INTRODUCTION:

The sudden outbreak of the 2019 coronavirus (COVID-19) in Wuhan, China due to the SARS-CoV-2 virus, in just two months, after which the epidemic spread rapidly in the rest of the world¹. Coronaviruses target the human respiratory system, where previous coronavirus outbreaks (CoVs) include Middle East Respiratory Syndrome (MERS-CoV) and severe acute respiratory syndrome (SARS-CoV), which poses a major threat to public health².

The configurations of metabolism cellular is very important in determining the state of the immune cell (activation, growth and proliferation, Differentiation and homeostasis) and that's mean determining a response immune³.Many studies have suggested that the cause of progression of several disease is reactive oxygen species and oxidative stress⁴. Reactive oxygen species (ROS) are free radicals resulting from the metabolism of oxygen⁵. The increased free radical production and antioxidant depletion in diabetes to be a causative factor in increasing the risk of infection and some investigators have reported increased lipid peroxidation and significant depletion in antioxidant capacity during the development of diabetes⁶. Phytochemicals in the diet can exert on different targets that can relieve multiple pathological processes, including oxidative damage, epigenetic alterations, chronic inflammation, active stimulators, inhibitors and growth terminators and prevention of various diseases associated with oxidative stress⁷. In recent years, interest and highlighting the use of traditional medicine information on plants has increased. Research has focused on medicinal plants in herbal remedies among indigenous peoples around the world⁸. Complementary, alternative, and traditional medicines are the primary source of guidance for herbal medicines. However, scientific evidence of these various uses must be proven by modern medicine in order to expand its use and benefit from the experiences of traditional medicine in treating several infection diseases⁹. This review focuses on the role of herbal pharmaceutical in improving immune response and reducing the spread or complications of COVID-19 infection.

COVID-19 INFECTION AND IMMUNE SYSTEM:

COVID-19 is more likely to infect elderly men with chronic comorbidities due to weaker immune functions¹⁰. Active innate immune response against viral infection greatly depend on the interferon type I responses and its downstream cascade that culminates in controlling viral replication and induction of effective adaptive immune response¹¹. While SARS-CoV and SARS-CoV-2 seem to share the entry receptor of ACE2. This receptor is mainly expressed in a small subset of cells in the lung called type 2 alveolar cells¹². One of the mechanisms of immune response against COVID19 is the cytokine release syndrome (CRS)which seems to affect patients with severe conditions¹³. Since lymphocytopenia is often seen in severe COVID-19 patients, the CRS caused by SARS-CoV-2 virus has to be mediated by leukocytes other than T cells, as in patients receiving CAR-T therapy; a high WBC-count is common, suggesting it, in association with lymphocytopenia, as a differential diagnostic criterion for COVID-19¹⁴. Also the immune system change induced by COVID19 infection presented by increases in NLR and T lymphopenia in particular, a decrease in CD4+ T cells were common among patients with COVID-19, and more evident in the severe cases¹⁵, but there was no significant change in the number of CD8+ cells and B cells. Based on these data, we suggest that COVID-19 might damage lymphocytes, especially T lymphocytes, and the immune system is impaired during the period of disease¹⁶.

HERBAL MEDICINE AND IMMUNE SYSTEM:

Anti-inflammatory activity of herbal medicine:

Inflammation is a complex process that the body uses to defend itself, but excessive inflammatory mediators may lead to chronic disease ¹⁷. In fact, there are four main indicators of inflammation: pain, redness, heat, warmth, and swelling. The arteries expand in the surrounding tissues, which gives the high blood circulation to the area, which indicates that the body is affected in some part of it¹⁸. There are many non-steroidal anti-inflammatory drugs that contribute to reducing pain and inflammation by blocking metabolism of Arachidonic acid, but these drugs are characterized by their side effects on the body¹⁹. Therefore, there are many medicinal plants that have a major therapeutic effect as antioxidant and anti-inflammatory and have low or no side effects that can be used²⁰. The free radicals that leads to lipid peroxidation are just inflammation, macrophages and neutrophils can produce very high amounts of reactive oxygen species, which produces via membrane NADPH oxidases²¹. According to the sources of the World Health Organization (WHO), about three quarters of the world's population rely on traditional medicines (mainly herbal) for their health care, as Ayurveda and Chinese medical systems are the most accepted traditional system in that it has a great interest in research in pharmacology. Chemistry, pharmacy and clinical treatments²². The use of medicinal plants because they contain many active compounds as secondary metabolites, some of which have been discovered and many are still in the framework of the research to know the therapeutic effects²³. Medicines of plant origin aroused a lot of interest due to their wide use, abundance, high efficacy and lack of secondary effects as an anti-inflammatory agent²⁴. Salicin and then aspirin from Salix fragilis of plant origin are a strong example to confirm the ability of plants to produce anti-inflammatory compounds. Hence the widespread and effective use Many plant-based medications, such as Capsicum annum, Curcuma (Curcuma longa) and frankincense (Boswellia serrata), are anti-inflammatory and anti-pain medications²⁵. These plant compounds are also known to be free of toxic effects on the body’s organs, such as the liver and kidneys, unlike other chemical compounds, which indicates that natural compounds are considered clean and strong alternatives to classic medicines²⁶. There are several proposals for anti-inflammatory mechanisms of action for medicinal plants, among which they work to inhibit various types of pro-inflammatory cytokines that regulate inflammatory reactions either directly or through their ability to stimulate cellular adhesion molecules or other cytokines²⁷. On the other hand, flavonoids, which are plant compounds that act as anti-inflammatory drugs, by blocking the production of nitric oxide (NO) by either inhibiting iNOS or reducing its regulation²⁸. Plant compounds also inhibit signal transmission by inhibiting some of the kinase enzymes involved in this process such as protein kinase C and mitogen-activated protein kinase²⁹. This inhibition includes control of the genes transcription responsible for the synthesis of these proteins by controlling the transcription factors such as the nuclear factor Kappa B Or activated protein 1³⁰.

