Motivation Scale (AMS), a 28-item 7-point Likert scale consisting of three subdimensions (amotivation, intrinsic motivation, and extrinsic motivation), was used to assess the motivational status of participants. Results: The rate of participants who survived COVID-19 was 35.9% (n = 568). There was no significant difference in AMS subscores between participants who routinely used dietary supplements and those who did not. Participants who used dietary supplements preventively had higher intrinsic motivation scores than those who did not. Lastly, all AMS subscores of COVID-19 survivors who used dietary supplements therapeutically during treatment were found to be more favorable than those who did not. However, there was no significant difference in AMS subscores between the types of dietary supplements most frequently used therapeutically. Conclusions: The finding of higher post-COVID academic motivation in COVID-19 survivors who used dietary supplements as an adjunct to treatment will make an important contribution to the literature. However, longitudinal intervention studies examining the effectiveness of specific dietary supplements in COVID-19 will undoubtedly provide more valuable results.
... literature suggests the possible role of nutraceutical intervention in boosting immunity against covid-19 (Akour, 2020;infusino et al., 2020;Khaled, 2021;Morais et al., 2020;olaimat et al., 2020;Sundararaman et al., 2020). Probiotics improve the mucosal-barrier function, antagonize pathogens, inhibit pathogen adherence, and enhance the immunity angulating the in a recent research conducted by Mccarty and colleagues, it has been suggested that certain nutraceuticals could potentially alleviate the effects of encapsulated RnA viruses in infected individuals, such as influenza and coronavirus, by boosting immune responses (Mccarty & dinicolantonio, 2020). Probiotics are viable, non-pathogenic bacteria that, when consumed, improve host health or physiology (george Kerry et al., 2018;Maldonado galdeano et al., 2019). ...
Nutraceuticals have generated an interest among clinicians for their applicability in the prevention and treatment of many ailments. Literature suggests the possible role of nutraceuticals in COVID-19. However, substantial uncertainty related to their safety and efficacy still exists. The aim of this study is to assess the efficacy and safety of nutraceuticals in preventing or treating COVID-19. We searched electronic databases, registries, websites, and e-libraries of development agencies. We included randomized controlled trials (RCTs), quasi-experiments, pre-post studies, and other experimental study designs. We assessed the risk of bias (RoB) using the RoB2 tool for RCTs and the ROBINS-I tool for non-RCTs. We assessed the overall certainty of the evidence using GRADEpro GDT. The outcomes assessed were the number of COVID-19 cases, change in disease severity, days of hospitalization, deaths, and adverse events. We performed the last search on 13th December 2023. After screening 481 studies, our analysis of five revealed one study with ‘low risk’ and four studies with ‘some concerns’ regarding bias. Our findings indicated that nutraceuticals did not significantly reduce COVID-19 mortality; their effect on hospitalization duration was uncertain. Furthermore, our assessment found no substantial evidence of increased adverse effects with probiotic use (RR 0.11, 95% CI 0.01 to 1.89, P = 0.13). Importantly, none of the studies investigated nutraceuticals’ preventive effects or their role in mitigating COVID-19 severity. There is limited evidence available on the use of nutraceuticals (probiotics, prebiotics, or synbiotics) for the treatment and prevention of COVID-19. Conducting methodologically robust RCTs with large population samples is recommended.PROSPERO REGISTRATION ID CRD42021284923
... Most importantly, SARS coronavirus (SARS-CoV) multiplication was reduced in Vero-E6 cell lines when incubation with low quantities of Zn (2 M) inhibited its RNA polymerase [156]. Additionally, Zn can boost interferon (IFN-α) cytokine signaling, which is effective against RNA-based viruses [160][161][162], and prevent SARS-CoV-2 from entering host cells by blocking angiotensin-converting enzyme 2 (ACE2) activity [163,164]. ...
Several nutrients are crucial in enhancing the immune system and preserving the structural integrity of bodily tissue barriers. Vitamin D (VD) and zinc (Zn) have received considerable interest due to their immunomodulatory properties and ability to enhance the body’s immune defenses. Due to their antiviral, anti-inflammatory, antioxidative, and immunomodulatory properties, the two nutritional powerhouses VD and Zn are crucial for innate and adaptive immunity. As observed with COVID-19, deficiencies in these micronutrients impair immune responses, increasing susceptibility to viral infections and severe disease. Ensuring an adequate intake of VD and Zn emerges as a promising strategy for fortifying the immune system. Ongoing clinical trials are actively investigating their potential therapeutic advantages. Beyond the immediate context of the pandemic, these micronutrients offer valuable tools for enhancing immunity and overall well-being, especially in the face of future viral threats. This analysis emphasizes the enduring significance of VD and Zn as both treatment and preventive measures against potential viral challenges beyond the current health crisis. The overview delves into the immunomodulatory potential of VD and Zn in combating viral infections, with particular attention to their effects on animals. It provides a comprehensive summary of current research findings regarding their individual and synergistic impacts on immune function, underlining their potential in treating and preventing viral infections. Overall, this overview underscores the need for further research to understand how VD and Zn can modulate the immune response in combatting viral diseases in animals.
Graphical Abstract
... (35) However, it is stated that in case of adults, 30-50 mg/day for a short duration might be helpful in coronavirus infection. (36) Lemon Drink: Lemons also contain Vitamin-C, which is an antibrotic, antioxidant as well as an immunomodulator (37). Lemon essential oils have shown dose dependant reduction of human ACE2 levels and Transmembrane Protease Serine 2 (TMPRSS2) mRNA levels in HT-29 cells.(37) ...
... Torque Teno virus (TTV), and have a positive response after an influenza vaccination challenge (Wu and Zha, 2020). Additionally, several nutraceuticals and probiotics have also revealed a supportive role in improving immunity towards viral infections including influenza such as oily fish, garlic, cranberry juices and broccoli sprouts are relatively readily available options (Müller et al., 2016, McCarty andDiNicolantonio, 2020). Individuals with chronic comorbid, i.e. ...
Background: The world witnessed a sudden outbreak of a new strand of a deadly disease that rapidly spread throughout the globe. The spread of coronavirus (COVID-19) first originated in Wuhan, Hubei province of China in December 2019. This virus strain extended quickly throughout China and became a pandemic in the country. On March 11, 2020, the World Health Organisation (WHO) confirmed the COVID-19 novel coronavirus as a universal pandemic. Methods: Appropriate keywords were included in Scopus, PubMed, and Google Scholar to identify the available data. Result: Due to the rapid spread and fatality of the COVID-19, the 2020 Olympic Games formally slated for July 24 until August 9, 2020, will commence on July 23 to August 8, 2021. In March 2020, most of the European professional sports leagues, including football, were discontinued for the predictable future. Conclusion: Football resumption after the lockdown was challenging because of the inability to affirm the health status of the players when they return to their clubs. Every measure must be clear to reduce the risk of the disease and to clarify the response strategy about self-protection to the public. The sport organizing-bodies control-outlines for sports events should be strategized based on the laydown sports rules and quarantine protocols. National public health organizations and sports associations should work together to protect every level of human health and sport all over the world.
... Torque Teno virus (TTV), and have a positive response after an influenza vaccination challenge (Wu and Zha, 2020). Additionally, several nutraceuticals and probiotics have also revealed a supportive role in improving immunity towards viral infections including influenza such as oily fish, garlic, cranberry juices and broccoli sprouts are relatively readily available options (Müller et al., 2016, McCarty andDiNicolantonio, 2020). Individuals with chronic comorbid, i.e. ...
Background: The world witnessed a sudden outbreak of a new strand of a deadly disease that rapidly spread throughout the globe., most of the European professional sports leagues, including football, were discontinued for the predictable future. Conclusion: Football resumption after the lockdown was challenging because of the inability to affirm the health status of the players when they return to their clubs. Every measure must be clear to reduce the risk of the disease and to clarify the response strategy about self-protection to the public. The sport organizing-bodies control-outlines for sports events should be strategized based on the laydown sports rules and quarantine protocols. National public health organizations and sports associations should work together to protect every level of human health and sport all over the world.
... The anti-inflammatory impact of antioxidant nutraceuticals, such as phenolics from Salicornia spp., might also quell the excessive inflammatory reaction within lung parenchyma evoked by viral H1N1 [93,97]. McCarty et al. suggested that a very low daily dosage ranging from 500 to 1000 mg of ferulic acid could aid in the control of H1N1 by decreasing infection response by suppressing viral spread and dampening proinflammatory signaling, which promotes an influx of inflammatory cells [98]. ...
Despite public health risk mitigation measures and regulation efforts by many countries, regions, and sectors, viral outbreaks remind the world of our vulnerability to biological hazards and the importance of mitigation actions. The saltwater-tolerant plants in the Salicornia genus belonging to the Amaranthaceae family are widely recognized and researched as producers of clinically applicable phytochemicals. The plants in the Salicornia genus contain flavonoids, flavonoid glycosides, and hydroxycinnamic acids, including caffeic acid, ferulic acid, chlorogenic acid, apigenin, kaempferol, quercetin, isorhamnetin, myricetin, isoquercitrin, and myricitrin, which have all been shown to support the antiviral, virucidal, and symptom-suppressing activities. Their potential pharmacological usefulness as therapeutic medicine against viral infections has been suggested in many studies, where recent studies suggest these phenolic compounds may have pharmacological potential as therapeutic medicine against viral infections. This study reviews the antiviral effects, the mechanisms of action, and the potential as antiviral agents of the aforementioned phenolic compounds found in Salicornia spp. against an influenza A strain (H1N1), hepatitis B and C (HBV/HCV), and human immunodeficiency virus 1 (HIV-1), as no other literature has described these effects from the Salicornia genus at the time of publication. This review has the potential to have a significant societal impact by proposing the development of new antiviral nutraceuticals and pharmaceuticals derived from phenolic-rich formulations found in the edible Salicornia spp. These formulations could be utilized as a novel strategy by which to combat viral pandemics caused by H1N1, HBV, HCV, and HIV-1. The findings of this review indicate that isoquercitrin, myricetin, and myricitrin from Salicornia spp. have the potential to exhibit high efficiency in inhibiting viral infections. Myricetin exhibits inhibition of H1N1 plaque formation and reverse transcriptase, as well as integrase integration and cleavage. Isoquercitrin shows excellent neuraminidase inhibition. Myricitrin inhibits HIV-1 in infected cells. Extracts of biomass in the Salicornia genus could contribute to the development of more effective and efficient measures against viral infections and, ultimately, improve public health.
