In addition, no significant changes were seen following lutein supplementation table 2 , although due to a technical problem, LFA-3 expression was not evaluated in this study. There were no significant changes in the relative number of MHC class II molecules expressed on blood monocytes following lycopene supplementation, but there was a significant increase in LFA-1 expression table 3.

In contrast, the only significant difference seen in the lutein study was a decrease in the expression of HLA-DQ table 3. Relative median intensity of fluorescence of each monocyte surface molecule.

To investigate whether this effect of β-carotene was common to other dietary carotenoids, we undertook two further studies. Both studies had the same design and level of supplementation: dietary enrichment with lycopene study 1 and with lutein study 2. The only common effect we observed between either of these studies and our previous trial with β-carotene was an increase in the expression of HLA-DR following supplementation with lycopene.

In contrast to β-carotene, no changes were observed in the expression of ICAM-1 or LFA-3 in either study; however, there was a significant increase in the expression of LFA-1 following lycopene supplementation, which was not seen after either β-carotene or lutein supplementation.

The less striking effect of either lycopene or lutein supplementation on monocyte surface marker expression than seen after β-carotene supplementation might be related to the lower plasma levels found after supplementation.

We previously observed a possible threshold effect of plasma β-carotene concentration on the expression of ICAM-1 and LFA-3 [ 14 ], and it is possible that the plasma levels of lycopene or lutein achieved in our studies were not high enough to cause a significant change in the expression of most of the monocyte surface molecules examined.

The reason for the difference in plasma levels of these carotenoids following the same level of supplementation is uncertain but could reflect differences in their uptake, metabolism, and excretion or the selective sequestration of different carotenoids to specific sites in the body.

It is unlikely that absorption of lycopene from the supplements provided is a problem, since the bioavailability of lycopene from tomato juice and dietary supplements is very similar [ 21 ].

However, lycopene is found in higher concentrations in the prostate [ 22 ] than in serum, which might contribute to the reduced prostate cancer risk associated with the consumption of tomato-based foods [ 23 ]. It is possible that not all beneficial effects bestowed by carotenoids are observed systemically, instead being found only at specific locations in the body.

We know of only one other group that has reported the comparative effects of dietary enrichment with different carotenoids on human immune function, and that group also found contrasting effects.

These findings emphasize that different carotenoids can affect immune function in different ways. The possibility of an interactive or additive effect of different carotenoids on immune function is also suggested by the results of a study undertaken in a group of premenopausal women.

Following dietary depletion of carotenoids, mitogen-stimulated lymphocyte proliferation was reduced compared with baseline. This suppression was not corrected with low-level β-carotene supplementation 0.

Therefore, in fruits and vegetables, the influence of the combination of carotenoids they contain on immune function may represent the sum total of different effects and synergistic effects within these combinations [ 26 ].

There are several potential mechanisms for an effect of carotenoids on the immune system. It is possible that their ability to quench singlet oxygen an energized form of oxygen capable of generating free radicals might lower the free radical burden and protect membrane lipids from peroxidation.

Free radicals suppress the expression of the major MHC class II molecule, HLA-DR [ 27 ], and we recently showed that dietary supplementation with fish oil containing n-3 polyunsaturated fatty acids PUFAs , which are more vulnerable to lipid peroxidation than saturated fatty acids, inhibits the expression of HLA-DR and ICAM-1 on human monocytes [ 18 ].

However, although there were changes in plasma fatty acid composition associated with the different supplements, there was no evidence that enriching the diets with these carotenoids engenders antioxidant effects that lead to a widespread conservation of plasma PUFAs [ 20 ].

Nevertheless, it is possible that the antioxidant properties of carotenoids might still act to modulate immune cell function by modulating the activity of redox-sensitive transcription factors.

It is now appreciated that the transcription factor nuclear factor-κB NF-κB is required for maximal transcription of many inflammatory cytokines and adhesion molecules, and it is thought that the generation of reactive oxygen species is a vital link in mediating NF-κB activation by a variety of stimuli [ 28 , 29 ].

Therefore, it is possible that antioxidant nutrients can influence a variety of inflammatory processes by inhibiting NF-κB activity.

If so, this might explain the decrease in surface expression of LFA-1 on monocytes following dietary supplementation with lutein, but the opposite effect following β-carotene supplementation cannot be explained by this mode of action. The divergent effects seen with different carotenoids might be explained by the preferred location of these compounds within the cell.

Carotenoids are lipid soluble and thus will be concentrated in the lipid-rich membranes of the cell. However, their exact location may influence their effectiveness in modulating specific cellular events. To date, little work has been undertaken to explore the distribution of individual carotenoids within mammalian cells.

Changes in eicosanoid production can also influence the expression of cell membrane molecules. Prostaglandin PG E2, the major eicosanoid synthesized by monocytes and macrophages, possesses a number of immunosuppressive properties. For instance, it can inhibit the expression of Ia molecules the murine equivalent of human MHC class II molecules on stimulated macrophages [ 30 ].

