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Antioxidants and inflammatory food supplements targeting COVID 19

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Immunity through Nutrition and Natural Product

The COVID-19 infection is caused by the SARS-CoV-2 virus and is characterized by pneumonia and ARDS. It easily spreads through droplets exhaled from an infected person to the surrounding. The pathogenesis of COVID-19 is very complex and causes suppression of host antiviral and innate immune response. 1

Studies have revealed that SARS-CoV-2 interferes with the stability of hemoglobin and causes the release of iron in large amounts which may cause hemoglobinopathy and iron dysmetabolism. Both may hinder the oxygen-transporting capacity of erythrocytes causing hypoxia and increasing oxidative stress. Further, oxidative stress and hyper inflammation due to cytokine storm may lead to lung injury, pneumonia and ARDS. 2

Several vaccines and drugs are being evaluated for the efficacy, safety and dose to act against the COVID-19 virus, but this is a tedious and long process. Hence, boosting immunity using bioactive substituents are becoming an alternative area of interest among researchers and scientists. From ancient times records reveal the efficacy of several naturally occurring bioactive substituents having antioxidants, anti-inflammatory, antiviral, antibacterial, wound healing properties and immune-boosting properties present in foods. Hence, a properly balanced diet containing recommended daily amount of vitamins and minerals are essential in this pandemic situation This is available in the currently available food supplements which contain vitamins A, B complex, C, D, E, K, minerals like, zinc, selenium, some probiotics and other phytoconstituents like curcumin, quercetin, Mangiferin, cinnamaldehyde, lactoferrin, etc. These naturally occurring phytoconstituents suppress oxidative stress and reduce hyper inflammation providing both prophylactic and therapeutic support against COVID-19. Some of them are discussed below:

Curcumin: A recent in-silico docking study reveals that curcumin bind to the SARS-CoV-2 target receptor, which indicate inhibitory activities to the viral infection.3 Further, studies have shown that curcumin exhibits its antiviral property by different mechanisms such as inhibiting the virus entry into cells, inhibiting encapsulation of the virus and viral protease, inhibiting the virus replication, as well as modulating several signalling pathways. It further helps in the formation of host interferon which activates the host innate immunity. Also, Curcumin shows an anti-inflammatory effect which is mediated through the induction of PPAR-γ up-regulation and represses the inflammatory process by reducing cytokine production. Curcumin present in turmeric may further help protect lung injury associated with VILI in COVID 4. Also, curcumin is a potent antioxidant and acts by neutralizing free radicals and enhancing the production of antioxidant enzymes. This evidence makes curcumin useful for preventive or prophylaxis treatments of virus infections including SARS-CoV-2 effects 1

Vitamin C is regarded as an excellent antioxidant and it exerts its antiviral properties by helping lymphocyte activity, increasing interferon-α production, modulating cytokines, reducing inflammation, improving endothelial dysfunction, and restoring mitochondrial function.5 The recommended dose of vitamin C varied from 1 to 3 g/day. It is an active antioxidant and reduces reactive oxygen species preventing lipid peroxidation and protein alkylation, thus providing a protective shield to the cells from oxidative stress and preventing cellular damage.1 Studies have shown that vitamin C in combination with quercetin exerts synergistic antiviral action due to the combined effect of antiviral and immunomodulatory properties. Also, ascorbic acid helps to recycle quercetin and enhances its effectiveness 5. Recent clinical trials have suggested that significant recovery was observed in high risk and mild symptomatic SARS-CoV-2 patients who were being administered 250–500 mg quercetin and 500 mg vitamin C orally, twice daily for 7 days and also in ARDS (assisted ventilation/intubation) patients who were being administered 3g of vitamin C and 500mg quercetin twice daily for 7 days 5. Thus, vitamin C incorporation in food supplements may help boost the overall immunity, anti-inflammatory and antioxidant effects against COVID infection.

Vitamin B6 supports the intestinal immune system, helps in enhancing the cytotoxic effects of natural killer cells (NK cells), restricts the spread of any infection, tissue damage, and reduces inflammation. Further, Vitamin B12 helps in the formation of red blood cells and white blood cells along with folic acid, enhancing the formation of T-cells and maintaining cellular immunity. 