... Because of their likeness to biological membranes [12], they are a perfect system for studying not only modern biomembranes [13,14] but also the emergence, function and evolution of primitive cell membranes [15,16]. These structures are also employed as carrier systems by the food, cosmetics, agricultural [17,18] and pharmaceutical industries [19] for the protection [20] and transportation of various materials like medicines [21], nutraceuticals [22], insecticides [23] and genetic material [24,25]. Liposomes are made up of one or more concentric or nonconcentric lipid and phospholipid bilayers and biodegradable substrates for biomarkers and in drug delivery [26][27][28], and they can also contain other molecules like proteins [29,30]. ...
Nanoliposomes with a great surface area within nano scales of about 20–100 nm have acceptable stability profiles for direct drug carriers. The present study focuses on the nanoliposomes loaded with α-Al2O3 quantum dots nanoparticles (QDNPs) for the in vivo imaging study. The final nanoliposomes loaded with α-Al2O3 QDNPs were synthesized with the microwave irradiation method and characterized with scanning electron microscopy (SEM), Fourier transformed infrared spectrum (FT-IR), thermo-gravimetric analysis (TGA), the average particle size can estimate between about 11 and 20 with transmission electron microscopy (TEM) and dynamic light scattering (DLS). The optical properties were evaluated with Uv-vis spectroscopy, and injected 0.001 mg/mL nanoliposomes loaded with α-Al2O3 NPs to the right leg (Balb/c male). The synthesis parameters such as power, irradiation time and concentration were designed by 2 k factorial. According to the analysis of variance experiments, it was found that the size of the minimum nanoparticles in this study was achieved at the highest irradiation time (15 min) and the lowest microwave power (180 watts) and α-Al2O3 concentration (0.05 g).
... Zhang et al. (2020) have reported a positive effect of adequate selenium on a higher recovery rate from COVID-19 infection. Zinc has a beneficial effect on COVID-19 infections by reducing gastrointestinal and lower respiratory symptoms (McCarty & DiNicolantonio, 2020). Copper supplementation against COVID-19 is essential to maintain DNA integrity by preventing oxidative DNA damage (Liu et al., 2016). ...
This study investigates the effects of COVID‐19 on fish consumption and nutrition intake based on a random survey of 247 fish consumers in Bangladesh. The Propensity Score Matching technique is used to compare fish consumption and fish‐sourced nutrition intake between two groups of consumers before and during COVID‐19. The result shows that 38% overall reduction in fish consumption for the low‐income group compared to lower‐middle, upper‐middle‐ and high‐income groups. Furthermore, per capita consumption of culture and capture fish species decreased significantly for low‐income, lower‐middle‐income, and upper‐middle‐income groups of consumers. It indicates that nutrition and mineral intake have reduced sharply as well Higher energy and K reduction are observed for Pangasius hypophthalmus among different culture fish species while energy and Ca reduction were higher for Wallago attu and Mystus vittatus respectively. Therefore, the government might place a greater emphasis on excluding the food supply chain from lockdown restrictions during a COVID‐19‐like pandemic.
... It demonstrates an activity against a large number of viruses and is able to bind to crucial receptors [45], preventing the virus RBD-human ACE2 interaction, which results in an attenuated SARS-CoV-2 infection [39]. Sulforaphane is a sulphur-containing compound, mainly found in broccoli, which has protective properties in the lungs and, through exerting an anti-inflammatory activity, is effective in coronaviral diseases by attenuating the effects of inflammation [46,47]. However, clinical trials are still needed to definitely prove the clinical efficacy of sulforaphane in COVID-19 patients [40]. ...
A complex network of processes inside the human immune system provides resistance against a wide range of pathologies. These defenses form an innate and adaptive immunity, in which certain immune components work together to counteract infections. In addition to inherited variables, the susceptibility to diseases may be influenced by factors such as lifestyle choices and aging, as well as environmental determinants. It has been shown that certain dietary chemical components regulate signal transduction and cell morphologies which, in turn, have consequences on pathophysiology. The consumption of some functional foods may increase immune cell activity, defending us against a number of diseases, including those caused by viruses. Here, we investigate a range of functional foods, often marketed as immune system boosters, in an attempt to find indications of their potential protective role against diseases caused by viruses, such as the influenza viruses (A and B), herpes simplex virus (HSV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in some cases mediated by gut microbiota. We also discuss the molecular mechanisms that govern the protective effects of some functional foods and their molecular constituents. The main message of this review is that discovering foods that are able to strengthen the immune system can be a winning weapon against viral diseases. In addition, understanding how the dietary components function can aid in the development of novel strategies for maintaining human bodily health and keeping our immune systems strong.
... Apart from the nutritional benefits, compounds sourced from alga have therapeutic properties as well. The bioactive secondary metabolites derived from algae such as cyanobacteria (Spirulina) can activate our immune response and alleviate RNA virus induced oxidative stress [107]. Spirulina derived nutraceuticals have been well explored in clinical studies and reported to boost our innate and adaptive immunity; therefore, it can act as potential therapeutic against the deadly viral infections including the COVID-19 [108]. ...
Our planet is facing a wide range of inevitable and unprecedented changes such as, the water and food scarcity to the natural calamities, namely flooding, droughts and rising sea levels. All these global challenges had been addressed through the Sustainable Development Goals (SDGs) drafted by the general assembly of the United Nations. In light of the current population growth, it is difficult to attain the sustainable development using conventional and non-renewable natural resources by remaining within the planetary boundaries of Earth. In order to maintain the environment and ecological integrity, the utilization of renewable living natural resources such as microbes become inevitable. Due to their roles in geo physio-chemical processes and bioenergy transformations, microbes allow 'cradle-to-cradle' model of development using wastewater as a renewable resource. The circular wastewater economy is the sole sustainable method to achieve the SDGs of providing clean water and the sanitation to address the issue of water insecurity. The review presents an inter-connected overview on the roles and functions performed by the prokaryotic (bacteria) and eukaryotic (algae and fungi) microorganisms, which are crucial for attaining the environment sustainability within the planetary boundaries. Apart from the environmental roles of microbes, the review also highlights the importance of human-microbe interactions (gut microbiome) and edible microbial species (algae and fungi) which are essential for developing sustainable future alternatives to human nutrition, well being and prevention of diseases.
... IFNs are able to inhibit the replication of the SARStype coronavirus, so they can be useful in the treatment of COVID-19. Additionally, activation of TLR7 by single-stranded viral RNA, entrapped within endosomes, provides a key stimulus for the induction of IFN-1 by the RNA virus [33]. Moreover, some evidence indicates that hydrogen sulfide (H 2 S) acts as an antiviral host factor in patients with COVID-19; as the endogenous H 2 S production can be therapeutically augmented by administration of NAC, this strategy has the potential to provide clinical benefit [34]. ...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes coronavirus disease 2019 (COVID-19) and can be associated with serious complications, including acute respiratory distress syndrome. This condition is accompanied by a massive release of cytokines, also denominated cytokine storm, development of systemic oxidative stress and a prothrombotic state. In this context, it has been proposed a role for acetylcysteine (NAC) in the management of patients with COVID-19. NAC is a molecule classically known for its mucolytic effect, but it also has direct and indirect antioxidant activity as a precursor of reduced glutathione. Other effects of NAC have also been described, such as modulating the immune and inflammatory response, counteracting the thrombotic state, and having an antiviral effect. The pharmacological activities of NAC and its effects on the mechanisms of disease progression make it a potential therapeutic agent for COVID-19. NAC is safe, tolerable, affordable, and easily available. Moreover, the antioxidant effects of the molecule may even prevent infection and play an important role as a complement to vaccination. Although the clinical efficacy and dosing regimens of NAC have been evaluated in the clinical setting with small series of patients, the results are promising. In this article, we review the pathogenesis of SARS-CoV-2 infection and the current knowledge of the mechanisms of action of NAC across disease stages. We also propose NAC posology strategies to manage COVID-19 patients in different clinical scenarios.
... McCarty and DiNicolantonio [152] recently described the potential role of β-glucan as a natural nutraceutical to boost the response of interferon type 1 to RNA viruses such as the influenza and the coronavirus. Therefore, the intake of oat products provides a rich source of phytochemicals that provides health benefits such as decreasing high blood pressure and influencing the immunotherapies against infections such as COVID-19 due to the presence of inhibitory peptides of ACE and of β-glucans. ...
Cereals have phytochemical compounds that can diminish the incidence of chronic diseases such as hypertension. The angiotensin-converting enzyme 2 (ACE2) participates in the modulation of blood pressure and is the principal receptor of the virus SARS-CoV-2. The inhibitors of the angiotensin-converting enzyme (ACE) and the block receptors of angiotensin II regulate the expression of ACE2; thus, they could be useful in the treatment of patients infected with SARS-CoV-2. The inferior peptides from 1 to 3 kDa and the hydrophobic amino acids are the best candidates to inhibit ACE, and these compounds are present in rice, corn, wheat, oats, sorghum, and barley. In addition, the vitamins C and E, phenolic acids, and flavonoids present in cereals show a reduction in the oxidative stress involved in the pathogenesis of hypertension. The influence of ACE on hypertension and COVID-19 has turned into a primary point of control and treatment from the nutritional perspective. The objective of this work was to describe the inhibitory effect of the angiotensin-converting enzyme that the bioactive compounds present in cereals possess in order to lower blood pressure and how their consumption could be associated with reducing the virulence of COVID-19.
... Though zinc is an essential and physiologically relevant cofactor in hemostasis, the role of zinc in platelet activation and pathophysiological thrombus formation has not been well investigated.The demand for nutritional supplements and nutraceuticals has increased during the COVID-19 pandemic due to their perceived immune-boosting effects. Both in vitro and in vivo studies have shown that nutraceuticals containing phycocyanobilin, N-acetylcysteine, glucosamine, selenium, or phase 2 inductive nutraceuticals (e.g., lipoic acid, ferulic acid) can inhibit and modulate RNA virus infections through an increase in mitochondrial antiviral-signalling protein activation and TLR7 activation(McCarty & DiNicolantonio, 2020). ...
In addition to hemostasis and thrombosis, blood platelets are involved in various processes such as inflammation, infection, immunobiology, cancer metastasis, wound repair and angiogenesis. Platelets' hemostatic and non‐hemostatic functions are mediated by the expression of various membrane receptors and the release of proteins, ions and other mediators. Therefore, specific activities of platelets responsible for the non‐hemostatic disease are to be inhibited while leaving the platelet's hemostatic function unaffected. Platelets' anti‐aggregatory property has been used as a primary criterion for antiplatelet drugs/bioactives; however, their non‐hemostatic activities are not well known. This review describes the hemostatic and non‐hemostatic function of human blood platelets and the modulatory effects of bioactive food components.
Practical applications
In this review, we have discussed the antiplatelet effects of several food components. These bioactive compounds inhibit both hemostatic and non‐hemostatic pathways involving blood platelet. Platelets have emerged as critical biological factors of normal and pathologic vascular healing and other diseases such as cancers and inflammatory and immune disorders. The challenge for therapeutic intervention in these disorders will be to find drugs and bioactive compounds that preferentially block specific sites implicated in emerging roles of platelets' complicated contribution to inflammation, tumour growth, or other disorders while leaving at least some of their hemostatic function intact.