It has been suggested that one mechanism by which β-carotene might enhance immune responses is by altering the activation of the arachidonic acid cascade from which PGE2 is derived , since β-carotene suppresses the generation of arachidonic acid products in vitro from nonlymphoid tissues [ 31 ].

The possibility that other carotenoids can modulate the arachidonic acid pathway has not yet been investigated. In summary, we found that day supplementation with lycopene or lutein, at a dietary achievable level, did not produce as striking an effect on the expression of peripheral blood monocyte surface molecules as we observed following β-carotene supplementation.

Thus, if enhancement of these surface molecules is a mechanism by which antioxidant nutrients can enhance immune responsiveness and consequently defense against infection and tumor development, our results suggest that β-carotene is more effective than lycopene or lutein.

We thank the volunteers from the Norfolk Fire Service Headquarters, Hethersett, and the Institute of Food Research, Norwich, for taking part in these studies. Google Scholar. Google Preview. Informed consent was obtained from all volunteers in these studies. The studies were approved by the ethics committee, Institute of Food Research.

Financial support: Ministry of Agriculture, Fisheries and Food, UK. Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide.

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Materials and Methods. Journal Article. Effects of Lycopene and Lutein Supplementation on the Expression of Functionally Associated Surface Molecules on Blood Monocytes from Healthy Male Nonsmokers. Hughes , David A. Diet, Health and Consumer Science Division, Institute of Food Research, Norwich Research Park.

Reprints or correspondence: Dr. Hughes, Diet, Health and Consumer Science Division, Institute of Food Research, Norwich Research Park, Colney, Norwich, Norfolk, NR4 7UA, UK davida. hughes bbsrc. Oxford Academic. Anthony J. Paul M. Abigael C.

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Abstract It has been suggested that dietary carotenoids can enhance immune function. Table 1. Open in new tab Download slide. Table 2. Percentage of monocytes expressing each surface molecule. Table 3. Effects of dietary antioxidants on the immune function of middle-aged adults.

Google Scholar Crossref. Search ADS. Natural killer cell activity in elderly men is enhanced by beta-carotene supplementation. Google Scholar PubMed. OpenURL Placeholder Text.

Effect of vitamin and trace-element supplementation on immune responses and infection in elderly subjects. Dietary carotenes vitamin C and vitamin E as protective antioxidants in human cancers.

Quantitative variation in Ia antigen expression plays a central role in immune regulation. The effect of beta-carotene supplementation on the immune function of blood monocytes from healthy male non-smokers. The correlation between two dietary assessments of carotenoid intake and plasma carotenoid concentrations: application of a carotenoid food-composition database.

Development evaluation of an HPLC method for the analysis of carotenoids in foods and the measurement of the carotenoid content of vegetables and fruits commonly consumed in the UK. Enhancement of the antigen-presenting function of monocytes by cholesterol: possible relevance to inflammatory mechanisms in extrinsic allergic alveolitis and atherosclerosis.

Fish oil supplementation inhibits the expression of major histocompatibility complex class II molecules and adhesion molecules on human monocytes. Google Scholar Google Preview OpenURL Placeholder Text.

Beta-carotene lycopene but not lutein supplementation changes the plasma fatty acid profile of healthy male non-smokers. Chronic ingestion of lycopene-rich tomato juice or lycopene supplements significantly increases plasma concentrations of lycopene and related tomato carotenoids in humans.

Modulation of human T-lymphocyte functions by the consumption of carotenoid-rich vegetables. Modulated mitogenic proliferative responsiveness of lymphocytes in whole-blood cultures after a low-carotene diet and mixed-carotenoid supplementation in women.

Beta-carotene and immune function: is it a case of defining the right intake? Modulation of interferon-gamma—induced HLA-DR expression on the human keratinocyte cell line SCC by ultraviolet radiation. Inhibition of arachidonic acid oxidation by beta-carotene retinol and alpha-tocopherol.

Issue Section:. Such pro-inflammatory endothelium changes, on the other hand, appear to occur even when there is no significant vascular inflammation. It's possible that if pericytes become infected with SARS-CoV-2, they'll become immunological targets.

The increase in inflammation in severe COVID cases could be due to the spread of microvascular inflammation Varga et al.

Currently there are no treatment medicines that have been demonstrated to be effective against the virus Ofuyatan et al. As a result of the pandemic, many supportive medications, such as ivermectin, and remdesivir which reduce viral RNA activity, were deployed.

In combination with favipiravir, nafamostat mesylate therapy may allow for virus entry and replication suppression as well as prevention of the pathogenic host response, i. hyper-coagulopathy Ikeda et al. The most promising antiviral agent is remdesivir, which has been licensed by the FDA for emergency use, although clinical trials are still underway Mahboobipour and Baniasadi ; Wang et al.

Immunotherapy can be employed in the most serious and life-threatening situations. Immunotherapy should not be given to patients who are currently unwell, such as those who have tuberculosis Prattes et al. The MERS and SARS outbreaks generated interest in such viruses, and researchers have found several antiviral targets, including polymerases, entry proteins, and viral proteases.

However, more work is still needed to create drugs that target these pathways and can inhibit viral replication. Because SARS-CoV2 is an RNA virus, it can be detected using any of the existing RNA detection formats.

