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Researchers in the UK 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 coronavirus disease 2019 (COVID-19) and other coronavirus infections.
The team – from the University of Huddersfield, PhytoQuest Ltd in Aberystwyth, and Obafemi Awolowo University in IleIfe – says that treatment with these natural products may reduce the cytokine storm that can develop following infection with severe acute respiratory syndrome coronavirus 2 (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 say 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.
More about the cytokine storm in COVID-19
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,” writes Olajide and colleagues.
What did the researchers do?
The team investigated the effects that an extract of G.kola seed and garcinoic acid had on SARS-CoV-2 spike protein S1-induced hyper-inflammation in human PBMCs.
The PBMCs were incubated with either 6.25, 12.5 and 25µg/mL of G. kola extract or 1.25, 2.5 and 5µM of garcinoic acid for 60 minutes and then stimulated with 10µg/mL of spike S1 for 24 hours.
The results of enzyme-linked immunosorbent assays showed that both the seed extract and garcinoic acid significantly reduced the S1-induced secretion of TNFa, IL-6, IL-1β and IL-8 in a concentration-dependent manner.
The researchers say they previously showed that activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) is a mechanism for the spike S1-induced exaggerated production of TNFa, IL-6, IL-1β and IL-8 in PBMCs.
They, therefore, conducted in-cell western assays to investigate whether inhibition of NF-kB activation may contribute to the effects the products had on the secretion of the cytokines.
Both the seed extract and garcinoic acid inhibited cytoplasmic activation, DNA binding and transcriptional activity of NF- kB in the PBMCs, thereby suggesting that this transcription factor plays a role in their anti-inflammatory activities.
The results of reporter gene assays also showed that stimulation of NF-kB luciferase reporter transfected cells with spike S1 activated NF-kB-driven luciferase expression, which was significantly reduced by treatment with all concentrations of G. kola extract.
“Further investigations are required to identify specific molecular targets involved in NF-kB-mediated inhibition of SARS-CoV-2 spike protein S1-induced inflammation by G. kola and garcinoic acid,” says the team.
Treatment with G. kola reduced damage to A549 lung epithelial cells
Finally, the researchers tested the effects of the seed extract and garcinoic acid on the viability of A549 human lung alveolar epithelial cells that were co-cultured with spike S1-stimulated PBMCs.
When the PBMCs were treated with 6.25µg/mL of the G. kola extract prior to stimulation with spike S1, no significant reduction in toxicity to the A549 lung epithelial cells was observed.
However, increasing the concentration of G. kola to 12.5 and 25 µg/mL significantly reduced damage to the A549 cells.
Pre-treatment of the PBMCs with 1.25, 2.5 and 5 µM garcinoic acid did not significantly reduce toxicity to A549 cells, but levels of TNFa and IL-6 were reduced in the PBMCs at all concentrations tested.
The products could be beneficial in the treatment of severe COVID-19
Olajide and colleagues say 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 conclude.
*Important Notice
bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.