... McCarty and DiNicolantonio recently described the potential role of β-glucan for enhancing type 1 interferon activity against influenza and coronavirus. 19 As an immunomodulating agent, β-glucan acts through the activation of innate immune cells such as macrophages, dendritic cells, granulocytes, and natural killer cells; resulting in β-glucan exert multiple effects against various ailments. In a previous research conducted in our Lab, the phenolic, flavonoid and vitamin contents followed by untargeted LC/MS-TripleTOF based proteomics analysis of L. edodes, P. ostreatus and A. bisporus mushrooms were carried out. ...
Background:
Fungi are rich source of biologically active metabolites aimed for the improvement of human health through the prevention of various diseases, including infections and inflammatory disorders.
Aim:
We aimed to in vitro examine the anti-SARS CoV-2 activity of the aqueous extract of each Pleurotus (P.) ostreatus, Lentinula (L.) edodes and Agaricus (A.) bisporus edible mushroom followed by docking analysis of certain metabolites against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-main protease (protease Mpro).
Methods:
Antiviral and cytotoxic effects were tested on hCoV-19/Egypt/NRC-3/2020/Vero-E6 cells and analyzed via (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide Assay (MTT) assay. Ligand-protein and protein-protein docking studies were performed to explore the interaction of different mushroom extracts at the binding site of protease Mpro. Molecular dynamics (MD) simulations were performed on the most promising ligand-target complexes to investigate their dynamic properties and confirm docking results.
Results:
Substantial antiviral activities with an IC50 of 39.19, 26.17, and 10.3.3 µg/mL and a selectivity index (SI) of 4.34, 3.44, and 1.5 for P. ostreatus, L. edodes and A. bisporus, were observed, respectively. Docking analysis revealed that, catechin from three mushroom isolates, chlorogenic acid from A. bisporus, kamperferol of P. ostreatus and quercetin from L. edodes, with a C-DOCKER interaction energy in the range of 22.8-37.61 (Kcal/mol) with protease compared to boceprevir ligand of 41.6 (Kcal/mol). Docking of superoxide dismutase, catalase from the three mushrooms, tyrosinase from A. bisporus showed ligand contact surface area with the protein as 252.74 Å2 while receptor contact surface area was 267.23 Å2.
Conclusion:
P. ostreatus, L. edodes and A. bisporus have potential and remarkable in vitro antiviral activities against SARS-CoV-2. Quercetin from L. edodes, Kaempferol from P. ostreatus, chlorogenic acid and ascorbic acid, catechin, superoxide dismutase and catalase of the three mushrooms extracts were effectively bounded to Mpro of SARS-CoV-2 as conferred by docking analysis.
Dapsone (4,4′-diamino diphenyl sulfone, DDS) is an acetylation agent, anticatalysis for Alzheimer’s disease (AD) exacerbation in the previous report. We analyzed the viral respiratory disease (VRD) (+)/(−) and DDS (+)/(−) groups with the ICD-10 from 2005 to 2021. We used to evaluate the associations statistical methods the correlation of VRD, its interferon responses, chronic obstructive pulmonary disease (COPD) incidence, excess acetylcholine (ACh) by the use of anti-AD drugs (AADs), and AD on Sorok Island in South Korea. All significance levels were set at 0.05. We investigated 93 non-COPD subjects with AD. Their prevalence of AD increased more than twofold fold in 2010 after the endemic disease during 2007–2010. AD increased again in 2013 from the medical data of Hansen's people and a correlation graph was drawn and analyzed. A total of 4772 subjects were randomized. Subjects with DDS have a very low prevalence of VRDs. In the tracking results within the cohort, 31 ADs were found from 107 COPD patients. The COPD ⁺ AAD ⁺ DDS ⁻ subjects correlated most strongly to AD ⁺ . ACh excess exacerbated AD in COPD patients and exacerbates AD despite of the acetylation by DDS according to Fisher’s exact test. Moreover, a survey of COVID-19 reinfection conducted in April 2022 in South Korea revealed that ACh excess aggravated severity and mortality. AD can be caused by the VRDs, acute or chronic bronchitis, and pneumonia. This indicates that AD starts from their acquired interferon upregulation and its glycolysis. This study elucidated AD genetics related to infections, inflammation, and immune responses by pathogens in the isolated cohort.
Cardiovascular diseases represent a significant global health burden, necessitating effective prevention and treatment strategies to mitigate their impact. Anticoagulant therapy plays a crucial role in managing these diseases by preventing the formation of blood clots, which can lead to life-threatening complications such as heart attacks and strokes. However, conventional anticoagulants are associated with limitations, including the risk of bleeding complications and the need for frequent monitoring. In recent years, there has been increasing interest in exploring natural alternatives to conventional anticoagulants, with Cayenne pepper (Capsicum annuum) emerging as a potential candidate due to its bioactive compound, capsaicin. This paper aims to review the existing literature on the anticoagulant properties of Cayenne pepper lozenges. By examining the pharmacological mechanisms of capsaicin and summarizing preclinical and clinical studies, this paper evaluates the efficacy, safety, and therapeutic potential of Cayenne pepper as an alternative or adjunctive therapy for cardiovascular diseases. The findings suggest that Cayenne pepper lozenges may hold promise as a novel anticoagulant agent, offering potential benefits in terms of cardiovascular health and reducing the burden associated with conventional anticoagulant therapy
Although the world is acquitting from the throes of COVID-19 and returning to the regularity of life, its effects on physical and mental health are prominently evident in the post-pandemic era. The pandemic subjected us to inadequate sleep and physical activities, stress, irregular eating patterns, and work hours beyond the regular rest-activity cycle. Thus, perturbing the synchrony of the regular circadian clock functions led to chronic psychiatric and neurological disorders and poor immunological response in several COVID-19 survivors. Understanding the links between the host immune system and viral replication machinery from a clock-infection biology perspective promises novel avenues of intervention. Behavioral improvements in our daily lifestyle can reduce the severity and expedite the convalescent stage of COVID-19 by maintaining consistent eating, sleep, and physical activity schedules. Including dietary supplements and nutraceuticals with prophylactic value aids in combating COVID-19, as their deficiency can lead to a higher risk of infection, vulnerability, and severity of COVID-19. Thus, besides developing therapeutic measures, perpetual healthy practices could also contribute to combating the upcoming pandemics. This review highlights the impact of the COVID-19 pandemic on biological rhythms, sleep–wake cycles, physical activities, and eating patterns and how those disruptions possibly contribute to the response, severity, and outcome of SARS-CoV-2 infection.
Wuhan, China reported a novel coronavirus-related sickness in late 2019, which quickly spread into a global epidemic. One crucial factor in combating the coronavirus infection appears to be the presence of a robust, long-lasting, and active immune system. The immune response is affected by several factors, including food. Nutritional insufficiency can cause immune deficits, making infections more likely to cause fatality. Thus, understanding numerous behaviors, particularly dietary habits, is essential to determining their capacity to reduce severe acute respiratory syndrome coronavirus 2 risks and improve prognosis. In this paper, the authors summarize the complex interaction between nutritional status and severe acute respiratory syndrome corona virus 2 infections, as well as the consequences of poor nutrients with regard of the extent to which disease is affected. The literature was compiled by searching a number of reputable scientific databases including Scopus, Science Direct, Springer, Nature, PubMed, Web of Science resources. The accumulating evidence demonstrates that malnutrition impairs the immune system's ability to function, weakening the body's infection resistance. This review emphasizes the significance of nutritional status in the care of coronavirus disease patients as well as demonstrates that functional foods may contribute to better outcomes. Ageing, Obesity, Malnutrition, Undernutrition, Lack of exercise are having a devastating effect on people's health in general and during this coronavirus disease. The severity and prognosis of coronavirus illness seem to be significantly influenced by lifestyle choices, nutritional imbalances, and impaired immune response.
COVID-19 has posed unprecedented challenges to global public health since its outbreak. The Qing-Fei-Pai-Du decoction (QFPDD), a Chinese herbal formula, is widely used in China to treat COVID-19. It exerts an impressive therapeutic effect by inhibiting the progression from mild to critical disease in the clinic. However, the underlying mechanisms remain obscure. Both SARS-CoV-2 and influenza viruses elicit similar pathological processes. Their severe manifestations, such as acute respiratory distress syndrome (ARDS), multiple organ failure (MOF), and viral sepsis, are correlated with the cytokine storm. During flu infection, QFPDD reduced the lung indexes and downregulated the expressions of MCP-1, TNF-[Formula: see text], IL-6, and IL-1[Formula: see text] in broncho-alveolar lavage fluid (BALF), lungs, or serum samples. The infiltration of neutrophils and inflammatory monocytes in lungs was decreased dramatically, and lung injury was ameliorated in QFPDD-treated flu mice. In addition, QFPDD also inhibited the polarization of M1 macrophages and downregulated the expressions of IL-6, TNF-[Formula: see text], MIP-2, MCP-1, and IP-10, while also upregulating the IL-10 expression. The phosphorylated TAK1, IKK[Formula: see text]/[Formula: see text], and I[Formula: see text]B[Formula: see text] and the subsequent translocation of phosphorylated p65 into the nuclei were decreased by QFPDD. These findings indicated that QFPDD reduces the intensity of the cytokine storm by inhibiting the NF-[Formula: see text]B signaling pathway during severe viral infections, thereby providing theoretical and experimental support for its clinical application in respiratory viral infections.
Setelah terjadinya pandemi Covid-19 dalam beberapa tahun terakhir yang banyak menimbulkan korban dan terhambatnya berbagai aktivitas di masyarakat serta kekhawatiran terjadinya penurunan kondisi kesehatan masyarakat maka perhatian dalam meningkatkan kesadaran dan pemahaman terhadap hidup sehat perlu digiatkan oleh berbagai pihak termasuk dari Perguruan Tinggi. Kegiatan sosialisasi cara hidup sehat dan upaya peningkatan imunitas tubuh terhadap penyakit di masyarakat dan pemanfaatan bahan alam tumbuhan untuk meningkatkan sistim imun menjadi perhatian utama untuk bisa tetap sehat di masa dan pasca pandemi. Tujuan kegiatan ini adalah mendampingi masyarakat Korong Tarok Kapalo Hilalang Kabupaten Padang Pariaman dalam memanfaatkan dan pengolahan tanaman temulawak (Curcuma xanthorryza) untuk dijadikan minuman kesehatan peningkat imunitas. Kegiatan ini dilaksanakan dengan dua metode yaitu (1) penyuluhan atau sosialisasi tumbuhan temulawak yang bermanfaat sebagai peningkat imunitas dan (2) pelatihan pengolahannya menjadi minuman kesehatan dalam rangka swamedikasi dalam memelihara kesehatan secara mandiri. Kegiatan ini diikuti oleh komunitas, ibu-ibu PKK dan aparat nagari setempat. Melalui kegiatan ini masyarakat dapat memahami dan mampu mengolah serta memanfaatkan tanaman temulawak menjadi sediaan dalam bentuk minuman kesehatan secara mandiri. Masyarakat terlihat sangat antusias dan bersemangat dalam mengikuti kegiatan ini. Kegiatan ini dapat mendorong masyarakat untuk mampu menerapkan perilaku hidup sehat dengan mengembangkan serta mengoptimalkan pemanfaatan tanaman obat temulawak yang ada di lingkungan menjadi sediaan minuman kesehatan instan.