When nasopharyngeal swabs are initially negative, repeat testing can be done to boost the chances of discovering SARS-CoV-2 in the nasopharynx Loeffelholz and Tang Globally, COVID treatment strategies are still limited.

Vitamin VA has pharmacological efficacy in the treatment of pneumonia, it could be used in a SARS-CoV-2 antiviral treatment. VA's methods of action against SARS-CoV-2, according to bioinformatics research, include immunoreaction enrichment, inflammatory reaction suppression, and biological processes involving reactive oxygen species Li et al.

In humans, high amounts of lycopene can be found in the prostate, testes human plasma, and adrenal gland. Lycopene was shown to improve the status of enzymatic activity in the cell and act as an important antioxidant—both enzymatic catalase, glutathione reductase, and superoxide dismutase and nonenzymatic vitamins B, E, and C, carotenoids, and carnitines antioxidants under normal operating conditions Durairajanayagam et al.

Lycopene is a natural antioxidant, anti-inflammatory, and antiviral agent that can help prevent and treat inflammatory diseases like COVID Lycopene is a non-provitamin A and is well known for its antioxidant properties.

Lycopene could be an effective pharmacological therapy for treating liver damage induced by long-term CS treatment Rocha et al. In finishing pigs, dietary lycopene supplementation improved intestinal shape, and tight junction function inhibited inflammatory response and increased antioxidant capacity Liu et al.

Currently, there is no effective anti-SARS-CoV-2 drug available to treat COVID patients worldwide. In many diverse cultures, natural herbal treatments have been utilized for a long time to treat ailments. The effectiveness of traditional remedies produced from medicinal plants has contributed to the success of modern medicine.

Antiviral drugs given early after the onset of symptoms can reduce viral shedding in patients' respiratory secretions, which lowers the risk of infection for contacts of those who are receiving treatment. The most prevalent clinical problems associated with the antiviral drug have been reported to be decreased appetite, constipation, and diarrhea Ağagündüz et al.

Remdesivir has been shown to have viral activity against coronaviruses in both Vitro and Vivo studies. Remdesivir inhibits SARS-CoV-2 SARS-CoV-2 RdRp replication, suppresses viral load, and protects animals infected with SARS-CoV-2 Frediansyah et al.

Therefore, the most promising Remdesivir antiviral drugs were taken into consideration to assess both their effectiveness and potential side effects on individuals with varying levels of COVID Additionally, type I interferons are immunomodulatory medications that have been effective in treating COVID early on because they have antiviral and pro-inflammatory properties Hossain et al.

Understanding food-drug interactions are essential for improving the health of patients. Some antiviral drugs, including hydroxychloroquine, umifenovir, remdesvir, favipiravir, ribavirin, lopinavir, nitazoxanide, and oseltamivir, have the capability to interfere with food-drug and nutrition-drug interactions.

However, it has been noted that the use of these drugs may have some negative adverse effects and comorbidities. Furthermore, the pharmacokinetic and pharmacodynamic alterations generated by these supportive care drugs can impact nutrient metabolism both acutely and chronically Ağagündüz et al.

The molecular docking analysis revealed that 20 naturally occurring molecules from popular Iranian medicinal plants such as astragalin, adlumidine, chelidimerine, catechin gallate, rutin, fumariline, somniferine, etc. have antiviral properties that could protect individuals from contracting SARS-CoV-2 due to their potent binding patterns to the pocket of SARS-CoVRdRp.

As a result, these molecules act as inhibitors of the SARS-CoV-2 M pro and RBD receptors Mousavi et al. Lycorine, gemcitabine, and oxysophoridine are examples of bioactive alkaloids extracted from Chinese herbal remedies that have antiviral activity against SARS-CoV The three compounds have also been reported to inhibit SARS-CoV-2 replication in Vero E6 cells at noncytotoxic concentrations.

Zhang et al. Phytochemicals extracted from Avicennia officinalis have excellent antioxidant and cytotoxic properties. Using molecular docking assays, the three compounds hydrocinnamic acid, dihydroartemisinin, and phenethyl alcohol reported the highest binding affinities against the main protease of SARS-CoV As a result, A.

officinalis fruit and leaf extract compounds could be employed therapeutically in response to COVID Mahmud et al. Andrographis paniculate extracts and their andrographolide component significantly inhibited the SARS-CoV-2 in Calu-3 cells through their anti-SARS-CoV-2 activities Sa-Ngiamsuntorn et al.

Scutellaria baicalensis Georgi, a traditional medicine with several pharmacological properties, contains the major active component baicalein. As a result, baicalein may be a potential therapeutic solution for COVID treatment Song et al.

Curcumin has antiviral and anti-inflammatory properties, and it could be used to treat COVID patients by reducing pro-inflammatory cytokine levels in the blood Amalraj et al. Flavonoids and the medicinal plants from which they are derived have a wide range of biological applications, including antioxidants, antivirals, antifungals, antibacterial, anti-inflammatory agents, and so on.