Vitamin D is a fat-soluble vitamin having immunomodulatory, antioxidant and antiviral activity. Vitamin D reduces oxidative stress-related protein oxidation, lipid peroxidation and DNA damage, increases the levels of antioxidant NRF-2 and facilitates balanced mitochondrial functions.1

Quercetin is well known to have antioxidant and anti-inflammatory properties. Recent animal studies revealed that quercetin exhibits antiviral activity against both RNA and DNA viruses. It inhibits the virus entry and viral-cell fusion and reduces the expression of pro-inflammatory cytokines and lung inflammation induced.6 Studies have shown that quercetin WITH vitamin C HAS a combined effect of antiviral and immunomodulatory properties. Also ascorbic acid helps to recycle quercetin and enhances its effectiveness 5.

Mangiferin is obtained from the mango and has different pharmacological properties like such as antioxidant, anti-inflammatory, antimicrobial, antidiabetic, antiallergic, anticancer, hypocholesterolemic, and immunomodulatory. Studies in animal models have shown that oral administration (40 mg/kg/day) of Mangiferin reduced blood sugar, elevated plasma insulin levels, and increased antioxidant enzymes such as SOD, CAT and glutathione peroxidase (GPx). It shows antioxidant properties by protecting against oxidative stress and by significantly increasing levels of SOD, GSH, CAT, GST, and by quenching free radicals. It also has anti-inflammatory properties, reduces mortality and acute lung injury (ALI).7

Iron plays an important role in the growth of epithelial cells and T cells. It maintains a balance between the helper T cells and cytotoxic T cells.

Zinc (Zn) has antiviral, antioxidant andante- inflammatory activity. Studies in an animal model have revealed that deficiency of Zn enhances the oxidative stress pro-inflammatory TNF-α and vascular cell adhesion molecule (VCAM)-1 expression and causes lung tissue remodeling which was partially reversed by the Zn supplementation. Also, studies have proved that oral supplementation of zinc decreased the incidences of acute respiratory infections by 35%. 1

Commonly used probiotics include Bifidobacterium and Lactobacillus species, followed by Streptococcus, Enterococcus, Bacillus, and Escherichia coli. Probiotics enhance the gut microbiome, which impacts systemic immune responses and local immune responses at distal mucosal sites, including the lungs.8

Conclusion: Therefore, the use of natural compounds containing macro and micronutrients in proper combination and formulation in the form of food supplements may provide alternative prophylactic, therapeutic and adjuvant support along with the therapy for COVID-19.

References:

  1. M. Mrityunjaya, V. P., R. Neelam, P. Janhavi P. M. Halami and P. V. Ravindra. Immune-Boosting, Antioxidant and Anti-inflammatory Food Supplements Targeting Pathogenesis of COVID-19. Front. Immunol. 2020, Volume 11 ,  Article 570122, 1-12.
  2. Carmen Lammi, A. A. Food-derived antioxidants and COVID-19. Food Biochem 2021, Volume45, Issue1, 1-6.
  3. Rohmad Yudi Utomo, M. I. E. M. Revealing the Potency of Citrus and Galangal Constituents  to Halt SARS-CoV-2 Infection. 2020, 10.20944/preprints202003.0214.v1. .
  4. Carmen Ciavarella 1, I. M., Sabrina Valente 1, Gianandrea Pasquinelli 1. Pharmacological (or Synthetic) and Nutritional Agonists of PPAR-γ as Candidates for Cytokine Storm Modulation in COVID-19 Disease. Molecules, 2020, 25, 1-15.
  5. Ruben Manuel Luciano Colunga Biancatelli , M. B., John D Catravas , Paul E Marik Quercetin and Vitamin C: An Experimental, Synergistic Therapy for the Prevention and Treatment of SARS-CoV-2 Related Disease (COVID-19). Front Immunol 2020, 11:1451, 1-11.
  6. Shyamala Ganesan , A. N. F., Adam T Comstock, Qiong Wang, Suparna Nanua, Marc B Hershenson, Uma S Sajjan. Quercetin inhibits rhinovirus replication in vitro and in vivo. Antiviral Res 2012, 94(3), 258-271.
  7. Muhammad Imran, M. S. A., Masood Sadiq Butt, Joong-Ho Kwon, Muhammad Umair Arshad,4 and Muhammad Tauseef Sultan. Mangiferin: a natural miracle bioactive compound against lifestyle related disorders, Lipids Health Dis. 2017, 16: 84., 1-17.
  8. David Baud , V. D. A., Glenn R Gibson , Gregor Reid , Eric Giannoni Using Probiotics to Flatten the Curve of Coronavirus Disease COVID-2019 Pandemic, Front Public Health 2020, ;8:186, 1-5
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