Background:
and Purposes: The terminology "immune boost-up" was the talk of the topic in this Covid-19 pandemic. A significant number of the people took initiative to increase the body's defense capacity through boosting up immunity worldwide. Considering this, the study was designed to explain the natural products, vitamins and mineral that were proved by clinical trail as immunity enhancer.
Methods:
Information was retrieved from SciVerse Scopus ® (Elsevier Properties S. A, USA), Web of Science® (Thomson Reuters, USA), and PubMed based on immunity, nutrients, natural products in boosting up immunity, minerals and vitamins in boosting up immunity, and immune booster agents.
Result:
A well-defined immune cells response provide a-well functioning defense system for the human physiological system. Cells of the immune system must require adequate stimulation so that these cells can prepare themselves competent enough to fight against any unintended onslaught. Several pharmacologically active medicinal plants and plants derived probiotics or micronutrients have played a pivotal role in enhancing the immune boost-up process. Their role has been well established from the previous study. Immune stimulating cells, especially cells of acquired immunity are closely associated with the immune-boosting up process because all the immunological reactions and mechanisms are mediated through these cells.
Conclusion:
This article highlighted the mechanism of action of different natural products, vitamins and mineral in boosting up the immunity of the human body and strengthening the body's defense system. Therefore, it is recommended that until the specific immune-boosting drugs are available in pharma markets, anyone can consider the mentioned products as dietary supplements to boost up the immunity.
Biomass of Arthrospira platensis has a long history of consumption as a source of protein, a number of micronutrients and minor biologically active compounds. Specific organoleptic properties of Arthrospira platensis biomass (pronounced bitter taste) limit its use as a source of phycocyanins. The developed modern methods of phycocyanin extraction from A. platensis biomass make it possible to obtain concentrates with improved sensory characteristics destined for the inclusion in foods for special dietary uses. The aim of this brief review was to analyze the results of the studies on the assessment of the biological activity of phycocyanin extracted from the Arthrospira platensis biomass, substantiating the prospects of using their concentrates for inclusion in foods for various dietary purposes. Material and methods. The PubMed Web Database, including MEDLINE article database, covering about 75% of the world's medical publications, was used for the main search for the literature. In addition, Scopus and Web of Science databases were used. Search depth - 15 years. Search keywords: Arthrospira platensis, phycocyanins, safety, antioxidant activity, immunomodulatory properties. Results and discussion. C-phycocyanin and allophycocyanin are complexes of proteins with the pigment phycocyanobilin, their total content is about 50% of the content of all proteins in the A. platensis biomass. A significant number of toxicological studies indicate that there are no risks to human health when using phycocyanin-containing extracts of A. platensis. Evidence of the antioxidant effect of phycocyanins extracted from A. platensis biomass, their anti-inflammatory activity, immunomodulatory properties, was obtained experimentally in vitro and in vivo, as well as in clinical studies. Conclusion. Toxicological studies and experimental in vivo tests have shown the safe and effective use of Arthrospira platensis biomass extracts with a high content of phycocyanins as an additional means of dietary prevention and diet therapy. These data indicate the prospects for conducting additional studies on the possibility of including phycocyanin concentrates in specialized foods for various purposes.
Background: The aim of the present study was to analyze any relations existed between sampling characteristics and the onset of the SARS-CoV-2 infection, also by considering the number of times that it occurred in a cohort of Italian nurses interviewed. Additionally, by considering the nutritional supplemental taking, this research wanted to assess any differences both in the onset and in the number of times which the infection occurred among participants.
Method: An observational cohort study was carried out thorough all Italian nurses by advertising the questionnaire through some professional internet pages.
Results: Work typology (p=0.021), ward Covid-19 (p=0.002) and regular meal assumption (p=0.019) significantly associated to the onset of the SARS-CoV-2 infection. Most of nurses who contracted the SARS-CoV-2 infection worked during the night shift (53.7%), 44.3% worked in a no-Covid-19 ward and 53% declared to have a regular meals’ assumption. Ward typology significantly associated to the times of the SARS-CoV-2 onset (p=0.003), as most of nurses who contracted almost one time the SARS-CoV-2 infection were employed in a no-Covid-19 ward (55.5%) and 54.1% of them declared to have a regular meals’ assumption. The onset of the Sars-CoV-2 infection seemed to be more present in the most part of the sample collect.
Conclusion: The present study could be considered as pilot in this sense and also more studies will be performed in order to better relate the function of supplemental food intakes with a better functioning of the immune system.
Background:
The aim of this study was to evaluate the effect and safety of N-acetylcysteine (NAC) inhalation spray in the treatment of patients with coronavirus disease 2019 (COVID-19).
Methods:
This randomized controlled clinical trial study was conducted on patients with COVID-19. Eligible patients (n=250) were randomly allocated into the intervention group (routine treatment + NAC inhaler spray one puff per 12 hours, for 7 days) or the control group who received routine treatment alone. Clinical features, hemodynamic, hematological, biochemical parameters and patient outcomes were assessed and compared before and after treatment.
Results:
The mortality rate was significantly higher in the control group than in the intervention group (39.2% vs 3.2%, P<0.001). Significant differences were found between the two groups (intervention and control, respectively) for white blood cell count (6.2 vs 7.8, P<0.001), hemoglobin (12.3 vs 13.3, P=0.002), C-reactive protein (CRP: 6 vs 11.5, P<0.0001) and aspartate aminotransferase (AST: 32 vs 25.5, P<0.0001). No differences were seen for hospital length of stay (11.98±3.61 vs 11.81±3.52, P=0.814) or the requirement for ICU admission (7.2% vs 11.2%, P=0.274).
Conclusions:
NAC was beneficial in reducing the mortality rate in patients with COVID-19 and inflammatory parameters, and a reduction in the development of severe respiratory failure; however, it did not affect the length of hospital stay or the need for ICU admission. Data on the effectiveness of NAC for SARS-CoV-2 is limited and further research is required.
Clinical trial registration:
This study Registered at Iranian Registry of Clinical Trials (IRCT20080901001165N55) dated 23-05-2020. This article is protected by copyright. All rights reserved.
Glutathione is one of the foremost human body antioxidant that enables him to cope with the oxidative stress and its by‐products. This compound is depleted by age, illness, viral infections, including Severe Acute Respiratory Syndrome infections (SARS). Restoring its levels is therefore crucial to good health. Since its oral bioavailability is very poor, it is important to develop stable derivatives or fragments with improved antioxidant properties. The relationship between chronic inflammation, chronic diseases and oxidative stress is widely documented. Compounds that have high antioxidant activities arouse much interest as they could contribute to cope with detrimental health conditions because of oxidative stress, thus chronic inflammation. We synthesized some interesting glutathione‐inspired fragments from available starting materials and assessed their antioxidant power. Our compounds were analysed and identified by usual physicochemical and spectroscopic techniques. Their antioxidant activity was assessed using Diphenylpicrylhydrazine radical and Ferric Reducing Antioxidant Power assays. Our results showed interesting antioxidant activities IC50 values ranging from 1.35 mg/mL to 3.40 mg/mL, some among them with values (2.32 mg/mL) better than cysteine (IC50=3.025 mg/mL) (IC50=3.03), which is the best precursor of glutathione.
The cyanobacterium Arthrospira platensis biomass is a promising food source of biologically active substances with pharmacological activity. The aim of this research was a brief review and analysis of experimental in vitro and in vivo studies of the antioxidant, hypoglycemic and hypolipidemic properties of A. platensis biomass, phycocyanins, and their chromophore - phycocyanobilin. Material and methods. For the main search of the literature, the PubMed Internet resource was used, the key component of which is the Medline article database, covering about 75% of the world's medical publications. In addition, Scopus and Web of Science databases were used. Search depth - 20 years. Search keywords: Arthrospira platensis, phycobiliprotein, C-phycocyanin, allophycocyanin, hypoglycemic effect, hypolipidemic effect, antioxidant activity, in vitro and in vivo studies. Results. A brief description of the composition of the cyanobacterium Arthrospira platensis biomass, methods of its cultivation, phycocyanins extraction methods is presented. The results of experimental studies indicate the presence of pronounced antioxidant properties of A. platensis biomass, mainly due to phycocyanins in its composition. The hypoglycemic and hypolipidemic effects of A. platensis biomass and extracted phycocyanins intake have been established in vivo when modeling carbohydrate and/or lipid metabolism disorders. The results of in vitro and in vivo studies indicate the presence of pronounced antioxidant properties of phycocyanins. Hypoglycemic effects are shown in particular in experiments on rats with hyperlipidemia and alloxan diabetes fed a diet enriched with A. platensis biomass and on KKAy mice, treated with C-phycocyanin extract. Conclusion. The analysis of the results of in vitro and in vivo studies of the antioxidant, hypoglycemic and hypolipidemic properties of A. platensis biomass and extracts with a high content of phycocyanins, presented in a brief review, suggests that their use in the diet of people with impaired carbohydrate and lipid metabolism is promising. Accordingly, from the standpoint of evidence-based medicine, clinical studies on the use of spirulina biomass and/or its extracts with a high content of phycocyanins as part of specialized foods intended for the prevention and/or dietary correction of carbohydrate and lipid metabolism disorders should be preceded by additional experimental physical-chemical, physiological and biochemical research.
The pandemic spread of coronavirus (COVID-19) has been reported first at the end of 2019. It continues disturbing various human aspects with multiple pandemic waves showing more fatal novel variants. Now Egypt faces the sixth wave of the pandemic with controlled governmental measures. COVID-19 is an infectious respiratory disease-causing mild to moderate illness that can be progressed into life-threatening complications based on patients- and variant type-related factors. The symptoms vary from dry cough, fever to difficulty in breathing that required urgent hospitalization. Most countries have authorized their national protocols for managing manifested symptoms and thus lowering the rate of patients’ hospitalization and boosting the healthcare systems. These protocols are still in use even with the development and approval of several vaccines. These protocols were instructed to aid home isolation, bed rest, dietary supplements, and additionally the administration of antipyretic, steroids, and antiviral drugs. The current review aimed to highlight the administered protocols in the Middle East, namely in Egypt and the Kingdom of Saudi Arabia demonstrating how these protocols have shown potential effectiveness in treating patients and saving many soles.