Flavonoids and antiviral drugs mundulinol and luteolin have the maximum binding affinity and can act as potential inhibitors for the M pro and SP of SARS-CoV-2 as compared to the antiviral drugs that are being used in COVID treatment Abd El-Mageed et al.

The polyphenols extracted from the leaves and bud of Camellia sinensis were found to have potent antiviral activities and powerful M pro inhibitors. It has also been reported that a large number of C. sinensis polyphenols such as theaflavin TF1 , theaflavin-3O-O-gallate TF2a , theaflavin-3O-gallate TF2b , theaflavin-3,3O-gallate TF3 , epicatechingallate EGCG , myricetin, hesperidin, and quercetin serve as SARS-CoV-2 RdrP inhibitors Tallei et al.

Naringenin exhibited moderate anti-SARS-CoV-2 efficacy and its treatment potential for COVID infection. It was observed that it reduced the expression of ACE2, SARS-CoV-2 3CLpro inhibition, and targeted TPCs in Vero E6 cells Abdallah et al.

COVID patients have been linked to a wide spectrum of symptoms, from moderate to severe. The most common are headache, cough, fever or chill, vomiting, difficulty breathing, lack of smell or taste, body aches, and fatigue.

However, many patients also have congestion, dyspnea, cardiac damage, multi-organ failure, and shock. Symptoms emerge 2—14 days after exposure to the virus Zhong et al. A nasopharyngeal or oropharyngeal swab is used to diagnose a patient, which permits the virus to be isolated and verifies the infection Holshue et al.

Severe COVID patients might suffer a second set of symptoms and problems later in the disease's progression, including neurological manifestations, pulmonary embolism, stroke, myocardial infection, acute renal injury, and venous and arterial thrombosis.

In COVID, extrapulmonary symptoms have a substantially higher death rate than pulmonary signs Diao et al. When the virus enters the host, the viral RNA genome is released into the host cell cytoplasm and then replicates.

The ACE2 receptor is being used by the SARS-CoV-2 virus to enter cells Fig. SARS-CoV-2 can be transmitted through direct human-to-human and indirect contact airborne contagion and contaminated objects.

This virus can persist in the human body for at least four days Bandyopadhyay ; Chu et al. The spread of COVID to healthcare personnel poses the greatest danger.

The spike protein's furin-cleaved S1 component binds directly to NRP1 on the cell surface, and utilizing a small-molecule inhibitor or monoclonal antibodies to block this interaction prevented virus replication in cell culture Cantuti-Castelvetri et al.

SARS-CoV-2 binds to ACE 2 as the host target cell receptor, resulting in viral cell fusion with the host cell membrane via transmembrane serine protease 2. The pathogenic characteristics of COVID are strikingly similar to those of SARS and MERS coronavirus infections but have a lower overall fatality rate.

In severe cases of COVID infection, the cytokine storm could trigger a strong immune system attack on the host, resulting in ARDS, multiple organ failure, and death Li et al. Currently, it is considered that these coronaviruses can only survive for a few days outside of living cells in the environment, but this may be enough time for them to spread to other organisms, mutate and change their properties, and so on.

For the foreseeable future, a variety of situations should be addressed Núñez-Delgado In DT-induced mice, lycopene therapy improved mitochondrial performance by reducing oxidative stress, heart hypertrophy, cardiac fatty acid accumulation and viral infection Wang et al.

Lycopene has a protective effect against an increase in the serum level of creatine kinase MB in individuals undergoing percutaneous coronary intervention PCI. This could point to lycopene's possible function in preventing PCI-induced myocardial damage Arakeri et al.

Age, male gender, and underlying health issues like asthma, diabetes, cardiovascular disease, obesity, neurological, diabetes, hypertension, chronic lung diseases, and kidney diseases, all of which are thought to be the risk factors for COVID 19 Table 1.

The majority of the patients exhibited lymphopenia, thrombocytopenia, abnormal liver functions, and immune responses Goyal et al. SARS-CoV-2 is mostly a respiratory infection, but it has the potential to impact other organ systems as well.

COVID has been demonstrated to disrupt practically every organ system, including the heart, brain, vascular, hematopoietic, liver, skin, and others, causing concerns such as abrupt cardiac failure, thrombosis, immunological dysfunction, and metabolic abnormalities Li et al.

Diabetes, dyslipidemia, and oxidative stress are examples of proatherogenic stimuli that can cause endothelial dysfunction and, as a result, vascular dysfunction, leading to the development of atherosclerotic arterial disease, which can lead to coronary artery disease, acute coronary syndrome, stroke, and thrombosis.

The disorders have also been linked to severe COVID infections Chistiakov et al. COVID patients with severe CKD have a far higher risk of mortality than other known high-risk categories, such as those with obesity, hypertension, chronic heart disease, or lung illness Gansevoort and Hilbrands Pregnant women are also at a high risk of contracting COVID, because the presence of ACE2 receptors in the placenta may further increase the risk of virus transmission from mother to baby.

Normal pregnancy and COVID both have decreased lymphocytes and NKG2A inhibitory receptors, as well as elevated ACE2 Fig. Obesity was linked to a threefold increase in the risk of COVID Diabetes patients are more likely to develop an inflammatory storm, which leads to the rapid deterioration of COVID Guo et al.

