Immune boosters against viral diseases

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•Dates, garlic, ginger, bitter kola, bitter gourd, black seed, oil palm extract, watermelon validated to stop replication of COVID-19

Medicinal plants are not only popular for their ample store of active ingredients but also boast of several pharmacological properties including the modulation of components of the immune system. Several studies have shown that an adequate immune response is vital in counteracting the unwanted activities of pathogens such as bacteria, protozoa, and viruses.

Some diseases caused by viral pathogens such as measles, chickenpox, Ebola, Lassa fever, Yellow fever, viral Cerebro Spinal Meningitis (CSM) and Human Immuno-deficiency Virus (HIV) may result in death or dire consequences in mammals with inadequate immunity.

Infections by the Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2) virus causing COVID-19 are presently a global emergency. The current vaccination effort may reduce the infection rate, but strain variants are emerging under selection pressure. Thus, there is an urgent need to find drugs that treat COVID-19 and save human lives.

Scientists have identified local plants that affect the SARS-CoV-2 spike protein and boosts immune system against viral diseases, especially COVID-19.

The study titled “Medicinal plants as immune booster in the palliative management of viral diseases: A perspective on coronavirus” was published in the journal Food Frontiers.

Top on the list according to the study are: Citrullus lanatus, which inhibited the growth of a human T-cell leukemia line Jurkat cell; Momordica charantia, which induced proliferation of T-helper 2 cell inducing in vitro; Garcinia kola, which reduced IL-6 and TNFα levels in hyperglycemic rats induced; Nigella sativa that change in pro and anti-inflammatory cytokines profiles in male wistar rats; Aloe vera, which increased CD4 lymphocyte frequency in blood and serum immunoglobulin concentration in rabbits; Zingiber officinale- ginger extract inhibited pro inflammatory cytokines (IL-12, TNF-alpha, IL-1beta) and T cell proliferation in mice.

Others are: Allium sativum- garlic oil enhanced an anti-inflammatory environment by shifting T-helper 1/T-helper 2 balance toward the T-helper 2 type; Elaeis guineensis- oil palm leaf extract promoted leukocyte responses (phagocytosis) and B cell activation (antibody production) in aged rats; and Phoenix dactylifera- polyphenols identified in the date fruit extract, such as chlorogenic caffeic acid, pelargonin, and ferulic acid, stimulated IFN-γ mRNA expression significantly in mouse Peyer’s patch cell cultures.

The researchers wrote: “Plant-based chemicals can also counteract oxidative stress and inflammation, two conditions that usually characterise immune depletion. There is a plethora of evidence demonstrating the potential of medicinal plants in modulating both innate and adaptive arms of the immune system. It is a well-known fact that COVID-19 pathogenesis involves the release of enormous amounts of pro-inflammatory cytokines and chemokines.

“Several medicinal plants have been reported to increase the activity and number of inflammatory suppressors, lymphocytes, natural killer cells, and macrophages, making the plants potential candidates for COVID-19 pre- and post-exposure prophylactic agents. Active agents in these plants could be isolated and investigated as potential drug agents to reverse immunological abnormalities seen in COVID-19 infection. Either through inhibiting viral penetration and replication in host cell or stimulating the immune system, medicinal plants are attractive candidates in the fight against infections caused by viruses. With a dire need to contain the ongoing COVID-19 outbreak, medicinal plants’ immunological effects may offer benefits by acting as the first line of defense.”
Momordica charantia (Bitter melon)

Commonly called bitter melon, bitter gourd, African cucumber or balsam pear, Momordica charantia belongs to the plant family Cucurbitaceae. In Nigeria, bitter melon is called ndakdi in Dera; dagdaggi in Fula-Fulfulde; hashinashiap in Goemai; daddagu in Hausa; iliahia in Igala; akban ndene in Igbo (Ibuzo in Delta State); dagdagoo in Kanuri; akara aj, ejinrin nla, ejinrin weeri, ejirin-weewe or igbole aja in Yoruba.