Background
: Transplant-associated thrombotic microangiopathy (TA-TMA) is a life-threatening complication for patients undergoing hematopoietic stem cell transplantation (HSCT). N-acetylcysteine (NAC) has recently been considered as a potential treatment for patients with thrombotic thrombocytopenic purpura.
Objectives
: To assess the value of NAC for the prevention of TA-TMA, we conducted a prospective study at the First Affiliated Hospital of Soochow University.
Study Design
: This open-label, randomized placebo-controlled trial included 160 patients who were scheduled to receive allogeneic HSCT. Participants were randomly assigned 1:1 to either oral NAC (50 mg/kg daily from 9 days before HSCT to 30 days after HSCT) or placebo treatment. The primary outcome was the incidence of TA-TMA. Overall survival (OS) and event-free survival (EFS) were assessed between NAC and placebo cohorts.
Results
: The incidence of TA-TMA in the NAC cohort was 9.1% (95% confidence interval (CI), 0.02-0.162), compared with 23% (95% CI, 0.132-0.328) in placebo cohort, with a rate ratio of 0.34 (95% CI, 0.123-0.911; p=0.039). The median time to onset of TA-TMA was 60 (interquartile range [IQR] 42-129) and 36 (IQR 30.5-51) days in the NAC and control groups, respectively (p=0.063). The 2-year rates of OS in the NAC and placebo groups were 75.4% (95% CI, 2.865-7.353) and 63.0% (95% CI, 0.508-0.735), respectively, with a hazard ratio (HR) of 0.622 (95% CI, 0.334-1.155; p=0.132). The EFS rate was 25.8% in NAC patients and 8.1% in placebo patients, with an HR of 0.254 (95% CI, 0.094-0.692; p=0.024). The median time of EFS was 60 and 38 days in NAC and placebo cohorts.
Conclusion
: Our findings suggest that NAC may be a potential treatment to reduce TA-TMA incidence.
Mushrooms are among the few natural products that have been relied upon for prophylactic and therapeutic applications in human diseases. They have been referred to as forest gems since they can be picked in the wild or better domesticated for appropriate use. Several scientific studies have been conducted to establish claimed potentials or further probe new areas into which mushrooms can find application. Many disciplines, including mycology, microbiology, physiology, chemistry, genetics, and medicine, among others, conduct research on mushrooms. These enable broad and in-depth studies of mushrooms, to include in vitro and in vivo demonstrations of their bioactivity, structural characterization, and isolation of bioactive components. This chapter highlights the bioactive composition of mushrooms by relating structure to bioactivity and demonstrating therapeutic effects on some human diseases using existing literature. The potentials of mushrooms or their products for the treatment or management of diseases, such as tropical illnesses and COVID-19 pandemic, among other issues, have been discussed. Chemistry of bioactive compounds, structure–activity relationships, patents, and analyses of data obtained have been reported and studied for interpretation of results.
It is known that lethal viruses profoundly manipulate host metabolism, but how the metabolism alternation affects the immediate host antiviral immunity remains elusive. Here, we report that the O-GlcNAcylation of mitochondrial antiviral-signaling protein (MAVS), a key mediator of interferon signaling, is a critical regulation to activate the host innate immunity against RNA viruses. We show that O-GlcNAcylation depletion in myeloid cells renders the host more susceptible to virus infection both in vitro and in vivo. Mechanistically, we demonstrate that MAVS O-GlcNAcylation is required for virus-induced MAVS K63-linked ubiquitination, thereby facilitating IRF3 activation and IFNβ production. We further demonstrate that D-glucosamine, a commonly used dietary supplement, effectively protects mice against a range of lethal RNA viruses, including human influenza virus. Our study highlights a critical role of O-GlcNAcylation in regulating host antiviral immunity and validates D-glucosamine as a potential therapeutic for virus infections.
RIG-I-MAVS antiviral signaling represents an important pathway to stimulate interferon production and confer innate immunity to the host. Upon binding to viral RNA and Riplet-mediated polyubiquitination, RIG-I promotes prion-like aggregation and activation of MAVS. MAVS subsequently induces interferon production by activating two signaling pathways mediated by TBK1-IRF3 and IKK-NF-κB respectively. However, the mechanism underlying the activation of MAVS downstream pathways remains elusive. Here, we demonstrated that activation of TBK1-IRF3 by MAVS-Region III depends on its multimerization state and identified TRAF3IP3 as a critical regulator for the downstream signaling. In response to virus infection, TRAF3IP3 is accumulated on mitochondria and thereby facilitates the recruitment of TRAF3 to MAVS for TBK1-IRF3 activation. Traf3ip3-deficient mice demonstrated a severely compromised potential to induce interferon production and were vulnerable to RNA virus infection. Our findings uncover that TRAF3IP3 is an important regulator for RIG-I-MAVS signaling, which bridges MAVS and TRAF3 for an effective antiviral innate immune response.
Glucans are part of a group of biologically active natural molecules and are steadily gaining strong attention not only as an important food supplement, but also as an immunostimulant and potential drug. This paper represents an up-to-date review of glucans (β-1,3-glucans) and their role in various immune reactions and the treatment of cancer. With more than 80 clinical trials evaluating their biological effects, the question is not if glucans will move from food supplement to widely accepted drug, but how soon.
Background and objective
Influenza A viruses (IAV) cause respiratory tract infections that can be fatal when the virus spreads to the alveolar space (i.e. alveolitis), and this is mainly observed with highly pathogenic strains. Reactive oxygen species (ROS) production by the NOX2 NADPH oxidase in endosomes has been directly implicated in IAV pathology. Recently, we demonstrated that treatment with a novel endosome‐targeted NOX2 oxidase inhibitor, cholestanol‐conjugated gp91dsTAT (Cgp91ds‐TAT), attenuated airway inflammation and viral replication to infection with a low pathogenic influenza A viral strain. Here, we determined whether suppression of endosome NOX2 oxidase prevents the lung inflammation following infection with a highly pathogenic IAV strain.
Methods
C57Bl/6 mice were intranasally treated with either DMSO vehicle (2%) or Cgp91ds‐TAT (0.2 mg/kg/day) 1 day prior to infection with the high pathogenicity PR8 IAV strain (500 PFU/mouse). At Day 3 post‐infection, mice were culled for the evaluation of airway and lung inflammation, viral titres and ROS generation.
Results
PR8 infection resulted in a marked degree of airway inflammation, epithelial denudation, alveolitis and inflammatory cell ROS production. Cgp91ds‐TAT treatment significantly attenuated airway inflammation, including neutrophil influx, the degree of alveolitis and inflammatory cell ROS generation. Importantly, the anti‐inflammatory phenotype affected by Cgp91ds‐TAT significantly enhanced the clearance of lung viral mRNA following PR8 infection.
Conclusion
Endosomal NOX2 oxidase promotes pathogenic lung inflammation to IAV infection. The localized delivery of endosomal NOX2 oxidase inhibitors is a novel therapeutic strategy against IAV, which has the potential to limit the pathogenesis caused during epidemics and pandemics.
The imminent threat of viral epidemics and pandemics dictates a need for therapeutic approaches that target viral pathology irrespective of the infecting strain. Reactive oxygen species are ancient processes that protect plants, fungi and animals against invading pathogens including bacteria. However, in mammals reactive oxygen species production paradoxically promotes virus pathogenicity by mechanisms not yet defined. Here we identify that the primary enzymatic source of reactive oxygen species, NOX2 oxidase, is activated by single stranded RNA and DNA viruses in endocytic compartments resulting in endosomal hydrogen peroxide generation, which suppresses antiviral and humoral signaling networks via modification of a unique, highly conserved cysteine residue (Cys98) on Toll-like receptor-7. Accordingly, targeted inhibition of endosomal reactive oxygen species production abrogates influenza A virus pathogenicity. We conclude that endosomal reactive oxygen species promote fundamental molecular mechanisms of viral pathogenicity, and the specific targeting of this pathogenic process with endosomal-targeted reactive oxygen species inhibitors has implications for the treatment of viral disease. Production of reactive oxygen species is an ancient antimicrobial mechanism, but its role in antiviral defense in mammals is unclear. Here, To et al. show that virus infection activates endosomal NOX2 oxidase and restricts TLR7 signaling, and that an endosomal NOX2 inhibitor decreases viral pathogenicity.
Previous work from our laboratory has demonstrated that infection with influenza A/Bangkok/1/79 (H3N2), a relatively mild strain of the virus, caused much more severe pneumonitis in selenium (Se)-deficient mice than in Se-adequate mice. Here we report that the increased virulence observed in the Se-deficient mice is due to mutations in the influenza virus genome, resulting in a more virulent genotype. Most of the mutations occurred in the gene for the M1 matrix protein, an internal protein that is thought to be relatively stable. A total of 29 nucleotide changes were observed in this gene, and all 29 changes were identical in three separate isolates taken from three different Se-deficient mice. In contrast, only one to three mutations were seen in the genes for the hemagglutinin or neuraminidase proteins, surface antigens that are known to be highly variable. Once the mutations have occurred, even hosts with normal nutritional status are susceptible to the newly virulent strain. This work, in conjunction with our earlier work with coxsackievirus, shows that specific nutritional deficiencies can have a profound impact on the genome of RNA viruses. Poor nutritional status in the host may contribute to the emergence of new viral strains.
Influenza is one of the most common human respiratory diseases, and represents a serious public health concern. However, the high mutability of influenza viruses has hampered vaccine development, and resistant strains to existing anti-viral drugs have also emerged. Novel anti-influenza therapies are urgently needed, and in this study, we describe the anti-viral properties of a Spirulina (Arthrospira platensis) cold water extract. Anti-viral effects have previously been reported for extracts and specific substances derived from Spirulina, and here we show that this Spirulina cold water extract has low cellular toxicity, and is well-tolerated in animal models at one dose as high as 5,000 mg/kg, or 3,000 mg/kg/day for 14 successive days. Anti-flu efficacy studies revealed that the Spirulina extract inhibited viral plaque formation in a broad range of influenza viruses, including oseltamivir-resistant strains. Spirulina extract was found to act at an early stage of infection to reduce virus yields in cells and improve survival in influenza-infected mice, with inhibition of influenza hemagglutination identified as one of the mechanisms involved. Together, these results suggest that the cold water extract of Spirulina might serve as a safe and effective therapeutic agent to manage influenza outbreaks, and further clinical investigation may be warranted.