Increased levels of ACE 2 could be one of the mechanisms by which COVID patients are affected by cardio-cerebrovascular illness. Patients with the cardio-cerebrovascular disease were more prone to developing a myocardial injury, increasing their risk of becoming critically ill and dying Yu et al.

Severe patients had lower levels of hemoglobin, monocytes, lymphocytes, eosinophils, and platelet counts than non-severe patients while having higher neutrophil counts among the CBC indices. Innate and adaptive immunity in women is stronger, and they are more resistant to viral infections than men Flanagan et al.

In children with COVID, blood levels of TNF-α and IL-6 were increased at diagnosis than in children with other infectious illnesses. However, these cytokine levels did not correspond with disease severity, which is likely due to the fact that the small cohort included mostly moderate cases Curatola et al.

Children who contract the SARS-CoV-2 have better results than adults Qian et al. Due to a less robust immune response, older age was linked to a higher risk of developing ARDS and death. Although the high temperature was linked to the development of ARDS, it was also linked to improved outcomes in ARDS patients.

Furthermore, methylprednisolone medication may be advantageous for people who develop ARDS Wu et al. This diagram demonstrates the entry of SARS-CoV-2 into the cell, as well as potential lycopene-based prevention measures Cantuti-Castelvetri et al.

Severe COVID infection is characterized by a large pro-inflammatory response or cytokine storm, which ultimately in ARDS and multi-organ failure. During COVID infection, proinflammatory cytokines are released, causing infection of endothelial inflammation. When pro-inflammatory cytokines activate endothelial cells, they become more permeability to macromolecules that might cause extensive lung damage Varga et al.

The cytokine release syndrome CRS can occur directly as a result of viral damage or indirectly by overactivation of the immune system that triggers the infiltration of immune cells such as neutrophils and macrophages into the tissue.

COVID Patients may experience mild to moderate symptoms due to massive cytokine production, which typically leads to elevated inflammation markers, and disease severity Darif et al.

A cytokine release syndrome CRS was linked to COVID The inflammatory pathway that promotes lung parenchymal injury and thromboembolic events appears to be triggered by CRS. Interleukin-6 is a key cytokine in the development of CRS, which causes hyper-inflammation, ALI, and, in some cases, irreversible lung tissue damage Alharthy et al.

SARS-CoV-2 infection increases the number of ACE2-positive endothelial cells in COVIDinduced respiratory failure ARDS. SARS-CoV-2 infection of endothelial cells produces endothelial cell swelling and disintegration, abnormal microvascular architecture, and endothelial dysfunction Ackermann et al.

ACE2 is a protein found in various human organs that serves as a negative regulator of the renin-angiotensin system. Patients with aberrant pulmonary inflammation and immune responses can have either very high or very low ACE2 levels Sodhi et al.

COVID severity is linked to secondary haemophagocytic lymphohistiocytosis sHLH , and several studies have found a significant increase in levels of various cytokines and chemokines such as TNF-α, IL-2, IL-7, macrophage inflammatory protein 1-α, interferon-γ inducible protein 10, granulocyte colony-stimulating factor, and monocyte chemoattractant protein 1 Huang et al.

IL-6 is a key proinflammatory cytokine that also plays a role in inflammation, immune system modulation, and hematopoiesis. As a result, IL-6 could be used to initiate therapies and monitor pro-and anti-inflammatory responses Ritchie and Singanayagam Indeed, inhibiting the NF-κB pathway could regulate the number of NOS and NO content, as well as diminish the production of cytokines and chemokines Li et al.

When the SARS-CoV-2 S protein binds to the ACE2 receptor, the pro-inflammatory pathway is activated, with the Ang II hormone directly activating pro-inflammatory responses and the release of cytokines.

The SARS-CoV-2 virus has recently been shown to use the TNF-α pathway to release pro-inflammatory cytokines such as TNF-α and IL TNF-α overproduction is caused by ADAM angiotensin II overactivation, which is mediated by virus-induced ACE2 deficiency Mahmud-Al-Rafat et al.

NF-κB is a key transcription factor for a wide range of genes involved in cellular immunity and inflammation. Activated NF-κB is crucial for a full-fledged cytokine storm because it regulates the transcription and synthesis of chemokines and inflammatory cytokines that are involved in the acute inflammatory response LIAO et al.

As a result of cytokine storms and inflammatory responses, many COVID patients may die. As a result, anti-inflammatory drugs may be able to reduce the severity of the condition and the rate of fatalities Dhama et al.

The release of IL-1β triggers the production of IL-6, a cytokine that raises C reactive protein CRP and has been associated with the COVID cytokine storm as a significant proinflammatory factor Qin et al.

Patients with COVID infection have been shown to have high amounts of pro-and anti-inflammatory cytokines in their blood than those with uncomplicated SARS. Airway epithelial cells infected with SARS-CoV also produce a high amount of CXCL, IL-6, CXCL8, IFN-α, and CCL5.