A study published in Journal of Ovarian Research and titled “Targeting novel coronavirus SARS-CoV-2 spike protein with phyto-constituents of Momordica charantia” concluded: “An in-silico approach to finding a natural compound that binds and prevents the attachment/internalization of the SARS-CoV-2 virus is a therapeutic and preventive option for the development of drugs with a time constraint. Bioinformatics approaches to make fast and more or less accurate predictions for potential drugs or inhibitors. In this study, we used multiple bioinformatics tools to identify potent natural compounds, mainly flavonoids, that target and bind to the spike protein of SARS-CoV-2. We identified 10 flavonoids capable of binding either to the S1 or S2 domain of the SARS-CoV-2 protein. Our findings suggest that compounds from Momordica charantia have the potential to inhibit the SARS-CoV-2 spike protein and should be explored further as agents for preventing COVID-19.”

Garcinia kola (Bitter kola) seeds CREDIT: Alibaba Garcinia kola (Bitter kola)
Researchers in the United Kingdom (U.K.) and Nigeria have conducted a study showing that Garcinia kola seed extract and garcinoic acid may provide therapeutic benefits in the late stage of severe COVID-19 and other coronavirus infections.

The team – from the University of Huddersfield, PhytoQuest Ltd in Aberystwyth, and Obafemi Awolowo University in Ile-Ife, Osun State – says that treatment with these natural products may reduce the cytokine storm that can develop following infection with SARS-CoV-2.

Treating human peripheral blood mononuclear cells (PBMCs) with G. kola seed extract and garcinoic acid prior to stimulation with subunit 1 (S1) of the SARS-CoV-2 spike protein reduced the secretion of tumor necrosis factor-a (TNFa), interleukin (IL) 6, IL-1β and IL-8 – all inflammatory cytokines that target the lung and other tissues. The spike protein is the main structure the virus uses to bind to and infect host cells.

Furthermore, pre-treating PBMCs with G. kola seed extract prior to stimulation with spike S1 reduced damage to A549 lung epithelial cells.

Olumayokun Olajide and colleagues said the anti-inflammatory effects of G. kola seed extract could be beneficial in the treatment of acute respiratory distress syndrome (ARDS) and lung damage in patients with severe COVID-19.

A pre-print version of the research paper is available on the bioRxiv* server, while the article undergoes peer review.

The study is titled “Garcinia kola and garcinoic acid suppress SARS-CoV-2 spike glycoprotein S1-induced hyper-inflammation in human PBMCs through inhibition of NF-κB activation.”

Among the complications associated with SARS-CoV-2 infection, ARDS and organ damage have been linked to an excessive release of inflammatory cytokines.

Studies have recently shown that this “cytokine storm” is induced by S1 of the viral spike protein that binds to the host cell receptor angiotensin-converting enzyme 2 (ACE2).

Although some studies have shown that certain plant-based products inhibit SARS-CoV-2 infection, none have yet reported the effects of such products on alleviating the cytokine storm in COVID-19.

The seed of the West African plant G. kola and the garcinoic acid that can be isolated from the seed have previously been shown to produce anti-inflammatory activity in a number of cellular and animal models.

“Considering the critical role of the SARS-CoV-2 cytokine storm in the pathogenesis of severe COVID-19, it is important to investigate natural products that could reduce exaggerated and organ damaging-inflammation of the disease,” wrote Olajide and colleagues.

Olajide and colleagues said the findings suggest that the G. kola seed and garcinoic acid are natural products that may possess pharmacological benefits in reducing the cytokine storm during the late stage of severe COVID-19 and other coronavirus infections.

“It is proposed that the anti-inflammatory effects of G. kola seed extract could be an important pharmacological attribute for the treatment of ARDS and lung damage in patients with severe COVID-19,” they concluded.

Nigella sativa (Black seed)
Nigella sativa is a medicinal plant commonly known as Black Cumin and has been proven to have anti-viral properties against many viruses, including mouse cytomegalovirus and Hepatitis C Virus (HCV). In vitro studies have shown that it can decrease the replication of SARS-CoV. Some of its components have a high affinity to many SARS-CoV-2 proteins and enzymes.