Hepatitis C virus (HCV) infection-induced oxidative stress is a major risk factor for the development of HCV-associated liver disease. Sulforaphane (SFN) is an antioxidant phytocompound that acts against cellular oxidative stress and tumorigenesis. However, there is little known about its anti-viral activity. In this study, we demonstrated that SFN significantly suppressed HCV protein and RNA levels in HCV replicon cells and infectious system, with an IC50 value of 5.7 ± 0.2 μM. Moreover, combination of SFN with anti-viral drugs displayed synergistic effects in the suppression of HCV replication. In addition, we found nuclear factor erythroid 2-related factor 2 (Nrf2)/HO-1 induction in response to SFN and determined the signaling pathways involved in this process, including inhibition of NS3 protease activity and induction of IFN response. In contrast, the anti-viral activities were attenuated by knockdown of HO-1 with specific inhibitor (SnPP) and shRNA, suggesting that anti-HCV activity of SFN is dependent on HO-1 expression. Otherwise, SFN stimulated the phosphorylation of phosphoinositide 3-kinase (PI3K) leading Nrf2-mediated HO-1 expression against HCV replication. Overall, our results indicated that HO-1 is essential in SFN-mediated anti-HCV activity and provide new insights in the molecular mechanism of SFN in HCV replication.
Unlabelled:
Beta interferon (IFN-β) is involved in a wide range of cellular functions, and its secretion must be tightly controlled to inhibit viral spreading while minimizing cellular damage. Intracellular viral replication triggers cellular signaling cascades leading to the activation of the transcription factors NF-κB and interferon regulatory factor 3 (IRF3) and IRF7 (IRF3/7), which synergistically bind to the IFN-β gene promoter to induce its expression. The mitochondrial antiviral signaling protein (MAVS) is a governing adaptor protein that mediates signaling communications between virus-sensing proteins and transcription factors. The activity of MAVS in the regulation of IFN-β secretion is affected by many cellular factors. However, the mechanism of MAVS-mediated IRF3/7 activation is not completely understood. Here, we identified a highly conserved DLAIS motif at amino acid positions 438 to 442 of MAVS that is indispensable for IRF3/7 activation. Specifically, the L439S and A440R mutations suppress IRF3/7 activation. Pulldown experiments using wild-type and mutant MAVS showed that mindbomb E3 ubiquitin protein ligase 2 (MIB2) binds to the DLAIS motif. Furthermore, the DLAIS motif was found to be critical for MIB2 binding, the ligation of K63-linked ubiquitin to TANK-binding kinase 1, and phosphorylation-mediated IRF3/7 activation. Our results suggest that MIB2 plays a putative role in MAVS-mediated interferon signaling.
Importance:
Mitochondrial antiviral signaling protein (MAVS) mediates signaling from virus-sensing proteins to transcription factors for the induction of beta interferon. However, the mechanism underlying activation of MAVS-mediated interferon regulatory factors 3 and 7 (IRF3/7) is not completely understood. We found a highly conserved DLAIS motif in MAVS that is indispensable for IRF3/7 activation through TANK-binding kinase 1 (TBK1) and identified it as the binding site for mindbomb E3 ubiquitin protein ligase 2 (MIB2). The mutations that targeted the DLAIS motif abolished MIB2 binding, attenuated the K63-linked ubiquitination of TBK1, and decreased the phosphorylation-mediated activation of IRF3/7.
We and other investigators have reported that bilirubin and its precursor biliverdin may have beneficial effects on diabetic vascular complications, including nephropathy, via its antioxidant effects. Here, we investigated whether phycocyanin derived from Spirulina platensis, a blue-green algae, and its chromophore phycocyanobilin, which has a chemical structure similar to that of biliverdin, protect against oxidative stress and renal dysfunction in db/db mice, a rodent model for type 2 diabetes. Oral administration of phycocyanin (300 mg/kg) for 10 weeks protected against albuminuria and renal mesangial expansion in db/db mice, and normalized tumor growth factor-β and fibronectin expression. Phycocyanin also normalized urinary and renal oxidative stress markers and the expression of NAD(P)H oxidase components. Similar antioxidant effects were observed following oral administration of phycocyanobilin (15 mg/kg) for 2 weeks. Phycocyanobilin, bilirubin and biliverdin also inhibited NADPH oxidase-dependent superoxide production in cultured renal mesangial cells. In conclusion, oral administration of phycocyanin and phycocyanobilin may offer a novel and feasible therapeutic approach for preventing diabetic nephropathy.
Chronic inflammation and oxidative stress are common risk factors for atherosclerosis. Zinc is an essential micronutrient that can function as an antiinflammatory and antioxidative agent, and as such, it may have atheroprotective properties.
We hypothesized that zinc down-regulates the production of atherosclerosis-related cytokines/molecules in humans.
To examine these effects, we conducted a randomized, double-blinded, placebo trial of zinc supplementation in elderly subjects. We recruited 40 healthy elderly subjects (aged 56-83 y) and randomly assigned them to 2 groups. One group was given an oral dose of 45 mg zinc/d as a gluconate for 6 mo. The other group was given a placebo. Cell culture models were conducted to study the mechanism of zinc as an atheroprotective agent.
After 6 mo of supplementation, the intake of zinc, compared with intake of placebo, increased the concentrations of plasma zinc and decreased the concentrations of plasma high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, macrophage chemoattractant protein 1 (MCP-1), vascular cell adhesion molecule 1 (VCAM-1), secretory phospholipase A2, and malondialdehyde and hydroxyalkenals (MDA+HAE) in elderly subjects. Regression analysis showed that changes in concentrations of plasma zinc were inversely associated with changes in concentrations of plasma hsCRP, MCP-1, VCAM-1, and MDA+HAE after 6 mo of supplementation. In cell culture studies, we showed that zinc decreased the generation of tumor necrosis factor-alpha, IL-1beta, VCAM-1, and MDA+HAE and the activation of nuclear transcription factor kappaB and increased antiinflammatory proteins A20 and peroxisome proliferator-activated receptor-alpha in human monocytic leukemia THP-1 cells and human aortic endothelial cells compared with zinc-deficient cells.
These findings suggest that zinc may have a protective effect in atherosclerosis because of its antiinflammatory and antioxidant functions.
N-acetylcysteine (NAC), an analogue and precursor of reduced glutathione, has been in clinical use for more than 30 yrs as a mucolytic drug. It has also been proposed for and/or used in the therapy and/or prevention of several respiratory diseases and of diseases involving an oxidative stress, in general. The objective of the present study was to evaluate the effect of long-term treatment with NAC on influenza and influenza-like episodes. A total of 262 subjects of both sexes (78% > or = 65 yrs, and 62% suffering from nonrespiratory chronic degenerative diseases) were enrolled in a randomized, double-blind trial involving 20 Italian Centres. They were randomized to receive either placebo or NAC tablets (600 mg) twice daily for 6 months. Patients suffering from chronic respiratory diseases were not eligible, to avoid possible confounding by an effect of NAC on respiratory symptoms. NAC treatment was well tolerated and resulted in a significant decrease in the frequency of influenza-like episodes, severity, and length of time confined to bed. Both local and systemic symptoms were sharply and significantly reduced in the NAC group. Frequency of seroconversion towards A/H1N1 Singapore 6/86 influenza virus was similar in the two groups, but only 25% of virus-infected subjects under NAC treatment developed a symptomatic form, versus 79% in the placebo group. Evaluation of cell-mediated immunity showed a progressive, significant shift from anergy to normoergy following NAC treatment. Administration of N-acetylcysteine during the winter, thus, appears to provide a significant attenuation of influenza and influenza-like episodes, especially in elderly high-risk individuals. N-acetylcysteine did not prevent A/H1N1 virus influenza infection but significantly reduced the incidence of clinically apparent disease.
Previous work from our laboratory has demonstrated that infection with influenza A/Bangkok/1/79 (H3N2), a relatively mild strain of the virus, caused much more severe pneumonitis in selenium (Se)-deficient mice than in Se-adequate mice. Here we report that the increased virulence observed in the Se-deficient mice is due to mutations in the influenza virus genome, resulting in a more virulent genotype. Most of the mutations occurred in the gene for the M1 matrix protein, an internal protein that is thought to be relatively stable. A total of 29 nucleotide changes were observed in this gene, and all 29 changes were identical in three separate isolates taken from three different Se-deficient mice. In contrast, only one to three mutations were seen in the genes for the hemagglutinin or neuraminidase proteins, surface antigens that are known to be highly variable . Once the mutations have occurred, even hosts with normal nutritional status are susceptible to the newly virulent strain. This work, in conjunction with our earlier work with coxsackievirus, shows that specific nutritional deficiencies can have a profound impact on the genome of RNA viruses. Poor nutritional status in the host may contribute to the emergence of new viral strains.
Reactive oxygen intermediates (ROI) and cytokines, particularly tumor necrosis factor (TNF) have been implicated in the pathogenesis of influenza. Using a murine model of influenza, we have studied the levels of TNF, interleukin 6 (IL-6) and of superoxide-generating xanthine oxidase (XO). Mice infected intranasally with influenza virus APR/8 had high levels of XO, TNF and IL-6 in the broncoalveolar lavage, as early as 3 d after infection. XO was elevated also in serum and lung tissue. Administration of the antioxidant N-acetylcysteine (NAC,1 g/kg per day, orally) significantly decreased the mortality in infected mice, indicating a role for RO1 in the lethality associated with influenza infection.
Phycocyanin (Pc) is a phycobiliprotein that has been recently reported to exhibit a variety of pharmacological properties. In this regard, antioxidant, anti-inflammatory, neuroprotective and hepatoprotective effects have been experimentally attributed to Pc. When it was evaluated as an antioxidant in vitro, it was able to scavenge alkoxyl, hydroxyl and peroxyl radicals and to react with peroxinitrite (ONOO(-);) and hypochlorous acid (HOCl). Pc also inhibits microsomal lipid peroxidation induced by Fe(+2)-ascorbic acid or the free radical initiator 2,2' azobis (2-amidinopropane) hydrochloride (AAPH). Furthermore, it reduces carbon tetrachloride (CCl(4))-induced lipid peroxidation in vivo. Pc has been evaluated in twelve experimental models of inflammation and exerted anti-inflammatory effects in a dose-dependent fashion in all of these. Thus, Pc reduced edema, histamine (Hi) release, myeloperoxidase (MPO) activity and the levels of prostaglandin (PGE(2)) and leukotriene (LTB(4)) in the inflamed tissues. These anti-inflammatory effects of Pc can be due to its scavenging properties toward oxygen reactive species (ROS) and its inhibitory effects on cyclooxygenase 2 (COX-2) activity and on Hi release from mast cells. Pc also reduced the levels of tumor necrosis factor (TNF-alpha) in the blood serum of mice treated with endotoxin and it showed neuroprotective effects in rat cerebellar granule cell cultures and in kainate-induced brain injury in rats.
