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Garcinia kola and garcinoic acid suppress SARS-CoV-2 spike glycoprotein S1-induced hyper-inflammation in human PBMCs through inhibition of NF-κB activation

View ORCID ProfileOlumayokun A Olajide, Victoria U Iwuanyanwu, Izabela Lepiarz-Raba, Alaa A Al-Hindawi, Mutalib A Aderogba, Hazel L Sharp, Robert J Nash
doi: https://doi.org/10.1101/2021.05.18.444690
Olumayokun A Olajide
1Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Huddersfield, HD1 3DH, United Kingdom
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  • For correspondence: o.a.olajide@hud.ac.uk
Victoria U Iwuanyanwu
1Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Huddersfield, HD1 3DH, United Kingdom
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Izabela Lepiarz-Raba
1Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Huddersfield, HD1 3DH, United Kingdom
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Alaa A Al-Hindawi
1Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Huddersfield, HD1 3DH, United Kingdom
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Mutalib A Aderogba
2Department of Chemistry, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Nigeria
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Hazel L Sharp
3PhytoQuest Ltd, Plas Gogerddan, Aberystwyth, Ceredigion, SY23 3EB, United Kingdom
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Robert J Nash
3PhytoQuest Ltd, Plas Gogerddan, Aberystwyth, Ceredigion, SY23 3EB, United Kingdom
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Abstract

Symptoms and complications associated with severe SARS-CoV-2 infection such as acute respiratory distress syndrome (ARDS) and organ damage have been linked to SARS-CoV-2 spike glycoprotein S1-induced increased production of pro-inflammatory cytokines by immune cells. In this study, the effects of an extract of Garcinia kola seeds and garcinoic acid were investigated in SARS-CoV-2 spike glycoprotein S1-stimulated human PBMCs. Results of ELISA experiments revealed that Garcinia kola extract (6.25, 12.5 and 25 μg/mL) and garcinoic acid (1.25, 2.5 and 5 μM) significantly reduced SARS-CoV-2 spike glycoprotein S1-induced increased secretion of TNFα, IL-6, IL-1β and IL-8 in PBMCs. In-cell western assays showed that pre-treatment with Garcinia kola extract and garcinoic acid reduced elevated expressions of both phospho-p65 and phospho-κBα proteins, as well as NF-κB DNA binding capacity and NF-κB-driven luciferase expression following stimulation of PBMCs with spike glycoprotein S1. Furthermore, pre-treatment of PBMCs with Garcinia kola extract prior to stimulation with SARS-CoV-2 spike glycoprotein S1 resulted in reduced damage to adjacent A549 lung epithelial cells. Gas Chromatography-Mass Spectrometry (GCMS) and HPLC-PDA confirmed the presence of garcinoic acid in the Garcinia kola extract used in this study. These results suggest that the seed of Garcinia kola and garcinoic acid are natural products which may possess pharmacological/therapeutic benefits in reducing cytokine storm during the late stage of severe SARS-CoV-2 and other coronavirus infections.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted May 19, 2021.
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Garcinia kola and garcinoic acid suppress SARS-CoV-2 spike glycoprotein S1-induced hyper-inflammation in human PBMCs through inhibition of NF-κB activation
Olumayokun A Olajide, Victoria U Iwuanyanwu, Izabela Lepiarz-Raba, Alaa A Al-Hindawi, Mutalib A Aderogba, Hazel L Sharp, Robert J Nash
bioRxiv 2021.05.18.444690; doi: https://doi.org/10.1101/2021.05.18.444690
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Garcinia kola and garcinoic acid suppress SARS-CoV-2 spike glycoprotein S1-induced hyper-inflammation in human PBMCs through inhibition of NF-κB activation
Olumayokun A Olajide, Victoria U Iwuanyanwu, Izabela Lepiarz-Raba, Alaa A Al-Hindawi, Mutalib A Aderogba, Hazel L Sharp, Robert J Nash
bioRxiv 2021.05.18.444690; doi: https://doi.org/10.1101/2021.05.18.444690

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