Severe SARS patients, on the other hand, had relatively low levels of the anti-inflammatory cytokine IL Cameron et al. The inflammatory response was triggered by ATR atrazine , which increased NO nitric oxide generation and caused heart injury.

By regulating NO nitric oxide and NOS nitric oxide synthase generating systems and inhibiting the TRAF6-NF-κB pathway, supplement lycopene dramatically reduces heart damage Li et al. Lycopene suppresses the production of proinflammatory cytokines and chemokines in macrophages Lee et al.

Lycopene improved blood cell and hepatic lipid function, boosted high-density lipoprotein cholesterol, reduced TNF-α and malondialdehyde, and increased hepatic antioxidant activity Róvero Costa et al. Lycopene's anti-inflammatory actions are mediated via a reduction in TNF-α, NO, and IL-6 release, which leads to a reduction in uveal inflammation.

Lycopene's anti-inflammatory and antioxidant properties may make it useful in the treatment of eye inflammation Göncü et al. Lycopene's anti-inflammatory properties were linked to an M2-dominant phenotype in adipose and hepatic macrophages.

Lycopene reduced HFD-stimulated insulin resistance and inflammation in epididymal white adipose tissues and the liver by easing M2-dominant polarization in adipose tissue macrophages Chen et al. Interleukin-1, Interleukin-6, and NF-κB-p65 expression were downregulated in the PA control, but Interleukine expression was elevated owing to lycopene therapy.

Lycopene normalized severe brain vacuolation was seen in the histopathology of PA control rats Ugbaja et al. Lycopene possesses anti-obesity and anti-diabetic properties in a variety of organs and tissues, including adipose tissue, liver, kidney, pancreas, brain, ovaries, stomach, and eyes. Several studies have revealed that lycopene consumption has antioxidant properties as well as immunological and inflammatory functions Agarwal and Rao ; Zhao et al.

COVID disease, which is occurred by the SARS-CoV-2 virus, is linked to several physiopathological mechanisms that mobilize a wide range of biomolecules, most of which are immunological Fig. In its most serious conditions, hyperproduction of primarily proinflammatory cytokines, which preferentially target lung tissue, can significantly worsen the prognosis Costela-Ruiz et al.

SARS-CoV-2 induces lymphopenia, dysfunction, lymphocyte activation, higher cytokine levels, as well as monocyte and granulocyte abnormalities, increase in immunoglobulin G IgG and total antibodies.

As a result, decreasing inflammation and improving lymphopenia may be beneficial therapeutic methods for COVID patients Yang et al.

A diagram showing COVID pathogenesis can lead to ARDS and multi-organ failure. Lycopene can disrupt excessive inflammatory cytokine production. Both T and B cell responses to SARS-CoV-2 are identified in the blood approximately one week after the start of COVID symptoms.

COVID 19 has a hyper-inflammatory innate immune system and a defective adaptive immune system due to severe lymphopenia, decreased functioning, and exhausted T lymphocytes. When SARS-CoV-2 attaches to Toll-like Receptors TLR , pro-IL1β is released, which leads to the production of mature IL-1β, which induces pulmonary inflammation, fever, and fibrosis.

Most members of the IL-1 family of cytokines produce inhibitory cytokines such as IL and IL Immunological cells include B cells and macrophages. IL is a cytokine that could be utilized to treat inflammation caused by viral infections, particularly coronavirus infections.

IL performs its anti-inflammatory function via interacting with the IL-R5 or ILRa receptors and may be explored as a therapeutic drug Conti et al. The N-COV virus enters the cell by latching onto the protein receptor ACE2 and slinking within, after which it replicates and weakens our immune system.

The lungs and colon have the most receptors. When the virus stays in the respiratory tract, it causes cough and cold, and when it inflames the hypothalamus, it causes diarrhea. When the virus inflames the hypothalamus, the fever rises Koff and Williams Innate immune cells have a vital role in activating a specific and effective immune response to SARS-CoV-2 infection, which is used as a biomarker for tissue damage in COVID cases with severe tissue damage.

The inflammatory response to SARS-CoV-2 has numerous clinical trials exploring the effectiveness of anti-inflammatory therapeutics against COVID Lycopene also influences immunoglobulin production, increases IgA, IgG, and IgM levels in the blood, and boosts immunity Kaneko et al.

Lycopene has immunomodulatory effects, as evidenced by the circulating percentage of lymphocytes, blood IgG concentrations, and ewe colostrum. Corn treated with lycopene increased the level of immunoglobulin G in sheep's blood, which facilitated passive immunity transfer to newborn lambs Fallah et al.

Dietary lycopene supplementation may increase antioxidant activity and ameliorate AFB1-induced intestinal immune function and barrier function impairment in the intestinal mucosa Sarker et al. In diabetic rats, lycopene has anti-anemic properties and improves immunity.

Low platelet counts, a low neutrophil—lymphocyte ratio, steady albumin, a drop in neutrophil counts, and low globulin content were among the findings. Lycopene may aid in the regulation of basic hemato-physiological variables Eze et al.