Oxidative stress is implicated in the pathogenesis of pulmonary damage during viral infections. In a previous study we observed a significant improvement of survival of influenza-infected mice with NAC, 1g/kg divided in two daily administrations, for 8 days including a pretreatment on day 1 before infection. In order to test NAC in a more realistic model, we studied the effect of combined treatment with NAC and the antiviral drug, ribavirin. Since in the present work we wanted to test a possible synergistic effect by combination of NAC and ribavirin, we used a different NAC's treatment regimen (1 g/kg, once a day for 4 days) that, alone, did not significantly protect mice from death. Mice (12 per group) infected intranasally with a lethal dose of influenza A virus APR/8. NAC was given as a single daily dose of 1000 mg/kg starting from 4 h after infection and until day 4 after infection, in association with ribavirin (100 mg/kg, i.p.). End-point evaluation was 14-day survival. With this schedule survival in infected mice was 17%, it was not significantly changed by NAC (25%). Survival increased to 58% with ribavirin and to 92% (n=12) with a combined treatment with ribavirin and NAC. This suggest that antioxidant therapy can increase survival by either improving the defenses against virus or by protecting from the pathogenesis of lung inflammation.
Zinc deficiency, cell-mediated immune dysfunction, susceptibility to infections, and increased oxidative stress have been observed in elderly subjects (ie, those >55 y old). Zinc is an effective antiinflammatory and antioxidant agent.
The primary objective was to determine the effect of zinc on the incidence of total infections in healthy elderly subjects. The secondary objective was to determine the effect of zinc on cytokines and oxidative stress markers.
A randomized, double-blind, placebo-controlled trial of zinc supplementation was conducted in elderly subjects. Fifty healthy subjects of both sexes aged 55-87 y and inclusive of all ethnic groups were recruited for this study from a senior center. The zinc-supplemented group received zinc gluconate (45 mg elemental Zn/d) orally for 12 mo. Incidence of infections during the supplementation period was documented. The generation of inflammatory cytokines, T helper 1 and T helper 2 cytokines, and oxidative stress markers and the plasma concentrations of zinc were measured at baseline and after supplementation.
Compared with a group of younger adults, at baseline the older subjects had significantly lower plasma zinc, higher ex vivo generation of inflammatory cytokines and interleukin 10, and higher plasma oxidative stress markers and endothelial cell adhesion molecules. The incidence of infections and ex vivo generation of tumor necrosis factor alpha and plasma oxidative stress markers were significantly lower in the zinc-supplemented than in the placebo group. Plasma zinc and phytohemagglutin-induced interleukin 2 mRNA in isolated mononuclear cells were significantly higher in the zinc-supplemented than in the placebo group.
After zinc supplementation, the incidence of infections was significantly lower, plasma zinc was significantly higher, and generation of tumor necrosis factor alpha and oxidative stress markers was significantly lower in the zinc-supplemented than in the placebo group.
Many studies have shown that oxidative stress is important in the pathogenesis of pulmonary damage during influenza virus infections. Antioxidant molecules are therefore potentially useful against viral infection. Our previous studies show that N-acetylcysteine (NAC) has a protective effect in a model of lethal influenza infection in mice. NAC administration significantly decreased the mortality in infected mice. Further studies have demonstrated that NAC enhanced survival in combination with the antiviral agent ribavirin. In the present study, we report the effect of combined treatment with NAC and Oseltamivir, clinically used in the treatment and prevention of influenza virus infection, in a murine model of lethal influenza infection. NAC was given as a single daily dose of 1000 mg/kg starting from 4 h before infection and until day 4 after infection; Oseltamivir was given twice daily at dose of 1 mg/kg/die for 5 days, starting from 4 h before infection. End-point evaluation was 21-days survival. NAC alone was slightly effective (20%), since a suboptimal treatment was used. Survival increased to 60% with Oseltamivir and to 100% with Oseltamivir and NAC used in combination. Since NAC alone does not show any antiviral action, the present findings suggest that antioxidant therapy increase survival by an improvement in host defense mechanisms, and/or by a direct antioxidant effect against oxidative stress associated with viral infection. Our studies demonstrate the effectiveness of combining agents acting through different mechanisms, such as antiviral drugs oseltamivir and the antioxidant NAC, indicating a possible advantage of combining the two treatments.
Influenza A virus (IAV) is highly contagious and causes considerable mortality worldwide. TLR3, 7, 8 and 9 recognize viral nucleic acids and rapidly trigger different signaling cascades that contribute to the production of interferons (IFNs) to antiviral defense. Therefore, a host immune response induced by the activation of these receptors can be used as a new antiviral strategy. In this study, the protective effect of sodium ferulate (SF) is investigated on mice infected with influenza virus A/FM/1/47(H1N1). SF improved survival and mitigated weight loss in infected mice. SF inhibited influenza virus replication by activating TLR7 and TLR9, which resulted in the promotion of IRF7 translocation into the nucleus and the production of typeⅠIFNs. Moreover, SF inhibited the NF-κB pathway by preventing p65 translocation from the cytoplasm to the nucleus. These findings demonstrate that SF plays a critical role in protection against IAV infection by activation of the TLR7/9-MyD88-IRF7 signaling pathway and inhibition of the NF-κB signaling pathway.
The innate immunity plays an essential role in defending infection of Influenza A virus (IAV). The regulatory effect of heme oxygenase-1 (HO-1), a cytoprotective enzyme, on innate immunity has been revealed. In this study, we aim to confirm the antiviral effect of CoPP (Cobaltic Protoporphyrin IX Chloride), a potent HO-1 inducer on IAV infection and elucidate the possible mechanism of HO-1-mediated host innate immune responses. Our results show that CoPP exhibits broad-spectrum antiviral activities against IAV. Furthermore, CoPP attenuates IAV replication through inducing type I IFNs response, not depending on HO-1 enzymatic activity. We also provide direct evidence that HO-1-mediated type I IFN response activation is largely due to its interaction with IRF3, which then promotes IRF3 phosphorylation and nuclear translocation. These results suggest that HO-1 agonist CoPP suppresses IAV replication through IRF3-mediated generation of IFN-α/β. Thus, therapeutic induction of HO-1 might be a promising strategy to combat IAV epidemics.
Upper respiratory symptoms are often treated with over the counter drugs, antibiotics, and antiviral medications. Due to concerns about safety and efficacy, there is a demand for an alternative solution. Black elderberry (Sambucus nigra) has been used to treat cold and flu symptoms, but there are no large-scale studies or meta-analyses. This meta-analysis quantifies the effects of elderberry supplementation and evaluates moderators including vaccination status and the underlying pathology. This analysis included a total of 180 participants and evaluates moderators such as vaccination status and cause of the upper respiratory symptoms. Supplementation with elderberry was found to substantially reduce upper respiratory symptoms. The quantitative synthesis of the effects yielded a large mean effect size. These findings present an alternative to antibiotic misuse for upper respiratory symptoms due to viral infections, and a potentially safer alternative to prescription drugs for routine cases of the common cold and influenza.
Although clinical trials with glucosamine in osteoarthritis have yielded mixed results, leading to doubts about its efficacy, the utility of glucosamine for preventing joint destruction and inflammation is well documented in rodent models of arthritis, including models of spontaneous osteoarthritis. The benefit of oral glucosamine in adjuvant arthritis is markedly dose dependent, likely reflecting a modulation of tissue levels of UDP-N-acetylglucosamine that in turn influences mucopolysaccharide synthesis and the extent of protein O-GlcNAcylation. Importantly, the minimal oral dose of glucosamine that exerts a detectible benefit in adjuvant arthritis achieves plasma glucosamine levels similar to those achieved when the standard clinical dose of glucosamine, 1.5 g daily, is administered as a bolus. The response of plasma glucosamine levels to an increase in glucosamine intake is nearly linear. Remarkably, every published clinical trial with glucosamine has employed the same 1.5 g dose that Rottapharm recommended for its proprietary glucosamine sulfate product decades ago, yet there has never been any published evidence that this dose is optimal with respect to efficacy and side effects. If this dose is on the edge of demonstrable clinical efficacy when experimental design is ideal, then variations in the patient populations targeted, the assessment vehicles employed, and the potency of glucosamine preparations tested could be expected to yield some null results. Failure to employ bolus dosing may also be a factor in the null results observed in the GAIT study and other trials. Clinical studies evaluating the dose dependency of glucosamine's influence on osteoarthritis are long overdue.
Glucosamine, used to treat osteoarthritis, has been shown to have anti-inflammatory and anti-atherosclerotic effects in experimental studies. A recent cohort study has demonstrated that the use of glucosamine was significantly associated with decreased total mortality. Vascular endothelial function is a potent surrogate marker of atherosclerosis and cardiovascular mortality where oxidative stress could participate. Therefore, we investigated whether glucosamine improves vascular endothelial function and intracellular redox state. We examined the effects of oral glucosamine administration (3000 mg/day) for 4 weeks on flow-mediated vasodilation (FMD) and intraerythrocyte glutathione parameters in 20 volunteers. Nineteen age-matched volunteers served as controls. Glucosamine administration significantly increased FMD (from 7.0 ± 2.3 to 8.7 ± 2.3%, P = 0.022). In the control group, FMD did not change. Glucosamine administration significantly increased intraerythrocyte total glutathione levels (from 212.9 ± 46.2 to 240.6 ± 49.4 μmol/L, P = 0.006), intraerythrocyte reduced form of glutathione (GSH) levels (from 124.7 ± 42.6 to 155.2 ± 47.7 μmol/L; P = 0.004) and intraerythrocyte GSH/oxidized form of glutathione (GSSG) ratios (from 3.18 ± 1.64 to 3.88 ± 1.61, P = 0.04). In the control group, any glutathione parameters did not change. Moreover, a stepwise multivariate analysis revealed percent change of GSH/GSSG is the only independent predictor for those of FMD (standardized β = 0.58, P = 0.007) in the glucosamine group. Glucosamine administration improved FMD in association with amelioration of intraerythrocyte GSH/GSSG ratios. These results suggest that oral glucosamine administration might improve vascular endothelial function by modulating intracellular redox state.