A study published in Journal of Advances in Medicine and Medical Research and titled “Fight against COVID-19: Nigella sativa, a Potential Curative” noted: “COVID-19 has rampaged across continents and has caused a devastating impact on life, economy, mobility, and health. Vaccines are still under clinical trials however there is no immediate solution or drug at hand for effective treatment. During this time, finding an unorthodox solution has become the need of the hour. Nigella sativa, commonly known as the black seed has been widely used as a traditional medicine in the past to fight illnesses.

“Chief compounds of N. Sativa seed, especially thymiquinone, α-hederin, and nigellidine, could be developed into promising herbal drugs to combat COVID-19 due to their therapeutic benefits. Extensive studies on N. Sativa have demonstrated its wide spectrum pharmacological properties which include immuno-modulatory, analgesic, anti-inflammatory, antiviral, broncho-dilatory, hepato-protective, reno-protective, gastro-protective, and antioxidant properties that can serve as a potent inhibitor for SARS-CoV-2.

“Furthermore, N. sativa has also exhibited anti-diabetic, antihypertensive, and antibacterial properties which would help COVID-19 patients with comorbidities.”

“This study was conducted in order to pinpoint the best drug candidates from the set of 10 compounds of Aloe vera using molecular docking and ADMET properties. The reactivity of the COVID-19 main protease (Mpro) with 10 isolated Aloe vera compounds showed that the most stable complex is obtained with feralolide or ligand 6 (−7.9 kcal/mol), followed by 9-dihydroxyl-2-O- (z)-cinnamoyl-7-methoxy-Aloesin or ligand 1 (−7.7 kcal/mol) and Aloeresin or ligand 8 (−7.7 kcal/mol). Finally, the Lipinski’s rule of five based-on ADME analysis confirms the ligand 6 to be the best drug candidate.”

Another study published in European Journal of Medicinal Plants and titled “Aloe vera (L.) as a Potential Anti-COVID-19 Plant: A Mini-review of Its Antiviral Activity” concluded: “The world is going through a major crisis due to
COVID-19. This pandemic still has no acceptable remedy. It is therefore important to search for alternative solutions, especially for African countries.

Aloe vera is a plant widely used for its various activities including antiviral activities. The purpose of this work was to do bibliographic research on the antiviral properties of this plant.

“The results obtained show that Aloe vera possesses not only antiviral properties but also anti-inflammatory and immune-stimulant properties which can be useful in the management of COVID-19. Molecular docking and clinical trials are nonetheless necessary to confirm these positive effects.”

[FILES] Ginger. CREDIT: DiabetesUK“The proteins of SARS-CoV-2, essential for its entry into human cells and highly expressed in the goblet and ciliated cells of nasal epithelium, play a significant role in contagiousness of the virus. Docking studies indicated that the specific compounds present in C. medica and Z. officinale have significant affinity in silico to spike protein of virus and ACE-2 receptor in the host.

“In silico studies suggest that the phytochemical compounds in C. medica and Z. officinale may have good potential in reducing viral load and shedding of SARS-CoV-2 in the nasal passages. Further studies are recommended to test its efficacy in humans for mitigating the transmission of COVID-19.”

Allium sativum (Garlic)
A study published in the journal Med Hypotheses and titled “The effects of Allium sativum on immunity within the scope of COVID-19 infection” noted: “The severity of COVID-19 infection is quite variable and the manifestations varies from asymptomatic disease to severe acute respiratory infection. Fever, dry cough, dyspnea, myalgia, fatigue, loss of appetite, olfactory and gustatory dysfunctions are the most prevalent general symptoms. Decreased immune system cells such as suppressed regulatory T cells, cytotoxic and helper T cells, natural killer cells, monocytes/macrophages and increased pro-inflammatory cytokines are the characteristic features. Compounds derived from Allium sativum (garlic) have the potential to decrease the expression of pro-inflammatory cytokines and to reverse the immunological abnormalities to more acceptable levels. Allium sativum is suggested as a beneficial preventive measure before being infected with SARS‐CoV‐2 virus.