Lycopene is an anti-inflammatory antioxidant with antioxidant effects. Lycopene reduced intestinal damage, intestinal immunoglobulin A depletion, and bacterial translocation when given before the ischemia—reperfusion event İkiz et al.

In severe COVID cases, there was increased pro-inflammatory cytokine and chemokine production. Lycopene inhibits the synthesis of proinflammatory cytokines and chemokines in macrophages, reducing inflammation in a variety of organs Lee et al.

Aside from regulating chronic immunological and inflammatory processes and delaying dendritic cell maturation Kim et al.

Severe COVID frequently experiences respiratory distress that is treated by oxygen medication and may result in oxidative stress and ARDS. It has been reported that increased nitro-oxidative stress contributes to the development of ARDS Mach et al.

Even in cases where people are dying from chronic ARDS, there is nitrosative stress. SARS-CoV-2 appears to be localized to macrophages and type I pneumocytes Massaro et al. Nearly all patients with viral infections have chronic oxidative stress, which has an impact on disease pathogenesis including impaired immune function and inflammatory response Nin According to some researchers, the development of severe lung damage in SARS-CoV patients is related to oxidative stress produced by cell activation, which may have a substantial effect on the pathogenesis of COVID In general, cytokine production, inflammation, and cell death are linked to respiratory virus infections, which could be associated with oxidative Delgado-Roche and Mesta ROS is well-known for both its beneficial and harmful characteristics.

Free radicals produced by RNA virus infections may have a function in a range of features of viral illness pathogenesis. During allergic and nonallergic inflammation, the inflammatory cells produce ROS Chernyak et al. However, ROS released by viral illness should not be regarded only as destructive agents, since they are crucial for the eradication of viruses phagocytosed by immune cells and also contribute to signaling between immune cells.

Antioxidants may also help to reduce the viral load by minimizing oxidative stress. Most importantly, antioxidants tend to be appropriate during the stage of COVID when inflammatory reactions must be inhibited.

Such therapy is believed to protect organs and tissues from cytokine storms or oxidative stress Assimakopoulos and Marangos ; Yang et al. ACE2 and TMPRSS2 gene expression has been found mostly in alveolar epithelial type II cells, which play a role in SARS-CoV pathogenesis Sungnak et al.

During COVID, increased levels of angiotensin-converting enzyme 2 ACE2 served as an entrance receptor for SARS-CoV Ang II is involved in the initiation and progression of inflammatory response. Low ANG II levels and high tACE2 levels give SARS-CoV-2 greater pathogenicity; a high ratio suggests the virus is less harmful and causes oxidative stress free RONS Ackermann et al.

When a patient is infected with SARS-CoV-2, phagocytes get activated, causing reactive oxygen species ROS to generate. Angiogenesis appears to be caused by endothelial dysfunction and hypoxia within lung injury foci during COVID19 Varga et al.

Endothelial NOX2 is a prominent ROS producer, and AT1R is a key ATII receptor that stimulates multi-layered signaling in endothelial cells Forrester et al.

The possible causes of the pore opening of the mitochondrial permeability transition pore mPTP , which is regulated by such a protein in the mitochondria, may increase the level of mtROS generated by NOX2.

As a result, ATII increased mtROS generation, which in turn increased NOX2 activity Bernardi et al. Endothelial cells may undergo ROS-dependent apoptosis as a result of cytokine storms. The activation of endogenous antioxidant mechanisms is another strategy for combating oxidative stress during COVID The transcription factor Nrf2, for example, regulates the production of antioxidants and other cell defense mechanisms Zinovkin and Grebenchikov The generation of ROS is a typical element of cellular aerobic metabolism, which involves the respiratory and oxidizing of nutrients to generate energy.

antioxidant mimetics or Nrf2 inducers could be used to treat viral-induced infections including respiratory problems and other infections that are correlated to a decrease in cellular antioxidative Komaravelli and Casola Hepcidin is important for maintaining iron homeostasis.

Although iron is essential, its free form is likely to be involved in oxidation—reduction reactions, resulting in free radical production and oxidative stress Daher et al.

The hyperferritinemia seen in COVID patients could be a result of inflammation. In an era of multidrug-resistant viruses, iron chelation appears to be a promising and logical adjuvant therapy for viral infections Schmidt Lycopene is an extremely strong antioxidant, and this is a key mechanism of lycopene action.

Its exceptional ability to quench ROS is due to its eleven conjugated double bonds Heber and Lu Lycopene's nutraceutical effects have been reported in cancer, infertility, metabolic syndrome, and liver damage patients Grabowska et al. For the rise in the COVIDrelated risk of death, Nrf2 has powerful antiapoptotic effects and anti-inflammatory in endothelial cells.

Lycopene reduced the oxidative damage caused by zearalenone ZEA in Sertoli cells SCs by increasing Nrf2 pathway expression and lowering autophagy and apoptosis in piglet SCs Cao et al.

Lycopene alleviated palmitic acid PA -induced neuroinflammation in female Wistar rats through lowering oxidative stress and downregulation of NF-ĸB-p65 expression Ugbaja et al. During transient ischemia, lycopene has been proven to protect the brain from ischemia-induced damage.