Type I Interferons (IFNs) is known for its antiviral activity; however, it is surprising that in vitro treatment of IFN-α and IFN-γ enhanced the replication of porcine circovirus type 2 (PCV2), indicating a complex relationship between interferon and PCV2. To date, it remains poorly understood how the interferon is produced during PCV2 infection and whether the interferon induced by PCV2 itself can promote viral replication. In this study, PCV2 induced the up-regulation of IFN-β in PK-15 cells, while treatment of PCV2-infected cells with the interferon regulatory factor-3 (IRF3) inhibitor, BX795, decreased the expression of IFN-β, whereas treatment with the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) inhibitor, BAY11-7082, did not. These findings indicate that PCV2 can induce IFN-β production via the IRF3-mediated rather than the NF-κB-mediated signal pathway. Moreover, PCV2 increased the protein expression levels of phosphorylation-IRF3 (p-IRF3), mitochondria antiviral-signaling protein (MAVS), retinoic acid-inducible gene I (RIG-1) and melanoma differentiation-associated protein 5 (MDA-5), and the knockdown of RIG-1 and MDA-5 decreased the expression level of IFN-β in PK-15 cells. Therefore, PCV2 induces IFN-β production via the RIG-1/MDA-5/MAVS/IRF signaling pathway. Furthermore, the PCV2 load and PCV2 infectivity decreased after knockdown of RIG-1 and MDA-5, indicating that RIG-1 and MDA-5 signaling pathways contribute to PCV2 replication. In conclusion, PCV2 induces the production of IFN-β via the RIG-1 and MDA-5 signaling pathways, and the IFN-β produced during PCV2 infection facilitates viral replication. These results will help us further understand the pathogenic mechanisms of PCV2.
Restricted dietary intakes of protein or essential amino acids tend to slow aging and boost lifespan in rodents, presumably because they downregulate IGF-I/Akt/mTORC1 signaling that acts as a pacesetter for aging and promotes cancer induction. A recent analysis of the National Health and Nutrition Examination Survey (NHANES) III cohort has revealed that relatively low protein intakes in mid-life (under 10 % of calories) are indeed associated with decreased subsequent risk for mortality. However, in those over 65 at baseline, such low protein intakes were associated with increased risk for mortality. This finding accords well with other epidemiology correlating relatively high protein intakes with lower risk for loss of lean mass and bone density in the elderly. Increased efficiency of protein translation reflecting increased leucine intake and consequent greater mTORC1 activity may play a role in this effect; however, at present there is little solid evidence that leucine supplementation provides important long-term benefits to the elderly. Aside from its potential pro-anabolic impact, higher dietary protein intakes may protect the elderly in another way—by providing increased amino acid substrate for synthesis of key protective factors. There is growing evidence, in both rodents and humans, that glutathione synthesis declines with increasing age, likely reflecting diminished function of Nrf2-dependent inductive mechanisms that boost expression of glutamate cysteine ligase (GCL), rate-limiting for glutathione synthesis. Intracellular glutathione blunts the negative impact of reactive oxygen species (ROS) on cell health and functions both by acting as an oxidant scavenger and by opposing the pro-inflammatory influence of hydrogen peroxide on cell signaling. Fortunately, since GCL’s K
m for cysteine is close to intracellular cysteine levels, increased intakes of cysteine—achieved from whole proteins or via supplementation with N-acetylcysteine (NAC)—can achieve a compensatory increase in glutathione synthesis, such that more youthful tissue levels of this compound can be restored. Supplementation with phase 2 inducers—such as lipoic acid—can likewise increase glutathione levels by promoting increased GCL expression. In aging humans and/or rodents, NAC supplementation has exerted favorable effects on vascular health, muscle strength, bone density, cell-mediated immunity, markers of systemic inflammation, preservation of cognitive function, progression of neurodegeneration, and the clinical course of influenza—effects which could be expected to lessen mortality and stave off frailty. Hence, greater cysteine availability may explain much of the favorable impact of higher protein intakes on mortality and frailty risk in the elderly, and joint supplementation with NAC and lipoic acid could be notably protective in the elderly, particularly in those who follow plant-based diets relatively low in protein. It is less clear whether the lower arginine intake associated with low-protein diets has an adverse impact on vascular health.
Objective: To assess the association of ocular disorders and high doses of antioxidants or zinc with mortality in the Age-Related Eye Disease Study (AREDS). Methods: Baseline fundus and lens photographs were used to grade the macular and lens status of AREDS participants. Participants were randomly assigned to receive oral supplements of high-dose antioxidants, zinc, antioxidants plus zinc, or placebo. Risk of all-cause and cause-specific mortality was assessed using adjusted Cox proportional hazards models. Results: During median follow-up of 6.5 years, 534 (11%) of 4753 AREDS participants died. In fully adjusted models, participants with advanced age-related macular degeneration (AMD) compared with participants with few, if any, drusen had increased mortality (relative risk [RR], 1.41; 95% confidence interval [CI], 1.08-1.86). Advanced AMD was associated with cardiovascular deaths. Compared with participants having good acuity in both eyes, those with visual acuity worse than 20/40 in 1 eye had increased mortality (RR, 1.36; 95% CI, 1.12-1.65). Nuclear opacity (RR, 1.40; 95% CI, 1.12-1.75) and cataract surgery (RR, 1.55; 95% CI, 1.18-2.05) were associated with increased all-cause mortality and with cancer deaths. Participants randomly assigned to receive zinc had lower mortality than those not taking zinc (RR, 0.73; 95% CI, 0.61-0.89). Conclusions: The decreased survival of AREDS participants with AMD and cataract suggests that these conditions may reflect systemic rather than only local processes. The improved survival in individuals randomly assigned to receive zinc requires further study.
The strong immunostimulating potential of β-glucans has been well established in numerous diseases. However, the effects on viral infection were less studied.
In our study, we focused on possible effects of a special combined glucan formulation on immunosuppression caused by influenza infection.
We found that a 2-week oral feeding with glucan mixture significantly reduced the effects of influenza infection in total mortality. Our study was focused on phagocytosis, cytokine levels, antibody response and cytotoxicity assay.
Based on our data, we concluded that these effects are caused by stimulation of both cellular and humoral immune reaction resulting in lower viral load.
This study investigated the effect of ferulic acid (FA) on the up-regulation of heme oxygenase-1 (HO-1) in lymphocytes and the molecular mechanisms involved. Lymphocytes were treated with FA (0.001-0.1 μM) for certain times. Cell viability, the activity and level of expression of HO-1, and signal pathways were analyzed. FA significantly up-regulated HO-1 expression both at the level of mRNA and protein in lymphocytes. Moreover, FA-induced NF-E2-related factor (Nrf2) nuclear translocation and transcriptional activity, which is upstream of FAinduced HO-1 expression. In addition, lymphocytes treated with FA exhibited activation of extracellular regulated kinase (ERK) and treatments with U0126 (an ERK kinase inhibitor) attenuated the FA-induced activation of Nrf2, resulting in a decrease in HO-1 expression. Zinc protoporphyrin (ZnPP, a HO-1 inhibitor) markedly suppressed cytoprotection from radiation-induced cell damage by FA. Results suggested that the ERK signaling pathway controlled the anti-oxidation of FA by regulating the expression of the antioxidant enzyme HO-1.
This study investigated the effect of ferulic acid (FA) on the up-regulation of heme oxygenase-1 (HO-1) in lymphocytes and the molecular mechanisms involved. Lymphocytes were treated with FA (0.001-0.1 μM) for certain times. Cell viability, the activity and level of expression of HO-1, and signal pathways were analyzed. FA significantly upregulated HO-1 expression both at the level of mRNA and protein in lymphocytes. Moreover, FA induced NF-E2-related factor (Nrf2) nuclear translocation and transcriptional activity, which is upstream of FA induced HO-1 expression. In addition, lymphocytes treated with FA exhibited activation of extracellular regulated kinase (ERK) and treatments with U0126 (an ERK kinase inhibitor) attenuated the FA induced activation of Nrf2, resulting in a decrease in HO-1 expression. Zinc protoporphyrin (ZnPP, a HO-1 inhibitor) markedly suppressed cytoprotection from radiation-induced cell damage by FA. Results suggested that the ERK signaling pathway controlled the anti-oxidation of FA by regulating the expression of the antioxidant enzyme HO-1.
Unlabelled:
The anti-inflammatory and antiapoptotic heme degrading enzyme heme oxygenase-1 (HO-1) has been shown recently to interfere with replication of hepatitis C virus (HCV). We investigated the effect of HO-1 products carbon monoxide (CO), iron and biliverdin on HCV replication using the replicon cell lines Huh-5-15 and LucUbiNeo-ET, stably expressing HCV proteins NS3 through NS5B. Incubation of these cell lines in the presence of the CO donor methylene chloride transiently reduced HCV replication, whereas an increase of iron in cell culture by administration of FeCl(3) or iron-saturated lactoferrin did not interfere with HCV replication. Likewise, depletion of iron by deferoxamine during induction of HO-1 by cobalt-protoporphyrin IX did not restore HCV replication. The most prominent effect was observed after incubation of replicon cell lines in the presence of biliverdin. Biliverdin seems to interfere with HCV replication-mediated oxidative stress by inducing expression of antiviral interferons, such as interferon alpha2 and alpha17.
Conclusion:
The antioxidant biliverdin reduces HCV replication in vitro by triggering the antiviral interferon response and might improve HCV therapy in the future.
A wide array of dietary phytochemicals have been reported to induce the expression of enzymes involved in both cellular antioxidant defenses and elimination/inactivation of electrophilic carcinogens. Induction of such cytoprotective enzymes by edible phytochemicals largely accounts for their cancer chemopreventive and chemoprotective activities. Nuclear factor-erythroid-2-related factor 2 (Nrf2) plays a crucial role in the coordinated induction of those genes encoding many stress-responsive and cytoptotective enzymes and related proteins. These include NAD(P)H:quinone oxidoreductase-1, heme oxygenase-1, glutamate cysteine ligase, glutathione S-transferase, glutathione peroxidase, thioredoxin, etc. In resting cells, Nrf2 is sequestered in the cytoplasm as an inactive complex with the repressor Kelch-like ECH-associated protein 1 (Keap1). The release of Nrf2 from its repressor is most likely to be achieved by alterations in the structure of Keap1. Keap1 contains several reactive cysteine residues that function as sensors of cellular redox changes. Oxidation or covalent modification of some of these critical cysteine thiols would stabilize Nrf2, thereby facilitating nuclear accumulation of Nrf2. After translocation into nucleus, Nrf2 forms a heterodimer with other transcription factors, such as small Maf, which in turn binds to the 5'-upstream CIS-acting regulatory sequence, termed antioxidant response elements (ARE) or electrophile response elements (EpRE), located in the promoter region of genes encoding various antioxidant and phase 2 detoxifying enzymes. Certain dietary chemopreventive agents target Keap1 by oxidizing or chemically modifying one or more of its specific cysteine thiols, thereby stabilizing Nrf2. In addition, phosphorylation of specific serine or threonine residues present in Nrf2 by upstream kinases may also facilitate the nuclear localization of Nrf2. Multiple mechanisms of Nrf2 activation by signals mediated by one or more of the upstream kinases, such as mitogen-activated protein kinases, phosphatidylionositol-3-kinase/Akt, protein kinase C, and casein kinase-2 have recently been proposed. This review highlights the cytoprotective gene expression induced by some representative dietary chemopreventive phytochemicals with the Nrf2-Keap1 system as a prime molecular target.