Immunomodulatory effect of medicinal plants:

The use of drugs that strengthen the immune response is important and effective, either with Enhance macrophage macrophage activity, an increase in the humoral responses by antibodies or modify immune responses by cells³¹. Therefore, the use of plant extracts is based on these effects to assess their therapeutic antimicrobial efficacy or in their preventive efficacy of the immune system³². Medicinal herbs with the therapeutic properties of the immune system work to enhance and stimulate the humoral and cellular immune response, and also work to enhance and stimulate the innate response by activating the complementary system, granulocytes, macrophages and natural killer cells³³. Then the activation of these primary immune cells begins to produce a different effect or molecules (such as cytokines) that are involved in modifying and enhancing immune responses³⁴. There are several studies through which the effectiveness of antiviral and antimicrobial plants has been proven by enhancing and activating the body's immune system³⁵ where some spices such as onions, garlic, mustard, red pepper, turmeric, cloves, cinnamon, saffron, curry leaves, fenugreek and ginger have been identified as medicinal plants, they have antimicrobial, immunomodulatory and antioxidant properties³⁶. Also, plant therapy for immunity can be considered as an alternative to the traditional chemotherapy for several diseases that are characterized by weak immune response or selective immunosuppression such as inflammatory diseases, autoimmune disorders, organ transplants and bone marrow³⁷. The use of medicinal plants to stimulate the immune system as an alternative treatment to traditional medications will be according to the active components that have a positive effect on the immune system such as polysaccharides, lectins, peptides, flavonoids and tannins³⁸. Besides these compounds, other phytochemicals including essential oils, stimulants, terpenoids, phenols, pigments and alkaloids have shown positive effects in stimulating the immune system³⁹. On the other hand, a lot of plant extracts that have a positive effect in stimulating the immune system have been identified, such as Coriolus versicolor extracts contains glucans containing (1,4) backbone with (1,3) and (1,6) glucocytic linkages, which are used as an adjuvant since to the immune system⁴⁰. Also Ginseng plant rich in saponin and steroid compounds known to have immunostimulating properties including cytokine production (IL-2, IL-6, TNF-α and IFN-γ), macrophage activation and lymphocyte activity, saponins also have the ability to stimulate the Cells immune response and enhancing antibody production⁴¹. There are other plant such as Astragalus root, Isatis root, Achyranthes root and Chinese Yam known to have polysaccharides that have wide immunomodulatory effects which considerably improves the antibody production⁴². Recent studies revealed that the genome sequence of SARS-CoV-2 is very similar to that of COVID-19⁴³. Therefore, in the study of Muhammad et al 2020 which analyzed the (3CLpro) enzyme controls coronavirus replication and is essential for its life cyclesequence, constructed its 3D homology model, and screened it against a medicinal plant library containing 32,297 potential anti-viral phytochemicals/traditional Chinese medicinal compounds. its analyses revealed that some of these plants serve as potential anti- SARS-CoV-2⁴⁴.

CONCLUSION:

The insufficiency of the immune system is negatively affects the resistance of the COVID-19, which leads to significant complications. Research on plants is one of the developing areas in modern bio-medicine, accordingly we can suggest treatment with medicinal plants because they contain antioxidants and anti-inflammatory substances and compounds that have high capabilities in eliminating and controlling the spread and reproduction of Viruses also enhance and activate the innate and specific immune response.

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Received on 12.05.2020 Modified on 08.06.2020

Res. J. Pharma. Dosage Forms and Tech.2020; 12(3):181-184.

DOI: 10.5958/0975-4377.2020.00031.2