Garlic“Allium sativum is a functional food well-known for its immuno-modulatory, antimicrobial, anti-inflammatory, anti-mutagenic, antitumor properties. Its antiviral efficiency was also demonstrated. Some constituents of this plant were found to be active against protozoan parasites. Within this context, it appears to reverse most immune system dysfunctions observed in patients with COVID-19 infection. The relations among immune system parameters, leptin, leptin receptor, adenosin mono phosphate-activated protein kinase, and peroxisome proliferator activated receptor-gamma have also been interpreted. Leptin’s role in boosting pro-inflammatory cytokines and in appetite decreasing suggest the possible beneficial effect of decreasing the concentration of this pro-inflammatory adipose tissue hormone in relieving some symptoms detected during COVID-19 infection.

“In conclusion, Allium sativum may be an acceptable preventive measure against COVID-19 infection to boost immune system cells and to repress the production and secretion of pro-inflammatory cytokines as well as an adipose tissue derived hormone leptin having the pro-inflammatory nature.”

Elaeis guineensis (palm tree) leaf extract
Researchers have demonstrated anti-inflammatory properties of oil palm leaf extract in aged rats. According to the researchers, most chronic conditions (aging, cancer, diabetes, cardiovascular disease, allergies, AIDS) are linked to hyper or hypo-active immune functions and therefore the need to look for new anti-inflammatory functional food. The research investigated the anti-inflammatory properties of oil palm leaf (Elaeis guineensis) ethanol extract in aged Sprague dawley rats.”

Phoenix dactylifera (Date palm)
Scientists have demonstrated the efficacy of palm leaf extract (Phoenix dactylifera) in patients with new COVID-19 in weak to moderate stages.

Date palmData showed that CRP levels decreased significantly in the intervention group compared with the placebo group on days seven and 14 post-treatment. Concurrently, Partial pressure of oxygen (PO2 levels) was elevated significantly on days seven and 14 in the same group. There was a statistical significant decrease of WBC, ESR and LDH levels in the intervention group on day 14 compared with the placebo group. In conclusion, date palm (Phoenix dactylifera) leaf extract solution (PHOENIX) can be administered to COVID-19 cases as a safe and efficient add-on medication along with routine treatments.

Diced Watermelons/ Credit: PintrestPrevious investigations on watermelon have highlighted its antioxidant activities, anti-inflammatory effects and several essential nutrients. Intake of watermelon has been associated with a reduced incidence of many diseases.

Watermelon fruit is a very rich source of vitamins A and C, and the therapeutic effects of the fruit have been reported and attributed to its antioxidant and certain phytochemical compounds. For instance, beta-carotene and lycopene have been established to play a key role in the treatment of cancer and cardiovascular diseases.

Phytol isolated from watermelon (Citrullus lanatus) sprouts induces cell death in human T-lymphoid cell line Jurkat cells via S-phase cell cycle arrest.

According to the study published in the journal Food and Chemical Toxicology, “the phytol isolated from watermelon (Citrullus lanatus) sprouts inhibited the growth of a human T-cell leukemia line Jurkat cell and suppressed tumor progression in a xenograft model of human lung adenocarcinoma epithelial cell line A549 in nude mice. To elucidate the mechanisms underlying the phytol-induced cell death in the present study, we examined the changes in cell morphology, DNA fragmentation, and intracellular reactive oxygen species (ROS) levels and performed flow cytometric analysis to evaluate cell cycle stage.

“There were no significant changes in apoptosis, autophagy, and necrosis marker in cells treated with the phytol. But, we found, for the first time, that phytol remarkably induced S-phase cell cycle arrest accompanied with intracellular ROS production. Western blot analyses showed that phytol-induced S-phase cell cycle arrest was mediated through the decreased expression of cyclins A and D and the down regulations of MAPK and PI3K/Akt. The tumour volume levels in mice treated with phytol were lower than those of non-treatment groups, and it showed very similar suppression compared with those of mice treated with cyclophosphamide. Based on the data of in vitro and in vivo studies and previous studies, we suggest phytol as a potential therapeutic compound for cancer.”

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