In vitro, neuronal damage was alleviated, reactive oxygen species generation was reduced, and cell viability was successfully increased by lycopene pre-treatment.

As a result, lycopene can be useful in the treatment of oxidative stress-related AD Huang et al. In the kidneys and testes, ZEA decreased GST activity while increasing SOD activity in the liver Boeira et al. Lycopene can lower the risk of varicocele brought on by oxidative stress by boosting TAC levels and TAC enzymatic activities Babaei et al.

Interleukin-6 IL-6 , tumor necrosis factor-α TNF-α interleukin-1β IL-1β , interleukin IL , heme oxygenase HO , monocyte chemotactic protein 1 MCP-1 , reactive protein CRP , JNK c-Jun N-terminal kinase , interferon-gamma induced protein IP , Quantitative polymerase chain reaction qPCR , Enzyme-linked immunosorbent Assay ELISA , Superoxide dismutase SOD , catalase CAT , glutathione peroxidase GPx , inducible nitric oxide synthase iNOS , glutathione GSH , Glutathione-S-transferase GST , catalase CAT , glutathione peroxidase GSH-Px , malondialdehyde MDA , non-alcoholic fatty liver disease NAFLD , Overall case-fatality rate CFR , SARS-CoV-2 severe acute respiratory syndrome coronavirus 2 , MERS Middle East respiratory syndrome , RNA-dependent RNA polymerase RdRp , main protease M pro and receptors binding domain RBD , two-pore calcium channel 2 TPC2.

Lycopene has been suggested to have clinical efficacy in the treatment of diabetes. The average daily intake of dietary lycopene among diabetics was 0. These data support the clinical use of lycopene in the treatment of OC R.

Wang et al. Lycopene 0. Therefore, it was considered that the antioxidant capabilities of lycopene would prevent cardiac hypertrophy Zeng et al. Lycopene enhanced angiotensin-II-induced vascular superoxide anion, cardiac fibrosis, hypertrophy, lipid peroxidation, and antioxidant enzyme activity.

Interestingly, lycopene showed antihypertensive potential without causing hypotension in normotensive rats Ferreira-Santos et al.

These results suggest an inverse U-shape relation between dose and serum concentration of lycopene Wang et al. As a result, lycopene may have a cardioprotective impact by inhibiting local myocardial inflammation and apoptosis He et al.

Lycopene 16 mg treatment for individuals with oral submucous fibrosis considerably lowered the expression levels of the IGF1 pathway, suggesting that it could be a promising drug for the pre-treatment of oral squamous cell carcinoma OSCC and significantly induced cell apoptosis, which inhibits tumor growth and cell migration Kumar et al.

Lycopene exhibits suppressive inhibitory effects on WSU-HN6 and CAL cells in vivo and in vitro, similar to prior findings. This study might treat oral squamous cell carcinoma with lycopene by acting as an anti-cancer agent Tao et al.

A clinical disorder called lycopenemia is characterized by yellowish-orange skin pigmentation. It results from the overconsumption of lycopene resources obtained through diet or caused by the deposition of lycopene in the stratum corneum Shaw and Koti The anti-oxidant lycopene does not prevent pre-eclampsia in healthy primigravidas, but it helps lessen pre-eclampsia and intrauterine development retardation.

As a result, there have been more premature and underweight babies born. Therefore, it is advisable to refrain from using lycopene supplements as well as lycopene found in food during pregnancy and lactation Banerjee et al.

Docetaxel with lycopene treatment was well tolerated, with no dose-limiting toxicities seen in the first six patients participating in the research. Lycopene is not benign. A significant number of individuals experienced gastrointestinal adverse symptoms such as nausea, vomiting, anorexia, flatulence, and abdominal distension.

Although the majority of these were minor, they nevertheless highlight the fact that even natural, nutrition-based medicines might have unintended repercussions Jatoi et al. Lycopene supplements were well tolerated. One patient discontinued treatment due to diarrhea grade 2 toxicity caused by lycopene supplementation.

Other toxicities were observed, but these were unlikely to be caused by lycopene supplementation Clark et al. Lycopene has not been linked to any negative side effects.

One patient reported an intense burning sensation and oral ulcers one week after starting treatment Kumar et al. According to the Common Toxicity Criteria of the National Cancer Institute, none of the investigations found any serious toxicity or intolerance associated with lycopene supplementation Kaba et al.

Lycopene appears to be a perfectly safe dietary component from a safety point of view. This review has presented the various mechanisms of SARS-CoV-2 infection along with the inflammatory, immunity, and oxidative properties of lycopene as COVID preventative measures in light of the COVID pandemic. COVID cytokinemia differs from other kinds of pneumonia in that it causes organ failure and ICU hospitalization.

SARS-CoVinduced hyper-inflammatory and immune responses are critical for not only understanding the pathogenesis of severe COVID disease but also for vaccine evaluation and design.

Many immunomodulatory, anti-inflammatory, and antiviral drugs have been tested in patients with COVID as well. We conclude that lycopene could be used as a drug for treating the inflammation of COVID infection because of its antioxidant, anti-inflammatory and antivirals properties.

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